humulene and Pain

Approximately 18% of patients with cancer use cannabis at one time as palliation or treatment for their cancer. We performed a systematic review of randomized cannabis cancer trials to establish a guideline for its use in pain and to summarize the risk of harm and adverse events when used for any indication in cancer patients.. A systematic review of randomized trials with or without meta-analysis was carried out from MEDLINE, CCTR, Embase, and PsychINFO. The search involved randomized trials of cannabis in cancer patients. The search ended on November 12, 2021. The Jadad grading system was used for grading quality. Inclusion criteria for articles were randomized trials or systematic reviews of randomized trials of cannabinoids versus either placebo or active comparator explicitly in adult patients with cancer.. Thirty-four systematic reviews and randomized trials met the eligibility criteria for cancer pain. Seven were randomized trials involving patients with cancer pain. Two trials had positive primary endpoints, which could not be reproduced in similarly designed trials. High-quality systematic reviews with meta-analyses found little evidence that cannabinoids are an effective adjuvant or analgesic to cancer pain. Seven systematic reviews and randomized trials related to harms and adverse events were included. There was inconsistent evidence about the types and levels of harm patients may experience when using cannabinoids.. The MASCC panel recommends against the use of cannabinoids as an adjuvant analgesic for cancer pain and suggests that the potential risk of harm and adverse events be carefully considered for all cancer patients, particularly with treatment with a checkpoint inhibitor.

Topics: Adjuvants, Immunologic; Adult; Cancer Pain; Cannabinoids; Cannabis; Humans; Neoplasms; Pain

Topics: Animals; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Dronabinol; Epilepsy; Humans; Pain

Cannabis use among the elderly has increased over the previous 2 decades. This has translated to a greater proportion of orthopedic procedures being undertaken on these patients. This review provides clinicians with evidence-based information on the effects of cannabis on pain control in THA and TKA, to help counsel these patients and facilitate their perioperative management. The review specifically focuses on the following: origins of cannabis; biochemistry of cannabis; medical versus recreational cannabis; pharmacology of cannabis; effects of cannabis on bone metabolism; preoperative pain control; preoperative systemic considerations; intraoperative considerations; postoperative pain control, postoperative systemic considerations; and scope for future work.

Topics: Aged; Arthroplasty, Replacement, Knee; Cannabis; Humans; Orthopedic Procedures; Pain; Pain Management

Cannabidiol (CBD), a major metabolite of Cannabis sativa, is popularized as a medicinal product, with potential for analgesic, antiinflammatory, and antioxidant effects. CBD may hold promise as a treatment in rheumatic diseases, but evidence to date remains preclinical. Preclinical effects on pain and inflammation is encouraging, but clinical study is lacking, with only a single study in knee osteoarthritis reporting a promising effect on symptoms. CBD products are freely available over the counter and marketed as food supplements or wellness products. The World Health Organization has identified pure CBD as safe and without abuse potential, but products are not subject to drug regulatory standards, leading to inconsistency in manufacturing practices and quality of products. Not only have molecular concentrations of CBD been identified as inaccurate, but concerns exist regarding contaminants, including heavy metals, pesticides, microbes, and mycotoxins, as well as added tetrahydrocannabinol. Drug-drug interactions pose a potential risk due to metabolism via the cytochrome P450 enzyme pathway. Patients wishing to use CBD should obtain a product with certification of Good Manufacturing Practices, initiate treatment with a nighttime low dose, and have defined outcome goals within a reasonable time frame. Treatments should not be managed by nonmedical dispensary personnel. The hope that CBD may be a useful therapy must be substantiated by sound scientific study.

Topics: Cannabidiol; Cannabis; Dronabinol; Humans; Pain; Rheumatology

Various preclinical and clinical studies exhibited the potential of cannabis against various diseases, including cancer and related pain. Subsequently, many efforts have been made to establish and develop cannabis-related products and make them available as prescription products. Moreover, FDA has already approved some cannabis-related products, and more advancement in this aspect is still going on. However, the approved product of cannabis is in oral dosage form, which exerts various limitations to achieve maximum therapeutic effects. A considerable translation is on a hike to improve bioavailability, and ultimately, the therapeutic efficacy of cannabis by the employment of nanotechnology. Besides the well-known psychotropic effects of cannabis upon the use at high doses, literature has also shown the importance of cannabis and its constituents in minimising the lethality of cancer in the preclinical models. This review discusses the history of cannabis, its legal aspect, safety profile, the mechanism by which cannabis combats with cancer, and the advancement of clinical therapy by exploiting nanotechnology. A brief discussion related to the role of cannabinoid in various cancers has also been incorporated. Lastly, the information regarding completed and ongoing trials have also been elaborated.

Topics: Cannabinoids; Cannabis; Humans; Nanotechnology; Neoplasms; Pain

Topics: Cannabinoids; Cannabis; Chronic Pain; Female; Humans; Medical Marijuana; Pain

Topics: Analgesics; Cannabis; Humans; Pain

Persistent pain is a common and disabling health problem that is often difficult to treat. There is an increasing interest in medicinal cannabis for treatment of persistent pain; however, the limited superiority of cannabinoids over placebo in clinical trials suggests that positive expectations may contribute to the improvements.. To evaluate the size of placebo responses in randomized clinical trials in which cannabinoids were compared with placebo in the treatment of pain and to correlate these responses to objective estimates of media attention.. A systematic literature search was conducted within the MEDLINE and Embase databases. Studies published until September 2021 were considered.. Cannabinoid studies with a double-blind, placebo-controlled design with participants 18 years or older with clinical pain of any duration were included. Studies were excluded if they treated individuals with HIV/AIDS or severe skin disorders.. The study followed the Preferred Reporting Items for Systematic Review and Meta-analyses reporting guideline. Data were extracted by independent reviewers. Quality assessment was performed using the Risk of Bias 2 tool. Attention and dissemination metrics for each trial were extracted from Altmetric and Crossref. Data were pooled and analyzed using a random-effects statistical model.. Change in pain intensity from before to after treatment, measured as bias-corrected standardized mean difference (Hedges g).. Twenty studies, including 1459 individuals (mean [SD] age, 51 [7] years; age range, 33-62 years; 815 female [56%]), were included. Pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean [SE] Hedges g, 0.64 [0.13]; P < .001). Trials with low risk of bias had greater placebo responses (q1 = 5.47; I2 = 87.08; P = .02). The amount of media attention and dissemination linked to each trial was proportionally high, with a strong positive bias, but was not associated with the clinical outcomes.. Placebo contributes significantly to pain reduction seen in cannabinoid clinical trials. The positive media attention and wide dissemination may uphold high expectations and shape placebo responses in future trials, which has the potential to affect the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief.

Topics: Adult; Attention; Cannabinoids; Cannabis; Female; Humans; Middle Aged; Pain; Placebo Effect; Randomized Controlled Trials as Topic

The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development. The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases. This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of

Topics: Anxiety; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Cardiovascular Diseases; Depression; Endocannabinoids; Feeding Behavior; Homeostasis; Humans; Neurodegenerative Diseases; Neurogenesis; Pain; Receptors, Cannabinoid

Cannabis is widely used for both recreational and medicinal purposes on a global scale. There is accumulating interest in the use of cannabis and its constituents for athletic recovery, and in some instances, performance. Amidst speculation of potential beneficial applications, the effects of cannabis and its two most abundant constituents, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), remain largely un-investigated. The purpose of this review is to critically evaluate the literature describing the effects of whole cannabis, THC, and CBD, on athletic performance and recovery. While investigations of whole cannabis and THC have generally shown either null or detrimental effects on exercise performance in strength and aerobic-type activities, studies of sufficient rigor and validity to conclusively declare ergogenic or ergolytic potential in athletes are lacking. The ability of cannabis and THC to perturb cardiovascular homeostasis warrants further investigation regarding mechanisms by which performance may be affected across different exercise modalities and energetic demands. In contrast to cannabis and THC, CBD has largely been scrutinized for its potential to aid in recovery. The beneficial effects of CBD on sleep quality, pain, and mild traumatic brain injury may be of particular interest to certain athletes. However, research in each of these respective areas has yet to be thoroughly investigated in athletic populations. Elucidating the effects of whole cannabis, THC, and CBD is pertinent for both researchers and practitioners given the widespread use of these products, and their potential to interact with athletes' performance and recovery.

Topics: Athletic Performance; Cannabidiol; Cannabis; Dronabinol; Humans; Pain

Regulatory approvals for Epidiolex (purified cannabidiol) in the treatment of childhood drug resistant epilepsy have set a precedent for the use of cannabinoids as a prescribed medicine. Two common reasons cited for the use and prescription of cannabis-based products are pain and insomnia. Unlike drug resistant epilepsy, the level of evidence of efficacy in pain is poorly developed. The lowest quality trials with the greatest methodological shortcomings suggest some benefit, a level of evidence that is inconsistent with widespread prescribing. The evidence in insomnia is scant. Ongoing trial development and critical review of the literature should not be overshadowed by increasing permissiveness towards cannabis use and anecdotal reports of efficacy.

Topics: Cannabidiol; Cannabinoids; Cannabis; Drug Resistant Epilepsy; Humans; Pain

Gaps in research evidence and inconsistent policies regarding use of cannabis for pain and associated symptoms result in confusion for healthcare providers and patients. The objective of this review was to synthesize information on cannabis use for pain with legal and policy implications to create a shared decision-making model that can be used to guide patient care interactions.. Current cannabis policies, state laws, research, and patient care practices related to medical and recreational cannabis in the United States were reviewed, along with best practices in shared decision-making. Reviewed literature was then synthesized to create a model that can be used by registered nurses and others to address cannabis use, where legal, for pain and related symptoms.. Cannabis is a legal option for many patients with pain. To minimize harms and optimize benefits, nurses can play a key role when authorized by law in assisting with decision-making surrounding cannabis use.

Topics: Analgesics; Cannabis; Humans; Medical Marijuana; Pain; United States

This narrative review represents an output from the International Association for the Study of Pain's global task force on the use of cannabis, cannabinoids, and cannabis-based medicines for pain management, informed by our companion systematic review and meta-analysis of preclinical studies in this area. Our aims in this review are (1) to describe the value of studying cannabinoids and endogenous cannabinoid (endocannabinoid) system modulators in preclinical/animal models of pain; (2) to discuss both pain-related efficacy and additional pain-relevant effects (adverse and beneficial) of cannabinoids and endocannabinoid system modulators as they pertain to animal models of pathological or injury-related persistent pain; and (3) to identify important directions for future research. In service of these goals, this review (1) provides an overview of the endocannabinoid system and the pharmacology of cannabinoids and endocannabinoid system modulators, with specific relevance to animal models of pathological or injury-related persistent pain; (2) describes pharmacokinetics of cannabinoids in rodents and humans; and (3) highlights differences and discrepancies between preclinical and clinical studies in this area. Preclinical (rodent) models have advanced our understanding of the underlying sites and mechanisms of action of cannabinoids and the endocannabinoid system in suppressing nociceptive signaling and behaviors. We conclude that substantial evidence from animal models supports the contention that cannabinoids and endocannabinoid system modulators hold considerable promise for analgesic drug development, although the challenge of translating this knowledge into clinically useful medicines is not to be underestimated.

Topics: Animals; Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Endocannabinoids; Pain; Pain Management; Receptors, Cannabinoid

The medicolegal landscape of cannabis continues to change, and with ever increasing access there has been a concurrent proliferation of research seeking to understand the utility of cannabinoids in treating innumerable conditions with pain at the forefront. This article seeks to summarize clinically relevant findings in cannabinoid research to better prepare clinicians in the utility of cannabis in the treatment of pain.

Topics: Cannabinoids; Cannabis; Humans; Pain

The high frequency and painful profile of inflammatory oral lesions and the lack of an effective drug protocol for their management stimulate the search for pharmacological alternatives for the treatment of these conditions. Cannabidiol is the major non-psychotropic constituent of Cannabis sativa, receiving lately scientific interest because of its potential in the treatment of inflammatory disorders such as asthma, colitis and arthritis. There is little published in the current literature about the use of cannabidiol in oral health. Among its many protective functions, the ability to attenuate inflammation through the modulation of cytokines and its antiedema and analgesic effects may be important features in the treatment of oral lesions. In this review, we suggest that cannabidiol can be useful in the management of oral inflammatory disorders.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cannabidiol; Cannabis; Cytokines; Humans; Inflammation; Mouth Diseases; Pain

Osteoarticular equine disease is a common cause of malady; in general, its therapy is supported on steroids and nonsteroidal anti-inflammatories. Nevertheless, many side effects may develop when these drugs are administered. Nowadays, the use of new alternatives for this pathology attention is demanded; in that sense, cannabinoid CB2 agonists may represent a novel alternative. Cannabinoid belongs to a group of molecules known by their psychoactive properties; they are synthetized by the Cannabis sativa plant, better known as marijuana. The aim of this study was to contribute to understand the pharmacology of cannabinoid CB2 receptors and its potential utilization on equine veterinary patients with a chronic degenerative painful condition. In animals, two main receptors for cannabinoids are recognized, the cannabinoid receptor type 1 and the cannabinoid receptor type 2. Once they are activated, both receptors exert a wide range of physiological responses, as nociception modulation. Recently, it has been proposed the use of synthetic cannabinoid type 2 receptor agonists; those receptors looks to confer antinociceptive properties but without the undesired psychoactive side effects; for that reason, veterinary patients, whit chronical degenerative diseases as osteoarthritis may alleviate one of the most common symptom, the pain, which in some cases for several reasons, as patient individualities, or side effects produced for more conventional treatments cannot be attended in the best way.

Topics: Analgesics; Animals; Cannabinoids; Cannabis; Horse Diseases; Horses; Pain; Receptors, Cannabinoid

Topics: Amputation, Surgical; Analgesics; Cannabis; Humans; Pain; Pain Management

An online questionnaire about cannabis medication (CAM) was sent to German pain therapists 1 year after the introduction of the new act "Amendment to drug and other regulations" of 06.03.2017.. A total of 120 pain therapists participated. Information on 1560 treated patients was analyzed. Only in the case of Dronabinol and Sativex® did at least 50% of physicians feel well informed. Requests for the coverage of costs were sent to the statuary health insurance companies for 1521 patients. These requests had already been decided for 1265 patients (83%) at the time of the questionnaire. A total of 457 requests (36.1%) were denied, including 28 requests from palliative care patients. Most of the pain therapists (67.5%) were well informed about Dronabinol, but less so about the other CAM.. The study shows an information deficit in knowledge and handling of selected CAM among physicians. Given the high rejection rate, there may also be a knowledge gap on the side of the health insurances. From a certain number of patients upwards, the non-interventional accompanying survey required by law was deemed to be barely practicable from both a time and an economical point of view.

Topics: Cannabis; Germany; Humans; Internet; Pain; Pain Management; Palliative Medicine; Practice Patterns, Physicians'; Societies; Surveys and Questionnaires

Since March 2017, the prescription of medical cannabis at the expense of the statutory health insurance is possible after approval by the respective medical services. Chronic pain is the most common indication, as health claims data and the accompanying survey show. From the point of view of the law, a prescription is indicated in cases of serious illness, missing or not indicated established therapeutic approaches and a not entirely remote prospect of improvement of the illness or its symptoms. This describes a broader indication spectrum than can currently be based on randomised controlled clinical trials. There is weak evidence of low efficacy for neuropathic pain. For pain related to spasticity and cancer-related pain there is evidence of improvements in quality of life, but effects on pain are of little relevance. For all other indications, only an individual therapeutic trial can be justified based on the available external evidence. However, this usually corresponds to the demand of "a not entirely remote prospect" of a noticeably positive effect of medical cannabis. It is also problematic that almost no long-term studies for the application and efficacy of flowers and extracts are available.Current knowledge on the use of cannabis-based drugs and, more clearly, medical cannabis for chronic pain is insufficient. The increase in the number of countries with marketing authorisations or exemptions for medicinal cannabis or cannabis-based drugs for chronic pain will also pave the way for larger empirical and population-based studies that will further improve the evidence base of research and clinical use.

Topics: Analgesics; Cannabis; Chronic Pain; Humans; Medical Marijuana; Pain; Quality of Life

In Germany, medical doctors who prescribe cannabis medicines at the expense of the statutory health insurance are obliged to take part in a noninterventional survey on the use of these cannabis medicines. The survey collects and evaluates anonymized treatment data and runs until 31 March 2022. Amongst other things, the results of the accompanying survey are the basis on which the Joint Federal Committee (G-BA) regulates the future assumption of treatment costs in the context of a therapy with cannabis medicines in accordance with the Social Code (SGB) V. The transmission of the data for the survey takes place via an online portal operated by the Federal Institute for Drugs and Medical Devices (BfArM). The first data transmission takes place after a treatment period of one year or, if the treatment discontinued before the end of one year, directly after discontinuation of therapy.At the time of the interim evaluation, 01 February 2019, there were 4153 complete datasets collected. Most frequently, the symptom "pain" was treated (69%), followed by spasticity (11%), and anorexia/wasting (8%). The observed adverse reactions correspond with those listed in the product information for the two cannabis-based proprietary medicinal products, Sativex® (GW Pharma Ltd, Salisbury, Wiltshire, UK) and Canemes® (AOP Orphan Pharmaceuticals AG, Vienna, Austria). Most often, insufficient effect was the reason for a discontinuation of treatment. The main indication of pain was already apparent in the licensing procedure for the acquisition of cannabis for medical purposes between the years 2005 and 2016. Further evaluations and subgroup analysis will be carried out when higher case numbers are available.

Topics: Cannabis; Germany; Humans; Pain; Prescriptions; Surveys and Questionnaires

Cannabis has been employed medicinally throughout history, but its recent legal prohibition, biochemical complexity and variability, quality control issues, previous dearth of appropriately powered randomised controlled trials, and lack of pertinent education have conspired to leave clinicians in the dark as to how to advise patients pursuing such treatment. With the advent of pharmaceutical cannabis-based medicines (Sativex/nabiximols and Epidiolex), and liberalisation of access in certain nations, this ignorance of cannabis pharmacology and therapeutics has become untenable. In this article, the authors endeavour to present concise data on cannabis pharmacology related to tetrahydrocannabinol (THC), cannabidiol (CBD) et al., methods of administration (smoking, vaporisation, oral), and dosing recommendations. Adverse events of cannabis medicine pertain primarily to THC, whose total daily dose-equivalent should generally be limited to 30mg/day or less, preferably in conjunction with CBD, to avoid psychoactive sequelae and development of tolerance. CBD, in contrast to THC, is less potent, and may require much higher doses for its adjunctive benefits on pain, inflammation, and attenuation of THC-associated anxiety and tachycardia. Dose initiation should commence at modest levels, and titration of any cannabis preparation should be undertaken slowly over a period of as much as two weeks. Suggestions are offered on cannabis-drug interactions, patient monitoring, and standards of care, while special cases for cannabis therapeutics are addressed: epilepsy, cancer palliation and primary treatment, chronic pain, use in the elderly, Parkinson disease, paediatrics, with concomitant opioids, and in relation to driving and hazardous activities.

Topics: Cannabidiol; Cannabis; Dose-Response Relationship, Drug; Dronabinol; Drug Administration Schedule; Drug Combinations; Humans; Inflammation; Medical Marijuana; Pain

Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms. This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects.. We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs. Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms. Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.

Topics: Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Combinations; Humans; Multiple Sclerosis; Pain; Quality of Life; Randomized Controlled Trials as Topic; Systematic Reviews as Topic

Review the medical literature for the use of cannabis/cannabinoids in the treatment of migraine, headache, facial pain, and other chronic pain syndromes, and for supporting evidence of a potential role in combatting the opioid epidemic. Review the medical literature involving major and minor cannabinoids, primary and secondary terpenes, and flavonoids that underlie the synergistic entourage effects of cannabis. Summarize the individual medicinal benefits of these substances, including analgesic and anti-inflammatory properties.. There is accumulating evidence for various therapeutic benefits of cannabis/cannabinoids, especially in the treatment of pain, which may also apply to the treatment of migraine and headache. There is also supporting evidence that cannabis may assist in opioid detoxification and weaning, thus making it a potential weapon in battling the opioid epidemic. Cannabis science is a rapidly evolving medical sector and industry with increasingly regulated production standards. Further research is anticipated to optimize breeding of strain-specific synergistic ratios of cannabinoids, terpenes, and other phytochemicals for predictable user effects, characteristics, and improved symptom and disease-targeted therapies.

Topics: Cannabinoids; Cannabis; Flavonoids; Headache; Humans; Migraine Disorders; Pain; Terpenes

Cannabis sativa has long been used for medicinal purposes. To improve safety and efficacy, compounds from C. sativa were purified or synthesized and named under an umbrella group as cannabinoids. Currently, several cannabinoids may be prescribed in Canada for a variety of indications such as nausea and pain. More recently, an increasing number of reports suggest other salutary effects associated with endogenous cannabinoid signaling including cardioprotection. The therapeutic potential of cannabinoids is therefore extended; however, evidence is limited and mechanisms remain unclear. In addition, the use of cannabinoids clinically has been hindered due to pronounced psychoactive side effects. This review provides an overview on the endocannabinoid system, including known physiological roles, and conditions in which cannabinoid receptor signaling has been implicated.

Topics: Affect; Amidohydrolases; Analgesics; Animals; Appetite Regulation; Canada; Cannabinoid Receptor Agonists; Cannabinoid Receptor Antagonists; Cannabinoids; Cannabis; Cardiovascular System; Central Nervous System; Endocannabinoids; Humans; Medical Marijuana; Multiple Sclerosis; Neoplasms; Neurodegenerative Diseases; Pain; Receptors, Cannabinoid; Signal Transduction; Sleep; Vomiting

Herbal cannabis has been used for thousands of years for medical purposes. With elucidation of the chemical structures of tetrahydrocannabinol (THC) and cannabidiol (CBD) and with discovery of the human endocannabinoid system, the medical usefulness of cannabinoids has been more intensively explored. While more randomized clinical trials are needed for some medical conditions, other medical disorders, like chronic cancer and neuropathic pain and certain symptoms of multiple sclerosis, have substantial evidence supporting cannabinoid efficacy. While herbal cannabis has not met rigorous FDA standards for medical approval, specific well-characterized cannabinoids have met those standards. Where medical cannabis is legal, patients typically see a physician who "certifies" that a benefit may result. Physicians must consider important patient selection criteria such as failure of standard medical treatment for a debilitating medical disorder. Medical cannabis patients must be informed about potential adverse effects, such as acute impairment of memory, coordination and judgment, and possible chronic effects, such as cannabis use disorder, cognitive impairment, and chronic bronchitis. In addition, social dysfunction may result at work/school, and there is increased possibility of motor vehicle accidents. Novel ways to manipulate the endocannbinoid system are being explored to maximize benefits of cannabinoid therapy and lessen possible harmful effects.

Topics: Analgesics, Non-Narcotic; Cannabinoids; Cannabis; Drug and Narcotic Control; Endocannabinoids; Humans; Marijuana Abuse; Medical Marijuana; Meta-Analysis as Topic; Pain; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Receptors, Cannabinoid; United States

Chronic neuropathic pain, the most frequent condition affecting the peripheral nervous system, remains underdiagnosed and difficult to treat. Inhaled cannabis may alleviate chronic neuropathic pain. Our objective was to synthesize the evidence on the use of inhaled cannabis for chronic neuropathic pain. We performed a systematic review and a meta-analysis of individual patient data. We registered our protocol with PROSPERO CRD42011001182. We searched in Cochrane Central, PubMed, EMBASE, and AMED. We considered all randomized controlled trials investigating chronic painful neuropathy and comparing inhaled cannabis with placebo. We pooled treatment effects following a hierarchical random-effects Bayesian responder model for the population-averaged subject-specific effect. Our evidence synthesis of individual patient data from 178 participants with 405 observed responses in 5 randomized controlled trials following patients for days to weeks provides evidence that inhaled cannabis results in short-term reductions in chronic neuropathic pain for 1 in every 5 to 6 patients treated (number needed to treat = 5.6 with a Bayesian 95% credible interval ranging between 3.4 and 14). Our inferences were insensitive to model assumptions, priors, and parameter choices. We caution that the small number of studies and participants, the short follow-up, shortcomings in allocation concealment, and considerable attrition limit the conclusions that can be drawn from the review. The Bayes factor is 332, corresponding to a posterior probability of effect of 99.7%.. This novel Bayesian meta-analysis of individual patient data from 5 randomized trials suggests that inhaled cannabis may provide short-term relief for 1 in 5 to 6 patients with neuropathic pain. Pragmatic trials are needed to evaluate the long-term benefits and risks of this treatment.

Topics: Administration, Inhalation; Adult; Aged; Bayes Theorem; Cannabis; Chronic Pain; Female; Humans; Male; Medical Marijuana; Middle Aged; Pain; Peripheral Nervous System; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Young Adult

Cannabis, or marijuana, has been used for medicinal purposes for many years. Several types of cannabinoid medicines are available in the United States and Canada. Dronabinol (schedule III), nabilone (schedule II), and nabiximols (not U.S. Food and Drug Administration approved) are cannabis-derived pharmaceuticals. Medical cannabis or medical marijuana, a leafy plant cultivated for the production of its leaves and flowering tops, is a schedule I drug, but patients obtain it through cannabis dispensaries and statewide programs. The effect that cannabinoid compounds have on the cannabinoid receptors (CB(1) and CB(2) ) found in the brain can create varying pharmacologic responses based on formulation and patient characteristics. The cannabinoid Δ(9) -tetrahydrocannabinol has been determined to have the primary psychoactive effects; the effects of several other key cannabinoid compounds have yet to be fully elucidated. Dronabinol and nabilone are indicated for the treatment of nausea and vomiting associated with cancer chemotherapy and of anorexia associated with weight loss in patients with acquired immune deficiency syndrome. However, pain and muscle spasms are the most common reasons that medical cannabis is being recommended. Studies of medical cannabis show significant improvement in various types of pain and muscle spasticity. Reported adverse effects are typically not serious, with the most common being dizziness. Safety concerns regarding cannabis include the increased risk of developing schizophrenia with adolescent use, impairments in memory and cognition, accidental pediatric ingestions, and lack of safety packaging for medical cannabis formulations. This article will describe the pharmacology of cannabis, effects of various dosage formulations, therapeutics benefits and risks of cannabis for pain and muscle spasm, and safety concerns of medical cannabis use.

Topics: Animals; Cannabis; Clinical Trials as Topic; Dronabinol; Humans; Pain; Phytotherapy; Receptor, Cannabinoid, CB1; Spasm; Treatment Outcome

Biological activity of cannabinoids is caused by binding to two cannabinoid receptors CB1 and CB2. Psychoactive is not only tetrahydrocannabinol (THC) but also: cannabidiol, cannabigerol or cannabichromen. Formerly, the usefulness of hemp was assessed in the relation to temporary appeasement of the symptoms of some ailments as nausea or vomiting. Present discoveries indicates that cannabis-based drugs has shown ability to alleviate of autoimmunological disorders such as: Multiple sclerosis (MS), Rheumatoid arthritis (RA) or inflammatory bowel disease. Another studies indicates that cannabinoids play role in treatment of neurological disorders like Alzheimer disease or Amyotrophic lateral sclerosis (ALS) or even can reduce spreading of tumor cells. Cannabinoids stand out high safety profile considering acute toxicity, it is low possibility of deadly overdosing and side-effects are comprise in range of tolerated side-effects of other medications. In some countries marinol and nabilone are used as anti vomiting and nausea drug. First cannabis-based drug containg naturally occurring cannabinoids is Sativex. Sativex is delivered in an mucosal spray for patients suffering from spasticity in MS, pain relevant with cancer and neuropathic pain of various origin. Despite the relatively low acute toxicity of cannabinoids they should be avoid in patients with psychotic disorders, pregnant or breastfeeding woman. Cannabinoids prolong a time of reaction and decrease power of concentration that's why driving any vehicles is forbidden. Cannabis side-effects varies and depend from several factors like administrated dose, rout of administration and present state of mind. After sudden break from long-lasting use, withdrawal symptoms can appear, although they entirely disappear after a week or two.

Topics: Arthritis, Rheumatoid; Cannabidiol; Cannabinoids; Cannabis; Contraindications; Dronabinol; Drug Combinations; Humans; Inflammatory Bowel Diseases; Multiple Sclerosis; Muscle Spasticity; Nausea; Nervous System Diseases; Pain; Plant Extracts; Vomiting

In the last 15 years there has been a major shift in the laws governing medical use of cannabis in the United States. Corresponding with this change there has been escalating interest in the role that cannabis, commonly referred to as marijuana, and cannabinoids play in the care of patients with cancer. This review will examine cannabis' and cannabinoids' current and potential roles in cancer care. Specifically, we will examine five areas of cannabis medicine: (1) pharmacologic properties of cannabis; (2) its potential role in the development of human cancers, particularly smoking-related malignancies; (3) cannabinoids' potential as anti-cancer therapies; (4) cannabis and cannabinoids in the palliation of common cancer-associated symptoms; (5) current legal status of cannabis for medical purposes in the United States.

Topics: Animals; Biological Availability; Cannabinoids; Cannabis; Humans; Marijuana Smoking; Mice; Neoplasms; Pain; Palliative Care; Phytotherapy; United States

Marijuana has been used medically since antiquity. In recent years there has been a resurgence of interest in medical applications of various cannabis preparations. These drugs have been cited in the medical literature as potential secondary treatment agents for severe pain, muscle spasticity, anorexia, nausea, sleep disturbances, and numerous other uses. This article reviews the research literature related to medical applications of various forms of cannabis. Benefits related to medical use of cannabinoids are examined and a number of potential risks associated with cannabis use, both medical and recreational, are considered. There is a clearly identified need for further research to isolate significant benefits from the medical application of cannabinoids and to establish dosage levels, appropriate delivery mechanisms and formulations, and to determine what role, if any, cannabinoids might play in legitimate medical applications. It is also imperative to determine if reported dangers pose a significant health risks to users.

Topics: Cannabinoids; Cannabis; Clinical Trials as Topic; Dronabinol; Humans; Marijuana Abuse; Muscle Spasticity; Nausea; Pain; Quality of Life; United States

Chronic pain is a common and debilitating symptom experienced in the context of numerous other physical and emotional symptoms by many patients with chronic kidney disease (CKD). Management of pain with opioids in CKD can be problematic given the prominence of adverse effects of opioids in CKD, which may exacerbate symptoms, such as nausea, anorexia, pruritus, and insomnia, all of which impact negatively on patients' health-related quality of life. Novel therapeutic approaches for pain and symptom management in CKD are required. Recent research in the area of cannabinoids (CBs) is legitimizing the use of cannabis-based medicine. In this review, we describe the symptom burden borne by patients with CKD and review some of the key basic science and clinical literature to evaluate the potential use of CBs for the management of overall symptom burden in CKD.

Topics: Analgesics; Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Humans; Kidney Failure, Chronic; Pain; Quality of Life; Receptors, Cannabinoid

In recent times, our knowledge of cannabinoids and the endocannabinoid system has greatly advanced. With expanding knowledge, synthetic cannabinoids - including nabilone, dronabinol and a combination of synthetic Delta9-THC and cannabidiol - have been developed and tested for benefit in a variety of therapeutic indications.. The aim of this article is to provide a summative review of the vast amount of clinical trial data now available on these agents.. To locate clinical trials for review, a literature search was performed using PubMed between the dates of 25 May and 30 June 2009. Search parameters were set to isolate only human randomized controlled trials (RCTs) published between 1990 and 2009. Keywords consistently used for each search include: cannabinoids, marijuana, THC, nabilone and dronabinol. Preferential selection was given to the best-designed trials, focusing on placebo-controlled, double-blind RCTs with the largest patient populations, if available.. As efficacy and tolerability of these agents remain questionable, it is important that cannabinoids not be considered 'first-line' therapies for conditions for which there are more supported and better-tolerated agents. Instead, these agents could be considered in a situation of treatment failure with standard therapies or as adjunctive agents where appropriate.

Topics: Activities of Daily Living; Cannabinoids; Cannabis; Combined Modality Therapy; Double-Blind Method; Dronabinol; Humans; Hypersensitivity; Pain; Pain Measurement

The specialty of oral and maxillofacial surgery has had at its core the foundations of anesthesia and pain and anxiety control. This article attempts to refamiliarize the reader with clinical pearls helpful in the management of patients with chronic pain conditions. The authors also hope to highlight the interplay of chronic pain and psychology as it relates to the oral and maxillofacial surgery patient. To that end, the article outlines and reviews the neurophysiology of pain, the definitions of pain, conditions encountered by the oral and maxillofacial surgeon that produce chronic pain, the psychological impact and comorbidities associated with patients experiencing chronic pain conditions, and concepts of multimodal treatment for patients experiencing chronic pain conditions.

Topics: Adrenergic alpha-Antagonists; Analgesics; Anticonvulsants; Antidepressive Agents; Cannabis; Chronic Disease; Cognitive Behavioral Therapy; Comorbidity; Dental Care for Chronically Ill; Humans; Muscle Relaxants, Central; Oral Surgical Procedures; Pain

Advances in cannabis research have paralleled developments in opioid pharmacology whereby a psychoactive plant extract has elucidated novel endogenous signalling systems with therapeutic significance. Cannabinoids (CBs) are chemical compounds derived from cannabis. The major psychotropic CB delta-9-tetrahydrocannabinol (Delta(9)-THC) was isolated in 1964 and the first CB receptor (CB(1)R) was cloned in 1990. CB signalling occurs via G-protein-coupled receptors distributed throughout the body. Endocannabinoids are derivatives of arachidonic acid that function in diverse physiological systems. Neuronal CB(1)Rs modulate synaptic transmission and mediate psychoactivity. Immune-cell CB(2) receptors (CB(2)R) may down-regulate neuroinflammation and influence cyclooxygenase-dependent pathways. Animal models demonstrate that CBRs play a fundamental role in peripheral, spinal, and supraspinal nociception and that CBs are effective analgesics. Clinical trials of CBs in multiple sclerosis have suggested a benefit in neuropathic pain. However, human studies of CB-mediated analgesia have been limited by study size, heterogeneous patient populations, and subjective outcome measures. Furthermore, CBs have variable pharmacokinetics and can manifest psychotropism. They are currently licensed as antiemetics in chemotherapy and can be prescribed on a named-patient basis for neuropathic pain. Future selective peripheral CB(1)R and CB(2)R agonists will minimize central psychoactivity and may synergize opioid anti-nociception. This review discusses the basic science and clinical aspects of CB pharmacology with a focus on pain medicine.

Topics: Analgesics, Non-Narcotic; Cannabinoids; Cannabis; Humans; Pain; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Receptor, Cannabinoid, CB1

Topics: Cannabinoids; Cannabis; Humans; Pain; Plant Preparations; Substance-Related Disorders

Hemp (Cannabis sativa L.) has been used since remotes ages as a herbal remedy. Only recently the medical community highlighted the pharmacological scientific bases of its effects. The most important active principle, Delta-9-tetrahydrocannabinol, was identified in the second half of the last century, and subsequently two receptors were identified and cloned: CB1 that is primarily present in the central nervous system, and CB2 that is present on the cells of the immune system. Endogenous ligands, called endocannabinoids, were characterized. The anandamide was the first one to be discovered. The effectiveness of the cannabinoids in the treatment of nausea and vomit due to anti-neoplastic chemotherapy and in the wasting-syndrome during AIDS is recognized. Moreover, the cannabinoids are analgesic, and their activity is comparable to the weak opioids. Furthermore, parallels exist between opioid and cannabinoid receptors, and evidence is accumulating that the two systems sometimes may operate synergistically. The interest of the pharmaceutical companies led to the production of various drugs, whether synthetic or natural derived. The good ratio between the polyunsatured fatty acids omega-3 and omega-6 of the oil of Cannabis seeds led to reduction of the phlogosis and an improvement of the pain symptoms in patients with chronic musculo-skeletal inflammation.

Topics: Amino Acid Sequence; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Antiemetics; Arachidonic Acids; Cachexia; Cannabinoids; Cannabis; Dronabinol; Endocannabinoids; Humans; Molecular Sequence Data; Nausea; Pain; Phytotherapy; Polyunsaturated Alkamides; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2

Cannabis sativa L. has been utilized for treatment of pain and sleep disorders since ancient times. This review examines modern studies on effects of Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on sleep. It goes on to report new information on the effects on sleep in the context of medical treatment of neuropathic pain and symptoms of multiple sclerosis, employing standardized oromucosal cannabis-based medicines containing primarily THC, CBD, or a 1 : 1 combination of the two (Sativex). Sleep-laboratory results indicate a mild activating effect of CBD, and slight residual sedation with THC-predominant extracts. Experience to date with Sativex in numerous Phase I-III studies in 2000 subjects with 1000 patient years of exposure demonstrate marked improvement in subjective sleep parameters in patients with a wide variety of pain conditions including multiple sclerosis, peripheral neuropathic pain, intractable cancer pain, and rheumatoid arthritis, with an acceptable adverse event profile. No tolerance to the benefit of Sativex on pain or sleep, nor need for dosage increases have been noted in safety extension studies of up to four years, wherein 40-50% of subjects attained good or very good sleep quality, a key source of disability in chronic pain syndromes that may contribute to patients' quality of life.

Topics: Cannabidiol; Cannabis; Clinical Trials as Topic; Dronabinol; Drug Combinations; Humans; Pain; Phytotherapy; Plant Extracts; Plant Preparations; Sleep; Sleep Wake Disorders

In The Netherlands, since September 2003, a legal medicinal cannabis product, constituting the whole range of cannabinoids, is available for clinical research, drug development strategies, and on prescription for patients. To date, this policy, initiated by the Dutch Government, has not yet led to the desired outcome; the amount of initiated clinical research is less than expected and only a minority of patients resorts to the legal product. This review aims to discuss the background for the introduction of legal medicinal cannabis in The Netherlands, the past years of Dutch clinical experience in oncology practice, possible reasons underlying the current outcome, and future perspectives.

Topics: Anorexia; Attitude to Health; Cannabinoids; Cannabis; Forecasting; Health Policy; Humans; Legislation, Drug; Nausea; Neoplasms; Netherlands; Pain; Phytotherapy; Vomiting

Although used for more than 4000 years for recreational and medicinal purposes, Cannabis and its best-known pharmacologically active constituents, the cannabinoids, became a protagonist in medical research only recently. This revival of interest is explained by the finding in the 1990s of the mechanism of action of the main psychotropic cannabinoid, Delta9-tetrahydrocannabinol (THC), which acts through specific membrane receptors, the cannabinoid receptors. The molecular characterization of these receptors allowed the development of synthetic molecules with cannabinoid and noncannabinoid structure and with higher selectivity, metabolic stability, and efficacy than THC, as well as the development of antagonists that have already found pharmaceutical application. The finding of endogenous agonists at these receptors, the endocannabinoids, opened new therapeutic possibilities through the modulation of the activity of cannabinoid receptors by targeting the biochemical mechanisms controlling endocannabinoid tissue levels.

Topics: Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Emaciation; Humans; Nausea; Nervous System Diseases; Pain; Phytotherapy; Plant Extracts; Receptors, Cannabinoid

For centuries extracts from the Cannabis sativa plant have been used for recreational use and as remedies. Anecdotal reports from patients with multiple sclerosis (MS) experiencing relief of their spasticity and pain after smoking marihuana have prompted discussions about a potential therapeutic application of cannabis preparations in MS. Only recently the first large, multicenter, double-blind, placebo controlled study was conducted evaluating the use of cannabinoids for treatment of spasticity and other symptoms related to MS. Based on this trial and previous uncontrolled observations together with insights from basic research and animal experiments there is reasonable evidence for the therapeutical employment of cannabinoids in the treatment of MS related symptoms. Furthermore, data are arising that cannabinoids have immunomodulatory and neuroprotective properties. However, results from clinical trials do not allow the recommendation for the general use of cannabinoids in MS. This article summarizes the present knowledge of clinical and experimental research regarding the therapeutic potential of cannabinoids for the treatment of MS.

Topics: Cannabinoids; Cannabis; Humans; Immunologic Factors; Multiple Sclerosis; Muscle Spasticity; Neuroprotective Agents; Pain; Phytotherapy

Cannabis has been known as a medicine for several thousand years across many cultures. It reached a position of prominence within Western medicine in the nineteenth century but became mired in disrepute and legal controls early in the twentieth century. Despite unremitting world-wide suppression, recreational cannabis exploded into popular culture in the 1960s and has remained easily obtainable on the black market in most countries ever since. This ready availability has allowed many thousands of patients to rediscover the apparent power of the drug to alleviate symptoms of some of the most cruel and refractory diseases known to humankind. Pioneering clinical research in the last quarter of the twentieth century has given some support to these anecdotal reports, but the methodological challenges to human research involving a pariah drug are formidable. Studies have tended to be small, imperfectly controlled, and have often incorporated unsatisfactory synthetic cannabinoid analogues or smoked herbal material of uncertain composition and irregular bioavailability. As a result, the scientific evaluation of medicinal cannabis in humans is still in its infancy. New possibilities in human research have been opened up by the discovery of the endocannabinoid system, a rapidly expanding knowledge of cannabinoid pharmacology, and a more sympathetic political environment in several countries. More and more scientists and clinicians are becoming interested in exploring the potential of cannabis-based medicines. Future targets will extend beyond symptom relief into disease modification, and already cannabinoids seem to offer particular promise in the treatment of certain inflammatory and neurodegenerative conditions. This chapter will begin with an outline of the development and current status of legal controls pertaining to cannabis, following which the existing human research will be reviewed. Some key safety issues will then be considered, and the chapter will conclude with some suggestions as to future directions for human research.

Topics: Appetite; Cannabinoids; Cannabis; Cognition; Epilepsy; Glaucoma; Humans; Marijuana Abuse; Multiple Sclerosis; Nausea; Neoplasms; Neuroprotective Agents; Pain; Phytotherapy; Spinal Cord Injuries; Vomiting

Growing basic research in recent years led to the discovery of the endocannabinoid system with a central role in neurobiology. New evidence suggests a therapeutic potential of cannabinoids in cancer chemotherapy-induced nausea and vomiting as well as in pain, spasticity and other symptoms in multiple sclerosis and movement disorders. Results of large randomized clinical trials of oral and sublingual Cannabis extracts will be known soon and there will be definitive answers to whether Cannabis has any therapeutic potential. Although the immediate future may lie in plant-based medicines, new targets for cannabinoid therapy focuses on the development of endocannabinoid degradation inhibitors which may offer site selectivity not afforded by cannabinoid receptor agonists.

Topics: Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Dronabinol; Endocannabinoids; Humans; Multiple Sclerosis; Muscle Spasticity; Pain; Phytotherapy; Plant Extracts; Receptors, Cannabinoid

Bayer AG has recently announced that it acquired exclusive rights for the marketing of GW Pharmaceuticals' new medicine Sativex in Europe and in other regions. Sativex is a sublingual spray on Cannabis extract basis, and is equipped with an electronic tool to facilitate accurate dosing and to prevent misuses. It is standardized for the THC and CBD. The new analgesic is proposed for the treatment of muscle spasticity and pains accompanying multiple sclerosis and as an efficient analgetic for neurogenic pain not responding well to opioids and to other therapies available. The entirely new mechanism of action through the recently discovered cannabinoid receptor system may offer a real therapeutic potential to the drug. Although the Government of Netherlands has authorized the sale of pharmaceutical grade Cannabis herb by pharmacies in the Netherlands, the availability on the pharmaceutical market of the registered preparation may render requests for the authorization of the smoking of Cannabis herb (marihuana) by individuals suffering of multiple sclerosis, neurogenic pain, AIDS wasting syndrome unnecessary. Nevertheless, the "old chameleon" plant Cannabis appears to gradually regain its previous status in mainstream therapy and pharmacy. As long as the plant Cannabis and its products continue to be classified as narcotic drugs, medical use of the new preparation will need close supervision.

Topics: Analgesics; Arachidonic Acids; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Combinations; Drugs, Investigational; Endocannabinoids; Europe; Humans; Multiple Sclerosis; Pain; Plant Extracts; Polyunsaturated Alkamides

A long-standing goal in cannabinoid research has been the discovery of potent synthetic analogs of the natural substances that might be developed as clinically useful drugs. This requires, among other things, that they be free of the psychotropic effects that characterize the recreational use of Cannabis. An important driving force for this goal is the long history of the use of Cannabis as a medicinal agent especially in the treatment of pain and inflammation. While few compounds appear to have these properties, ajulemic acid (AJA), also known as CT-3 and IP-751, is a potential candidate that could achieve this goal. Its chemical structure was derived from that of the major metabolite of Delta9-THC, the principal psychotropic constituent of Cannabis. In preclinical studies it displayed many of the properties of non-steroidal anti-inflammatory drugs (NSAIDs); however, it seems to be free of undesirable side effects. The initial short-term trials in healthy human subjects, as well as in patients with chronic neuropathic pain, demonstrated a complete absence of psychotropic actions. Moreover, it proved to be more effective than placebo in reducing this type of pain as measured by the visual analog scale. Unlike the narcotic analgesics, signs of dependency were not observed after withdrawal of the drug at the end of the one-week treatment period. Data on its mechanism of action are not yet complete; however, the activation of PPAR-gamma, and regulation of eicosanoid and cytokine production, appear to be important for its potential therapeutic effects.

Topics: Analgesics; Anti-Inflammatory Agents; Cannabis; Dronabinol; Drug Design; Pain; Receptors, Cytoplasmic and Nuclear; Transcription Factors

Marijuana contains over 60 different types of cannabinoids, which are its medicinally active ingredients. Cannabinoids have the capacity for neuromodulation--through direct, receptor-based mechanisms--at many levels within the nervous system, providing therapeutic properties that may be applicable to the treatment of neurologic disorders. These include antioxidation, neuroprotection, analgesia, anti-inflammation, immunomodulation, modulation of glial cells, and tumor growth regulation. This article reviews the current and emerging research on the physiologic mechanisms of endogenous and exogenous cannabinoids and their applications in the management of neurologic disease.

Topics: Analgesia; Cannabis; Humans; Legislation, Drug; Muscle Spasticity; Nervous System Diseases; Neuroglia; Neuroprotective Agents; Pain; Phytotherapy; Plant Preparations

--In 1996, the Netherlands Health Council issued a negative recommendation regarding the use of medication on the basis of cannabis (marihuana). However, interest in medicinal cannabis has certainly not waned since. --The neurological diseases for which cannabis could presently be used therapeutically are: multiple sclerosis, chronic (neuropathic) pain and the syndrome of Gilles de la Tourette. --Since September 2003, the Dutch Ministry of Health, Welfare and Sport delivers medicinal cannabis to Dutch pharmacies, so that now for the first time, medicinal cannabis can be given to patients on a prescription basis within the framework of the Opium Law. The result of this is that doctors and patients now assume that this is a medication for which the efficacy and safety have been established. --The question arises whether new scientific data have become available since 1996 that provide scientific support for the current Governmental policy. --In a recent clinical trial that has aroused much discussion, patients with multiple sclerosis and problematic spasticity were treated with oral cannabis or a placebo. There was no significant effect of treatment on the primary outcome measure, i.e. objectively determined spasticity. Nevertheless, it was concluded that the mobility was improved and that the pain was subjectively decreased. --Until now, convincing scientific evidence that cannabinoids are effective in neurological conditions is still lacking. --However, it is also not possible to conclude definitely that cannabinoids are ineffective; still, this is no basis for official stimulation of their use.

Topics: Cannabis; Humans; Muscle Spasticity; Nervous System Diseases; Pain; Phytotherapy; Plant Extracts; Safety; Treatment Outcome

Research of the cannabinoid system has many similarities with that of the opioid system. In both instances, studies into drug-producing plants led to the discovery of an endogenous control system with a central role in neurobiology. Few compounds have had as much positive press from patients as those of the cannabinoid system. While these claims are investigated in disorders such as multiple sclerosis spasticity and pain, basic research is discovering interesting members of this family of compounds that have previously unknown qualities, the most notable of which is the capacity for neuroprotection. Large randomised clinical trials of the better known compounds are in progress. Even if the results of these studies are not as positive as many expect them to be, that we are only just beginning to appreciate the huge therapeutic potential of this family of compounds is clear.

Topics: Cannabinoids; Cannabis; Clinical Trials as Topic; Humans; Pain; Phytotherapy; Receptors, Cannabinoid; Receptors, Drug; Spasm; Urinary Bladder Diseases

The principal constituent of cannabis, Delta(9)-tetrahydrocannabinol (THC), is moderately effective in treating nausea and vomiting, appetite loss, and acute and chronic pain. Oral THC (dronabinol) and the synthetic cannabinoid, nabilone, have been registered for medical use in the US and UK, but they have not been widely used because patients find it difficult to titrate doses of these drugs. Advocates for the medical use of cannabis argue that patients should be allowed to smoke cannabis to relieve these above-mentioned symptoms. Some US state governments have legislated to allow the medical prescription of cannabis, but the US federal government has tried to prevent patients from obtaining cannabis and threatened physicians who prescribe it with criminal prosecution or loss of their licence to practise. In the UK and Australia, committees of inquiry have recommended medical prescription (UK) and exemption from criminal prosecution (New South Wales, Australia), but governments have not accepted these recommendations. The Canadian government allows an exemption from criminal prosecution to patients with specified medical conditions. It has recently legislated to provide cannabis on medical prescription to registered patients, but this scheme so far has not been implemented. Some advocates argue that legalising cannabis is the only way to ensure that patients can use it for medical purposes. However, this would be contrary to international drug control treaties and is electorally unpopular. The best prospects for the medical use of cannabinoids lie in finding ways to deliver THC that do not involve smoking and in developing synthetic cannabinoids that produce therapeutic effects with a minimum of psychoactive effects. While awaiting these developments, patients with specified medical conditions could be given exemptions from criminal prosecution to grow cannabis for their own use, at their own risk.

Topics: Antiemetics; Cannabis; HIV Wasting Syndrome; Humans; Legislation, Drug; Nausea; Pain; Phytotherapy; Plant Preparations; Treatment Outcome; Vomiting

GW Pharmaceuticals is undertaking a major research programme in the UK to develop and market distinct cannabis-based prescription medicines [THC:CBD, High THC, High CBD] in a range of medical conditions. The cannabis for this programme is grown in a secret location in the UK. It is expected that the product will be marketed in the US in late 2003. GW's cannabis-based products include selected phytocannabinoids from cannabis plants, including D9 tetrahydrocannabinol (THC) and cannabidiol (CBD). The company is investigating their use in three delivery systems, including sublingual spray, sublingual tablet and inhaled (but not smoked) dosage forms. The technology is protected by patent applications. Four different formulations are currently being investigated, including High THC, THC:CBD (narrow ratio), THC:CBD (broad ratio) and High CBD. GW is also developing a specialist security technology that will be incorporated in all its drug delivery systems. This technology allows for the recording and remote monitoring of patient usage to prevent any potential abuse of its cannabis-based medicines. GW plans to enter into agreements with other companies following phase III development, to secure the best commercialisation terms for its cannabis-based medicines. In June 2003, GW announced that exclusive commercialisation rights for the drug in the UK had been licensed to Bayer AG. The drug will be marketed under the Sativex brand name. This agreement also provides Bayer with an option to expand their license to include the European Union and certain world markets. GW was granted a clinical trial exemption certificate by the Medicines Control Agency to conduct clinical studies with cannabis-based medicines in the UK. The exemption includes investigations in the relief of pain of neurological origin and defects of neurological function in the following indications: multiple sclerosis (MS), spinal cord injury, peripheral nerve injury, central nervous system damage, neuroinvasive cancer, dystonias, cerebral vascular accident and spina bifida, as well as for the relief of pain and inflammation in rheumatoid arthritis and also pain relief in brachial plexus injury. The UK Government stated that it would be willing to amend the Misuse of Drugs Act 1971 to permit the introduction of a cannabis-based medicine. GW stated in its 2002 Annual Report that it was currently conducting five phase III trials of its cannabis derivatives, including a double-blind, placebo-controlled tr

Topics: Administration, Sublingual; Analgesics, Opioid; Cannabis; Clinical Trials as Topic; Humans; Pain; Phytotherapy; Plant Preparations

To present the cannabinoid system together with recent findings on the pharmacology of these compounds in the treatment of pain.. Search through Medline database of articles published in French and English since 1966. Also use of other publications such as books on cannabis.. All the relevant documents within the theme of this review were used.. All the data linked to the present topic were searched.. Recent advances have dramatically increased our understanding of cannabinoid pharmacology. The psychoactive constituents of Cannabis sativa have been isolated, synthetic cannabinoids described and an endocannabinoid system identified, together with its component receptors and ligands. Strong laboratory evidence now underwrites anecdotal claims of cannabinoid analgesia in inflammatory and neuropathic pain. Sites of analgesic action have been identified in brain, spinal cord and the periphery, with the latter two presenting attractive targets for divorcing the analgesic and psychotrophic effects of cannabinoids. Clinical trials are now required, but are hindered by a paucity of cannabinoids of suitable bioavailability and therapeutic ratio.. The cannabinoid system is a major target in the treatment of pain and its therapeutic potential should be assessed in the near future by the performance of new clinical trials.

Topics: Analgesics, Non-Narcotic; Animals; Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Humans; Pain; Receptors, Cannabinoid; Receptors, Drug; Signal Transduction

There is a large amount of evidence to support the view that the psychoactive ingredient in cannabis, delta9-tetrahydrocannabinol (delta9-THC), and cannabinoids in general, can reduce muscle spasticity and pain under some circumstances. Cannabinoid (CB1) receptors in the CNS appear to mediate both of these effects and endogenous cannabinoids may fulfil these functions to some extent under normal circumstances. However, in the context of multiple sclerosis (MS), it is still questionable whether cannabinoids are superior to existing, conventional medicationsfor the treatment of spasticity and pain. In the case of spasticity, there are too few controlled clinical trials to draw any reliable conclusion at this stage. In the case of pain, most of the available trials suggest that cannabinoids are not superior to existing treatments; however, few trials have examined chronic pain syndromes that are relevant to MS. Whether or not cannabinoids do have therapeutic potential in the treatment of MS, a further issue will be whether synthetic cannabinoids should be used in preference to cannabis itself. Smoking cannabis is associated with significant risks of lung cancer and other respiratory dysfunction. Furthermore, delta9-THC, as a broad-spectrum cannabinoid receptor agonist, will activate both CB1 and CB2 receptors. Synthetic cannabinoids, which target specific cannabinoid receptor subtypes in specific parts of the CNS, are likely to be of more therapeutic use than delta9-THC itself. If rapid absorption is necessary, such synthetic drugs could be delivered via aerosol formulations.

Topics: Analgesics, Non-Narcotic; Animals; Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Disease Models, Animal; Dronabinol; Fatty Acids, Unsaturated; Humans; Multiple Sclerosis; Muscle Weakness; Pain; Receptors, Cannabinoid; Receptors, Drug; Spasm

Topics: Anorexia; Cachexia; Cannabinoids; Cannabis; Epilepsy; Hiccup; Humans; Migraine Disorders; Muscle Spasticity; Nausea; Pain; Palliative Care; Randomized Controlled Trials as Topic; Seizures; Vomiting

This review highlights the pharmacology, pharmacokinetics, pharmacological actions, therapeutic uses and adverse effects of cannabinoids. The effect of cannabinoids on anaesthesia is mentioned briefly. Important advances have taken place in cannabinoid research over the last few years and have led to the discovery of novel ligands. The possible clinical applications of these ligands and the direction of future research are discussed.

Topics: Anesthesia; Cannabinoids; Cannabis; Drug Interactions; Humans; Muscle Spasticity; Pain; Phytotherapy; Plant Extracts

In response to public pressure to allow the medical use of marijuana, the Office of National Drug Control Policy, Washington, DC, funded a study by the Institute of Medicine evaluating the scientific evidence for benefits and risks of using marijuana as a medicine. The report used scientific reviews, public hearings, and reports from other agencies, and was evaluated by knowledgeable advisors and reviewers. It called for heavier investment in research on the biology of cannabinoid systems, careful clinical studies of cannabinoids in clinical syndromes, analysis of cannabinoids' psychological effects on symptoms, and evaluations of the health consequences of heavy marijuana use; recommends against the use of smoked marijuana in medicine and for the development of a medical cannabinoid inhaler; and recommends that compassionate use of marijuana be considered under carefully reviewed protocols. Finally, the report evaluates the abuse potential, tolerance, withdrawal, and gateway risks of medical use of cannabinoid drugs.

Topics: Cannabinoids; Cannabis; Drug and Narcotic Control; Feeding and Eating Disorders; Humans; Marijuana Abuse; National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division; Nausea; Pain; Phytotherapy; Practice Patterns, Physicians'; Risk Assessment; Risk Factors; United States; Vomiting; Wasting Syndrome

Although the WHO edited guidelines for pain treatment as early as 1986, practical management has frequently remained inadequate, especially in cancer patients. Traditional adherence to restrictions from the former Austrian Controlled Drug Act which have resulted in ongoing limitations in the prescription of opioids as well as complicated formal regulations in the current law represent two major obstacles. As a consequence, recent legislation of a "state of the art" pain management in Austria facilitates adequate provision of analgesics on the one hand, and may, on the other, even result in claims for indemnity should these be withhold.

Topics: Analgesics, Opioid; Austria; Cannabis; Drug and Narcotic Control; Humans; Jurisprudence; Legislation, Hospital; Legislation, Medical; Pain; Phytotherapy

Cannabinoids have significant analgesic properties in animal models, particularly for chronic pain states, but there are few human studies. An endogenous cannabinoid system, with specific receptors and transmitters, has recently been discovered. This discovery has led pharmacologists to explore the potential of synthetic cannabinoids to selectively target chronic pain disorders without producing the side effects associated with cannabis. Well-controlled clinical trials on cannabinoids, and cannabinoid delivery systems, are now required.

Topics: Animals; Cannabinoids; Cannabis; Dronabinol; Humans; Marijuana Smoking; Pain

Topics: Anesthesia; Cannabinoids; Cannabis; Humans; Marijuana Abuse; Mental Processes; Nausea; Pain; United Kingdom; Vomiting

Topics: Analgesics; Animals; Cannabinoids; Cannabis; Humans; Pain; Phytotherapy; Primates; Rats

Topics: Cannabinoids; Cannabis; Humans; Pain; Receptors, Cannabinoid; Receptors, Drug

Topics: Animals; Asthma; Cannabis; Dronabinol; Epilepsy; Glaucoma; Humans; Nausea; Neoplasms; Pain

Topics: Airway Resistance; Alcoholism; Animals; Asthma; Cannabinoids; Cannabis; Depression; Dose-Response Relationship, Drug; Epilepsy; Glaucoma; Humans; Intraocular Pressure; Neoplasms, Experimental; Pain; Preanesthetic Medication; Seizures; Sleep

Mood, sleep and pain problems are common comorbidities among treatment-seeking cannabis-dependent patients. There is limited evidence suggesting treatment for cannabis dependence is associated with their improvement. This study explored the impact of cannabis dependence treatment on these comorbidities.. This is a secondary analysis from a 12-week double-blind placebo-controlled trial testing the efficacy of a cannabis agonist (nabiximols) against placebo in reducing illicit cannabis use in 128 cannabis-dependent participants. Outcome measurements including DASS-21 (Depression, Anxiety, and Stress subscales); Insomnia Severity Index (ISI); and Brief Pain Inventory (BPI), were performed at weeks 0, 4, 8, 12 and 24. Each was analysed as continuous outcomes and as binary cases based on validated clinical cut-offs.. Among those whose DASS and ISI scores were in the moderate to severe range at baseline, after controlling for cannabis use, there was a gradual decrease in severity of symptoms over the course of the trial. BPI decreased significantly until week 12 and then rose again in the post-treatment period during weeks 12-24. Neither pharmacotherapy type (nabiximols vs placebo) nor number of counselling sessions contributed significant explanatory power to any of the models and were excluded from the final analyses for both continuous and categorical outcomes.. Participants in this trial who qualified as cases at baseline had elevated comorbidity symptoms. There was no evidence that nabiximols treatment is a barrier to achieving reductions in the comorbid symptoms examined. Cannabis dependence treatment reduced illicit cannabis use and improved comorbidity symptoms, even when complete abstinence was not achieved.

Topics: Analgesics; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Comorbidity; Double-Blind Method; Dronabinol; Drug Combinations; Hallucinogens; Humans; Marijuana Abuse; Medical Marijuana; Pain; Sleep; Treatment Outcome

There is increasing interest and evidence for the use of cannabinoid medications in the treatment of cannabis use disorder, but little examination of the correlates of successful treatment. This paper is a secondary analysis of a randomised placebo-controlled trial of nabiximols for the treatment of cannabis use disorder (CUD), aiming to identify which client and treatment characteristics impact treatment engagement and outcomes.. Bayesian multiple regression models were used to examine the impact of age, gender, duration of regular cannabis use, daily quantity of cannabis, cannabis use problems, self-efficacy for quitting, sleep, mental health, pain measures, and treatment group upon treatment engagement (retention, medication dose, and counselling participation) and treatment outcomes (achieving end-of-study abstinence, and a 50% or greater reduction in cannabis use days) among the 128 clients participating in the 12-week trial.. Among the treatment factors, greater counselling attendance was associated with greater odds of abstinence and ≥ 50% reduction in cannabis use; nabiximols with greater odds of ≥ 50% reduction and attending counselling, and reduced hazard of treatment dropout; and higher dose with lower odds of ≥ 50% reduction. Among the client factors, longer duration of regular use was associated with higher odds of abstinence and 50% reduction, and lower hazard of treatment dropout; greater quantity of cannabis use with reduced hazard of dropout, greater odds of attending counselling, and higher average dose; greater pain at baseline with greater odds of ≥ 50% reduction and higher average dose; and more severe sleep issues with lower odds of ≥ 50% reduction. Males had lower odds of attending counselling.. These findings suggest that counselling combined with agonist pharmacotherapy may provide the optimal treatment for cannabis use disorder. Younger clients, male clients, and clients with sleep issues could benefit from extra support from treatment services to improve engagement and outcomes.. Australian New Zealand Clinical Trials Registry (ACTRN12616000103460) https://www.anzctr.org.au.

Topics: Australia; Bayes Theorem; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Combinations; Humans; Male; Marijuana Abuse; Pain; Substance-Related Disorders

The prevalence of medical cannabis (MC) use in patients with cancer is growing, but questions about safety, efficacy, and dosing remain. Conducting randomized, controlled trials (RCTs) using state-sponsored MC programs is novel and could provide data needed to guide patients and providers.. A pilot RCT of patients with stage IV cancer requiring opioids was conducted. Thirty patients were randomized 1:1 to early cannabis (EC, n = 15) versus delayed start cannabis (DC, n = 15). The EC group obtained 3 months (3 M) of MC through a state program at no charge, while the DC group received standard oncology care without MC for the first 3 M. Patients met with licensed pharmacists at one of two MC dispensaries to determine a suggested MC dosing, formulation, and route. Patients completed surveys on pain levels, opioid/MC use, side effects, and overall satisfaction with the study.. Interest in the study was high as 36% of patients who met eligibility criteria ultimately enrolled. The estimated mean daily THC and CBD allotments at 3 M were 34 mg and 17 mg, respectively. A higher proportion of EC patients achieved a reduction in opioid use and improved pain control. No serious safety issues were reported, and patients reported high satisfaction.. Conducting RCTs using a state cannabis program is feasible. The addition of MC to standard oncology care was well-tolerated and may lead to improved pain control and lower opioid requirements. Conducting larger RCTs with MC in state-sponsored programs may guide oncology providers on how to safely and effectively incorporate MC for interested patients.

Topics: Analgesics, Opioid; Cannabis; Feasibility Studies; Humans; Medical Marijuana; Neoplasms; Pain; Patient Satisfaction

Over the last 2 decades, affirmative diagnoses of osteoarthritis (OA) in the United States have tripled due to increasing rates of obesity and an aging population. Hemp-derived cannabidiol (CBD) is the major nontetrahydrocannabinol component of cannabis and has been promoted as a potential treatment for a wide variety of disparate inflammatory conditions. Here, we evaluated CBD for its ability to modulate the production of proinflammatory cytokines in vitro and in murine models of induced inflammation and further validated the ability of a liposomal formulation to increase bioavailability in mice and in humans. Subsequently, the therapeutic potential of both naked and liposomally encapsulated CBD was explored in a 4-week, randomized placebo-controlled, double-blinded study in a spontaneous canine model of OA. In vitro and in mouse models, CBD significantly attenuated the production of proinflammatory cytokines IL-6 and TNF-α while elevating levels of anti-inflammatory IL-10. In the veterinary study, CBD significantly decreased pain and increased mobility in a dose-dependent fashion among animals with an affirmative diagnosis of OA. Liposomal CBD (20 mg/day) was as effective as the highest dose of nonliposomal CBD (50 mg/day) in improving clinical outcomes. Hematocrit, comprehensive metabolic profile, and clinical chemistry indicated no significant detrimental impact of CBD administration over the 4-week analysis period. This study supports the safety and therapeutic potential of hemp-derived CBD for relieving arthritic pain and suggests follow-up investigations in humans are warranted.

Topics: Animals; Cannabidiol; Cannabis; Dogs; Double-Blind Method; Mice; Osteoarthritis; Pain

Preclinical studies demonstrate that cannabinoid-mediated antinociceptive effects vary according to sex; it is unknown if these findings extend to humans.. This retrospective analysis compared the analgesic, subjective and physiological effects of active cannabis (3.56-5.60% THC) and inactive cannabis (0.00% THC) in male (N=21) and female (N=21) cannabis smokers under double-blind, placebo-controlled conditions. Pain response was measured using the Cold-Pressor Test (CPT). Participants immersed their hand in cold water (4°C); times to report pain (pain sensitivity) and withdraw the hand (pain tolerance) were recorded. Subjective drug ratings were also measured.. Among men, active cannabis significantly decreased pain sensitivity relative to inactive cannabis (p<0.01). In women, active cannabis failed to decrease pain sensitivity relative to inactive. Active cannabis increased pain tolerance in both men women immediately after smoking (p<0.001); a trend was observed for differences between men and women (p<0.10). Active cannabis also increased subjective ratings of cannabis associated with abuse liability ('Take again,' 'Liking,' 'Good drug effect'), drug strength, and 'High' relative to inactive in both men and women (p<0.01).. These results indicate that in cannabis smokers, men exhibit greater cannabis-induced analgesia relative to women. These sex-dependent differences are independent of cannabis-elicited subjective effects associated with abuse-liability, which were consistent between men and women. As such, sex-dependent differences in cannabis's analgesic effects are an important consideration that warrants further investigation when considering the potential therapeutic effects of cannabinoids for pain relief.

Topics: Adult; Analgesia; Cannabis; Double-Blind Method; Female; Humans; Male; Marijuana Smoking; Pain; Pain Threshold; Retrospective Studies; Sex Factors; Young Adult

To evaluate whether pain was associated with increased risk of using heroin, stimulants or cannabis among HIV-infected drinkers in Russia.. Secondary analysis of longitudinal data from the HERMITAGE study (HIV's Evolution in Russia-Mitigating Infection Transmission and Alcoholism in a Growing Epidemic), a behavioral randomized controlled trial, with data collected at baseline, 6-month and 12-month visits.. Recruitment occurred at HIV and addiction treatment sites in St Petersburg, Russian Federation.. Six hundred and ninety-nine HIV-infected adult drinkers.. The primary outcome was past month illicit drug use; secondary outcomes examined each drug (heroin, stimulants and cannabis) separately. The main predictor was pain that interfered at least moderately with daily living. General estimating equations (GEE) logistic regression models were used to evaluate the association between pain and subsequent illicit drug use, adjusting for potential confounders.. Participants reporting pain appeared to have higher odds of using illicit drugs, although the results did not reach statistical significance [adjusted odds ratio (OR) = 1.32; 95% confidence interval (CI) = 0.99, 1.76, P = 0.06]. There was a significant association between pain and heroin use (OR = 1.54; 95% CI = 1.11-2.15, P = 0.01) but not use of other drugs (OR = 0.75; 95% CI =0.40-1.40, P = 0.35 for stimulants and OR = 0.70; 95% CI = 0.45-1.07, P = 0.09 for cannabis).. HIV-infected Russian drinkers who report pain are more likely to use heroin over time than HIV-infected Russian drinkers who do not report pain. Pain may be an unrecognized risk factor for persistent heroin use with implications for HIV transmission in Russia.

Topics: Adult; Alcohol Drinking; Alcoholism; Cannabis; Central Nervous System Stimulants; Female; Heroin Dependence; HIV Infections; Humans; Longitudinal Studies; Male; Pain; Risk Factors; Russia; Substance-Related Disorders

Cannabinoid-induced analgesia was shown in animal studies of acute inflammatory and neuropathic pain. In humans, controlled clinical trials with Delta-tetrahydrocannabinol or other cannabinoids demonstrated analgesic efficacy in chronic pain syndromes, whereas the data in acute pain were less conclusive. Therefore, the aim of this study was to investigate the effects of oral cannabis extract in two different human models of acute inflammatory pain and hyperalgesia.. The authors conducted a double-blind, crossover study in 18 healthy female volunteers. Capsules containing Delta-tetrahydrocannabinol-standardized cannabis extract or active placebo were orally administered. A circular sunburn spot was induced at one upper leg. Heat and electrical pain thresholds were determined at the erythema, the area of secondary hyperalgesia, and the contralateral leg. Intradermal capsaicin-evoked pain and areas of flare and secondary hyperalgesia were measured. Primary outcome parameters were heat pain thresholds in the sunburn erythema and the capsaicin-evoked area of secondary hyperalgesia. Secondary measures were electrical pain thresholds, sunburn-induced secondary hyperalgesia, and capsaicin-induced pain.. Cannabis extract did not affect heat pain thresholds in the sunburn model. Electrical thresholds (250 Hz) were significantly lower compared with baseline and placebo. In the capsaicin model, the area of secondary hyperalgesia, flare, and spontaneous pain were not altered.. To conclude, no analgesic or antihyperalgesic activity of cannabis extract was found in the experiments. Moreover, the results even point to the development of a hyperalgesic state under cannabinoids. Together with previous data, the current results suggest that cannabinoids are not effective analgesics for the treatment of acute nociceptive pain in humans.

Topics: Acute Disease; Administration, Oral; Adult; Analgesia; Cannabis; Cross-Over Studies; Double-Blind Method; Female; Humans; Hyperalgesia; Inflammation Mediators; Pain; Pain Measurement; Pain Threshold; Plant Extracts

To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model.. Prospective randomized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV-associated sensory neuropathy. Patients were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days. Primary outcome measures included ratings of chronic pain and the percentage achieving >30% reduction in pain intensity. Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model.. Fifty patients completed the entire trial. Smoked cannabis reduced daily pain by 34% (median reduction; IQR = -71, -16) vs 17% (IQR = -29, 8) with placebo (p = 0.03). Greater than 30% reduction in pain was reported by 52% in the cannabis group and by 24% in the placebo group (p = 0.04). The first cannabis cigarette reduced chronic pain by a median of 72% vs 15% with placebo (p < 0.001). Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli (p < or = 0.05) but appeared to have little effect on the painfulness of noxious heat stimulation. No serious adverse events were reported.. Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain.

Topics: Affect; Cannabis; Female; HIV Infections; Hot Temperature; Humans; Hyperalgesia; Male; Middle Aged; Pain; Pain Management; Palliative Care; Peripheral Nervous System Diseases; Physical Stimulation; Phytotherapy; Sensation Disorders; Smoking

Although the preclinical literature suggests that cannabinoids produce antinociception and antihyperalgesic effects, efficacy in the human pain state remains unclear. Using a human experimental pain model, the authors hypothesized that inhaled cannabis would reduce the pain and hyperalgesia induced by intradermal capsaicin.. In a randomized, double-blinded, placebo-controlled, crossover trial in 15 healthy volunteers, the authors evaluated concentration-response effects of low-, medium-, and high-dose smoked cannabis (respectively 2%, 4%, and 8% 9-delta-tetrahydrocannabinol by weight) on pain and cutaneous hyperalgesia induced by intradermal capsaicin. Capsaicin was injected into opposite forearms 5 and 45 min after drug exposure, and pain, hyperalgesia, tetrahydrocannabinol plasma levels, and side effects were assessed.. Five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 min after cannabis exposure, however, there was a significant decrease in capsaicin-induced pain with the medium dose and a significant increase in capsaicin-induced pain with the high dose. There was no effect seen with the low dose, nor was there an effect on the area of hyperalgesia at any dose. Significant negative correlations between pain perception and plasma delta-9-tetrahydrocannabinol levels were found after adjusting for the overall dose effects. There was no significant difference in performance on the neuropsychological tests.. This study suggests that there is a window of modest analgesia for smoked cannabis, with lower doses decreasing pain and higher doses increasing pain.

Topics: Adult; Analgesics, Non-Narcotic; Cannabinoids; Cannabis; Capsaicin; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Dronabinol; Female; Humans; Hyperalgesia; Male; Marijuana Smoking; Neuropsychological Tests; Pain; Pain Measurement; Reference Values; Sensory System Agents; Sensory Thresholds; Time Factors

Despite the major benefits of antiretroviral therapy on survival during HIV infection, there is an increasing need to manage symptoms and side effects during long-term drug therapy. Cannabis has been reported anecdotally as being beneficial for a number of common symptoms and complications in HIV infections, for example, poor appetite and neuropathy. This study aimed to investigate symptom management with cannabis. Following Ethics Committee approval, HIV-positive individuals attending a large clinic were recruited into an anonymous cross-sectional questionnaire study. Up to one-third (27%, 143/523) reported using cannabis for treating symptoms. Patients reported improved appetite (97%), muscle pain (94%), nausea (93%), anxiety (93%), nerve pain (90%), depression (86%), and paresthesia (85%). Many cannabis users (47%) reported associated memory deterioration. Symptom control using cannabis is widespread in HIV outpatients. A large number of patients reported that cannabis improved symptom control.

Topics: Adult; Aged; Cannabinoids; Cannabis; Comorbidity; Cross-Sectional Studies; Data Collection; Drug Therapy; Female; HIV Infections; Humans; Male; Middle Aged; Nausea; Pain; Phytotherapy; Plant Preparations; Severity of Illness Index; United Kingdom

The objective was to determine whether a cannabis-based medicinal extract (CBME) benefits a range of symptoms due to multiple sclerosis (MS). A parallel group, double-blind, randomized, placebo-controlled study was undertaken in three centres, recruiting 160 outpatients with MS experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. The interventions were oromucosal sprays of matched placebo, or whole plant CBME containing equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) at a dose of 2.5-120 mg of each daily, in divided doses. The primary outcome measure was a Visual Analogue Scale (VAS) score for each patient's most troublesome symptom. Additional measures included VAS scores of other symptoms, and measures of disability, cognition, mood, sleep and fatigue. Following CBME the primary symptom score reduced from mean (SE) 74.36 (11.1) to 48.89 (22.0) following CBME and from 74.31 (12.5) to 54.79 (26.3) following placebo [ns]. Spasticity VAS scores were significantly reduced by CBME (Sativex) in comparison with placebo (P =0.001). There were no significant adverse effects on cognition or mood and intoxication was generally mild.

Topics: Aerosols; Cannabidiol; Cannabis; Disability Evaluation; Dose-Response Relationship, Drug; Double-Blind Method; Dronabinol; Humans; Mouth Mucosa; Multiple Sclerosis; Muscle Spasticity; Pain; Pain Measurement; Plant Extracts; Tremor; Urinary Bladder Diseases

To determine whether plant-derived cannabis medicinal extracts (CME) can alleviate neurogenic symptoms unresponsive to standard treatment, and to quantify adverse effects.. A consecutive series of double-blind, randomized, placebo-controlled single-patient cross-over trials with two-week treatment periods.. Patients attended as outpatients, but took the CME at home.. Twenty-four patients with multiple sclerosis (18), spinal cord injury (4), brachial plexus damage (1), and limb amputation due to neurofibromatosis (1).. Whole-plant extracts of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), 1:1 CBD:THC, or matched placebo were self-administered by sublingual spray at doses determined by titration against symptom relief or unwanted effects within the range of 2.5-120 mg/24 hours. Measures used: Patients recorded symptom, well-being and intoxication scores on a daily basis using visual analogue scales. At the end of each two-week period an observer rated severity and frequency of symptoms on numerical rating scales, administered standard measures of disability (Barthel Index), mood and cognition, and recorded adverse events.. Pain relief associated with both THC and CBD was significantly superior to placebo. Impaired bladder control, muscle spasms and spasticity were improved by CME in some patients with these symptoms. Three patients had transient hypotension and intoxication with rapid initial dosing of THC-containing CME.. Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to standard treatments. Unwanted effects are predictable and generally well tolerated. Larger scale studies are warranted to confirm these findings.

Topics: Administration, Oral; Analgesics, Non-Narcotic; Cannabidiol; Cannabis; Cross-Over Studies; Double-Blind Method; Dronabinol; Humans; Hypotension; Muscle Spasticity; Nervous System Diseases; Pain; Phytotherapy; Placebos; Plant Preparations; Severity of Illness Index; Spasm; Urination Disorders

The administration of single oral doses of delta-9-tetrahydrocannabinol (THC) to patients with cancer pain demonstrated a mild analgesic effect. At a dose of 20 mg, however, THC induced side effects that would prohibit its therapeutic use including somnolence, dizziness, ataxia, and blurred vision. Alarming adverse reactions were also observed at this dose. THC, 10 mg, was well tolerated and, despite its sedative effect, may analgesic potential.

Topics: Analgesics; Aspirin; Cannabis; Clinical Trials as Topic; Codeine; Dextropropoxyphene; Dronabinol; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neoplasms; Pain; Palliative Care; Phytotherapy; Placebos

The effect of marijuana and placebo on pain tolerance was compared in cannabis-experienced and naive subjects. A statistically significant increase in tolerance was observed after smoking marijuana. Although there was no statistically significant interaction between the drug effect and having had previous cannabis experience, there was a definite trend towards a greater increase for the experienced (16%) compared to the naive group(8%).

Topics: Adult; Analysis of Variance; Cannabis; Female; Humans; Male; Pain; Placebos; Pressure; Reaction Time; Sex Factors

The interaction of delta9-tetrahydrocannabinol (delta9-THC) and cannabinol (CBN) was studied in man. Five male volunteers were given placebo, 50 mg CBN, 25 mg delta9-THC, 12.5 mg delta9-THC + 25 mg CBN, and 25 mg delta9-THC + 50 mg CBN (orally). Administrations were spaced 1 week apart. With physiological measures, delta9-THC produced an increase in heart rate while CBN did not. When combined, no change of the delta9-THC effect occurred. No changes occurred on the electrocardiogram, blood pressure, or body temperature. With psychophysical measures no changes occurred in pain thresholds or skin sensitivity as a function of drug treatment. In time estimates of the passage of 1 minute, delta9-THC alone produced underestimates of the passage of 1 minute and CBN alone had no effect. In combination the two drugs had a tendency to produce significant overestimates and underestimates of the passage of 1 minute. On a 66-item adjective-pair drug reaction scale, the volunteers reported feeling drugged, drunk, dizzy, and drowsy under the delta9-THC condition, but not under the CBN condition. With combined drug treatment, volunteers reported feeling more drugged, drunk, dizzy, and drowsy than under the delta9-THC condition alone. None of the drug treatments produced significant changes on other items which included items on perception, emotion, cognition and sociability. It appears that CBN increases the effect of delta9-THC on some aspects of physiological and psychological processes, but that these effects are small and cannot account for the greater potency which has been reported when plant material is used.

Topics: Administration, Oral; Adult; Body Temperature; Cannabis; Dronabinol; Drug Interactions; Heart Rate; Humans; Male; Pain; Phytotherapy; Placebos; Pulse; Reaction Time

Topics: Adult; Aspirin; Cannabis; Clinical Trials as Topic; Codeine; Differential Threshold; Electric Stimulation; Hot Temperature; Humans; Male; Morphine; Pain; Placebos; Vibration

Topics: Adult; Arousal; Brain; Cannabis; Contingent Negative Variation; Depression, Chemical; Differential Threshold; Dronabinol; Electric Stimulation; Flicker Fusion; Humans; Male; Pain; Photic Stimulation; Placebos; Stimulation, Chemical; Substance-Related Disorders; Touch

Our study sought to further characterize patterns of medical cannabis use in elderly cancer patients. Furthermore, we sought to assess efficacy of medical cannabis for the treatment of pain, nausea, anorexia, insomnia and anxiety in elderly cancer patients.. Medical cannabis use is growing for symptom management in cancer patients, but limited data exists on the safety or efficacy of use in elderly patients.. A retrospective chart review assessing changes in numerical symptom scores reported at clinic visits before and after medical cannabis initiation.. There was no statistically significant difference in pain, nausea, appetite, insomnia or anxiety scores reported before and after initiation of medical cannabis. Oil was the most common form used, followed by vape, and the most common ratios used were high tetrahydrocannabinol (THC) to cannabidiol (CBD) and equal parts THC/CBD products.. This study did not find a statistically significant change in symptom scores with medical cannabis use, although further study is warranted given the limitations of the present study. Elderly patients most commonly are using equal parts THC/CBD or high THC ratio products initially.

Topics: Aged; Cannabidiol; Cannabis; Dronabinol; Humans; Medical Marijuana; Nausea; Neoplasms; Pain; Retrospective Studies; Sleep Initiation and Maintenance Disorders

Cannabis is frequently used recreationally and medicinally, including for symptom management in patients with kidney disease.. We elicited the views of Canadian adults with kidney disease regarding their cannabis use. Participants were asked whether they would try cannabis for anxiety, depression, restless legs, itchiness, fatigue, chronic pain, decreased appetite, nausea/vomiting, sleep, cramps and other symptoms. The degree to which respondents considered cannabis for each symptom was assessed with a modified Likert scale ranging from 1 to 5 (1, definitely would not; 5, definitely would). Multilevel multivariable linear regression was used to identify respondent characteristics associated with considering cannabis for symptom control.. Of 320 respondents, 290 (90.6%) were from in-person recruitment (27.3% response rate) and 30 (9.4%) responses were from online recruitment. A total of 160/320 respondents (50.2%) had previously used cannabis, including smoking [140 (87.5%)], oils [69 (43.1%)] and edibles [92 (57.5%)]. The most common reasons for previous cannabis use were recreation [84/160 (52.5%)], pain alleviation [63/160 (39.4%)] and sleep enhancement [56/160 (35.0%)]. Only 33.8% of previous cannabis users thought their physicians were aware of their cannabis use. More than 50% of respondents probably would or definitely would try cannabis for symptom control for all 10 symptoms. Characteristics independently associated with interest in trying cannabis for symptom control included symptom type (pain, sleep, restless legs), online respondent {β = 0.7 [95% confidence interval (CI) 0.1-1.4]} and previous cannabis use [β = 1.2 (95% CI 0.9-1.5)].. Many patients with kidney disease use cannabis and there is interest in trying cannabis for symptom control.

Topics: Adult; Canada; Cannabis; Humans; Pain; Renal Insufficiency, Chronic; Restless Legs Syndrome; Surveys and Questionnaires

Fibromyalgia is a complex pain-focused syndrome. Previous studies showed that Cannabis is efficacious in promoting sleep, deepening and lengthening the sleep cycle, and good pain relief (compared with the SSRIs and SNRIs).. This study aimed to use the World Health Organization Quality of Life Bref questionnaire (WhoQoL-bref) to characterize the impact of Cannabis Treatment initiation on the quality of life in women suffering from treatment-resistant fibromyalgia.. A prospective cohort study involving 30 women aged 18-70 years old diagnosed with fibromyalgia, exhausted pharmacological fibromyalgia treatment, and started Cannabis treatment. Pregnant women were excluded. WhoQoL-bref was filled before Cannabis treatment initiation and 1 month following treatment.. Women's average age was 46 years (±5), with a poor general quality of life (1.47 ± 0.63), poor general health (1.47 ± 0.78), pain and discomfort, and dependence on medication (3.77 ± 1.3 and 3.07 ± 1.74, respectively) prior to Cannabis intervention. Cannabis treatment for 30 days showed a marked improvement in general quality of life (1.97 scores, p < 0.01), general health (1.83, p < 0.01), physical health (1.5, p < 0.01), and psychological domain (1.3, p < 0.01). Financial resources and home environment were not influenced by cannabis treatment (p = 0.07, p = 0.31, respectively).. Results suggest a potentially significant role of Cannabis in treatment-resistant Fibromyalgia women. Early Cannabis treatment may result in a beneficial short-term effect on the quality of life through its influence on pain, sleep, and physical and psychological domains. Further studies are still indicated to understand this potential and its long-term beneficial impact.

Topics: Adolescent; Adult; Aged; Cannabis; Female; Fibromyalgia; Humans; Middle Aged; Pain; Pregnancy; Prospective Studies; Quality of Life; Young Adult

Topics: Cancer Pain; Cannabidiol; Cannabis; Humans; Medical Marijuana; Neoplasms; Pain

Topics: Cannabis; Humans; Medical Marijuana; Pain

The past two decades have seen an increase in cannabis use due to both regulatory changes and an interest in potential therapeutic effects of the substance, yet many aspects of the substance and their health implications remain controversial or unclear.. In November 2020, the American Society of Regional Anesthesia and Pain Medicine charged the Cannabis Working Group to develop guidelines for the perioperative use of cannabis. The Perioperative Use of Cannabis and Cannabinoids Guidelines Committee was charged with drafting responses to the nine key questions using a modified Delphi method with the overall goal of producing a document focused on the safe management of surgical patients using cannabinoids. A consensus recommendation required ≥75% agreement.. Nine questions were selected, with 100% consensus achieved on third-round voting. Topics addressed included perioperative screening, postponement of elective surgery, concomitant use of opioid and cannabis perioperatively, implications for parturients, adjustment in anesthetic and analgesics intraoperatively, postoperative monitoring, cannabis use disorder, and postoperative concerns. Surgical patients using cannabinoids are at potential increased risk for negative perioperative outcomes.. Specific clinical recommendations for perioperative management of cannabis and cannabinoids were successfully created.

Topics: Analgesics; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Humans; Pain; Pain Management

Topics: Analgesics; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Data Visualization; Humans; Pain

Topics: Cannabis; Endometriosis; Female; Humans; Pain

Topics: Cannabinoids; Cannabis; Hallucinogens; Humans; Pain; Physicians

Tinnitus has a significant impact on quality of life and causes considerable psychological distress. Cannabis is known to modulate neuron hyperexcitability, provide protection against auditory damage, and has been used for treatment for many diseases which have physiological similarities with tinnitus. The objective of this study was to survey patients presenting with tinnitus regarding their perspectives and usage patterns of cannabis.. Patients with a primary presenting complaint of tinnitus in a tertiary neuro-otology clinic completed a 18-item questionnaire assessing perception, attitudes, and cannabis usage patterns.. Forty five patients completed the survey (mean age: 54.5 years, 31 females and 14 males). Overall, 96% of patients reported that they would consider cannabis as treatment for their tinnitus. Patients considered cannabis use for auditory symptoms (91%), and symptoms related to their tinnitus, such as emotional complaints (60%), sleep disturbances (64%), and functional disturbances (56%). 36% of patients had previously used cannabis and 22% of patients reported cannabis use at the time of the study. 80% of patients that were actively using cannabis reported that it helped with tinnitus-related symptoms, such as dizziness, anxiety, bodily pain, and sleep disturbances. Most patients would prefer to use edibles (62%), tablet (58%) and cream (47%) formulations of cannabis. Patients were concerned about the cost (29%), potential physical health implications (53%) and psychosocial side effects (60%) of cannabis. Over half of patients learned about cannabis from a friend or family member and only 22% of patients learned about cannabis from a physician or nurse.. Cannabis use is common amongst patients with tinnitus and current users of cannabis reported that it helped with their symptoms. Most patients would consider its use as a potential treatment to alleviate their tinnitus-related symptoms and are interested in learning more regarding its use. By understanding how cannabis is perceived by tinnitus patients, healthcare providers can provide appropriate patient education.

Topics: Attitude; Cannabis; Female; Humans; Male; Middle Aged; Pain; Quality of Life; Tinnitus

We aimed to identify correlates of cannabinoid-based products (CBP) use in patients with multiple sclerosis (MS) in France and Spain.. MS is responsible for a wide range of symptoms, including pain. Access to CBP differs according to local legislation. The French context is more restrictive than the Spanish one, and no data regarding cannabis use among MS patients has yet been published. Characterizing MS patients who use CBP constitutes a first step toward identifying persons most likely to benefit from them.. An online cross-sectional survey was submitted to MS patients who were members of a social network for people living with chronic diseases and were living in France or Spain.. Two study outcomes measured therapeutic CBP use and daily therapeutic CBP use. Seemingly unrelated bivariate probit regression models were used to test for associations between the outcomes and patients' characteristics while accounting for country-related differences. STROBE guidelines were followed in reporting this study.. Among 641 study participants (70% from France), the prevalence of CBP use was similar in both countries (23.3% in France vs. 20.1% in Spain). MS-related disability was associated with both outcomes, with a gradient observed between different degrees of disability. MS-related pain level was associated with CBP use only.. CBP use is common in MS patients from both countries. The more severe the MS, the more participants turned to CBP to alleviate their symptoms. Easier access to CBP should be ensured for MS patients in need of relief, especially from pain.. This study highlights the characteristics of MS patients using CBP. Such practices should be discussed by healthcare professional with MS patients.

Topics: Cannabinoids; Cannabis; Cross-Sectional Studies; Humans; Multiple Sclerosis; Pain

Cannabis has been used for centuries to treat pain. The antinociceptive activity of tetrahydrocannabinol (THC) or cannabidiol (CBD) has been widely studied. However, the antinociceptive effects of other cannabis components, such as cannabichromene (CBC) and cannabigerol (CBG), have rarely been revealed. The antinociceptive mechanism of CBG is not yet clear, so we investigated the antinociceptive effect of CBG on different pain models, and explored the mechanism of action of CBG to exert antinociceptive effects. In the current study, we compared the antinociceptive effects of CBC, CBD, and CBG on the carrageenan-induced inflammatory pain model in mice, and the results showed that CBG had a better antinociceptive effects through intraplantar administration. On this basis, we further investigated the antinociceptive effect of CBG on CIA-induced arthritis pain model and nerve pain model in mice, and found that CBG also relieved on both types of pain. Then, we explored the antinociceptive mechanism of CBG, which revealed that CBG can activate TRPV1 and desensitize it to block the transmission of pain signals. In addition, CBG can further activate CB2R, but not CB1R, to stimulate the release of β-endorphin, which greatly promotes the antinociceptive effect. Finally, the safety test results showed that CBG had no irritating effect on the rabbits' skin, and it did not induce significant biochemical and hematological changes in mice. Transdermal delivery results also indicated that CBG has certain transdermal properties. Overall, this study indicates that CBG is promising for developing a transdermal dosage for pain management.

Topics: Analgesics; Animals; Cannabidiol; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Hallucinogens; Mice; Pain; Rabbits

Cannabis is marketed as a treatment for pain. There is limited data on the prevalence of cannabis use and its correlates among Veterans prescribed opioids.. To examine the prevalence and correlates of cannabis use among Veterans prescribed opioids.. Cross-sectional study.. Veterans with a urine drug test (UDT) from Primary Care 2014-2018, in 50 states, Washington, D.C., and Puerto Rico. A total of 1,182,779 patients were identified with an opioid prescription within 90 days prior to UDT.. Annual prevalence of cannabis positive UDT by state. We used multivariable logistic regression to assess associations of demographic factors, mental health conditions, substance use disorders, and pain diagnoses with cannabis positive UDT.. Annual prevalence of cannabis positive UDT ranged from 8.5% to 9.7% during the study period, and in 2018 was 18.15% in Washington, D.C. and 10 states with legalized medical and recreational cannabis, 6.1% in Puerto Rico and 25 states with legalized medical cannabis, and 4.5% in non-legal states. Younger age, male sex, being unmarried, and marginal housing were associated with use (p < 0.001). Post-traumatic stress disorder (adjusted odds ratio [AOR] 1.17; 95% confidence interval [CI] 1.13-1.22, p < 0.001), opioid use disorder (AOR 1.14; CI 1.07-1.22, p < 0.001), alcohol use disorder or positive AUDIT-C (AOR 1.34; 95% CI 1.28-1.39, p < 0.001), smoking (AOR 2.58; 95% CI 2.49-2.66, p < 0.001), and other drug use disorders (AOR 1.15; 95% CI 1.03-1.29, p = 0.02) were associated with cannabis use. Positive UDT for amphetamines AOR 1.41; 95% CI 1.26-1.58, p < 0.001), benzodiazepines (AOR 1.41; 95% CI 1.31-1.51, p < 0.001) and cocaine (AOR 2.04; 95% CI 1.75-2.36, p < 0.001) were associated with cannabis positive UDT.. Cannabis use among Veterans prescribed opioids varied by state and by legalization status. Veterans with PTSD and substance use disorders were more likely to have cannabis positive UDT. Opioid-prescribed Veterans using cannabis may benefit from screening for these conditions, referral to treatment, and attention to opioid safety.

Topics: Analgesics, Opioid; Cannabis; Cross-Sectional Studies; Hallucinogens; Humans; Male; Pain; Primary Health Care; United States; Veterans

Little is known about the prospective relationship between cannabis use and pain reliever misuse. This study examined associations of non-medical and medical cannabis use with onset of non-medical pain reliever misuse among young adults in Washington State (WA), where non-medical cannabis is legal.. Data were from a cohort-sequential study of adults 18-25 residing in WA. Four annual surveys were used from cohorts recruited in 2014, 2015, and 2016. Participants who had not reported non-medical pain reliever misuse at baseline were included in discrete time survival analyses (N = 4,236). Odds ratios (ORs) were estimated for new onset of non-medical pain reliever misuse in any given follow-up year over the course of three years according to baseline non-medical and medical cannabis use.. When included separately in models, non-medical and medical cannabis use at baseline were associated with increased risk of non-medical pain reliever misuse adjusting for demographic characteristics as well as past year cigarette use and alcohol use (non-medical OR = 5.27; 95 % CI: 3.28, 8.48; medical OR = 2.21; 95 % CI: 1.39, 3.52). Including both forms of use in the model, associations of non-medical and medical cannabis use with non-medical pain reliever misuse onset remained (non-medical OR = 4.64; 95 % CI: 2.88, 7.49; medical OR = 1.65; 95 % CI: 1.04, 2.62).. Despite claims that cannabis use may reduce opioid use and related harms, findings suggest that cannabis use, including medical use, may not be protective, but instead may increase risk for non-medical pain reliever misuse.

Topics: Analgesics, Opioid; Cannabis; Humans; Medical Marijuana; Opioid-Related Disorders; Pain; Prescription Drug Misuse; Prospective Studies; Young Adult

Cannabis is often used by people with HIV (PWH) for pain, yet study results are inconsistent regarding whether and how it affects pain. This study examines whether greater cannabis use frequency is associated with lower pain interference and whether cannabis use modifies the association of pain severity and pain interference among 134 PWH with substance dependence or a lifetime history of injection drug use. Multi-variable linear regression models examined the association between past 30-day cannabis use frequency and pain interference. Additional models evaluated whether cannabis use modified the association between pain severity and pain interference. Cannabis use frequency was not significantly associated with pain interference. However, in a model with interaction between cannabis use frequency and pain severity, greater cannabis use frequency attenuated the strength of the association between pain severity and pain interference (

Topics: Cannabis; HIV Infections; Humans; Pain; Substance-Related Disorders

Demand for medical cannabis (MC) is growing among Israeli patients with cancer.. The study sought to assess factors contributing to the demand for MC among patients with cancer.. Patients applying for a permit to receive MC at a pain and palliative clinic of a university-affiliated cancer center in Israel in 2020-2021 were asked to complete self-report questionnaires assessing attitudes, knowledge, and expectations regarding MC use. Findings were compared between first-time and repeat applicants. Repeat applicants were asked to report their indications for requesting MC, patterns of use, and treatment effect.. The cohort included 146 patients: 63 first-time applicants and 83 repeat applicants. First-time applicants were more likely to consult sources other than their oncologist for MC-related information (P < 0.01) and expressed more concern about addiction (P < 0.001) and side effects (P < 0.05). They often erroneously assumed the treatment was subsidized (P < 0.001). Repeat applicants were younger (P < 0.05) and included more smokers (P < 0.05) and recreational cannabis users (P < 0.05); 56.6% were cancer survivors and 78% used high-potency MC. Most patients believed to some degree that MC is more effective than conventional medications for symptom control, and over half thought that MC helps to cure cancer.. Misconceptions regarding the effectiveness of MC for symptom management and treatment may explain the motivation of patients with cancer to apply for a permit. There seems to be an association of young age, cigarette smoking, and recreational cannabis use with ongoing use of MC among cancer survivors.

Topics: Attitude; Cannabis; Humans; Medical Marijuana; Neoplasms; Pain

Little is known about the risks and benefits of cannabis use in the context of cancer care. This study characterized the prevalence, reasons for use, and perceived benefits of cannabis and compared symptoms and perceived risks between those who reported past 30-day cannabis use and those who did not.. Adults undergoing cancer treatment at a National Cancer Institute-designated cancer center completed measures of sociodemographic characteristics, cannabis use, use modalities, reasons for use, perceived harms/benefits of use, physical and psychological symptoms, and other substance/medication use. Analyses compared patients who used or did not use cannabis in the past 30 days.. Participants (N = 267) were 58 years old on average, primarily female (70%), and predominantly White (88%). Over a quarter of respondents (26%) reported past 30-day cannabis use, and among those, 4.5% screened positive for cannabis use disorder. Participants who used cannabis most often used edibles (65%) or smoked cannabis (51%), and they were younger and more likely to be male, Black, and disabled, and to have lower income and Medicaid insurance than participants who did not use cannabis. Those who used cannabis reported more severe symptoms and perceived cannabis as less harmful than those who did not use cannabis. The most common medical reasons for cannabis use were pain, cancer, sleep problems, anxiety, nausea/vomiting, and poor appetite. Participants reported the greatest cannabis-related symptom relief from sleep problems, nausea/vomiting, headaches, pain, muscle spasms, and anxiety.. Patients with cancer who used cannabis perceived benefits for many symptoms, although they showed worse overall symptomatology.. Among adults undergoing cancer treatment, 26% reported cannabis use in the past 30 days. Those who used cannabis were more likely to be male and disabled and to have lower income and Medicaid insurance than those who did not use cannabis. Participants most commonly reported using cannabis for pain, cancer, sleep, anxiety, and nausea/vomiting and reported the greatest perceived benefits for sleep, nausea/vomiting, headaches, pain, muscle spasms, and anxiety, yet participants who used cannabis also reported feeling worse physically and psychologically compared to those who did not use cannabis. Participants who used cannabis were more likely to report that cannabis was less risky to their health than alcohol, smoking, and opioids than those who did not use cannabis.

Topics: Adult; Cancer Pain; Cannabis; Female; Headache; Humans; Male; Medical Marijuana; Middle Aged; Nausea; Neoplasms; Pain; Sleep Wake Disorders; Spasm; Vomiting

This Viewpoint reviews the evidence for using cannabis and cannabinoids to treat pain and PTSD in military and veteran populations.

Topics: Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Hallucinogens; Humans; Military Personnel; Pain; Stress Disorders, Post-Traumatic; Veterans

Topics: Cannabis; Dronabinol; Humans; Multiple Sclerosis; Pain

Cannabis may have therapeutic benefits to relieve symptoms of amyotrophic lateral sclerosis (ALS) thanks to its pleiotropic pharmacological activity. This study is the first to present a large questionnaire-based survey about the "real-life" situation regarding cannabis use in the medical context in ALS patients in France. There were 129 respondents and 28 reported the use of cannabis (21.7%) to relieve symptoms of ALS. Participants mostly reported the use of cannabidiol (CBD) oil and cannabis weed and declared benefits both on motor (rigidity, cramps, fasciculations) and non-motor (sleep quality, pain, emotional state, quality of life, depression) symptoms and only eight reported minor adverse reactions (drowsiness, euphoria and dry mouth). Even if cannabis is mostly used outside medical pathways and could expose patients to complications (street and uncontrolled drugs, drug-drug interactions, adverse effects…), most of the participants reported "rational" consumption (legal cannabinoids, with only few combustion and adverse reactions). Despite some limitations, this study highlights the need for further research on the potential benefits of cannabis use for the management of ALS motor and non-motor symptoms. Indeed, there is an urgent need and call for and from patients to know more about cannabis and secure its use in a medical context.

Topics: Amyotrophic Lateral Sclerosis; Cannabinoids; Cannabis; Humans; Pain; Quality of Life

Topics: Analgesics, Opioid; Cannabis; Chronic Pain; Humans; Medical Marijuana; Pain; Prescriptions

Rates of tobacco and cannabis use are disproportionately high among individuals with pain, and evidence suggests that pain may engender greater likelihood of substance co-use, yielding additive risk. This study examined national associations of pain with past-month tobacco use, cannabis use, and co-use of tobacco and cannabis.. Data came from a nationally representative US sample of adults in Wave 5 (2018-2019) of the Population Assessment of Tobacco and Health study (N = 32,014). The sample included civilian, non-institutionalized people who use tobacco and people who do not use tobacco. Past-week pain intensity (0-10) was dichotomized (0-4 no/low pain; 5-10 moderate/severe pain). Multinomial models adjusted for demographics examined substance use category membership (no tobacco or cannabis use, exclusive cannabis use, exclusive tobacco use, co-use) as a function of pain status.. Moderate/severe pain was associated with increased relative risk of exclusive tobacco use (RRR [CI] 2.26 [2.05, 2.49], p <.001), exclusive cannabis use (1.49 [1.22, 1.82], p <.001), and co-use of tobacco and cannabis (2.79 [2.51, 3.10], p <.001), in comparison to no tobacco or cannabis use. Additionally, moderate/severe pain was associated with increased risk of co-use compared to exclusive tobacco use (1.23 [1.11, 1.37], p <.001) and exclusive cannabis use (1.88 [1.54, 2.29], p <.001).. Findings suggest that not only is pain independently associated with greater risk of exclusively using tobacco or cannabis, but pain is also associated with heightened risk of co-using both products. Future work should examine the dynamic and potentially bidirectional relationships between pain and use of cannabis and tobacco.

Topics: Adult; Cannabis; Humans; Nicotiana; Pain; Substance-Related Disorders; Tobacco Products; Tobacco Use

Topics: Cannabis; Humans; Pain

Symptoms such as pain, nausea, and anxiety are common in individuals with cancer. Treatment of these issues is often challenging. Cannabis products may be helpful in reducing the severity of these symptoms. While some studies include data on the prevalence of cannabis use among patients with cancer, detailed data remain limited, and none have reported the prevalence of cannabidiol (CBD) use in this population.\ \ Adult patients with cancer attending eight clinics at a large, NCI-designated Comprehensive Cancer Center completed a detailed, cannabis-focused questionnaire between 2021 and 2022. Eligible participants were diagnosed with invasive cancer and treated in the past 12 months. Summary statistics were calculated to describe the sample regarding cannabis use.\ \ Approximately 15% (n = 142) of consented patients (n = 934) reported current cannabis use (defined as use within the past 12 months). Among which, 75% reported cannabis use in the past week. Among current cannabis users, 39% (n = 56; 6% overall) used CBD products. Current users reported using cannabis a median of 4.5 (interquartile range: 0.6–7.0) days/week, 2.0 (1.0–3.0) times per use/day, and for 3 years (0.8–30.0). Use patterns varied by route of administration. Patients reported moderate to high relief of symptoms with cannabis use.\ \ This study is the most detailed to date in terms of cannabis measurement and provides information about the current state of cannabis use in active cancer. Future studies should include complete assessments of cannabis product use, multiple recruitment sites, and diverse patient populations.. Clinicians should be aware that patients are using cannabis products and perceive symptom relief with its use.

Topics: Adult; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Hallucinogens; Humans; Medical Marijuana; Neoplasms; Pain; Prevalence

Topics: Aged; Cannabis; Humans; Legislation, Drug; Medical Marijuana; Pain

» Cannabinoids, such as D9-tetrahydrocannabinol and cannabidiol, interact with endocannabinoid receptors in the central nervous system and immune system, potentially offering pain relief. The entourage effect, resulting from the interaction of multiple cannabis components, may enhance therapeutic impact and efficacy, making them promising candidates for exploring pain relief in spine operations, known to be among the most painful operative procedures.» The use of cannabinoids in pain management requires careful consideration of safety, including their cognitive and psychomotor effects, potential cardiovascular risks, risk of dependence, mental health implications, and drug interactions.» Few studies have analyzed cannabinoid use in relation to spine surgery, with variable results reported, indicating possible effects on reoperation rates, mortality, complications, postoperative opioid use, and length of hospital stay.» Current knowledge gaps exist in the understanding of cannabinoid effects on spine surgery, including the exploration of different administration routes, timing, dosage, and specific outcomes. In addition, mechanistic explanations for the observed results are lacking.» Ethical considerations related to informed consent, medical expertise, societal impact, and legal compliance must also be thoroughly addressed when considering the utilization of cannabinoids in spinal pathologies and back pain treatment.

Topics: Cannabinoids; Cannabis; Dronabinol; Humans; Pain; Pain Management

The legalization of medicinal use of Cannabis sativa in most US states and the removal of hemp from the Drug Enforcement Agency (DEA) controlled substances act has resulted in a proliferation of products containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) for oral consumption (e.g., edibles, oils, and tinctures) that are being used for recreational and medicinal purposes.. This study examined the effects of cannabinoids THC and CBD when administered orally on measures of pain sensitivity, body temperature, locomotor activity, and catalepsy (i.e., cannabinoid tetrad) in male and female Sprague Dawley rats.. Rats (N = 24, 6 per sex/drug group) were administered THC (1-20 mg/kg), CBD (3-30 mg/kg), or sesame oil via oral gavage. Thermal and mechanical pain sensitivity (tail flick assay, von Frey test), rectal measurements for body temperature, locomotor activity, and the bar-test of catalepsy were completed. A separate group of rats (N = 8/4 per sex) was administered morphine (5-20 mg/kg; intraperitoneal, IP) and evaluated for pain sensitivity as a positive control.. We observed classic tetrad effects of antinociception, hypothermia, hyper- and hypolocomotion, and catalepsy after oral administration of THC that were long lasting (> 7 h). CBD modestly increased mechanical pain sensitivity and produced sex-dependent effects on body temperature and locomotor activity.. Oral THC and CBD produced long lasting effects that differed in magnitude and time course when compared with other routes of administration. Examination of cannabinoid effects administered via different routes of administration, species, and in both males and females is critical to enhance translation.

Topics: Animals; Cannabidiol; Cannabinoids; Cannabis; Catalepsy; Dronabinol; Female; Male; Pain; Rats; Rats, Sprague-Dawley

To assess the correlation between cannabis use and psoriatic disease severity, health-related quality of life, pain, psychosocial outcomes, and cytokine levels in psoriasis (PsC) and psoriatic arthritis (PsA) patients.. PsC and PsA patients enrolled in the International Psoriasis and Arthritis Research Team (IPART) program were surveyed on cannabis use and were asked to provide a serum and urine sample. Demographic and clinical variables were compared between users and non-users using Student's t-test or Mann-Whitney U test for continuous variables, and chi-square or Fisher's exact test for categorical variables.. Of 151 respondents, 30% reported current cannabis use within the last year. Compared to non-users, cannabis users were younger and had a shorter PsA duration and poorer mental health as measured by the SF-36. Other measures of health-related quality of life and pain were comparable between the groups. Respondents' primary perceived benefits of cannabis use were aid in sleep and arthritis pain relief, but there was no difference in pain between users and non-users. No THC was detected in the urine of non-users while users had a mean level of 19.6 ng/ml. Serum IL-23 levels were statistically significantly higher in non-users than in users.. A third of the patients used cannabis within the past year, and 54.3% of users reported the use of cannabis for arthritis pain relief. However, there was no difference in pain scores. Comprehensive education for providers on the current body of evidence and further studies on cannabis use and outcomes in psoriatic disease are needed. Key Points • A third of patients with psoriatic arthritis have used cannabis in the past year. • Most used it for better sleep and control of pain. • There was no difference in pain scores between users and non-users. • IL-23 levels were significantly higher in non-users.

Topics: Analgesics; Arthritis, Psoriatic; Cannabis; Humans; Interleukin-23; Male; Pain; Prostate-Specific Antigen; Psoriasis; Quality of Life

Prior research has examined the prevalence and correlates of cannabis use disorder (CUD) in people who use cannabis; however, these are poorly described for people using cannabis for medical reasons.. Data came from a 2018 to 2019 online, anonymous, cross-sectional survey of Australians reporting using either illicit or licit cannabis for medical reasons within the past year. Included were questions on demographics, current and lifetime patterns of cannabis use, clinical conditions for which medical cannabis was used, and individual criteria for CUD and cannabis withdrawal syndrome. Bayesian Horseshoe logistic regression models were used to identify covariates associated with meeting CUD DSM-5 conditions for any-CUD (≥2/11 criteria) and moderate-severe-CUD (≥4/11).. A total of 905 participants were included in the analysis. The majority (98%) used illicit cannabis products. Criteria for any-CUD criteria were met by 290 (32.0%), and 117 (12.9%) met criteria for moderate-severe-CUD. Tolerance (21%) and withdrawal (35%) were the most commonly met criteria. Correlates with the strongest association with CUD were inhaled route of administration [odds ratio (OR) = 2.96, 95% credible interval 1.11, 7.06], frequency of cannabis use (OR = 1.24, 1.11-1.35), proportion of cannabis for medical reasons (OR = 0.83, 0.74, 0.94), frequency of tobacco use (OR = 1.10, 1.03, 1.17), age (OR = 0.75, 0.64, 0.90) and pain as main clinical indication (OR = 0.58, 0.36, 1.00).. Prevalence of CUD in medical cannabis users appears comparable to 'recreational' users, with many similar correlates. CUD was associated with using cannabis to treat mental health rather than pain conditions and inhaled over other routes of administration.

Topics: Analgesics; Australia; Bayes Theorem; Cannabis; Cross-Sectional Studies; Hallucinogens; Humans; Marijuana Abuse; Medical Marijuana; Pain; Prevalence; Substance-Related Disorders

The aim of this study was to investigate the frequency of use, attitudes toward, and experiences with cannabis and cannabis-related products among people with Parkinson's disease (PwP) living in Norway.. Between February and August 2021, PwP and their caregivers were invited to participate in an anonymous online survey study on cannabis use. N = 530 PwP completed the 24-item survey collecting data on the participants' history of cannabis use, perceived benefits and adverse effects of cannabis use, and expectations toward health care professionals. N = 108 caregivers completed a brief survey detailing their experience with cannabis use.. A total of 59 (11.3%) of PwP reported previous or current use of cannabis, compared to 7 (6.6%) of caregivers. Cannabis use was associated with increased disease duration, but not age or gender. Improvement in motor function (69.5%), sleep (52.5%), and pain (37.3%) was the most frequently perceived benefits of cannabis use, with benefits more frequently reported by current than previous users. While half (50.8%) of cannabis users had sought advice from a health care professional regarding cannabis use, only 55 (19.9%) of non-users with an interest in cannabis use had discussed the topic with health care professionals. Principal barriers for discussing cannabis use with health care professionals are discussed.. One in 20 PwP reports cannabis use, and non-users report widespread interest in cannabis. The use of cannabis is often not reported and unknown for health care professionals, arguing for a vigilant approach to non-prescribed cannabis use in clinical follow-up of PwP.

Topics: Analgesics; Cannabis; Health Personnel; Humans; Pain; Parkinson Disease

Topics: Analgesics, Opioid; Canada; Cannabis; Cross-Sectional Studies; Humans; Pain; Prescription Drugs; Prescriptions; Self Report; United States

Liberalization of cannabis laws may be accompanied by changes in the use of substances other than cannabis and changes in associations of cannabis use with other types of substance use. This study assessed (1) trends in alcohol, nicotine, and nonprescribed pain reliever use and (2) changes in associations of cannabis use with these other substances among young adults in Washington State after nonmedical cannabis legalization.. Regression models stratified by age (18-20 vs. 21-25) were used to analyze six annual waves of cross-sectional survey data from a statewide sample from 2014 through 2019 (N = 12,694).. Prevalence of past-month alcohol use, heavy episodic drinking (HED), and cigarette use and prevalence of past-year pain reliever misuse decreased, while the prevalence of past-month e-cigarette use increased since 2016 (the first year assessed). Across years and age groups, the prevalence of substance use other than cannabis was higher among occasional and frequent cannabis users compared to cannabis nonusers. However, associations between both occasional (1-19 days in the prior month) and frequent (20+ days) cannabis use and pain reliever misuse and between frequent cannabis use and HED weakened over time among individuals ages 21-25.. Contrary to concerns about spillover effects, implementation of legalized nonmedical cannabis coincided with decreases in alcohol and cigarette use and pain reliever misuse. The weakening association of cannabis use with the use of other substances among individuals ages 21-25 requires further research but may suggest increased importance of cannabis-specific prevention and treatment efforts.

Topics: Adult; Cannabis; Cross-Sectional Studies; Electronic Nicotine Delivery Systems; Humans; Pain; Substance-Related Disorders; Tobacco Products; Washington; Young Adult

Cannabis products, including the cannabinoids CBD and THC, are rising in popularity and increasingly used for medical purposes. While there is some evidence that cannabinoids improve cancer-associated symptoms, understanding regarding appropriate use remains incomplete.. To describe patient experiences with medical cannabis with focus on use contexts and patients' reported benefits and harms.. A standardized intake form was implemented in a dedicated medical cannabis clinic at an NCI-designated cancer center; data from this form was abstracted for all initial visits from October 2019 to October 2020. We report descriptive statistics, chi-square analysis, and multivariate logistic regression.. Among 163 unique new patients, cannabis therapy was commonly sought for sleep, pain, anxiety, and appetite. Twenty-nine percent expressed interest for cancer treatment; 40% and 46% reported past use of CBD and THC, respectively, for medical purposes. Among past CBD users, the most commonly reported benefits were less pain (21%) or anxiety (17%) and improvement in sleep (15%); 92% reported no side effects. Among those with past THC use, reported benefits included improvement in appetite (40%), sleep (32%), nausea (28%), and pain (17%); side effects included feeling "high." Seeking cannabis for anti-neoplastic effects was associated with receipt of active cancer treatment in both univariate and multivariate analysis.. Cancer patients seek medical cannabis to address a wide variety of concerns despite insufficient evidence of benefits and harms. As more states move to legalize medical and recreational cannabis, cancer care providers must remain aware of emerging data and develop knowledge and skills to counsel their patients about its use.

Topics: Analgesics; Cannabinoids; Cannabis; Dronabinol; Drug-Related Side Effects and Adverse Reactions; Humans; Medical Marijuana; Neoplasms; Pain; Retrospective Studies

Topics: Cannabis; Endometriosis; Female; Humans; Pain

This study explored whether symptom relief differs by sex in patients with cancer receiving medical cannabis (MC) therapy.. This is an analysis of data collected from patients with cancer enrolled in the Quebec Cannabis Registry. MC was initiated for the therapeutic management of cancer symptoms. Patients completed the revised Edmonton Symptom Assessment System (ESAS-r) questionnaire at baseline and 3-month follow-up. We examined the interaction between sex and time on each ESAS-r symptom and the interaction between time and tetrahydrocannabinol:cannabidiol (THC:CBD) ratios for each sex on total symptom burden.. The analysis included 358 patients (M: 171). There were no sex differences in baseline ESAS-r scores. Three months of MC therapy led to significant improvements in pain (M: - 1.4 ± 0.3, p < 0.001; F: - 1.1 ± 0.3, p < 0.01), tiredness (M: - 1.7 ± 0.4, p < 0.001; F: - 1.2 ± 0.4, p < 0.05), anxiety (M: - 1.1 ± 0.4, p < 0.05; F: - 1.2 ± 0.4, p < 0.001), and well-being (M: - 1.2 ± 0.4, p < 0.05; F: - 1.4 ± 0.4, p < 0.01) in both sexes. Only F perceived improved drowsiness (- 1.1 ± 0.4, p < 0.05), nausea (- 0.9 ± 0.3, p < 0.05), lack of appetite (- 1.7 ± 0.4, p < 0.001), and shortness of breath (- 0.9 ± 0.3, p < 0.05). From baseline to 3-month follow-up, THC-dominant MC significantly reduced pain (- 1.52 ± 0.52, p < 0.05) in M, whereas in F it diminished nausea (- 2.52 ± 0.70, p < 0.01) and improved well-being (- 2.41 ± 0.79, p < 0.05). THC:CBD-balanced products significantly reduced pain (- 1.48 ± 0.49, p < 0.05), tiredness (- 1.82 ± 0.62, p < 0.05), anxiety (- 1.83 ± 0.54, p < 0.05), and improved well-being (- 2.01 ± 0.56, p < 0.01) in M. CBD-dominant products did not offer significant symptom relief in either sex.. The perceived relief of cancer symptoms from MC differs between sexes. More randomized controlled trials are needed to confirm our findings.

Topics: Analgesics; Cannabidiol; Cannabis; Dronabinol; Fatigue; Female; Humans; Male; Medical Marijuana; Nausea; Neoplasms; Pain; Quebec; Registries

Topics: Adult; Aged; Analgesics; Analgesics, Opioid; Cannabis; Cross-Sectional Studies; Female; Hallucinogens; Humans; Male; Medical Marijuana; Middle Aged; Opiate Alkaloids; Opioid-Related Disorders; Pain; Quality of Life; Young Adult

Topics: Analgesics, Opioid; Cannabis; Humans; Marijuana Abuse; Mindfulness; Opioid-Related Disorders; Pain

Topics: Analgesics; Cannabis; Humans; Medical Marijuana; Pain

Topics: Analgesics, Opioid; Cannabis; Humans; Medical Marijuana; Pain; Physicians; Practice Patterns, Physicians'

Pain is associated with increased risk for harmful substance use. Substance use also may increase levels of pain, suggesting that these two factors may reciprocally increase risk. The current study examined the reciprocal association between pain and substance use outcomes (i.e., alcohol, cannabis, and painkillers/sedatives/tranquilizers [PSTs]) longitudinally in a nationally representative cohort of non-incarcerated U.S. citizens.. Adult (≥18 years old) survey data from Waves 2-4 of the Population Assessment of Tobacco and Health (PATH) study were used. The PATH is a nationally representative multiwave cohort survey (Wave 2: October 2014-October 2015, Wave 3: October 2015-October 2016, Wave 4: December 2016-January 2018). Cross-lagged panel models were used to estimate the reciprocal effects of pain intensity and substance use on subsequent changes in both variables. Substance use outcomes were substance use problems and greater-than-weekly use for cannabis and PSTs, total past-month drinks, and alcohol use exceeding moderate drinking guidelines. All models controlled for autoregressive effects and demographic covariates.. Pain intensity showed a positive prospective association with all substance use outcomes. All cannabis and PST use were positively associated with subsequent pain intensity. Alcohol use problems also predicted higher levels of pain intensity. Neither total past-month drinks nor exceeding moderate drinking guidelines predicted subsequent pain intensity.. Pain and substance use show a reciprocal association and may act in a positive feedback loop to worsen both conditions over time in people with a history of use.

Topics: Adolescent; Adult; Alcohol Drinking; Alcoholism; Cannabis; Cohort Studies; Humans; Pain; Substance-Related Disorders; United States

Use of cannabis is increasing in a variety of populations in the United States; however, few investigations about how and for what reasons cannabis is used in older populations exist.. Anonymous survey.. Geriatrics clinic.. A total of 568 adults 65 years and older.. Not applicable.. Survey assessing characteristics of cannabis use.. Approximately 15% (N = 83) of survey responders reported using cannabis within the past 3 years. Half (53%) reported using cannabis regularly on a daily or weekly basis, and reported using cannabidiol-only products (46%). The majority (78%) used cannabis for medical purposes only, with the most common targeted conditions/symptoms being pain/arthritis (73%), sleep disturbance (29%), anxiety (24%), and depression (17%). Just over three-quarters reported cannabis "somewhat" or "extremely" helpful in managing one of these conditions, with few adverse effects. Just over half obtained cannabis via a dispensary, and lotions (35%), tinctures (35%), and smoking (30%) were the most common administration forms. Most indicated family members (94%) knew about their cannabis use, about half reported their friends knew, and 41% reported their healthcare provider knowing. Sixty-one percent used cannabis for the first time as older adults (aged ≥61 years), and these users overall engaged in less risky use patterns (e.g., more likely to use for medical purposes, less likely to consume via smoking).. Most older adults in the sample initiated cannabis use after the age of 60 years and used it primarily for medical purposes to treat pain, sleep disturbance, anxiety, and/or depression. Cannabis use by older adults is likely to increase due to medical need, favorable legalization, and attitudes.

Topics: Aged; Anxiety; Cannabis; Depression; Humans; Medical Marijuana; Pain; Sleep Wake Disorders; Surveys and Questionnaires; United States

Cannabis motivations have been studied extensively among patients of medicinal cannabis dispensaries, but less is known about motivations in community samples of opioid-using people who inject drugs. Our objective is to describe cannabis use motivations associated with self-treatment of physical pain, emotional issues, and as an opioid substitute.. Data come from 6-month follow-up interviews with people who inject drugs who participated in a study on the efficacy of an injection initiation prevention intervention in Los Angeles and San Francisco, California from 2016-18. The analytic sample consists of 387 people who inject drugs who reported past-month cannabis use. We developed multivariable logistic regression models by reported cannabis use motivations: physical pain relief, emotional problems, and opioid substitute.. The most common cannabis use motivations reported by people who inject drugs was to "get high," relieve physical pain and emotional problems, and reduce opioid use. In separate multivariate models, using cannabis for physical pain relief was associated with higher odds of using cannabis as a substitute for opioids; cannabis for emotional problems was associated with being diagnosed with depression; and cannabis as a substitute for opioids was associated with non-prescribed, non-injection methadone use.. People who inject drugs reported using cannabis for health-related motivations. This motivation aligns with health needs and suggests the acceptability of cannabis use for health reasons in this population. Studies to determine the medical effectiveness of cannabis products for these common health and mental health needs among people who inject drugs are needed.

Topics: Adult; Analgesics; Analgesics, Opioid; Cannabis; Female; Humans; Injections; Intention; Logistic Models; Los Angeles; Male; Marijuana Smoking; Medical Marijuana; Middle Aged; Motivation; Opioid-Related Disorders; Pain; Pain Management; San Francisco; Substance Abuse, Intravenous

Despite medicalization and legalization of marijuana use, factors influencing demand for marijuana among persons living with HIV (PLWH) are incompletely understood. This knowledge gap undermines effective clinical management and policies. This study used demand curve simulation methods to address these issues.. Marijuana-using PLWH (N = 119) completed experimental tasks to simulate amount of marijuana purchasing/use across different costs (money or time), and likelihood of reselling marijuana or marijuana therapeutic-use registration card in relation to profits. Additional simulations assessed purchasing of marijuana relative to other drug and non-drug goods.. Simulated marijuana use decreased as money and time costs increased. Consumption was greater for participants with more severe Cannabis Use Disorder (CUD) and anxiety, intermediate pain levels, and past 90-day opioid use. Whereas few participants chose to sell their registration card, marijuana resale (diversion) steeply increased with profit. Likelihood of seeking marijuana therapeutic-use certification decreased in relation to registration card money cost, having to visit more physicians to get a signature, and delay to receiving the card, and increased with duration of certification. Participants who reported recent opioid use were more likely to seek certification. Consumption of several commodities assessed was independent of marijuana.. Simulated marijuana use was related to participants' clinical profile (CUD, anxiety and pain symptoms, recent opioid use), and unrelated to purchasing other goods. Likelihood of seeking marijuana therapeutic-use registration was affected by several types of costs and recent opioid use. Participants were unlikely to divert registration cards. We discuss clinical and policy implications of these findings.

Topics: Adult; Anxiety; Cannabis; Female; Hallucinogens; HIV Infections; Humans; Male; Marijuana Abuse; Marijuana Smoking; Marijuana Use; Medical Marijuana; Opioid-Related Disorders; Pain; Surveys and Questionnaires

Wound-related pain poses a serious challenge for patients and physicians. It is a complex pathophysiologic construct that may be stratified, from the patient's perspective, into baseline pain and breakthrough pain. The current paradigm for treating wound related pain involves the overuse of opioids and other co-analgesics with little regard for breakthrough pain. These standard medications have a propensity for deleterious side effects while some of them inhibit wound healing, effectively perpetuating the wound and the related pain. In particular, the overuse of opioids is a contributor to the global opioid crisis. It is evident that a new paradigm needs to be considered. Cannabis-based medicines are a prominent prospect under investigation for their potential to reduce dosages of status quo analgesics while effectively reducing pain. The authors propose a new paradigm that emphasizes the use of Cannabis-Based Medicines, delivered through multiple routes, while recommending the need for more foundational scientific investigation into mechanisms, and clinical controlled trials to determine optimal combinations, dosages, and protocols.

Topics: Analgesics; Analgesics, Opioid; Cannabis; Humans; Pain; Pain Management; Wound Healing

Topics: Analgesics; Arthritis, Rheumatoid; Cannabis; Humans; Pain

Cannabidiol (CBD) is purportedly a promising therapeutic agent to provide relief for a variety of medical conditions with mild or no psychoactive effects. However, little is known about young adults who use cannabis and CBD-dominant products, and associations between CBD use and other drug use.. Young adults (aged 24-32) who currently used cannabis (n = 239) were surveyed in Los Angeles in March 2019 through March 2020. The sample was divided into CBD-dominant (at least 1:1 CBD:THC ratio) and THC-dominant product users. We described CBD forms, reasons and conditions for CBD use and examined between-group differences in sociodemographic characteristics, cannabis practices, health and other drug use.. CBD-dominant users were more likely to be female, use cannabis at lower frequency and amount (except for edible/drinkable/oral products), self-report medical motivation for cannabis use, use cannabis for pain and report more health problems. Oil, flower, topicals and sprays/drops/tinctures were the most prevalent CBD forms. Psychological problems and pain were commonly reported conditions and medical reasons for CBD use. CBD-dominant users were more likely to report illicit drug use, where psilocybin use was markedly different between the two groups.. CBD use was associated with health histories and motivations linked to pain and psychological problems. Positive association between CBD use and illicit drug use may indicate self-medication for psychological conditions. Future studies should evaluate the effectiveness of various CBD forms and dose regimens for treatment of pain and psychological problems, and as a potential intervention for decreasing other drug use and associated harms.

Topics: Adolescent; Adult; Cannabidiol; Cannabis; Cohort Studies; Dronabinol; Female; Hallucinogens; Humans; Longitudinal Studies; Los Angeles; Male; Marijuana Use; Pain; Self Report; Substance-Related Disorders; Young Adult

Topics: Analgesia; Analgesics; Cannabinoids; Cannabis; Humans; Pain

Topics: Analgesia; Analgesics; Cannabinoids; Cannabis; Humans; Pain

Limited evidence has suggested that terpenes found in Cannabis sativa are analgesic, and could produce an "entourage effect" whereby they modulate cannabinoids to result in improved outcomes. However this hypothesis is controversial, with limited evidence. We thus investigated Cannabis sativa terpenes alone and with the cannabinoid agonist WIN55,212 using in vitro and in vivo approaches. We found that the terpenes α-humulene, geraniol, linalool, and β-pinene produced cannabinoid tetrad behaviors in mice, suggesting cannabimimetic activity. Some behaviors could be blocked by cannabinoid or adenosine receptor antagonists, suggesting a mixed mechanism of action. These behavioral effects were selectively additive with WIN55,212, suggesting terpenes can boost cannabinoid activity. In vitro experiments showed that all terpenes activated the CB1R, while some activated other targets. Our findings suggest that these Cannabis terpenes are multifunctional cannabimimetic ligands that provide conceptual support for the entourage effect hypothesis and could be used to enhance the therapeutic properties of cannabinoids.

Topics: Animals; Behavior, Animal; Benzoxazines; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Catalepsy; CHO Cells; Cricetulus; Drug Synergism; Female; Locomotion; Male; Mice; Mice, Inbred ICR; Morpholines; Naphthalenes; Nociception; Pain; Receptor, Cannabinoid, CB1; Terpenes

The activation of cannabinoid CB

Topics: Administration, Oral; Amino Acid Sequence; Analgesics; Animals; Behavior, Animal; Binding Sites; Blood-Brain Barrier; Cannabinoids; Cannabis; Dimerization; Mice; Mice, Inbred ICR; Molecular Dynamics Simulation; Pain; Peptides; Receptor, Cannabinoid, CB1; Receptor, Serotonin, 5-HT2A

Topics: Analgesics; Cannabis; Chronic Pain; Humans; Medical Marijuana; Pain; Pain Management

Many studies are performed with the aerial parts of Cannabis sativa L. (Cannabaceae). However, roots remain poorly studied, despite citations in the scientific literature. The C. sativa roots are indicated for the treatment of pain, inflammation, fever, among other health problems.. This study aimed to evaluate the antinociceptive, antipyretic, antiasthmatic, and spasmolytic activities of C. sativa roots in experimental models using mice and rats.. The chemical composition of the aqueous extract of C. sativa roots (AECsR) was evaluated by LC-MS. The antinociceptive activity was assessed in mice by the induction of writhing with acetic acid, paw licking with formalin, and reactivity in the hot plate test. Fever was induced by the administration of a suspension of Saccharomyces cerevisiae in young rats. The asthmatic activity was performed with ovalbumin (OVA)-immunized mice with cellular and histological analysis. Finally, the spasmolytic activity was performed using mice isolated trachea. For in vivo studies, the doses were 12.5, 25, or 50 mg/kg whereas for in vitro, the concentration of AECsR was 729 μg/mL.. From the LC-MS data, we identified p-coumaroyltyramine, feruloyltyramine canabissativine in AECsR. The extract promoted a reduction of writhing in all tested doses (12.5, 25, or 50 mg/kg). Similarly, it reduced the pain in the formalin test at doses of 12.5 and 50 mg/kg (first phase) and 12.5 and 25 mg/kg (second phase). In the hot plate test, the doses of 12.5, 25, and 50 mg/kg promoted antinociceptive effect at different times, and the lowest dose maintained its action in the analyzes performed at 60, 90, and 120 min after administration. The anti-inflammatory activity of AECsR was observed in the mouse model of asthma, reducing the total leukocyte count in the bronchoalveolar fluid (BALF) at a dose of 25 mg/kg, as well as reducing eosinophilia in all tested doses (12.5, 25, and 50 mg/kg). Histological analysis of lungs stained with H&E and PAS showed a reduction in the number of inflammatory cells in the perivascular and peribronchial region, as well as reduced mucus production.. The results suggest that AECsR promotes pain control, either by a central or inflammatory mechanism, and has antiasthmatic activity. However, there was no antipyretic or spasmolytic effect.

Topics: Analgesics; Animals; Anti-Asthmatic Agents; Antipyretics; Brazil; Cannabis; Disease Models, Animal; Dose-Response Relationship, Drug; Fever; Inflammation; Male; Mice; Pain; Parasympatholytics; Plant Extracts; Plant Roots; Rats; Rats, Wistar

The President of the International Association for the Study of Pain established a task force on cannabis and cannabinoid analgesia to systematically examine the evidence on (1) analgesic pharmacology of cannabinoids and preclinical evidence on their efficacy in animal models of injury-related or pathological persistent pain; (2) the clinical efficacy of cannabis, cannabinoids, and cannabis-based medicines for pain; (3) harms related to long-term use of cannabinoids; as well as (4) societal issues and policy implications related to the use of these compounds for pain management. Here, we summarize key knowledge gaps identified in the task force outputs and propose a research agenda for generating high-quality evidence on the topic. The systematic assessment of preclinical and clinical literature identified gaps in rigor of study design and reporting across the translational spectrum. We provide recommendations to improve the quality, rigor, transparency, and reproducibility of preclinical and clinical research on cannabis and cannabinoids for pain, as well as for the conduct of systematic reviews on the topic. Gaps related to comprehensive understanding of the endocannabinoid system and cannabinoid pharmacology, including pharmacokinetics and drug formulation aspects, are discussed. We outline key areas where high-quality clinical trials with cannabinoids are needed. Remaining important questions about long-term and short-term safety of cannabis and cannabinoids are emphasized. Finally, regulatory, societal, and policy challenges associated with medicinal and nonmedicinal use of cannabis are highlighted, with recommendations for improving patient safety and reducing societal harms in the context of pain management.

Topics: Analgesia; Analgesics; Animals; Cannabinoids; Cannabis; Humans; Pain; Pain Management; Reproducibility of Results; Systematic Reviews as Topic

Despite increasing rates of nonmedical and/or medical cannabis use in the 50+ age group, scant research exists on the associations between cannabis use and prescription medication use. In this study, we examined associations of use of prescription tranquilizers, sedatives, stimulants, and pain relievers, tobacco products, any/binge/heavy alcohol, and illicit drugs with cannabis use and use characteristics among U.S. adults aged 50+ years with past-year mental illness (n = 6454).. Data are from the 2015-2019 National Survey on Drug Use and Health (NSDUH). We used logistic regression models to examine associations of past-month use of each substance with (1) cannabis use among all those with past-year mental illness, and (2) cannabis use characteristics among cannabis users, controlling for severity of mental illness and sociodemographic and health characteristics.. Of individuals aged 50+, 14.1 % had any past-year mental illness, and 9.7 % of those with mental illness, compared to 4.0 % of those without, reported past-month cannabis use. Compared to nonusers, cannabis users had higher odds of using each substance except antidepressants, with adjusted odds ratios ranging from 1.3 (sedatives) to 3.6 (illicit drugs). Compared to nonmedical cannabis users, medical users had 2-2.5 times higher likelihood of co-use of tranquilizers, sedatives, and prescription pain relievers but lower odds of binge and heavy alcohol use.. Cannabis users, especially medical cannabis users, are significantly more likely to use prescription psychotropic or pain medications. Healthcare professionals should assess for poly-substance use and potential adverse effects among older adults with mental illness.

Topics: Aged; Cannabis; Hallucinogens; Humans; Pain; Prescriptions; Substance-Related Disorders

Cannabis has been legalized, decriminalized, or medicalized in over half the U.S. states. With restrictions on cannabis research, accepted standards to guide clinical practice are lacking. Analyzing online communications through a digital health platform, we characterized patient questions about cannabis use and provider responses. Coded for content were 4579 questions posted anonymously online between March 2011 through January 2017, and the responses from 1439 U.S. licensed clinicians. Provider responses to medical cannabis use questions were coded for sentiment: "negative", "positive", and "mixed." Responses could be "thanked" by patients and receive "agrees" from providers. The most frequent themes were detection of cannabis use (25.3%), health harms (19.9%), co-use with other substances (9.1%), and medical use (8.2%). The 425 medical cannabis use questions most frequently related to treatment of mental illness (20.3%), pain (20.0%), and cancer care (6.7%). The 762 provider responses regarding medical cannabis use were coded for sentiment as 59.6% negative, 28.6% mixed, and 11.8% positive. Provider sentiment was most positive regarding cannabis use for palliative care and most negative for treating respiratory conditions, poor appetite, and mental illness. The proportion of positive sentiment responses increased from 17.6% to 32.4%. Provider responses coded as negative sentiment received more provider "Agrees" (mean rank = 280) than those coded as positive (mean rank = 215), beta coefficient = 0.33; 95% CI: 0.05, 0.62; p = .02. Cannabis use is a health topic of public interest. Variability in provider responses reflects the need for more research and consensus building to inform evidence-based clinical guidelines for cannabis use in medicine.

Topics: Cannabis; Humans; Medical Marijuana; Mental Disorders; Neoplasms; Pain; Palliative Care; Referral and Consultation; United States

Topics: Adult; Cannabis; Electronic Nicotine Delivery Systems; Electronics; Female; Humans; Male; Pain; Smokers; Tobacco Products

Medical cannabis (MC) is becoming more and more popular among patients with chronic pain syndromes. In this study we evaluated the characteristics of MC use among patients with fibromyalgia.. All patients with fibromyalgia who were followed up at Laniado Hospital in Netanya and at the Nazareth Hospital in Nazareth, in addition to all patients followed at the different health service organizations by the first author were located and contacted regarding a large number of parameters. The data included demographic information, duration of fibromyalgia symptoms and diagnosis, duration of MC use, monthly consumption of MC, frequency of daily use, number of species of MC currently used, number of species previously used, types and features of MC supplied, methods of MC consumption, delay in MC supply, symptoms of cannabis withdrawal during delay in supply or shortage of MC, familiarity with the content of (-)- trans-Δ⁹-tetrahydrocannabinol (THC) and Cannabidiol (CBD) of the current species used. Furthermore, information was retrieved on current medications for fibromyalgia and medications for fibromyalgia stopped after starting MC consumption, discontinuation of MC treatment, companies growing and supplying the currently consumed MC, names of current MC species, dominance of Sativa or Indica of the current MC species, and the impact of MC on clinical parameters such as pain, sleep, anxiety, depression, memory, concentration and weight. In addition, questions were presented regarding work, outdoor leisure time, driving, sharing their own MC with other people, opinion on the reform of MC in Israel and adverse effects of MC.. One-hundred and one patients completed the study; 73% of the participants were female with a mean age of 45±11.8 years. The mean duration of fibromyalgia symptoms and diagnosis were 8.39±6 and 4.69±3.9 years, respectively. The mean duration of MC consumption was 15.3±12.6 months and the mean monthly consumption amount was 28.6±10.2 g. 54% smoked pure cannabis, 18% used vaporized cannabis only and 3 participants only used MC oil. The rest used a variety of combinations. The mean minimal daily frequency of MC consumption was 4.11±2.9 times and the mean maximal daily frequency was 7.9±5.6 times. The mean number of current daily MC species was 2.11±1 and the mean number of tried species was 6.7±5.2 for each participant; 47% of all the participants stopped any other treatment for fibromyalgia and 51% reduced the dose or the number of other medications for fibromyalgia. One patient only stopped MC treatment. Tikun Olam was the manufacturing company with the largest number of clients and its most popular species for daytime was "Alaska" and "Erez" for night-time. Mean improvement in sleep and pain was slightly more than 77% with less improvement in other parameters; 36% of the patients reported weight gain, while 16% reported weight loss; 51% reported having more leisure time outdoors. Nearly all patients refused sharing any amount of their MC with friends or family members, and all patients recommended MC treatment for their loved ones once they develop severe fibromyalgia; 61% of the participants were against the reform of MC and 11% were in favor of it. Nearly one quarter of the patients reported mild adverse effects and one patient developed a psychotic attack (was consuming 70 gram of MC monthly).. MC is an effective treatment for fibromyalgia, with nearly zero % withdrawal from this treatment. The mean daily amount consumed was relatively low, less than 1 gram, and the main method of consumption was smoking with a huge variety in the frequency of smoking during the day and night among the participants. MC treatment enabled nearly half of the patients to discontinue any treatment for fibromyalgia and all participants recommended MC treatment for their loved ones in case they develop severe fibromyalgia. Most participants were against the reform of MC in Israel. Mild adverse effects were reported in nearly a quarter of the patients but did not result in discontinuing its consumption.

Topics: Adult; Cannabis; Female; Fibromyalgia; Humans; Israel; Medical Marijuana; Middle Aged; Pain

To explore patterns of medicinal cannabis use prior to implementation of the new Medicinal Cannabis Scheme (MCS) in New Zealand.. An anonymous online convenience survey of 3,634 last-year medicinal users of cannabis promoted via Facebook™ from May to August 2019.. Fifty percent of the sample were female, 18% were Māori and the median age was 38 years. The medical conditions for which cannabis was most often used were pain (81%), sleep (66%) and mental health conditions (64%). Respondents perceived cannabis to be an effective therapy and reported reducing use of other pharmaceutical medicines. Fifty-two percent reported side effects from cannabis use, including increased appetite (29%), drowsiness (12%), eye irritation (11%), dependency (10%), memory impairment (10%) and lack of energy (9%). Smoking was the dominant route of administration. Nearly half (47%) had discussed their use of cannabis with a medical professional in the previous year, while 14% had requested a prescription and 5% accessed a prescribed cannabis-based product (mostly oral CBD).. Respondents self-medicated with cannabis to treat a wide range of health complaints. Only half discussed medicinal cannabis use with their medical professional, and a minority requested a prescription and used a prescribed cannabis-based product.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cannabis; Female; Health Policy; Humans; Male; Marijuana Smoking; Medical Marijuana; Mental Disorders; Middle Aged; New Zealand; Pain; Phytotherapy; Plant Extracts; Sleep Wake Disorders; Surveys and Questionnaires; Young Adult

Topics: Adult; Analgesics; Cannabis; Humans; Medical Marijuana; Pain

Pinterest, a widely used social media platform, has shaped how people seek and share health information. Cannabidiol (CBD), a non-psychoactive component of cannabis is marketed as a treatment for many conditions and sales rose to more than 820 million in 2017. Yet CBD is mostly unregulated, legality is murky, and many of the health claims are not scientifically proven.

Topics: Anxiety; Cannabidiol; Cannabis; Humans; Pain; Social Media

In Germany, physicians who prescribe cannabis-based medicines at the expense of the statutory health insurance are obliged to take part in an accompanying survey. Pain was the most commonly reported diagnosis, making an interim evaluation for the indication of pain feasible.. Patient-related data was transmitted to the German Federal Institute for Drugs and Medical Devices via an online portal. In addition to demographic data, information on the treated disease or symptoms, the course of therapy, adverse reactions and treatment success were evaluated.. A total of 3138 data sets were evaluated for the main diagnosis of pain. Dronabinol was the most frequently (64%) prescribed cannabis-based drug. On average, patients were 57 years old and women and men were equally represented. Patients treated with cannabis flowers were significantly younger (48 years). The proportion of men in this group was 68% and 83% in the group of 18- to 40-year-olds. According to the assessment by treating physicians, pain was significantly improved in 35.5% of the patients. The most frequent side effects (fatigue, dizziness, nausea) corresponded to those already known from the product information of the cannabis-based medicinal products authorized under the pharmaceutical law. Treatment was discontinued in 1179 patients within 1 year.. Physicians should comply with their legal obligation to participate in the accompanying survey. Pain is by far the most common diagnosis in cannabis drugs. For about one third of these patients, physicians reported a clear improvement in pain. Due to the amount of data hitherto and the limitations in the accompanying survey, the results should not be overinterpreted in terms of efficacy and should always be related to existing reviews. The lower age and higher proportion of men among patients treated with cannabis flowers were remarkable. At 37.6%, the overall drop-out rate was high. The most frequent side effects related to vigilance and are therefore highly relevant in terms of driving ability, work ability and risk of falling. For a differentiated evaluation of treatment success, more data needs to be available.

Topics: Adolescent; Adult; Cannabis; Demography; Female; Germany; Humans; Male; Medical Marijuana; Middle Aged; Pain; Pain Management; Practice Patterns, Physicians'; Surveys and Questionnaires; Young Adult

The prior medical literature offers little guidance as to how pain relief and side effect manifestation may vary across commonly used and commercially available cannabis product types. We used the largest dataset in the United States of real-time responses to and side effect reporting from patient-directed cannabis consumption sessions for the treatment of pain under naturalistic conditions in order to identify how cannabis affects momentary pain intensity levels and which product characteristics are the best predictors of therapeutic pain relief. Between 06/06/2016 and 10/24/2018, 2987 people used the ReleafApp to record 20,513 cannabis administration measuring cannabis' effects on momentary pain intensity levels across five pain categories: musculoskeletal, gastrointestinal, nerve, headache-related, or non-specified pain. The average pain reduction was -3.10 points on a 0-10 visual analogue scale (SD = 2.16, d = 1.55, p < .001). Whole Cannabis flower was associated with greater pain relief than were other types of products, and higher tetrahydrocannabinol (THC) levels were the strongest predictors of analgesia and side effects prevalence across the five pain categories. In contrast, cannabidiol (CBD) levels generally were not associated with pain relief except for a negative association between CBD and relief from gastrointestinal and non-specified pain. These findings suggest benefits from patient-directed, cannabis therapy as a mid-level analgesic treatment; however, effectiveness and side effect manifestation vary with the characteristics of the product used.

Topics: Analgesics; Cannabidiol; Cannabis; Dronabinol; Drug-Related Side Effects and Adverse Reactions; Flowers; Humans; Medical Marijuana; Pain

Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management. However, there is a lack of research using individual-level data to explore this question. We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain.. This study included data from people in 2 prospective cohorts of PWUD in Vancouver, Canada, who reported major or persistent pain from June 1, 2014, to December 1, 2017 (n = 1,152). We used descriptive statistics to examine reasons for cannabis use and a multivariable generalized linear mixed-effects model to estimate the relationship between daily (once or more per day) cannabis use and daily illicit opioid use. There were 424 (36.8%) women in the study, and the median age at baseline was 49.3 years (IQR 42.3-54.9). In total, 455 (40%) reported daily illicit opioid use, and 410 (36%) reported daily cannabis use during at least one 6-month follow-up period. The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34-0.74, p < 0.001). Limitations of the study included self-reported measures of substance use and chronic pain, and a lack of data for cannabis preparations, dosages, and modes of administration.. We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain.

Topics: Adult; Analgesics; Analgesics, Opioid; Canada; Cannabis; Chronic Pain; Female; Humans; Longitudinal Studies; Male; Marijuana Smoking; Medical Marijuana; Middle Aged; Opioid-Related Disorders; Pain; Pain Management; Prospective Studies

To determine the baseline clinical characteristics of recreational marijuana users undergoing outpatient orthopaedic surgery. We hypothesized that patients who report marijuana use would have worse pain, function, and general health status.. Nine-hundred and thirty-seven patients undergoing outpatient orthopaedic surgery were asked to fill out patient-reported outcome (PRO) tools. These PROs included the Patient-Reported Outcomes Measurement Information Systems (PROMIS) computer adaptive tests and legacy PROs unique to each patients' surgical site.. Forty patients (4.2%) reported marijuana use. Marijuana use was associated with younger age (33 vs. 43 years, p < 0.001), having a history of fewer operations (1.8 vs. 3.2, p < 0.05), single marital status (68 vs. 38%, p < 0.01), and having a history of smoking cigarettes (63 vs. 31%, p < 0.0001). Marijuana use was found to be significantly associated with greater Marx lower extremity activity rating scale scores (8.5 points vs. 6.1 points, p < 0.05) and decreased pain intensity in the operative site (3.7 points vs. 5.0 points, p < 0.05). Multivariable analysis found that marijuana use was an independent factor associated with less pain intensity in the operative site (p < 0.05).. Our studies support other national studies that report increased marijuana use among younger patients and those who smoke cigarettes. The results do not support our hypothesis, as marijuana use was associated with less pain and better lower extremity activity rating scale scores when compared to non-users. Further research is warranted to analyze the effects of marijuana use on orthopaedic surgery patients.. Cross-sectional study.

Topics: Adolescent; Adult; Cannabis; Child; Cross-Sectional Studies; Female; Humans; Male; Orthopedic Procedures; Pain; Pain Measurement; Patient Reported Outcome Measures; Young Adult

To explore the subjective experience of pain relief by cannabis.. Qualitative data were collected through in-depth semistructured interviews. Interview transcripts were analyzed using interpretative phenomenological analysis (IPA).. Nineteen patients, aged 28 to 79, who were treated with medical cannabis under the supervision of a pain clinic in Israel.. Three key themes that emerged from the analysis were explored: 1) the Sigh of Relief, describing the corporal sensation of using cannabis, including a sense of relaxation and reduction in pain; 2) the Return to Normality, describing the comprehensive effect of using cannabis, including an increased ability to sleep, focus, and function; and 3) the Side Effects of using cannabis.. We propose the term Restored Self to conceptualize the effect of medical cannabis. Restored Self is the experience of regaining one's sense of self, sense of normality, and sense of control over one's life.

Topics: Adaptation, Psychological; Adult; Aged; Analgesics; Cannabis; Female; Humans; Male; Middle Aged; Pain; Pain Management; Qualitative Research; Self Concept; Social Support

Epidermolysis bullosa (EB) is a genetic blistering disorder characterized by intense pain related to disease pathology and care-based interventions. Opioid-based therapies underpin pain care in EB; however, they are unable to provide adequate analgesia in a significant proportion of patients. Cannabinoid-based medicines (CBMs) have been studied increasingly for pain conditions of various aetiologies and pose as a novel dimension for pain care in EB. We present three patients with EB who were prescribed pharmaceutical-grade sublingually administered CBMs comprising tetrahydrocannabinol and cannabidiol. All three patients reported improved pain scores, reduced pruritus and reduction in overall analgesic drug intake.

Topics: Administration, Sublingual; Adult; Analgesics, Opioid; Cannabidiol; Cannabis; Dronabinol; Drug Combinations; Drug Therapy, Combination; Epidermolysis Bullosa; Female; Humans; Male; Middle Aged; Netherlands; Pain; Pain Measurement; Plant Oils; Treatment Outcome

Topics: Cannabis; Humans; Medical Marijuana; Pain; Pain Management

Topics: Biomedical Research; Cannabinoids; Cannabis; Global Health; Government Regulation; Humans; Nausea; Neurodegenerative Diseases; Pain

Topics: Cannabis; Humans; Orthopedic Procedures; Orthopedics; Pain

Topics: Cannabis; Humans; Orthopedic Procedures; Orthopedics; Pain

Given the use of cannabis as an analgesic by a broadening age range of patients, the aim of this study was to determine whether the antinociceptive effects of Δ9-tetrahydrocannabinol (THC) differ by age. The antinociceptive potency and efficacy of THC (1.0-18 mg/kg ip) was compared in male and female rats aged postnatal day 35-40 (adolescent), 60-70 (young adult), and 291-325 (middle-aged adult), using warm water tail withdrawal and paw pressure tests. Motoric effects of THC were assessed using a locomotor activity test. On the tail withdrawal test, THC was significantly more effective in middle-aged adult than in young adult rats and significantly less effective in adolescent than in young adult rats. Similar but smaller age-related differences were observed on the paw pressure test. Sex differences in THC's antinociceptive effects were consistent across the 3 ages examined, with greater THC effects observed in females than males of each age. Age-related differences in THC's locomotor-suppressing effect were also observed, with the greatest effect in young adult female rats. Serum THC levels were slightly higher in adolescent than in young adult rats, and levels of the active metabolites 11-OH-THC and cannabinol, as well as the inactive metabolite 11-nor-9-carboxy-THC, did not differ between adolescent and young adult rats. These results suggest that the pain-relieving effects of THC may be more limited in adolescents than in adults and that these age-related differences in THC effect are not attributable to differential absorption or metabolism of THC. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Topics: Analgesics; Animals; Cannabinol; Cannabis; Dronabinol; Female; Locomotion; Male; Motor Activity; Pain; Pain Measurement; Rats; Sex Characteristics

No Abstract Available.

Topics: Anxiety; Cannabidiol; Cannabis; Humans; Medical Marijuana; Pain; Plant Oils; Sleep Initiation and Maintenance Disorders

Topics: Cannabis; Chronic Pain; Humans; Pain; Pain Management

Rates of cannabis use and related problems continue to rise, ranking as the third most common substance use disorder in the United States, behind tobacco and alcohol use. Past work suggests that perceived distress tolerance is related to several clinically significant features of cannabis use (e.g., coping-oriented use). However, there has been little exploration of the mechanisms that may underlie relations between perceived distress tolerance and cannabis use problems, withdrawal severity, and self-efficacy for quitting. The current study sought to examine the experience of pain, which frequently co-occurs with cannabis use (Ashrafioun, Bohnert, Jannausch, & Ilgen, 2015), as an underlying factor in the relation between perceived distress tolerance and cannabis related problems among 203 current cannabis-using adults (29.2% female, M = 37.7 years, SD = 10.2, 63% African American). Results indicated that perceived distress tolerance via pain related affective distress significantly predicted the severity of cannabis use problems (Pm = 0.60), degree of cannabis withdrawal (Pm = 0.39), and lower self-efficacy for quitting cannabis (Pm = 0.36). Future work may usefully explore the role of pain-related affective distress as a mechanistic factor in the context of perceived distress tolerance-cannabis relations.

Topics: Adaptation, Psychological; Adult; Affect; Cannabis; Female; Humans; Male; Marijuana Abuse; Middle Aged; Pain; Self Efficacy; Stress, Psychological; Substance Withdrawal Syndrome

Topics: Analgesics, Opioid; Cannabis; Humans; Neoplasms; Pain; Pain Management; Prospective Studies

Topics: Adrenal Cortex Hormones; Analgesia; Anesthetics; Anti-Inflammatory Agents, Non-Steroidal; Athletes; Cannabis; Humans; Injections; Pain; Pain Management

Previous research shows that between individuals there is a positive association between medically motivated use and cannabis use frequency and quantity. While between-subjects' analyses are useful for understanding shared vulnerabilities, research has so far not examined within-subjects' relationships which are closer to evaluating functional relationships (i.e., do individuals tend to use cannabis more heavily subsequent to elevations in pain experiences?). To better understand the association between experiences of pain and cannabis use, the current paper examines whether there is a functional within-subjects association between experiences of pain and heavy cannabis use.. 182 regular cannabis users without a medical cannabis license were asked to report momentary experiences of physical pain, whether they had used cannabis, and if so, quantity consumed five times per day over a five-day period on their smartphones. Mixed effects models examined the relations between within- and between-subjects experiences of pain and cannabis use and quantity consumed.. Elevated experiences of pain were not associated with cannabis use occasions at the within- or between-subjects level. Experiences of pain were associated with greater amount of cannabis consumed at the within-subjects level, but not at the between-subjects level.. Experiences of pain are not associated with decisions about whether or not to use cannabis. Once cannabis users are in cannabis-using situations, they tend to use larger amounts when they are experiencing elevated levels of pain. This may have implications for cannabis abuse treatment as pain may make it more difficult for users to reduce their consumption.

Topics: Adult; Cannabinoids; Cannabis; Ecological Momentary Assessment; Female; Habits; Humans; Male; Marijuana Abuse; Marijuana Smoking; Marijuana Use; Medical Marijuana; Motivation; Pain; Young Adult

To evaluate recreational and medical cannabis use in individuals with traumatic spinal cord injury, including reasons and predictors for use, perceived benefits and negative consequences.. Cross-sectional survey in Denmark.. A 35-item questionnaire was sent to 1,101 patients with spinal cord injury who had been in contact with a rehabilitation centre between 1990 and 2012.. A total of 537 participants completed the questionnaire. Of these, 36% had tried cannabis at least once and 9% were current users. Of current users, 79% had started to use cannabis before their spinal cord injury. The main reason for use was pleasure, but 65% used cannabis partly for spinal cord injury-related consequences and 59% reported at least good effect on pain and spasticity. Negative consequences of use were primarily inertia and feeling quiet/subdued. Lower age, living in rural areas/larger cities, tobacco-smoking, high alcohol intake and higher muscle stiffness were significantly associated with cannabis use. Those who had never tried cannabis reported that they would mainly use cannabis to alleviate pain and spasticity if it were legalized.. Cannabis use is more frequent among individuals with spinal cord injury in Denmark than among the general population. High muscle stiffness and various demographic characteristics (lower age, living in rural areas/larger cities, tobacco-smoking and high alcohol intake) were associated with cannabis use. Most participants had started using cannabis before their spinal cord injury. There was considerable overlap between recreational and disability-related use.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cannabis; Cross-Sectional Studies; Denmark; Female; Humans; Male; Middle Aged; Pain; Spinal Cord Injuries; Surveys and Questionnaires; Young Adult

Topics: Acupuncture Therapy; Analgesics; Analgesics, Opioid; Cannabis; Cognitive Behavioral Therapy; Complementary Therapies; Headache; Humans; Manipulation, Chiropractic; Massage; Migraine Disorders; Muscle Relaxants, Central; Pain; Pain Management; Physical Therapy Modalities

Topics: Analgesics, Opioid; Cannabis; Complementary Therapies; Drug Overdose; Drug Prescriptions; Humans; Medical Marijuana; Opioid-Related Disorders; Pain; Pain Management; United States

Topics: Cannabis; Drug Approval; Humans; Medical Marijuana; Nausea; Pain; Palliative Care; Peripheral Nervous System Diseases; Phytotherapy; Plant Preparations; Terminal Care; United States; United States Food and Drug Administration

Topics: Cannabinoids; Cannabis; Drug and Narcotic Control; Endocannabinoids; Health Policy; Humans; Medical Marijuana; Pain; Phytotherapy; Receptors, Cannabinoid

Topics: Acquired Immunodeficiency Syndrome; Biomedical Research; California; Canada; Cannabinoids; Cannabis; Clinical Trials as Topic; Crohn Disease; Drug and Narcotic Control; Female; Humans; Inflammation; Leadership; Male; Medical Marijuana; Multiple Sclerosis; Pain; Policy Making; Research Personnel; Seizures; Stress Disorders, Post-Traumatic

Topics: Aged; Breast Neoplasms; Cannabis; Doxorubicin; Fatigue; Female; Humans; Nausea; Pain; Phytotherapy; Plant Preparations; Plants, Medicinal; Spinal Neoplasms

Topics: Analgesics, Non-Narcotic; Cannabis; Carcinoma, Non-Small-Cell Lung; Coma; Dronabinol; Female; Humans; Lung Neoplasms; Middle Aged; Pain; Phytotherapy; Plant Extracts

Topics: Cannabis; Federal Government; Humans; Legislation, Drug; Nausea; Pain; Phytotherapy; Plant Leaves; Sleep Initiation and Maintenance Disorders; State Government; United States

Topics: Allied Health Personnel; Budgets; Cannabis; Documentation; Health Care Reform; Humans; Legislation, Drug; Liability, Legal; Medical Errors; Pain; Peer Review; Politics; Societies, Medical; Tennessee; United States

Topics: Analgesics; Cannabis; Chronic Disease; Humans; Legislation, Drug; Long-Term Care; Nurse-Patient Relations; Nurse's Role; Pain; Palliative Care; Quality of Health Care; United States

Stemming from the centuries-old and well known effects of Cannabis on intestinal motility and secretion, research on the role of the endocannabinoid system in gut function and dysfunction has received ever increasing attention since the discovery of the cannabinoid receptors and their endogenous ligands, the endocannabinoids. In this article, some of the most recent developments in this field are discussed, with particular emphasis on new data, most of which are published in Neurogastroenterology & Motility, on the potential tonic endocannabinoid control of intestinal motility, the function of cannabinoid type-1 (CB1) receptors in gastric function, visceral pain, inflammation and sepsis, the emerging role of cannabinoid type-2 (CB2) receptors in the gut, and the pharmacology of endocannabinoid-related molecules and plant cannabinoids not necessarily acting via cannabinoid CB1 and CB2 receptors. These novel data highlight the multi-faceted aspects of endocannabinoid function in the GI tract, support the feasibility of the future therapeutic exploitation of this signaling system for the treatment of GI disorders, and leave space for some intriguing new hypotheses on the role of endocannabinoids in the gut.

Topics: Animals; Cannabinoid Receptor Modulators; Cannabis; Endocannabinoids; Gastrointestinal Diseases; Gastrointestinal Motility; Gastrointestinal Tract; Inflammation; Medicine, Traditional; Molecular Structure; Pain; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2

Topics: Analgesics, Non-Narcotic; Brain; Cannabis; Dronabinol; Humans; Pain; Receptors, Glycine

Topics: Administration, Oral; Aerosols; Anorexia; Cannabinoids; Cannabis; Drug Approval; Humans; Nausea; Pain; Phytotherapy; Plant Preparations; Treatment Outcome; United States

Topics: Administration, Inhalation; Administration, Oral; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Health Knowledge, Attitudes, Practice; Humans; Marijuana Smoking; Nausea; Pain; Phytotherapy; Plant Preparations; Psychoses, Substance-Induced; United States

Topics: Canada; Cannabis; Drug and Narcotic Control; Humans; Pain; Phytotherapy; Plant Preparations

Topics: Cannabis; Fingers; Humans; Male; Marijuana Abuse; Middle Aged; Pain; Thromboangiitis Obliterans

Topics: Cannabis; Humans; Legislation, Drug; Legislation, Medical; Pain; Phytotherapy; Plant Preparations

Topics: Cannabidiol; Cannabis; Dronabinol; Drug Approval; Drug Combinations; Germany; Humans; Multiple Sclerosis; Muscle Spasticity; Pain; Palliative Care; Phytotherapy; Plant Extracts; Psychoses, Substance-Induced

Topics: Analgesics, Opioid; Cannabis; Ethanol; Health Education; Humans; Pain; Social Welfare

Since 2003, medicinal cannabis has been legally cultivated and distributed in the Netherlands under the auspices of the Dutch Office of Medicinal Cannabis (BMC), part of the Ministry of Health, Welfare and Sport. As a result of this measure, the indication, dosage, administration route, and safety of cannabis can now be investigated, information necessary for justifying its potentially future position as a standard medicinal product. Despite the current lack of reliable scientific efficacy data, standardised medicinal cannabis without microbes has also been made available on prescription. This has led to a safer and more responsible use. However, it is a bridge too far to say that 'it doesn't hurt to try'. The legalization of medicinal cannabis has also stimulated the development of new purified cannabis-based products, although it is claimed that some patients specifically benefit from using cannabis as a whole product. Despite disappointing sales at the end of 2007, the Minister of Health, Welfare and Sport has announced that the current policy will be extended for a further five years. The Minister also indicated that he would consider discontinuing the availability of medicinal cannabis for patients, if new cannabis products are granted market authorization. This might, however, give rise to a new era of illegal cannabis use for medicinal purposes, notably for the use as a whole product.

Topics: Analgesics, Opioid; Cannabis; Dose-Response Relationship, Drug; Humans; Legislation, Drug; Netherlands; Pain; Phytotherapy; Plant Preparations

Topics: Administration, Oral; Administration, Sublingual; Cannabinoids; Cannabis; Dronabinol; Humans; Marijuana Smoking; Meta-Analysis as Topic; Multiple Sclerosis; Neuralgia; Pain; Phytotherapy; Plant Preparations; Randomized Controlled Trials as Topic

This study aimed to give a rationale for the employment of phytocannabinoid formulations to treat neuropathic pain. It was found that a controlled cannabis extract, containing multiple cannabinoids, in a defined ratio, and other non-cannabinoid fractions (terpenes and flavonoids) provided better antinociceptive efficacy than the single cannabinoid given alone, when tested in a rat model of neuropathic pain. The results also demonstrated that such an antihyperalgesic effect did not involve the cannabinoid CB1 and CB2 receptors, whereas it was mediated by vanilloid receptors TRPV1. The non-psychoactive compound, cannabidiol, is the only component present at a high level in the extract able to bind to this receptor: thus cannabidiol was the drug responsible for the antinociceptive behaviour observed. In addition, the results showed that after chronic oral treatment with cannabis extract the hepatic total content of cytochrome P450 was strongly inhibited as well as the intestinal P-glycoprotein activity. It is suggested that the inhibition of hepatic metabolism determined an increased bioavailability of cannabidiol resulting in a greater effect. However, in the light of the well known antioxidant and antiinflammatory properties of terpenes and flavonoids which could significantly contribute to the therapeutic effects, it cannot be excluded that the synergism observed might be achieved also in the absence of the cytochrome P450 inhibition.

Topics: Analgesics; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cannabidiol; Cannabinoids; Cannabis; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Disease Models, Animal; Hyperalgesia; Liver; Male; Pain; Pain Threshold; Plant Extracts; Rats; Rats, Wistar; Receptors, Cannabinoid; Sciatic Neuropathy; TRPV Cation Channels

Cannabidiol, the major psycho-inactive component of cannabis, has substantial anti-inflammatory and immunomodulatory effects. This study investigated its therapeutic potential on neuropathic (sciatic nerve chronic constriction) and inflammatory pain (complete Freund's adjuvant intraplantar injection) in rats. In both models, daily oral treatment with cannabidiol (2.5-20 mg/kg to neuropathic and 20 mg/kg to adjuvant-injected rats) from day 7 to day 14 after the injury, or intraplantar injection, reduced hyperalgesia to thermal and mechanical stimuli. In the neuropathic animals, the anti-hyperalgesic effect of cannabidiol (20 mg/kg) was prevented by the vanilloid antagonist capsazepine (10 mg/kg, i.p.), but not by cannabinoid receptor antagonists. Cannabidiol's activity was associated with a reduction in the content of several mediators, such as prostaglandin E(2) (PGE(2)), lipid peroxide and nitric oxide (NO), and in the over-activity of glutathione-related enzymes. Cannabidiol only reduced the over-expression of constitutive endothelial NO synthase (NOS), without significantly affecting the inducible form (iNOS) in inflamed paw tissues. Cannabidiol had no effect on neuronal and iNOS isoforms in injured sciatic nerve. The compound's efficacy on neuropathic pain was not accompanied by any reduction in nuclear factor-kappaB (NF-kappaB) activation and tumor necrosis factor alpha (TNFalpha) content. The results indicate a potential for therapeutic use of cannabidiol in chronic painful states.

Topics: Administration, Oral; Animals; Cannabidiol; Cannabinoid Receptor Antagonists; Cannabis; Capsaicin; Chronic Disease; Dinoprostone; Freund's Adjuvant; Hyperalgesia; Inflammation; Lipid Peroxides; Male; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Pain; Pain Measurement; Rats; Rats, Wistar; Sciatic Neuropathy; Tumor Necrosis Factor-alpha

Topics: Analgesics; Analgesics, Opioid; Cannabinoids; Cannabis; Chronic Disease; Clinical Trials as Topic; Humans; Hyperalgesia; Pain; Randomized Controlled Trials as Topic; Substance-Related Disorders

North American studies suggest that as many as one-third of people living with HIV/AIDS self-medicate with cannabis for relief of physical and stress-related symptoms. Although cannabis remains a controlled substance in Canada, legal access has been granted to people with HIV/AIDS and other serious illness under the Marihuana Medical Access Regulations (MMAR) since 2001. Several years into the programme, however, few Canadians ( approximately 1400) have obtained MMAR approval, suggesting that substantial obstacles remain. This paper reports findings from a 2005 survey (n=197) and focus groups conducted to identify barriers to access to medical cannabis among people living with HIV/AIDS. Most (86%) respondents who reported using cannabis as medicine continue to rely on illegal sources for their supply. They cited lack of information, product quality concerns, and an onerous, confusing application process among other problems mentioned with the MMAR. The findings are discussed in terms of policy suggestions for facilitating access to a legal source of cannabis for medical users.

Topics: Adolescent; Adult; Aged; Canada; Cannabis; Drug and Narcotic Control; Focus Groups; Health Services Accessibility; Health Services Needs and Demand; HIV Infections; Humans; Male; Middle Aged; Pain; Phytotherapy; Self Medication

Topics: Access to Information; Cannabis; Federal Government; Government Regulation; Guidelines as Topic; Humans; Information Dissemination; Nausea; Pain; Phytotherapy; United States; United States Dept. of Health and Human Services

Topics: Analgesics, Opioid; Cannabis; Chronic Disease; Humans; Pain

An oromucosal spray has been developed from the major components of marijuana (cannabis), including tetrahydrocannabinol (THC) and cannabidiol (CBD), in alcohol with a peppermint flavouring, designed to be administered as a spray under the tongue or on the buccal mucosa to relieve pain in multiple sclerosis. Although the available evidence indicates its efficacy in this respect, some patients develop oral burning sensation, stinging or white lesions, probably burns.. To investigate the oral side-effects of oromucosal cannabis spray in multiple sclerosis (MS) patients.. A small open observational study.. A series of nine patients with MS who had been using a marijuana oromucosal spray for at least four weeks, were asked to attend for oral examination. Patients were asked whether they had ever experienced symptoms (dryness; bad taste; stinging) associated with use of the spray. A standard oral examination was carried out using a dental light, and the presence of any mucosal lesions recorded. Where mucosal lesions were present, patients were advised to discontinue the spray and re-attend after four weeks for re-examination. For ethical reasons, biopsies were not undertaken at the first visit.. Of nine patients invited to participate, eight attended. All admitted to a stinging sensation on using the oromucosal cannabis spray, and four had visible oral mucosal white lesions in the floor of the mouth.. Although the white lesions observed were almost certainly burns, resolving or improving on discontinuation of use of the medication, the high alcohol concentration of the oromucosal cannabis spray raises concern in relation to chronic oral use.

Topics: Administration, Oral; Adult; Aerosols; Aged; Burns, Chemical; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Mouth Mucosa; Multiple Sclerosis; Pain; Phytotherapy; Plant Extracts

This feature presents information for patients in a question and answer format. It is written to simulate actual questions that many pain patients ask and to provide answers in a context and language that most pain patients will comprehend. Issues addressed in this issue are carpel tunnel syndrome, fibromyalgia, glucosamine and chondroitin, hypnosis, marijuana.

Topics: Cannabis; Carpal Tunnel Syndrome; Chondroitin; Diabetic Neuropathies; Drug Combinations; Fibromyalgia; Glucosamine; Humans; Hypnosis; Pain; Pain Management; Phytotherapy; Plant Preparations

Topics: Analgesics; Cannabis; Humans; Marijuana Smoking; Pain; Phytotherapy; Plant Preparations

Topics: Analgesics; Cannabis; Humans; Pain; Phytotherapy; Plant Preparations

Topics: Analgesics; Cannabis; Dose-Response Relationship, Drug; Humans; Neoplasms; Pain; Phytotherapy; Plant Preparations; Practice Guidelines as Topic; United States

Topics: Analgesics; Arthritis, Rheumatoid; Cannabidiol; Cannabis; Dronabinol; Drug Combinations; Humans; Pain; Plant Extracts; Treatment Outcome

To determine the degree and duration of pain relief provided by specific pain treatments used by individuals with spinal cord injury (SCI) who have chronic pain.. Postal survey.. Community.. Participants were 117 individuals who had traumatic SCI, were 18 years of age or older, and reported a chronic pain problem.. Questions assessing current or past use of 26 different pain treatments, the amount of relief each treatment provided, and the length of time that any pain relief usually lasts.. The medications tried most often were nonsteroidal anti-inflammatory drugs (tried by 71%) and acetaminophen (tried by 70%); these medications were still being used by more than one half of the patients who had tried them. Opioids produced the greatest degree of pain relief on average (mean, 6.27 +/- 3.05 [SD] on a 0-10 scale, with 0 = no relief and 10 = complete relief) but were unlikely to be continued by those who tried them. Although 38% of respondents with pain had tried gabapentin, only 17% were still using it, and average pain relief was only moderate (mean, 3.32 +/- 3.03 on the 0-10 relief scale). Seventy-three percent of the respondents had tried at least 1 of 7 alternative pain treatments, and the most frequently tried were massage, marijuana, and acupuncture. The most relief was provided by massage (mean, 6.05 +/- 2.47] on the 0-10 relief scale) and marijuana (mean, 6.62 +/- 2.54 on the 0-10 relief scale). The relief from the various treatments, including most medications, tended to last only minutes or hours; however, pain relief from alternative treatments such as massage, acupuncture, and hypnosis was reported to last for days in 25% to 33% of those who tried these treatments.. Many patients are not finding adequate pain relief from commonly prescribed medications. Alternative therapies should be considered as additional treatment options in this population.

Topics: Acupuncture Therapy; Adult; Aged; Analgesics; Cannabis; Female; Health Surveys; Humans; Hypnosis; Male; Massage; Middle Aged; Pain; Pain Management; Pain Measurement; Spinal Cord Injuries; Treatment Outcome

The Canadian Marihuana Medical Access Regulations (MMAR) program allows Health Canada to grant access to marihuana for medical use to those who are suffering from grave and debilitating illnesses. This is a report on a case series of 30 patients followed at a tertiary care pain management center in Nova Scotia who have used medicinal marihuana for 1-5 years under the MMAR program. Patients completed a follow-up questionnaire containing demographic and dosing information, a series of 11-point numerical symptom relief rating scales, a side effect checklist, and a subjective measure of improvement in function. Doses of marihuana ranged from less than 1 to 5g per day via the smoked or oral route of administration. Ninety-three percent of patients reported moderate or greater pain relief. Side effects were reported by 76% of patients, the most common of which were increased appetite and a sense of well-being, weight gain, and slowed thoughts. Limitations of the study include self-selection bias, small size, and lack of a control group. The need for further study using controlled trials is discussed along with an overview of the MMAR program.

Topics: Adult; Cannabis; Chronic Disease; Drug and Narcotic Control; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nova Scotia; Pain; Phytotherapy; Plant Preparations; Treatment Outcome

Topics: Canada; Cannabis; Financing, Government; Health Policy; Humans; Marijuana Smoking; Pain; Phytotherapy; Research Support as Topic

The authors investigated the indications for cannabis prescription in the Netherlands and assessed its efficacy and side effects. A majority (64.1%) of patients reported a good or excellent effect on their symptoms. Of these patients, approximately 44% used cannabis for >/=5 months. Indications were neurologic disorders, pain, musculoskeletal disorders, and cancer anorexia/cachexia. Inhaled cannabis was perceived as more effective than oral administration. Reported side effects were generally mild.

Topics: Administration, Inhalation; Anorexia; Cannabis; Drug Utilization; Female; Humans; Male; Marijuana Smoking; Middle Aged; Musculoskeletal Diseases; Neoplasms; Nervous System Diseases; Netherlands; Pain; Patient Satisfaction; Phytotherapy; Plant Preparations; Surveys and Questionnaires; Treatment Outcome

Topics: Cannabinoids; Cannabis; Civil Rights; Humans; Legislation, Drug; Pain; Phytotherapy; Plant Preparations; Privacy; Right to Die; United States; Value of Life

Topics: Anorexia; California; Cannabis; Drug and Narcotic Control; Humans; Nausea; Pain; Phytotherapy; Plant Preparations; Supreme Court Decisions; United States

Topics: Appetite; Cannabis; Criminal Law; Drug and Narcotic Control; Federal Government; Government Regulation; Humans; Legislation, Medical; Nausea; Pain; Patient Advocacy; Phytotherapy; State Government; Supreme Court Decisions; United States

To estimate the patterns and prevalence of cannabis use among patients with multiple sclerosis (MS), 220 patients were surveyed in Halifax, Nova Scotia. Seventy-two subjects (36%) reported ever having used cannabis for any purpose; 29 respondents (14%) reported continuing use of cannabis for symptom treatment. Medical cannabis use was associated with male gender, tobacco use, and recreational cannabis use. The symptoms reported by medical cannabis users to be most effectively relieved were stress, sleep, mood, stiffness/spasm, and pain.

Topics: Administration, Oral; Adult; Cannabis; Cross-Sectional Studies; Drug Utilization; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Muscle Spasticity; Nova Scotia; Pain; Patients; Phytotherapy; Plant Preparations; Sleep Wake Disorders; Smoking; Surveys and Questionnaires; Treatment Outcome

Topics: Acquired Immunodeficiency Syndrome; Biomedical Research; Cannabinoids; Cannabis; Clinical Trials as Topic; Humans; Nausea; Nebulizers and Vaporizers; Pain; Phytotherapy; Time Factors; United States Government Agencies

Prior to 2002, few clinical data were available to indicate whether cannabis extracts may be beneficial. However, in the last two years, results of several placebo-controlled clinical trials of orally administered compounds have been published, and these cast doubt on the efficacy of delta9-tetrahydrocannabinol (delta9-THC) in objectively reducing spasticity in MS. By contrast, it has been claimed that sublingually administered cannabis extracts that contain approximately equal concentrations of delta9-THC and cannabidiol, a natural cannabinoid that does not act on the CB1 receptor, can produce a statistically and clinically significant reduction in spasticity, although this claim has yet to be thoroughly validated. Nonetheless, results of preclinical trials also lend support to the hypothesis that the endogenous cannabinoid system may be involved in the regulation of spasticity and pain. A better indication of the clinical potential of the different cannabis extracts will have to await the publication of the most recent clinical trial data. This review critically evaluates the most recent evidence available on the potential use of medicinal extracts of cannabis to relieve pain and spasticity in multiple sclerosis.

Topics: Animals; Cannabis; Chronic Disease; Clinical Trials, Phase III as Topic; Dronabinol; Humans; Multiple Sclerosis; Muscle Spasticity; Pain; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic

Topics: Animals; Anxiety; Brain; Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Dronabinol; Humans; Nausea; Neurotransmitter Agents; Obesity; Opium; Pain; Receptor, Cannabinoid, CB1; Receptors, Cannabinoid; Signal Transduction

Topics: Analgesics, Opioid; Cannabis; Education, Medical, Continuing; Humans; Joint Commission on Accreditation of Healthcare Organizations; Liability, Legal; Malpractice; Pain; Palliative Care; Practice Guidelines as Topic; Societies; Societies, Medical; State Government; United States

There has been a surge in interest in medicinal cannabis in Canada. We conducted a questionnaire survey to determine the current prevalence of medicinal cannabis use among patients with chronic non-cancer pain, to estimate the dose size and frequency of cannabis use, and to describe the main symptoms for which relief was being sought. Over a 6-week period in mid-2001, 209 chronic non-cancer pain patients were recruited in an anonymous cross-sectional survey. Seventy-two (35%) subjects reported ever having used cannabis. Thirty-two (15%) subjects reported having used cannabis for pain relief (pain users), and 20 (10%) subjects were currently using cannabis for pain relief. Thirty-eight subjects denied using cannabis for pain relief (recreational users). Compared to never users, pain users were significantly younger (P=0.001) and were more likely to be tobacco users (P=0.0001). The largest group of patients using cannabis had pain caused by trauma and/or surgery (51%), and the site of pain was predominantly neck/upper body and myofascial (68% and 65%, respectively). The median duration of pain was similar in both pain users and recreational users (8 vs. 7 years; P=0.7). There was a wide range of amounts and frequency of cannabis use. Of the 32 subjects who used cannabis for pain, 17 (53%) used four puffs or less at each dosing interval, eight (25%) smoked a whole cannabis cigarette (joint) and four (12%) smoked more than one joint. Seven (22%) of these subjects used cannabis more than once daily, five (16%) used it daily, eight (25%) used it weekly and nine (28%) used it rarely. Pain, sleep and mood were most frequently reported as improving with cannabis use, and 'high' and dry mouth were the most commonly reported side effects. We conclude that cannabis use is prevalent among the chronic non-cancer pain population, for a wide range of symptoms, with considerable variability in the amounts used. Discussions between patients and health care providers concerning cannabis use may facilitate education and follow up, and would allow side effects and potential interactions with other medications to be monitored. Clinical trials of cannabis for chronic non-cancer pain are warranted.

Topics: Adolescent; Adult; Aged; Canada; Cannabinoids; Cannabis; Chronic Disease; Data Collection; Drug Administration Routes; Female; Humans; Male; Marijuana Smoking; Middle Aged; Pain; Plant Preparations; Prospective Studies; Surveys and Questionnaires; Treatment Outcome

Topics: Adult; Analgesics, Opioid; Cannabis; Chronic Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pain; Phytotherapy; Plant Preparations

Health Canada finally produces a good marijuana crop, but its medical marijuana program is in a state of upheaval as it faces internal dissent regarding a crucial aspect of its mandate, as well as fundamental challenges from the courts. Meanwhile, the Justice Minister said that the government will introduce legislation to decriminalize the possession of small amounts of marijuana.

Topics: Canada; Cannabis; Chronic Disease; Glaucoma; HIV Infections; Humans; Pain; Phytotherapy

Topics: Administration, Inhalation; Adult; Cannabis; Dystonia; Female; Humans; Pain; Pain Management; Palliative Care; Thalamic Diseases

Significant attention has been given to the debate regarding allowances for medical marijuana use since the 1996 California and Arizona ballot initiatives. State medical marijuana allowances, however, have existed since the mid-1970s. Much of the current debate stems from confusion about the various ways states approach the issue. In this paper, we present original legal research on current state medical marijuana laws identifying four different ways states statutorily enable the medical use of marijuana. We discuss the tension these approaches have with federal law as well as their implications regarding real access for patients. In addition, we present information on how a small number of states are trying to deal with the issue of access within the context of their medical marijuana laws, and discuss the implication of various supply approaches on the enforcement of other state marijuana laws.

Topics: Acquired Immunodeficiency Syndrome; California; Cannabis; Drug and Narcotic Control; Drug Prescriptions; Federal Government; Glaucoma; Humans; Legislation, Medical; Neoplasms; Pain; Palliative Care; State Government; Therapeutic Human Experimentation; United States

Topics: Canada; Cannabis; Humans; Pain; Physician's Role; Phytotherapy; Risk Factors

Topics: Cannabis; Humans; Marijuana Smoking; Nausea; Pain; Spasm

Topics: Canada; Cannabis; Humans; Marijuana Smoking; Neoplasms; Pain; Phytotherapy; United States

Cannabis has been advocated as a treatment for nausea, vomiting, wasting, pain and muscle spasm in cancer, HIV/AIDS, and neurological disorders. Such uses are prohibited by law; cannabinoid drugs are not registered for medical use in Australia and a smoked plant product is unlikely to be registered. A New South Wales Working Party has recommended granting exemption from prosecution to patients who are medically certified to have specified medical conditions. This proposal deserves to be considered by other State and Territory governments.

Topics: Australia; Cannabis; Female; HIV Infections; Humans; Legislation, Drug; Male; Nausea; Nervous System Diseases; Pain

Topics: Canada; Cannabis; Clinical Trials as Topic; Drug Prescriptions; Humans; Pain; Phytotherapy

Topics: Cannabinoids; Cannabis; Humans; Pain; Phytotherapy; Plant Extracts

Topics: Cannabis; Controlled Clinical Trials as Topic; Humans; Pain; Phytotherapy; Plant Extracts; Systematic Reviews as Topic

The use of smoked marijuana as a therapeutic agent is presently a matter of considerable debate in the United States. Many people suffering from a variety of disorders maintain that it is necessary for their adequate treatment. Yet, the evidence to support claims is insufficient for FDA approval. An interim solution is proposed which would allow patients referred by their physicians to participate in a 6-month program of legal marijuana availability, similar to the 'compassionate IND' program of a number of years ago. A technique similar to that used for post-marketing surveillance is proposed for obtaining quantitative data for a limited number of potential indications. These are: (1) nausea and vomiting associated with cancer chemotherapy or other causes, (2) weight loss associated with debilitating illnesses, (3) spasticity secondary to neurological diseases, and (4) chronic pain syndromes.

Topics: Cannabis; Drug Approval; HIV Wasting Syndrome; Humans; Marijuana Smoking; Muscle Spasticity; Nausea; Pain; Phytotherapy; Referral and Consultation; United States; United States Food and Drug Administration; Vomiting

Topics: California; Cannabis; Civil Rights; Drug and Narcotic Control; Federal Government; Humans; Legislation, Medical; Liability, Legal; Marijuana Smoking; Pain; Physicians; Phytotherapy; Plant Preparations; Public Policy; State Government; United States

The Institute of Medicine (IOM) has issued a report on the medical uses of marijuana, coming in the aftermath of voter referenda supporting its medical use. For the purposes of the study, marijuana was defined as unpurified plant substances ingested by eating or smoking. The IOM panel looked at the effects of cannabinoids, health risks associated with medical marijuana use, and the efficacy of medical marijuana. Cannabinoids offer broad-spectrum relief for a variety of conditions, but the health risks associated with smoking remain. Medical marijuana can help patients with nausea, vomiting, anorexia, headache, and pain. There are concerns expressed that the drug diminishes psychomotor performance, and patients using marijuana should not drive a car. There are also short-term immunosuppressive effects that warrant further study.

Topics: Appetite Stimulants; Cannabis; HIV Infections; Humans; National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division; Nausea; Pain; Phytotherapy; Risk Factors

Topics: Cannabis; Humans; Pain

Topics: Cannabis; Chronic Disease; Cocaine; Ethanol; Humans; Opioid-Related Disorders; Pain; Substance-Related Disorders

Recent raids on buyers' clubs in San Francisco have focused attention on medicinal uses of marijuana. The Clinton administration's policy is that there is no scientific evidence that smoked marijuana is useful in treating pain and nausea in AIDS and cancer patients. However, mainstream medical literature has supported the use of cannabis in managing symptoms of diseases such as glaucoma and multiple sclerosis. Well designed, controlled studies of marijuana are needed to determine the effective medical uses of the drug and break the political stalemate on this issue.

Topics: Acquired Immunodeficiency Syndrome; Cannabinoids; Cannabis; Government; Health Policy; Humans; Neoplasms; Pain; Palliative Care; Politics; United States

Topics: Animals; Cannabis; Dronabinol; Female; Fetal Growth Retardation; Humans; Nausea; Pain; Pregnancy; Schizophrenia; Vomiting

A Pierce County judge has ruled that physicians can prescribe marijuana for medical purposes. Judge Rosanne Buckner decided that lawyer [name removed], who is undergoing treatment for bone cancer, can use marijuana to ease the pain associated with chemotherapy. Buckner ruled that the patient's interest in using marijuana as a medicine outweighs Washington's interest in outlawing prescriptions for it. Assistant Attorney General Melissa Burke-Cain plans to appeal this decision.

Topics: Acquired Immunodeficiency Syndrome; Bone Neoplasms; Cannabis; Humans; Marijuana Smoking; Minnesota; Pain; Washington

This article summarizes current knowledge about the medicinal value of cannabis and its principal psychoactive ingredient, delta 9-tetrahydrocannabinol (THC), particularly in the control of nausea and vomiting, in glaucoma, and in reduction of spasticity in multiple sclerosis. The major issues in the controversy about marijuana and medicine, primarily moral and ethical, are discussed.

Topics: Antineoplastic Agents; Anxiety; Bronchial Spasm; Cannabis; Dronabinol; Glaucoma; Humans; Muscle Spasticity; Nausea; Pain; Sleep Initiation and Maintenance Disorders; Vomiting

Topics: Amphetamines; Behavior; Cannabis; Drug Therapy; Epilepsy; Heroin; Humans; Illicit Drugs; Lysergic Acid Diethylamide; Mental Disorders; Nausea; Obesity; Pain; Vomiting

Topics: Cannabis; Dronabinol; Drug Prescriptions; Heroin; Humans; Legislation, Drug; Pain; Research; United States; United States Food and Drug Administration

Topics: Cannabis; Heroin; Humans; Neoplasms; Pain; Pharmaceutical Preparations; Terminal Care

Topics: Asthma; Cannabinoids; Cannabis; Depression; Dronabinol; Drug Stability; Epilepsy; Glaucoma; Humans; Pain; Vomiting

Topics: Adult; Bone Neoplasms; Cannabis; Dronabinol; Female; Humans; Hyperalgesia; Hyperesthesia; Leukemia, Myeloid, Acute; Male; Pain; Phytotherapy; Vomiting

The administration of delta9THC intravenously as a premedicant to oral surgery resulted in acute pronounced elevations in anxiety states, a predominance of dysphoria over euphoria, and varying degrees of psychotic-like paranoiac thought. Neural effects that appeared to promote these effects included distortions of perception with sensory delusions, and heightened sensory receptiveness including antalgesic impressions of surgery; autonomic and visceral arousal greater than control or placebo levels; lack of overt behavioral signals of distress due to depersonalization; and time disintegration leading to fear-inducing misinformation about real surgical events. Introverted subjects who generally were inclined to rely on drug solutions to their problems tended to respond poorly to surgical pain and anxiety with delta9THC. These results, obtained from subjects considered to have levels of presurgical apprehension that were average or below average, suggest that the environment in which high doses of cannabinols are experienced is a potent factor in determining the quality of the emotional response. A surgical environment containing even the mild stress of outpatient oral surgery appears to have the potential to precipitate undesirable emotional responses among cannabinol-intoxicated patients. There is continued high-level social use of cannabinols inour society, with an estimate of 40% to 55% among the college-age group seen frequently by oral surgeons. Results of this study suggest that clinicians should be prepared to detect the subtle signs of marijuana intoxication to protect their patients from further psychophysiologic complications during surgery.

Topics: Adolescent; Adult; Anxiety; Cannabis; Diazepam; Dronabinol; Emotions; Hippocampus; Humans; Injections, Intravenous; Male; Mouth; Pain; Placebos; Psychological Tests; Psychoses, Substance-Induced; Retrospective Studies; Septum Pellucidum; Time Factors

Topics: Cannabis; Florida; Humans; Male; Pain; Research Design; Self Concept; Self-Assessment; Spasm; Spinal Cord Injuries; Substance-Related Disorders

Topics: Animals; Ataxia; Auditory Perception; Avoidance Learning; Cannabis; Conditioning, Operant; Cues; Depression, Chemical; Discrimination Learning; Dose-Response Relationship, Drug; Dronabinol; Exploratory Behavior; Grooming; Male; Pain; Rats; Visual Perception

Topics: Adult; Aged; Analysis of Variance; Behavior; Cannabis; Fear; Female; Happiness; Humans; Male; Middle Aged; Pain; Skin; Substance-Related Disorders; Time Factors

Topics: Animals; Avoidance Learning; Behavior, Animal; Cannabis; Depression, Chemical; Drinking Behavior; Dronabinol; Electroshock; Fear; Learning; Male; Mice; Motor Activity; Pain; Rats; Reaction Time; Species Specificity; Stimulation, Chemical; Time Factors

Topics: Analgesia; Analgesics; Animals; Cannabis; Dronabinol; Hot Temperature; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Mice; Mice, Inbred Strains; Morphine; Pain; Rats; Rats, Inbred Strains; Time Factors

Topics: Animals; Cannabis; Charcoal; Dronabinol; Drug Antagonism; Gastrointestinal Motility; Ileum; Intestine, Small; Jejunum; Kinetics; Lethal Dose 50; Male; Mice; Pain; Parasympathomimetics; Quaternary Ammonium Compounds; Rats; Reaction Time; Spasm; Stereoisomerism; Tail; Vas Deferens

Topics: Abdomen; Adolescent; Adult; Alcohol Drinking; Cannabis; Diet; Female; Humans; Lysergic Acid Diethylamide; Obesity; Obstetric Labor, Premature; Orgasm; Pain; Physical Exertion; Pregnancy; Pregnancy Complications; Smoking; Socioeconomic Factors; Urinary Tract Infections