cannabidiol and Chronic-Pain

Topics: Adult; Cannabidiol; Cannabis; Child; Chronic Pain; Clinical Trials as Topic; Dronabinol; Drug-Related Side Effects and Adverse Reactions; Humans

The incidence of chronic pain is around 8% in the general population, and its impact on quality of life, mood, and sleep exceeds the burden of its causal pathology. Chronic pain is a complex and multifaceted problem with few effective and safe treatment options. It can be associated with neurological diseases, peripheral injuries or central trauma, or some maladaptation to traumatic or emotional events. In this perspective, animal models are used to assess the manifestations of neuropathy, such as allodynia and hyperalgesia, through nociceptive tests, such as von Frey, Hargreaves, hot plate, tail-flick, Randall & Selitto, and others. Cannabidiol (CBD) has been considered a promising strategy for treating chronic pain and diseases that have pain as a consequence of neuropathy. However, despite the growing body of evidence linking the efficacy of CBD on pain management in clinical and basic research, there is a lack of reviews focusing on chronic pain assessments, especially when considering pre-clinical studies, which assess chronic pain as a disease by itself or as a consequence of trauma or peripheral or central disease. Therefore, this review focused only on studies that fit our inclusion criteria: (1) used treatment with CBD extract; (2) used tests to assess mechanical or thermal nociception in at least one of the following most commonly used tests (von Frey, hot plate, acetone, Hargreaves, tail-flick, Randall & Selitto, and others); and (3) studies that assessed pain sensitivity in chronic pain induction models. The current literature points out that CBD is a well-tolerated and safe natural compound that exerts analgesic effects, decreasing hyperalgesia, and mechanical/thermal allodynia in several animal models of pain and patients. In addition, CBD presents several molecular and cellular mechanisms of action involved in its positive effects on chronic pain. In conclusion, using CBD seems to be a promising strategy to overcome the lack of efficacy of conventional treatment for chronic pain.

Topics: Animals; Behavioral Medicine; Cannabidiol; Chronic Pain; Disease Models, Animal; Forecasting

Chronic pain is now included in the designation of chronic diseases, such as cancer, diabetes, and cardiovascular disease, which can impair quality of life and are major causes of death and disability worldwide. Pain can be treated using cannabinoids such as Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) due to their wide range of therapeutic benefits, particularly as sedatives, analgesics, neuroprotective agents, or anti-cancer medicines. While little is known about the pharmacokinetics of these compounds, there is increasing interest in the scientific understanding of the benefits and clinical applications of cannabinoids. In this review, we study the use of nanomaterial-based electrochemical sensing for detecting Δ9-THC and CBD. We investigate how nanomaterials can be functionalized to obtain highly sensitive and selective electrochemical sensors for detecting Δ9-THC and CBD. Additionally, we discuss the impacts of sensor pretreatment at fixed potentials and physiochemical parameters of the sensing medium, such as pH, on the electrochemical performance of Δ9-THC and CBD sensors. We believe this review will serve as a guideline for developing Δ9-THC and CBD electrochemical sensors for point-of-care applications.

Topics: Cannabidiol; Cannabinoids; Chronic Pain; Dronabinol; Humans; Quality of Life

Chronic musculoskeletal (MSK) pain is one of the most prevalent causes, which lead patients to a physician's office. The most common disorders affecting MSK structures are osteoarthritis, rheumatoid arthritis, back pain, and myofascial pain syndrome, which are all responsible for major pain and physical disability. Although there are many known management strategies currently in practice, phytotherapeutic compounds have recently begun to rise in the medical community, especially cannabidiol (CBD). This natural, non-intoxicating molecule derived from the cannabis plant has shown interesting results in many preclinical studies and some clinical settings. CBD plays vital roles in human health that go well beyond the classic immunomodulatory, anti-inflammatory, and antinociceptive properties. Recent studies demonstrated that CBD also improves cell proliferation and migration, especially in mesenchymal stem cells (MSCs). The foremost objective of this review article is to discuss the therapeutic potential of CBD in the context of MSK regenerative medicine. Numerous studies listed in the literature indicate that CBD possesses a significant capacity to modulate mammalian tissue to attenuate and reverse the notorious hallmarks of chronic musculoskeletal disorders (MSDs). The most of the research included in this review report common findings like immunomodulation and stimulation of cell activity associated with tissue regeneration, especially in human MSCs. CBD is considered safe and well tolerated as no serious adverse effects were reported. CBD promotes many positive effects which can manage detrimental alterations brought on by chronic MSDs. Since the application of CBD for MSK health is still undergoing expansion, additional randomized clinical trials are warranted to further clarify its efficacy and to understand its cellular mechanisms.

Topics: Animals; Cannabidiol; Cannabis; Chronic Pain; Drug-Related Side Effects and Adverse Reactions; Humans; Mammals; Regenerative Medicine

Cannabidiol (CBD) is the primary non-psychoactive chemical from Cannabis Sativa, a plant used for centuries for both recreational and medicinal purposes. CBD lacks the psychotropic effects of Δ9-tetrahydrocannabinol (Δ9-THC) and has shown great therapeutic potential. CBD exerts a wide spectrum of effects at a molecular, cellular, and organ level, affecting inflammation, oxidative damage, cell survival, pain, vasodilation, and excitability, among others, modifying many physiological and pathophysiological processes. There is evidence that CBD may be effective in treating several human disorders, like anxiety, chronic pain, psychiatric pathologies, cardiovascular diseases, and even cancer. Multiple cellular and pre-clinical studies using animal models of disease and several human trials have shown that CBD has an overall safe profile. In this review article, we summarize the pharmacokinetics data, the putative mechanisms of action of CBD, and the physiological effects reported in pre-clinical studies to give a comprehensive list of the findings and major effects attributed to this compound.

Topics: Animals; Anxiety; Anxiety Disorders; Cannabidiol; Cell Survival; Chronic Pain; Humans

To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs).. Umbrella review.. PubMed, PsychInfo, Embase, up to 9 February 2022.. Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted.. 101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonata. Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events.. PROSPERO CRD42018093045.. None.

Topics: Adolescent; Adult; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Chronic Pain; Female; Hallucinogens; Humans; Infant, Newborn; Meta-Analysis as Topic; Observational Studies as Topic; Pregnancy; Randomized Controlled Trials as Topic; Risk Assessment; Sleepiness; Systematic Reviews as Topic

To review the available literature on the effect of cannabis-based products on the female reproductive system and establish whether there is any evidence that they benefit or harm patients with endometriosis and, therefore, whether there is sufficient evidence to recommend them.. An electronic-based search was performed in PubMed, Embase, and the Cochrane Database. Reference lists of articles retrieved were reviewed, and a gray literature search was also performed.. The original database search yielded 264 articles from PubMed, Embase, and the Cochrane Database, of which 41 were included. One hundred sixty-one studies relating to gynecologic malignancy, conditions unrelated to endometriosis, or therapies unrelated to cannabis-based products were excluded. Twelve articles were included from a gray literature search and review of references.. Most available evidence is from laboratory studies aiming to simulate the effects of cannabis-based products on preclinical endometriosis models. Some show evidence of benefit with cannabis-based products. However, results are conflicting, and the impact in humans cannot necessarily be extrapolated from these data. Few studies exist looking at the effect of cannabis or its derived products in women with endometriosis; the majority are in the form of surveys and are affected by bias. National guidance was also reviewed: at present, this dictates that cannabis-based products can only be prescribed for conditions in which there is clear published evidence of benefit and only when all other treatment options have been exhausted.. Current treatment options for endometriosis often affect fertility and/or have undesirable side effects that impede long-term management. Cannabis-based products have been suggested as a novel therapeutic option that may circumvent these issues. However, there is a paucity of well-designed, robust studies and randomized controlled trials looking at their use in the treatment of endometriosis. In addition, cannabis use has a potential for harm in the long term, with a possible association with "cannabis use disorder," psychosis, and mood disturbances. At present, national guidance cannot recommend cannabis-based products to patients in the UK owing to lack of clear evidence of benefit. More comprehensive research into the impact of endocannabinoids in the context of endometriosis is required before their use can be recommended or prescribed.

Topics: Cannabidiol; Chronic Pain; Endometriosis; Female; Humans; Pelvic Pain

Combination tetrahydrocannabinol (THC)/cannabidiol (CBD) medicines or CBD-only medicines are prospective treatments for chronic pain, stress, anxiety, depression, and insomnia. THC and CBD increase signaling from cannabinoid receptors, which reduces synaptic transmission in parts of the central and peripheral nervous systems and reduces the secretion of inflammatory factors from immune and glial cells. The overall effect of adding CBD to THC medicines is to enhance the analgesic effect but counteract some of the adverse effects. There is substantial evidence for the effectiveness of THC/CBD combination medicines for chronic pain, especially neuropathic and nociplastic pain or pain with an inflammatory component. For CBD-only medication, there is substantial evidence for stress, moderate evidence for anxiety and insomnia, and minimal evidence for depression and pain. THC/CBD combination medicines have a good tolerability and safety profile relative to opioid analgesics and have negligible dependence and abuse potential; however, should be avoided in patients predisposed to depression, psychosis and suicide as these conditions appear to be exacerbated. Non-serious adverse events are usually dose-proportional, subject to tachyphylaxis and are rarely dose limiting when patients are commenced on a low dose with gradual up-titration. THC and CBD inhibit several Phase I and II metabolism enzymes, which increases the exposure to a wide range of drugs and appropriate care needs to be taken. Low-dose CBD that appears effective for chronic pain and mental health has good tolerability and safety, with few adverse effects and is appropriate as an initial treatment.

Topics: Cannabidiol; Chronic Pain; Dronabinol; Humans; Mental Health; Sleep Initiation and Maintenance Disorders

To explore values and preferences towards medical cannabis among people living with chronic pain.. Mixed-methods systematic review.. We searched MEDLINE, EMBASE and PsycINFO from inception to 17 March 2020.. Pairs of reviewers independently screened search results and included quantitative, qualitative and mixed-methods studies reporting values and preferences towards medical cannabis among people living with chronic pain.. We analysed data using meta-narrative synthesis (quantitative findings were qualitised) and tabulated review findings according to identified themes. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess certainty of evidence.. Of 1838 initial records, 15 studies proved eligible for review. High to moderate certainty evidence showed that patient's use of medical cannabis for chronic pain was influenced by both positive (eg, support from friends and family) and negative social factors (eg, stigma surrounding cannabis use). Most patients using medical cannabis favoured products with balanced ratios of tetrahydrocannabinol (THC) and cannabidiol (CBD), or high levels of CBD, but not high THC preparations. Many valued the effectiveness of medical cannabis for symptom management even when experiencing adverse events related to concentration, memory or fatigue. Reducing use of prescription medication was a motivating factor for use of medical cannabis, and concerns regarding addiction, losing control or acting strangely were disincentives. Out-of-pocket costs were a barrier, whereas legalisation of medical cannabis improved access and incentivised use.Low to very low certainty evidence suggested highly variable values towards medical cannabis among people living with chronic pain. Individuals with pain related to life-limiting disease were more willing to use medical cannabis, and preferred oral over inhaled administration.. Our findings highlight factors that clinicians should consider when discussing medical cannabis. The variability of patients' values and preferences emphasise the need for shared decision making when considering medical cannabis for chronic pain.

Topics: Cannabidiol; Cannabis; Chronic Pain; Dronabinol; Humans; Medical Marijuana

Nociplastic pain is defined as pain due to sensitization of the nervous system, without a sufficient underlying anatomical abnormality to explain the severity of pain. Nociplastic pain may be manifest in various organ systems, is often perceived as being more widespread rather than localized and is commonly associated with central nervous system symptoms of fatigue, difficulties with cognition and sleep, and other somatic symptoms; all features that contribute to considerable suffering. Exemplified by fibromyalgia, nociplastic conditions also include chronic visceral pain, chronic headaches and facial pain, and chronic musculoskeletal pain. It has been theorized that dysfunction of the endocannabinoid system may contribute to persistent pain in these conditions. As traditional treatments for chronic pain in general and nociplastic pain in particular are imperfect, there is a need to identify other treatment options. Cannabis-based medicines and medical cannabis (MC) may hold promise and have been actively promoted by the media and advocacy. The medical community must be knowledgeable of the current evidence in this regard to be able to competently advise patients. This review will briefly explain the understanding of nociplastic pain, examine the evidence for the effect of cannabinoids in these conditions, and provide simplified guidance for healthcare providers who may consider prescribing cannabinoids for these conditions.

Topics: Cannabidiol; Chronic Pain; Dronabinol; Endocannabinoids; Humans; Medical Marijuana; Nociceptive Pain

Pooled analysis of nabiximols and placebo in randomized controlled studies (RCTs) of chronic neuropathic pain.. Systematic review and meta-analysis.. A systematic literature search was conducted to identify double-blind placebo-controlled RCTs of nabiximols for chronic neuropathic pain. The clinical endpoint of interest was change from baseline in mean pain score on 11-point numerical rating scales. Mean difference (MD) and standardized mean difference (SMD, Hedges' g) were calculated using fixed effect (FE) and random effects (RE) models. Strength of evidence was assessed using the Cochrane Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Risk of bias was assessed using the revised Cochrane risk-of-bias tool (RoB 2).. Nine RCTs with 1289 participants were included. Quality of evidence (GRADE) was moderate. One study had a high risk of bias (RoB 2) and five had some concerns. For the pooled endpoint of change from baseline in mean pain score, nabiximols was superior to placebo, with a MD of -0.40 (95% confidence interval [CI]: -.59 to -.21; FE, P < .0001) or -0.44 (95% CI: -.70 to -.19; RE, P = .0006). A SMD of -0.21 (95% CI: -.32 to -.10; FE) or -0.26 (95% CI: -.42 to -.10; RE) indicated an incremental benefit over background analgesia. Results in favor of nabiximols were maintained in sensitivity analyses.. Nabiximols was superior to placebo for reduction of chronic neuropathic pain, with a small effect size. Larger RCTs designed to assess the effect of nabiximols in neuropathic pain are required to reach more definitive conclusions.

Topics: Cannabidiol; Chronic Pain; Dronabinol; Drug Combinations; Humans; Neuralgia; Randomized Controlled Trials as Topic

: Nabiximols oromucosal spray,a cannabis-based medicine containing a balanced ratio of Δ-9-tetrahydrocannabinol and cannabidiol, is approved widely as an add-on therapy for symptomatic relief of spasticity in people with multiple sclerosis (MS). Most safety data for nabiximols derive from use in MS spasticity, with some data available from the analgesia area.. : This review compiles safety and tolerability data from all published observational studies, registry analyses, and case reports identified in systematic searches in which nabiximols oromucosal spray was investigated for spasticity (n = 20) and/or chronic non-cancer pain (n = 4). Aligning with the known safety profile of nabiximols as demonstrated in randomized controlled trials, common adverse events reported consistently across studies conducted under clinical practice conditions were dizziness, fatigue and somnolence. The serious adverse event (SAE) rate with nabiximols in MS spasticityobservational studies was 3.1% (137/4351). A total of 39 treatment-related SAEs were reported in 32 patients with spasticity, all of which (where specified) were resolved. No treatment-related SAEs were recorded in nabiximols pain studies.. : Real-world experience with nabiximols oromucosal spray in treating spasticity and chronic pain indicates that, overall, it is well tolerated and has a good safety profile.

Topics: Analgesics, Opioid; Cannabidiol; Chronic Pain; Dronabinol; Drug Combinations; Humans; Multiple Sclerosis; Muscle Spasticity; Registries

Legalization of cannabidiol (CBD) products has ignited interest in clinical practice and research. One desired indication includes possible pain-relieving effects of CBD. The purposes of the current article are to (1) clarify terminology relevant to cannabinoids; (2) explain and understand the pharmacotherapeutics of CBD; (3) examine research of the current use of CBD by older adults for treating pain; (4) discuss safety considerations with using CBD products; and (5) provide best practice recommendations for clinicians as they advise their older adult patients. A review of the literature demonstrated mixed results on the efficacy of CBD in relieving pain in older adults. There is inconsistency in the labeling of over-the-counter CBD products that can result in safety issues and will require more federal quality control. Likewise, gaps in knowledge regarding safety and efficacy of CBD use in older adults are vast and require further research. [

Topics: Aged; Cannabidiol; Chronic Pain; Humans

Since the Act on the medical use of cannabis, at which cannabis-based medicines and cannabinoids became law, there has been an exponential increase in prescriptions for the acquisition of cannabis for medical purposes. The aim of this leading article is to compile and assess the currently available relevant clinical evidence for the use of cannabis and cannabinoids for treatment of acute and chronic pain. Based on the systematic literature review "Cannabis-Potential and risks (CAPRIS)" commissioned by the German Federal Ministry of Health and the recently published recommendations of the European Pain Federation EFIC, this article aims to give an orientation aid for the decision-making process in the clinical routine.. Seit dem in Kraft getretenen Gesetz zum medizinischen Einsatz von Cannabis, cannabisbasierten Arzneimitteln und Cannabinoiden hat es einen exponentiellen Anstieg der erteilten Verschreibungen zum Erwerb von Cannabis zu medizinischen Zwecken gegeben. Ziel dieses Leitthemenbeitrags ist es, die bisher relevante klinische Evidenz für den Einsatz von Cannabis und Cannabinoiden zur Therapie akuter und chronischer Schmerzen zusammenzutragen und zu bewerten. In Anlehnung an die vom Bundesministerium für Gesundheit beauftragte systematische Literaturübersicht Cannabis – Potential und Risiko (CaPRis) und die kürzlich veröffentlichen Empfehlungen der European Pain Federation (EFIC) wird eine Orientierungshilfe für den Entscheidungsprozess im klinischen Alltag gegeben.

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

Cannabidiol and other cannabinoids are being used more frequently for sports medicine-related conditions. This review will help sports medicine clinicians answer questions that their athletes and active patients have about the potential effectiveness of cannabinoids on common sports medicine conditions. In the article, the authors compare cannabidiol and delta-9-tetrahydrocannabinol effects, noting the difference on the endocannabinoid and nonendocannabinoid receptors. The theoretical benefits of these two compounds and the current legality in the United States surrounding cannabidiol and delta-9-tetrahydrocannabinol use also are addressed.

Topics: Athletic Performance; Brain Concussion; Cannabidiol; Cannabinoids; Cannabis; Chronic Pain; Dronabinol; Endocannabinoids; Humans; Medical Marijuana; Osteoarthritis; Receptor, Serotonin, 5-HT1A; Receptors, Cannabinoid; Sports Medicine; TRPV Cation Channels; United States

Recent advances in cannabidiol (CBD) use in canines and felines for anxiety management, pain management, and anti-inflammatory effects were reviewed using a literature search conducted with the following keywords: CBD, anxiety, inflammation, pain, dogs, cats, and companion animals. For decades, research on CBD has been hindered due to the status of cannabis (C. sativa L.) as an illicit drug. Limited safety data show that CBD is well-tolerated in dogs, with insufficient information on the safety profile of CBD in cats. Upon oral supplementation of CBD, elevation in liver enzymes was observed for both dogs and cats, and pharmacokinetics of CBD are different in the two species. There is a significant gap in the literature on the therapeutic use of CBD in cats, with no feline data on anxiety, pain, and inflammation management. There is evidence that chronic osteoarthritic pain in dogs can be reduced by supplementation with CBD. Furthermore, experiments are required to better understand whether CBD has an influence on noise-induced fear and anxiolytic response. Preliminary evidence exists to support the analgesic properties of CBD in treating chronic canine osteoarthritis; however, there are inter- and intra-species differences in pharmacokinetics, tolerance, dosage, and safety of CBD. Therefore, to validate the anxiety management, pain management, and anti-inflammatory efficacy of CBD, it is essential to conduct systematic, randomized, and controlled trials. Further, the safety and efficacious dose of CBD in companion animals warrants investigation.

Topics: Animals; Anxiety; Biological Products; Cannabidiol; Cat Diseases; Cats; Chronic Pain; Dog Diseases; Dogs; Inflammation

There has been an explosion of interest in the utility of cannabinoids as potential analgesics. This systematic review critically synthesizes the evidence for cannabinoid analgesic effects on quantitative sensory testing outcomes in both healthy adults and patients with chronic noncancer pain. Our systematic review protocol is preregistered on PROSPERO (CRD42018117367). An electronic search was made in PsycINFO, Cochrane, Google Scholar, Embase, and Pubmed of all literature published until August 2018. Of the 1217 studies found from the search, a total 39 placebo-controlled studies that met the eligibility criteria were synthesized for this study. Because of substantial heterogeneity of study designs, populations, cannabinoid compounds, and quantitative sensory testing outcomes, meta-analysis was not conducted. More consistent evidence of cannabinoid analgesia was observed for inhaled cannabis than synthetic cannabinoids. Analgesic effects were most commonly observed in tests of cold pain sensitivity, and hyperalgesic effects were most commonly observed in tests of electrical stimulation. Patterns of findings from studies with healthy subjects did not substantively differ from those with chronic noncancer pain. However, these observations are qualified by the high degree of inconsistency across studies and methodological heterogeneity. We offer recommendations for future studies to improve study rigor and reproducibility.

Topics: Analgesics; Cannabidiol; Cannabinoid Receptor Agonists; Cannabinoids; Chronic Pain; Dronabinol; Humans; Hyperalgesia; Medical Marijuana; Pain Measurement; Pain Threshold

Given the growing challenges in chronic pain management coupled with the ongoing consequences of the opioid epidemic, pain management practitioners are looking into more effective, innovative, and safer alternatives to treat pain. Cannabis-based medicine had been described for hundreds of years but only recently have we seen the more scientific, evidence-based approach to its use, and ongoing investigations continue to explore its potential medical benefits. While historically more attention has been paid to the psychoactive component of the cannabis plant Δ. By examining recent literature, we investigated the use of CBD and its potential role in pain management. Since there are currently no approved pharmaceutical products that contain CBD alone for the management of pain, this review focused on nabiximols (which is a combined product of THC/CBD in a 1:1 ratio) as the only pharmaceutical product available that contains CBD and is being used for the management of pain. It is difficult to definitely attribute the therapeutic properties to CBD alone since it is always administered with THC. Based on the available literature, it is difficult to make a recommendation for the use of CBD in chronic pain management. It is also important to note that there are many CBD products currently available as supplements, but these products are non-pharmaceuticals and lack the appropriate clinical studies to support their efficacy claims.

Topics: Cannabidiol; Chronic Pain; Evidence-Based Medicine; Humans; Pain Management

To describe marijuana's clinical role for urologic symptoms.. Studies related to marijuana, voiding dysfunction, lower urinary tract symptoms (LUTS), and pain through January 2019 from PubMed were evaluated for relevance and quality.. Forty-eight studies were reviewed. Cannabinoids have mixed efficacy for neurogenic LUTS and little evidence for non-neurogenic LUTS, chronic non-cancer-related and perioperative pain. For cancer-related pain, high-level studies demonstrate cannabinoids are well-tolerated with unclear benefit.. Cannabinoids appear well-tolerated in the short-term, but their efficacy and long-term impact is unproven and unknown in urologic discomfort. Cannabinoids for urologic symptoms should be further explored with well-designed randomized controlled trials.

Topics: Cancer Pain; Cannabidiol; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Chronic Pain; Cystitis, Interstitial; Dronabinol; Drug Combinations; Humans; Lower Urinary Tract Symptoms; Male; Medical Marijuana; Multiple Sclerosis; Pain, Procedural; Pelvic Pain; Urinary Incontinence

An increasing number of patients are turning to cannabis and cannabinoids for management of their palliative and nonpalliative cancer pain and other cancer-related symptoms. Canadians have a legal framework for access to medical cannabis, which provides a unique perspective in a setting lacking robust clinical evidence. This review seeks to delineate the role of cannabis and cannabinoids in cancer pain management and offers insight into the Canadian practice.. A cohort study using nabiximols on advanced cancer pain in patients already optimized on opioids, over 3 weeks, demonstrated improved average pain score. A large observational study of cancer patients using cannabis over 6 months demonstrated a decreased number of patients with severe pain and decreased opioid use, whereas the number of patients reporting good quality of life increased.. Good preclinical animal data and a large body of observational evidence point to the potential efficacy of cannabinoids for cancer pain management. However, there are relatively weak data pointing to clinical efficacy from clinical trial data to date. In Canada, the burgeoning cannabis industry has driven the population to embrace a medicine before clinical evidence. There remains a need for high-quality randomized controlled trials to properly assess the effectiveness and safety of medical cannabis, compared with placebo and standard treatments for cancer-related symptoms.

Topics: Analgesics, Opioid; Canada; Cancer Pain; Cannabidiol; Chronic Pain; Clinical Trials as Topic; Dronabinol; Drug Combinations; Drug Evaluation, Preclinical; Humans; Medical Marijuana; Pain Management; Palliative Care; Quality of Life; Severity of Illness Index

Chronic pain can be recurrent or constant pain that lasts for longer than 3 months and can result in disability, suffering, and a physical disturbance. Related to the complex nature of chronic pain, treatments have a pharmacological and non-pharmacological approach. Due to the opioid epidemic, alternative therapies have been introduced, and components of the plant Cannabis Sativa, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have gained recent interest as a choice of treatment. The exact mechanism for CBD is currently unknown, but unlike the CBD's psychoactive counterpart, THC, the side effects of CBD itself have been shown to be overall much more benign. The current pharmaceutical products for the treatment of chronic pain are known as nabiximols, and they contain a ratio of THC combined with CBD, which has been promising. This review focuses on the treatment efficacy of CBD, THC: CBD-based treatments for chronic pain and adverse events with each.

Topics: Analgesics; Cannabidiol; Cannabinoid Receptor Agonists; Chronic Pain; Cross-Over Studies; Dronabinol; Drug Administration Routes; Drug Combinations; Drug Therapy, Combination; Humans; Treatment Outcome

Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have become very popular over the past few years. Patients report relief for a variety of conditions, particularly pain, without the intoxicating adverse effects of medical marijuana. In June 2018, the first CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of rare, severe epilepsy, further putting the spotlight on CBD and hemp oils. There is a growing body of preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction. Care must be taken when directing patients toward CBD products because there is little regulation, and studies have found inaccurate labeling of CBD and tetrahydrocannabinol quantities. This article provides an overview of the scientific work on cannabinoids, CBD, and hemp oil and the distinction between marijuana, hemp, and the different components of CBD and hemp oil products. We summarize the current legal status of CBD and hemp oils in the United States and provide a guide to identifying higher-quality products so that clinicians can advise their patients on the safest and most evidence-based formulations. This review is based on a PubMed search using the terms CBD, cannabidiol, hemp oil, and medical marijuana. Articles were screened for relevance, and those with the most up-to-date information were selected for inclusion.

Topics: Attitude of Health Personnel; Cancer Pain; Cannabidiol; Cannabis; Chronic Pain; Drug Approval; Female; Humans; Male; Medical Marijuana; Oils; Practice Guidelines as Topic; United States; United States Food and Drug Administration

Topics: Acute Pain; Analgesics, Non-Narcotic; Cannabidiol; Cannabinoids; Chronic Pain; Dronabinol; Humans; Marijuana Abuse; Medical Marijuana; Mental Status and Dementia Tests; Psychomotor Performance; Randomized Controlled Trials as Topic

This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain.. To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults.. In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles.. We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm.. Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For tolerability, we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawal due to adverse events and specific adverse events, nervous system disorders and psychiatric disorders. For safety, we calculated NNTH for serious adverse events. Meta-analysis was undertaken using a random-effects model. We assessed the quality of evidence using GRADE and created a 'Summary of findings' table.. We included 16 studies with 1750 participants. The studies were 2 to 26 weeks long and compared an oromucosal spray with a plant-derived combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (10 studies), a synthetic cannabinoid mimicking THC (nabilone) (two studies), inhaled herbal cannabis (two studies) and plant-derived THC (dronabinol) (two studies) against placebo (15 studies) and an analgesic (dihydrocodeine) (one study). We used the Cochrane 'Risk of bias' tool to assess study quality. We defined studies with zero to two unclear or high risks of bias judgements to be high-quality studies, with three to five unclear or high risks of bias to be moderate-quality studies, and with six to eight unclear or high risks of bias to be low-quality studies. Study quality was low in two studies, moderate in 12 studies and high in two studies. Nine studies were at high risk of bias for study size. We rated the quality of the evidence according to GRADE as very low to moderate.Primary outcomesCannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo (21% versus 17%; risk difference (RD) 0.05 (95% confidence interval (CI) 0.00 to 0.09); NNTB 20 (95% CI 11 to 100); 1001 participants, eight studies, low-quality evidence). We rated the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality (26% versus 21%;RD 0.09 (95% CI 0.01 to 0.17); NNTB 11 (95% CI 6 to 100); 1092 participants, six studies). More participants withdrew from the studies due to adverse events with cannabis-based medicines (10% of participants) than with placebo (5% of participants) (RD 0.04 (95% CI 0.02 to 0.07); NNTH 25 (95% CI 16 to 50); 1848 participants, 13 studies, moderate-quality evidence). We did not have enough evidence to determine if cannabis-based medicines increase the frequency of serious adverse events compared with placebo (RD 0.01 (95% CI -0.01 to 0.03); 1876 participants, 13 studies, low-quality evidence).Secondary outcomesCannabis-based medicines probably increase the number of people achieving pain relief of 30% or greater compared with placebo (39% versus 33%; RD 0.09 (95% CI 0.03 to 0.15); NNTB 11 (95% CI 7 to 33); 1586 participants, 10 studies, moderate quality evidence). Cannabis-based medicines may increase nervous system adverse events compared with placebo (61% versus 29%; RD 0.38 (95% CI 0.18 to 0.58); NNTH 3 (95% CI 2 to 6); 1304 participants, nine. The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes.

Topics: Adult; Analgesics, Non-Narcotic; Analgesics, Opioid; Cannabidiol; Chronic Pain; Codeine; Dronabinol; Humans; Medical Marijuana; Neuralgia; Numbers Needed To Treat; Randomized Controlled Trials as Topic

The management of chronic pain is a complex challenge worldwide. Cannabis-based medicines (CBMs) have proven to be efficient in reducing chronic pain, although the topic remains highly controversial in this field.. This study's aim is to conduct a conclusive review and meta-analysis, which incorporates all randomized controlled trials (RCTs) in order to update clinicians' and researchers' knowledge regarding the efficacy and adverse events (AEs) of CBMs for chronic and postoperative pain treatment.. A systematic review and meta-analysis.. An electronic search was conducted using Medline/Pubmed and Google Scholar with the use of Medical Subject Heading (MeSH) terms on all literature published up to July 2015. A follow-up manual search was conducted and included a complete cross-check of the relevant studies. The included studies were RCTs which compared the analgesic effects of CBMs to placebo. Hedges's g scores were calculated for each of the studies. A study quality assessment was performed utilizing the Jadad scale. A meta-analysis was performed utilizing random-effects models and heterogeneity between studies was statistically computed using I² statistic and tau² test.. The results of 43 RCTs (a total of 2,437 patients) were included in this review, of which 24 RCTs (a total of 1,334 patients) were eligible for meta-analysis. This analysis showed limited evidence showing more pain reduction in chronic pain -0.61 (-0.78 to -0.43, P < 0.0001), especially by inhalation -0.93 (-1.51 to -0.35, P = 0.001) compared to placebo. Moreover, even though this review consisted of some RCTs that showed a clinically significant improvement with a decrease of pain scores of 2 points or more, 30% or 50% or more, the majority of the studies did not show an effect. Consequently, although the primary analysis showed that the results were favorable to CBMs over placebo, the clinical significance of these findings is uncertain. The most prominent AEs were related to the central nervous and the gastrointestinal (GI) systems.. Publication limitation could have been present due to the inclusion of English-only published studies. Additionally, the included studies were extremely heterogeneous. Only 7 studies reported on the patients' history of prior consumption of CBMs. Furthermore, since cannabinoids are surrounded by considerable controversy in the media and society, cannabinoids have marked effects, so that inadequate blinding of the placebo could constitute an important source of limitation in these types of studies.. The current systematic review suggests that CBMs might be effective for chronic pain treatment, based on limited evidence, primarily for neuropathic pain (NP) patients. Additionally, GI AEs occurred more frequently when CBMs were administered via oral/oromucosal routes than by inhalation.Key words: Cannabis, CBMs, chronic pain, postoperative pain, review, meta-analysis.

Topics: Cannabidiol; Cannabis; Chronic Pain; Dronabinol; Drug Combinations; Humans; Medical Marijuana; Neuralgia; Pain Management; Pain, Postoperative; Randomized Controlled Trials as Topic; Treatment Outcome

Since the passage of the 2018 Farm Bill, practitioners have encountered more patients self-treating pain with over-the-counter topical cannabidiol (CBD) derived from hemp-Cannabis sativa with less than 0.3% delta-9-tetrahydrocannabinol-with reported improvements in pain control and activities of daily living. Cannabidiol has been touted for its capacity to improve inflammatory, arthritic, and neuropathic pain conditions, and increasing numbers of patients are exploring its use as potential replacement for opioids. However, limited rigorous clinical trials have been performed evaluating the safety and efficacy of cannabinoids for the treatment of pain.. A systematic search of PubMed was performed using the Medical Subject Headings (MeSH) terms "cannabinoid" or "CBD" or "cannabidiol" or "cannabis" or "medical marijuana" and "pain." It yielded 340 article titles. Twelve full-text primary studies of oral or topical CBD for chronic pain were selected for review, including 6 animal (2 randomized clinical trial and 4 prospective trials) and 6 human (4 randomized clinical trial and 2 prospective trials) studies.. With respect to the safety and efficacy of oral and topical CBD for treating pain, animal and human studies have shown early positive results with limited minor side effects. However, all human studies may be underpowered with small sample sizes.. With respect to the safety and efficacy of oral and topical CBD for treating pain, the evidence remains inconclusive in that we have a paucity of data to share with our patients who are considering the use of these products, which may be associated with significant costs.

Topics: Activities of Daily Living; Animals; Cannabidiol; Cannabinoids; Cannabis; Chronic Pain; Humans; Prospective Studies; Surgeons

Up to 80 % nursing home residents with dementia experiences chronic pain. Contextually, 97 % presents fluctuant neuropsychiatric symptoms (NPS). Among the most challenging is agitation, connected with undertreated pain and managed through neuroleptics doubling death risk. Evidence is accumulating in favor of the involvement of the endocannabinoid system in nociception and NPS. This double-blind, placebo-controlled, randomized trial (NAbiximols Clinical Translation To the treatment of Pain and Agitation In Severe Dementia [NACTOPAISD]) aims at investigating efficacy and safety of oral spray nabiximols, containing Δ9-tetrahydrocannabinol and cannabidiol (Sativex®), for pain and agitation treatment in severe dementia patients (Mini-Mental State Examination ≤ 12) over 65. The coprimary endpoints are efficacy on pain and agitation, assessed through the recently validated Italian Mobilization-Observation-Behavior-Intensity-Dementia and the Cohen-Mansfield Agitation Inventory. The secondary endpoint is the evaluation of efficacy duration after wash-out and the assessment of quality of life through the DEMQOL. Any adverse events will be reported. The results undergo statistical analysis plan. NACTOPAISD might provide rationale for a translational safer pain and agitation treatment in severe dementia. It is approved by Calabria Region Ethics Committee and follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and the Consolidated Standards of Reporting Trials (CONSORT) statements.

Topics: Aged; Cannabidiol; Chronic Pain; Dementia; Double-Blind Method; Dronabinol; Drug Combinations; Humans; Oral Sprays; Psychomotor Agitation; Randomized Controlled Trials as Topic

Patients with the genetic blistering skin condition epidermolysis bullosa (EB) report severe pain as a consequence of skin and mucous membrane lesions including blisters, wounds, and scars. Adequate symptom alleviation is not often achieved using conventional pharmacologic interventions. Finding novel approaches to pain care in EB is imperative to improve the quality of life of patients living with EB. There are several anecdotal reports on the use of cannabinoid-based medicines (CBMs) by EB patients to reduce the burden of symptoms. However, controlled clinical investigations assessing these reported effects are lacking. As the pain quality "unpleasantness" delineates EB pain, we hypothesize the modulation of affective pain processing in the brain by way of intervention with CBMs comprising the cannabinoids Δ-9-tetrahydrocannabinol and cannabidiol-objectified by functional magnetic resonance imaging (fMRI). The C4EB study is an investigator-initiated, single-centre, randomized, double-blind, placebo-controlled and crossover trial. Adult patients with the diagnosis epidermolysis bullosa, reporting chronic pain will be eligible to participate. Following baseline measurements, participants will be randomized to receive the sublingually administered interventions placebo and Transvamix® in forward or reversed orders, each for two weeks and separated by a washout. The primary outcome is the difference in numeric rating scale pain scores between grouped interventions, using affective descriptors within the Short-form McGill Pain Questionnaire-2. Secondary outcomes include pain self-efficacy, concomitant analgesic medication-use and adverse events. Additionally, fMRI will be employed to assess brain connectivity related to neuroanatomic pain circuits at baseline, placebo and Transvamix® interventions. The study was approved by the ethical committee at the University Medical Center of Groningen in the Netherlands. Results will be submitted for publication in a peer-reviewed journal. Trial registration number: Netherlands Trial Register: NL9347 (Acronym: C4EB).

Topics: Adult; Cannabidiol; Chronic Pain; Cross-Over Studies; Double-Blind Method; Dronabinol; Epidermolysis Bullosa; Humans; Quality of Life; Randomized Controlled Trials as Topic

Topics: Adult; Aged; Analgesics, Opioid; Cannabidiol; Cannabis; Chronic Pain; Female; Humans; Male; Middle Aged; Phytotherapy; Plant Extracts; Quality of Life; Surveys and Questionnaires

Peripheral neuropathy can significantly impact the quality of life for those who are affected, as therapies from the current treatment algorithm often fail to deliver adequate symptom relief. There has, however, been an increasing body of evidence for the use of cannabinoids in the treatment of chronic, noncancer pain. The efficacy of a topically delivered cannabidiol (CBD) oil in the management of neuropathic pain was examined in this four-week, randomized and placebocontrolled trial.. In total, 29 patients with symptomatic peripheral neuropathy were recruited and enrolled. 15 patients were randomized to the CBD group with the treatment product containing 250 mg CBD/3 fl. oz, and 14 patients were randomized to the placebo group. After four weeks, the placebo group was allowed to crossover into the treatment group. The Neuropathic Pain Scale (NPS) was administered biweekly to assess the mean change from baseline to the end of the treatment period.. The study population included 62.1% males and 37.9% females with a mean age of 68 years. There was a statistically significant reduction in intense pain, sharp pain, cold and itchy sensations in the CBD group when compared to the placebo group. No adverse events were reported in this study.. Our findings demonstrate that the transdermal application of CBD oil can achieve significant improvement in pain and other disturbing sensations in patients with peripheral neuropathy. The treatment product was well tolerated and may provide a more effective alternative compared to other current therapies in the treatment of peripheral neuropathy.

Topics: Administration, Cutaneous; Adult; Aged; Analgesics, Non-Narcotic; Cannabidiol; Chronic Pain; Cross-Over Studies; Double-Blind Method; Drug Carriers; Female; Humans; Lower Extremity; Male; Microglia; Neuralgia; Oils; Quality of Life; Receptor, Cannabinoid, CB2; Treatment Outcome

In this experimental randomized placebo-controlled 4-way crossover trial, we explored the analgesic effects of inhaled pharmaceutical-grade cannabis in 20 chronic pain patients with fibromyalgia. We tested 4 different cannabis varieties with exact knowledge on their [INCREMENT]-tetrahydrocannabinol (THC) and cannabidiol (CBD) content: Bedrocan (22.4-mg THC, <1-mg CBD; Bedrocan International BV, Veendam, the Netherlands), Bediol (13.4-mg THC, 17.8-mg CBD; Bedrocan International BV, Veendam, the Netherlands), Bedrolite (18.4-mg CBD, <1-mg THC; Bedrocan International BV, Veendam, the Netherlands), and a placebo variety without any THC or CBD. After a single vapor inhalation, THC and CBD plasma concentrations, pressure and electrical pain thresholds, spontaneous pain scores, and drug high were measured for 3 hours. None of the treatments had an effect greater than placebo on spontaneous or electrical pain responses, although more subjects receiving Bediol displayed a 30% decrease in pain scores compared to placebo (90% vs 55% of patients, P = 0.01), with spontaneous pain scores correlating with the magnitude of drug high (ρ = -0.5, P < 0.001). Cannabis varieties containing THC caused a significant increase in pressure pain threshold relative to placebo (P < 0.01). Cannabidiol inhalation increased THC plasma concentrations but diminished THC-induced analgesic effects, indicative of synergistic pharmacokinetic but antagonistic pharmacodynamic interactions of THC and CBD. This experimental trial shows the complex behavior of inhaled cannabinoids in chronic pain patients with just small analgesic responses after a single inhalation. Further studies are needed to determine long-term treatment effects on spontaneous pain scores, THC-CBD interactions, and the role of psychotropic symptoms on pain relief.

Topics: Adult; Aged; Analgesics; Cannabidiol; Chronic Pain; Cross-Over Studies; Dronabinol; Female; Fibromyalgia; Humans; Male; Middle Aged; Pain Measurement; Surveys and Questionnaires; Time Factors; Young Adult

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic, systemic, inflammatory diseases, primarily in the musculoskeletal system. Pain and fatigue are key symptoms of RA and AS. Treatment presents a clinical challenge for several reasons, including the progressive nature of the diseases and the involvement of multiple pain mechanisms. Moreover, side effects of pain treatment pose an implicit risk. Currently, no well-controlled studies have investigated how medical cannabis affects pain and cognitive functions in RA and AS. The present study aims to evaluate the efficacy and safety of medical cannabis in the treatment of persistent pain in patients with RA and AS with low disease activity.. A double-blinded, randomised, placebo-controlled study of cannabidiol (CBD), followed by an open label add-on of tetrahydrocannabinol (THC) with collection of clinical data and biological materials in RA and AS patients treated in routine care. The oral treatment with CBD in the experimental group is compared with placebo in a control group for 12 weeks, followed by an observational 12-week period with an open label add-on of THC in the primary CBD non-responders. Disease characteristics, psychological parameters, demographics, comorbidities, lifestyle factors, blood samples and serious adverse events are collected at baseline, after 12 and 24 weeks of treatment, and at a follow-up visit at 36 weeks. Data will be analysed in accordance with a predefined statistical analysis plan.. The Danish Ethics Committee (S-20170217), the Danish Medicines Agency (S-2018010018) and the Danish Data Protection Agency approved the protocol. The project is registered in the European Clinical Trials Database (EudraCT 2017-004226-15). All participants will give written informed consent to participate prior to any study-related procedures. The results will be presented at international conferences and published in peer-reviewed journals.

Topics: Arthritis, Rheumatoid; Cannabidiol; Chronic Pain; Double-Blind Method; Dronabinol; Humans; Multicenter Studies as Topic; Pain Management; Placebos; Randomized Controlled Trials as Topic; Research Design; Spondylitis, Ankylosing

Prior Phase 2/3 studies found that cannabinoids might provide adjunctive analgesia in advanced cancer patients with uncontrolled pain.. Phase 3, double-blind, randomized, placebo-controlled trial in patients with advanced cancer and average pain Numerical Rating Scale scores ≥4 and ≤8 despite optimized opioid therapy. Patients randomized to nabiximols (n = 199) or placebo (n = 198) self-titrated study medications over a two-week period, followed by a three-week treatment period at the titrated dose.. Median percent improvements in average pain Numerical Rating Scale score from baseline to end of treatment in the nabiximols and placebo groups were 10.7% vs. 4.5% (P = 0.0854) in the intention-to-treat population (primary variable) and 15.5% vs. 6.3% (P = 0.0378) in the per-protocol population. Nabiximols was statistically superior to placebo on two of three quality-of-life instruments at Week 3 and on all three at Week 5. In exploratory post hoc analyses, U.S. patients, but not patients from the rest of the world, experienced significant benefits from nabiximols on multiple secondary endpoints. Possible contributing factors to differences in nabiximols efficacy include: 1) the U.S. participants received lower doses of opioids at baseline than the rest of the world and 2) the subgroups had different distribution of cancer pain types, which may have been related to differences in pathophysiology of pain. The safety profile of nabiximols was consistent with earlier studies.. Although not superior to placebo on the primary efficacy endpoint, nabiximols had benefits on multiple secondary endpoints, particularly in the U.S.. Nabiximols might have utility in patients with advanced cancer who receive a lower opioid dose, such as individuals with early intolerance to opioid therapy.

Topics: Analgesics; Analgesics, Opioid; Cancer Pain; Cannabidiol; Chemotherapy, Adjuvant; Chronic Pain; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Oral Sprays; Pain Measurement; Quality of Life; Treatment Outcome

Chronic pain is a major therapeutic problem in kidney transplant patients owing to nephrotoxicity associated with nonsteroidal antiiflammatory drugs. Benefits in chronic pain treatment with cannabidiol (CBD) have been reported. This study assesses the effect, safety, and possible drug interactions in kidney transplant patients treated with CBD for chronic pain.. We assessed patients who asked to receive CBD for pain treatment. Doses were increased from 50 to 150 mg twice a day for 3 weeks. Creatinine, blood count, liver function, liver enzymes, and drug levels were determined every 48 hours the first week and then once a week thereafter.. We assessed 7 patients with a mean age of 64.5 years (range, 58-75 years). CBD initial dose was 100 mg/d, CBD dose reduction to 50 mg/d has been done on day 4 to patient 1 for persistent nausea. Tacrolimus dose reduction in patient 3 was undertaken on days 4, 7, and 21 owing to persisting elevated levels (even before CBD) and itching, and on day 21 in patient 5. Tacrolimus levels decreased in patient 2 but were normal in the control 1 week later. Patients on cyclosporine were stable. Adverse effects were nausea, dry mouth, dizziness, drowsiness, and intermittent episodes of heat. CBD dose decrease was required in 2 patients. Two patients had total pain improvement, 4 had a partial response in the first 15 days, and in 1 there was no change.. During this follow-up, CBD was well-tolerated, and there were no severe adverse effects. Plasma levels of tacrolimus were variable. Therefore, longer follow-up is required.

Topics: Aged; Cannabidiol; Chronic Pain; Cyclosporine; Female; Humans; Kidney Transplantation; Male; Middle Aged; Pain Management; Tacrolimus; Treatment Outcome; Uruguay

Patients with advanced cancer who have pain that responds poorly to opioid therapy pose a clinical challenge. Nabiximols (Nabiximols is the U.S. Adopted Name [USAN] for Sativex [GW Pharma Ltd, Wiltshire, U.K.], which does not yet have an INN), a novel cannabinoid formulation, is undergoing investigation as add-on therapy for this population. In a randomized, double-blind, placebo-controlled, graded-dose study, patients with advanced cancer and opioid-refractory pain received placebo or nabiximols at a low dose (1-4 sprays/day), medium dose (6-10 sprays/day), or high dose (11-16 sprays/day). Average pain, worst pain and sleep disruption were measured daily during 5 weeks of treatment; other questionnaires measured quality of life and mood. A total of 360 patients were randomized; 263 completed. There were no baseline differences across groups. The 30% responder rate primary analysis was not significant for nabiximols versus placebo (overall P = .59). A secondary continuous responder analysis of average daily pain from baseline to end of study demonstrated that the proportion of patients reporting analgesia was greater for nabiximols than placebo overall (P = .035), and specifically in the low-dose (P = .008) and medium-dose (P = .039) groups. In the low-dose group, results were similar for mean average pain (P = .006), mean worst pain (P = .011), and mean sleep disruption (P = .003). Other questionnaires showed no significant group differences. Adverse events were dose-related and only the high-dose group compared unfavorably with placebo. This study supports the efficacy and safety of nabiximols at the 2 lower-dose levels and provides important dose information for future trials.. Nabiximols, a novel cannabinoid formulation, may be a useful add-on analgesic for patients with opioid-refractory cancer pain. A randomized, double-blind, placebo-controlled, graded-dose study demonstrated efficacy and safety at low and medium doses.

Topics: Aged; Analgesics, Non-Narcotic; Analgesics, Opioid; Cannabidiol; Chronic Pain; Dose-Response Relationship, Drug; Double-Blind Method; Dronabinol; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neoplasms; Pain Measurement; Time Factors

Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), 2 of the primary constituents of cannabis, are used by some individuals to self-treat chronic pain. It is unclear whether the pain-relieving effects of CBD alone and in combination with THC are consistent across genders and among types of pain. The present study compared the effects of CBD and THC given alone and in combination in male and female rats with Complete Freund's adjuvant-induced inflammatory pain. After induction of hindpaw inflammation, vehicle, CBD (0.05-2.5 mg/kg), THC (0.05-2.0 mg/kg), or a CBD:THC combination (3:1, 1:1, or 1:3 dose ratio) was administered i.p. twice daily for 3 days. Then on day 4, mechanical allodynia, thermal hyperalgesia, weight-bearing, and locomotor activity were assessed 0.5 to 4 hours after administration of the same dose combination. Hindpaw edema and open field (anxiety-like) behaviors were measured thereafter. THC alone was anti-allodynic and anti-hyperalgesic, and decreased paw thickness, locomotion, and open field behaviors. CBD alone was anti-allodynic and anti-hyperalgesic. When combined with THC, CBD tended to decrease THC effects on pain-related behaviors and exacerbate THC-induced anxiety-like behaviors, particularly in females. These results suggest that at the doses tested, CBD-THC combinations may be less beneficial than THC alone for the treatment of chronic inflammatory pain. PERSPECTIVE: The present study compared CBD and THC effects alone and in combination in male and female rats with persistent inflammatory pain. This study could help clinicians who prescribe cannabis-based medicines for inflammatory pain conditions determine which cannabis constituents may be most beneficial.

Topics: Animals; Cannabidiol; Cannabinoid Receptor Agonists; Chronic Pain; Dronabinol; Female; Hyperalgesia; Male; Rats

This study aimed to explore the incidence of adverse events (AEs) reported by patients when initiating medicinal cannabis treatment for chronic pain, and the association of cannabis constituents, dose and concomitant medicines with AE incidence.. Patient demographics, cannabis products and AE data were collected as part of the Cannabis Access Clinics Observational Study, and concomitant medicines were obtained from patient health summaries provided by referring doctors. Cannabis products were grouped by their constituents as either cannabidiol-only or containing both cannabidiol and Δ-9-tetrahydrocannabinol.. From a total of 275 patients, each had a median of six concomitant medicines, with opioids (n = 179; 65%) the most common. A total of 35.6% patients took 10 or more other medicines, and they were associated with a 3.6 times higher likelihood to report the AE of fatigue (P = 0.048). Patients who received concomitant gabapentinoids were 2.4 times more likely to report dizziness (P = 0.036), patients on tricyclic antidepressants were 1.8 times more likely to report somnolence (P = 0.034) and 3.4 times more likely to report anxiety (P = 0.04), when compared with patients who were not prescribed those classes of medications. Those patients who were prescribed products containing both cannabidiol and Δ-9-tetrahydrocannabinol were 1.5 times more likely (P = 0.004) to have experienced an AE when compared with those prescribed only cannabidiol.. These findings show that certain concomitant medications and cannabis constituents may be associated with AE incidence when initiating medicinal cannabis. These potential pharmacokinetic and pharmacodynamic interactions require further study to develop guidance for prescribers and pharmacists.

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

Cannabinoids are a promising therapeutic avenue for chronic pain. However, clinical trials often fail to report analgesic efficacy of cannabinoids. Inhibition of voltage gate calcium (Ca. Electrophysiological recordings from tsA-201 cells expressing either Ca. HU-210 (1 μM) inhibited Ca. Our findings reveal differential modulation of Ca

Topics: Analgesics; Animals; Calcium Channels; Cannabidiol; Cannabinoids; Chronic Pain; Female; Male; Mice; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2

The most frequently reported use of medical marijuana is for pain relief. However, its psychoactive component Δ9-tetrahydrocannabinol (THC) causes significant side effects. Cannabidiol (CBD) and β-caryophyllene (BCP), two other cannabis constituents, possess more benign side effect profiles and are also reported to reduce neuropathic and inflammatory pain. We evaluated the analgesic potential of CBD and BCP individually and in combination in a rat spinal cord injury (SCI) clip compression chronic pain model. Individually, both phytocannabinoids produced dose-dependent reduction in tactile and cold hypersensitivity in male and female rats with SCI. When co-administered at fixed ratios based on individual A50s, CBD and BCP produced enhanced dose-dependent reduction in allodynic responses with synergistic effects observed for cold hypersensitivity in both sexes and additive effects for tactile hypersensitivity in males. Antinociceptive effects of both individual and combined treatment were generally less robust in females than males. CBD:BCP co-administration also partially reduced morphine-seeking behavior in a conditioned place preference (CPP) test. Minimal cannabinoidergic side effects were observed with high doses of the combination. The antinociceptive effects of the CBD:BCP co-administration were not altered by either CB2 or μ-opioid receptor antagonist pretreatment but, were nearly completely blocked by CB1 antagonist AM251. Since neither CBD or BCP are thought to mediate antinociception via CB1 activity, these findings suggest a novel CB1 interactive mechanism between these two phytocannabinoids in the SCI pain state. Together, these findings suggest that CBD:BCP co-administration may provide a safe and effective treatment option for the management of chronic SCI pain.

Topics: Analgesics; Animals; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Chronic Pain; Dronabinol; Female; Hallucinogens; Male; Rats; Spinal Cord Injuries

A 10-year-old mixed breed male cat presented with clinical signs related to chronic orthopaedic pain. Upon physical examination, pain was noted, based on the feline Musculoskeletal Pain Index (FMPI). An analgesic treatment with a full spectrum cannabis oil (1.8% CBD and 0.8% THC) was proposed for 30 days (0,5 mg/kg based on CBD). The FMPI scale score decreased more than 50%. This case reported a satisfactory outcome for the patient and the owner, although this medication could increase ALT. Given the paucity of literature published to date on the treatment of veterinary species with cannabis-based medications, further clinical and pharmacokinetic studies are necessary to study the safety and efficacy of its use.

Topics: Analgesics; Animals; Cannabidiol; Cats; Chronic Pain; Dronabinol; Male

Although preclinical studies generally report robust antinociceptive effects of cannabinoids in rodent persistent pain models, randomized controlled trials in chronic pain patients report limited pain relief from cannabis/cannabinoids. Differences between animal and human studies that may contribute to these discrepant findings include route of cannabis/cannabinoid administration, type of cannabis/cannabinoid, and how pain is measured. To address these factors, rats with complete Freund adjuvant (CFA)-induced hind paw inflammation were exposed acutely or repeatedly to vaporized cannabis extract that was either tetrahydrocannabinol (THC) or cannabidiol (CBD)dominant. One measure of evoked pain (mechanical threshold), 2 functional measures of pain (hind paw weight-bearing, and locomotor activity), and hind paw edema were assessed for up to 2 hours after vapor exposure. Acute exposure to vaporized THC-dominant extract (200 or 400 mg/mL) decreased mechanical allodynia and hind paw edema and increased hind paw weight-bearing and locomotor activity, with no sex differences. After repeated exposure to vaporized THC-dominant extract (twice daily for 3 days), only the antiallodynic effect was significant. Acute exposure to vaporized CBD-dominant cannabis extract (200 mg/mL) did not produce any effects in either sex; repeated exposure to this extract (100, 200, or 400 mg/mL) decreased mechanical allodynia in male rats only. Sex differences (or lack thereof) in the effects of vaporized cannabis extracts were not explained by sex differences in plasma levels of THC, CBD, or their major metabolites. These results suggest that although vaporized THC-dominant extract is likely to be modestly effective against inflammatory pain in both male and female rats, tolerance may develop, and the CBD-dominant extract may be effective only in male rats.

Topics: Animals; Cannabidiol; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Chronic Pain; Dronabinol; Edema; Female; Humans; Hyperalgesia; Male; Rats

Topics: Analgesics; Animals; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Chronic Pain; Hallucinogens; Mice; Micelles; Plant Extracts; Polymers; Renal Dialysis

Topics: Acyclic Monoterpenes; Alkenes; Analgesics; Animals; Anti-Inflammatory Agents; Arthralgia; Arthritis; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Chronic Pain; Hallucinogens; Inflammation; Male; Rats; Rats, Wistar; Terpenes

The therapeutic potential of medical cannabis to treat a variety of conditions is becoming increasingly recognised. Globally, a large number of countries have now legalised cannabis for medical uses and a substantial number of patients are able to access their medications. Yet in the UK, where medical cannabis was legalised in November 2018, only a handful of NHS prescriptions have been written, meaning that most patients are unable to access the medicine. Reasons for this are manyfold and include the perceived lack of clinical evidence due to the challenges of studying medical cannabis through randomised controlled trials. In order to develop the current evidence base, the importance of incorporating real-world data (RWD) to assess the effectiveness and efficacy of medical cannabis has gradually become recognised. The current paper provides a detailed outline of Project Twenty21 (T21), the UK's first medical cannabis registry, launched in August 2020. We provide the rationale for T21 and describe the methodology before reporting the characteristics of the 'first patients' enrolled in the registry. We describe the health status of all patients enrolled into the project during its first 7 months of operation and the sociodemographic characteristics and primary presenting conditions for these patients, as well as details of the medical cannabis prescribed to these individuals. By 12th March 2021, 678 people had been enrolled into T21; the majority (64%) were male and their average age was 38.7 years (range = 18-80). The most commonly reported primary conditions were chronic pain (55.6%) and anxiety disorders (32.0%) and they reported high levels of multi-morbidity, including high rates of insomnia and depression. We also present preliminary evidence from 75 patients followed up after 3 months indicating that receipt of legal, prescribed cannabis was associated with a significant increase in self-reported health, assessed using the visual analogue scale of the EQ-5D-5L (Cohen's d = .77, 95% CI = .51-1.03). Our initial findings complement reports from other large-scale databases globally, indicating that the current RWD is building up a pattern of evidence. With many clinicians demanding better and faster evidence to inform their decisions around prescribing medical cannabis, the current and future results of T21 will expand the existing evidence base on the effectiveness of cannabis-based medical products (CBMPs).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesics; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Chronic Pain; Female; Hallucinogens; Humans; Male; Medical Marijuana; Middle Aged; Young Adult

A small body of evidence suggests medical cannabis may facilitate wound healing, but the exact mechanism of this effect is unclear.. This case report describes a patient with a pressure injury (PI) who received cannabis oil treatment for pain management and sleep improvement.. A 37-year-old woman with multiminicore disease, scoliosis, short-chain acyl-CoA dehydrogenase deficiency, and epilepsy presented to the Neurology Centre of Toronto with chronic pain and sleep disturbance, including difficulty initiating and maintaining sleep. She also had a 5-year history of a PI between her right iliac crest and right rib cage that had progressively worsened. The patient received a medical cannabis oil protocol that used a combination of cannabidiol and tetrahydrocannabinol.. Cannabis oil was effective in treating pain and sleep difficulties. Unexpectedly, during the first 2 weeks of treatment, the PI started to heal and was almost completely closed at the 2-month follow-up.. Although it is unknown if the observed healing of this refractory PI was indirectly or directly related to the cannabidiol and tetrahydrocannabinol treatment, the potential relationships among pain, sleep disturbance, cannabis treatment, and healing should be explored.

Topics: Adult; Cannabidiol; Chronic Pain; Female; Humans; Medical Marijuana; Pressure Ulcer; Sleep; Wound Healing

Cannabidiol (CBD) is widely advertised as helpful for chronic pain management but research is limited. Using a cross-sectional, anonymous survey, we examined patterns of naturalistic CBD use among individuals with fibromyalgia (FM) and other chronic pain conditions. Our objective was to better understand rates of CBD use, reasons for use and discontinuation, communication with healthcare professionals about CBD, and perceptions of CBD effectiveness and safety among people with FM. After excluding incomplete surveys, our study population consisted of N = 2,701 participants with fibromyalgia, primarily in the United States. Overall, 38.1% reported never using CBD, 29.4% reported past CBD use, and 32.4% reported current CBD use. Past-year cannabis use was strongly associated with past or current CBD use. Those using CBD typically did so due to inadequate symptom relief, while those not using CBD typically cited safety concerns as their reason for not using CBD. Two-thirds of participants disclosed CBD use to their physician, although only 33% asked for physician advice on using CBD. Participants used CBD for numerous FM-related symptoms (most commonly pain), and generally reported slight to much improvement across symptom domains. Around half of participants reported side effects, which were typically minor. Our findings are limited by selection bias and our cross-sectional design, which prevents causal associations. In conclusion, CBD use is common among individuals with FM and many individuals using CBD report improvements across numerous FM-related symptoms. Our findings highlight the need for additional rigorous studies to better understand CBD's potential for FM management. PERSPECTIVE: This article indicates that CBD use is common among people with fibromyalgia, and the results suggest that many derive benefit from using CBD across multiple symptoms domains. Clinicians should discuss CBD use with fibromyalgia patients, and future studies are needed to rigorously assess CBD's therapeutic value for fibromyalgia symptoms.

Topics: Adult; Aged; Cannabidiol; Cannabinoid Receptor Modulators; Chronic Pain; Cross-Sectional Studies; Female; Fibromyalgia; Health Surveys; Humans; Male; Medical Marijuana; Middle Aged; Patient Outcome Assessment; Prevalence

Chronic pain is the most common reason reported for using medical cannabis. The goal of this research was to determine whether the two primary phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are effective treatments for persistent inflammatory pain. In experiment 1, inflammation was induced by intraplantar injection of Complete Freund's adjuvant (CFA). Then THC (0.0-4.0 mg/kg, i.p.) or CBD (0.0-10 mg/kg, i.p.) was administered twice daily for 3 days. On day 4, THC, CBD, or vehicle was administered, and allodynia, hyperalgesia, weight-bearing, locomotor activity, and hindpaw edema were assessed 0.5-4 hours postinjection. In experiment 2, CFA or mineral oil (no-pain control)-treated rats were given THC (2.0 mg/kg, i.p.), CBD (10 mg/kg, i.p.), or vehicle in the same manner as in experiment 1. Four hours postinjection on day 4, serum samples were taken for analysis of cytokines known to influence inflammatory pain: interleukin (IL)-1

Topics: Analgesics; Animals; Cannabidiol; Cannabinol; Chronic Pain; Cytokines; Dose-Response Relationship, Drug; Drug Tolerance; Female; Inflammation; Male; Rats; Rats, Sprague-Dawley; Sex Characteristics

Topics: Antiemetics; Antineoplastic Agents; Cannabidiol; Cannabinoid Receptor Agonists; Chronic Pain; Decision Making, Shared; Dronabinol; Drug and Narcotic Control; Drug Resistant Epilepsy; Epilepsies, Myoclonic; Humans; Lennox Gastaut Syndrome; Medical Marijuana; Multiple Sclerosis; Muscle Spasticity; Nausea; Needs Assessment; Physicians, Primary Care; Practice Guidelines as Topic; Specialization; United Kingdom; Vomiting

Cannabis has been used as a medicine for millennia. Prohibition in the mid-20th century precluded early scientific investigation. 'Cannabis' describes three separate forms - herbal cannabis, 'hemp' products, pharmaceutical-grade regulated cannabinoid-based medical products (CBMP). In Australia, CBMP became available for prescription in November 2016. Herbal cannabis with Δ9-tetrahydrocannabinol (THC), which is illegal, and cannabidiol (CBD) in herbal extracts, are both unregulated and unreliable sources of cannabinoids. The endocannabinoid system (ECS), delineated in the late 1990s, has increased the understanding and interest in research for appropriate clinical indications. The ubiquitous ECS has homeostatic and anti-inflammatory effects and comprises cannabinoid receptors, endocannabinoids and degrading enzymes. Phytocannabinoids are partial agonists of the ECS. In pre-clinical studies, THC and CBD produce beneficial effects in chronic pain, anxiety, sleep and inflammation. Systematic reviews often conflate herbal cannabis and CBMP, confusing the evidence. Currently large randomised controlled trials are unlikely to be achieved. Other methodologies with quality end-points are required. Rich, valuable high-quality real-world evidence for the safe and effective use of CBMP provides an opportunity to examine benefits and potential harms. Evidence demonstrates benefit of CBMP in multiple sclerosis, chronic neuropathic pain, chemotherapy induced nausea and vomiting, resistant paediatric epilepsy, anxiety and insomnia. CBMP are well tolerated with few serious adverse events. Additional clinical benefits are promising in many other resistant chronic conditions. Pharmaceutical grade prescribed CBMP has proven clinical benefits and provides another clinical option in the physician's pharmacopeia.

Topics: Australia; Cannabidiol; Cannabinoids; Cannabis; Child; Chronic Pain; Dronabinol; Humans

Rates of legal medical cannabis (MC) use are increasing, but little is known about the prevalence and correlates of recreational cannabis (RC) use among medical users (MC/R).. 348 MC users who resided in a state in which MC is legal and had medical authorization to use MC legally completed an anonymous survey in Spring 2017 (64.1% female, 82.8% White, mean age 33.03[±10.37] years). Rates of endorsing MC/R and the following potential correlates of MC/R were examined: the legal status of RC in participants' states of residence, sex, age, race, primary medical condition, MC product(s) used, MC expectancies, features of MC sought out (e.g., high tetrahydrocannabinol [THC] content), and negative cannabis use consequences.. 55.5% of MC users engaged in MC/R. MC/R was associated with residing in a state in which RC is legal, being female, using MC for pain or mental health conditions, vaping MC concentrates, holding positive expectancies for combustible MC, and seeking out MC products with high THC concentrations. Preferring MC products with high cannabidiol (CBD) concentrations protected against MC/R.. More than half of MC users endorsed MC/R, which is considerably higher than rates of misuse observed for other prescription medications. Findings raise concerns about circumvention of RC laws in states where RC remains illegal and could be used to inform MC regulatory efforts (e.g., reducing THC content, increasing CBD content). Findings also suggest that prevention/intervention efforts to reduce MC/R are needed, especially among high-risk populations of MC users (e.g., women, pain patients, psychiatric patients).

Topics: Adult; Cannabidiol; Chronic Pain; Dronabinol; Drug and Narcotic Control; Female; Humans; Male; Marijuana Use; Medical Marijuana; Mental Disorders; Motivation; Prevalence; Risk Factors; Sex Factors; United States; Young Adult

There is considerable public and political interest in the use of cannabis products for medical purposes.. The task force of the European Pain Federation (EFIC) conducted a survey with its national chapters representatives on the status of approval of all types of cannabis-based medicines, the covering of costs and the availability of a position paper of a national medical association on the use of medical cannabis for chronic pain and for symptom control in palliative/supportive care.. Thirty-one out of 37 contacted councillors responded. Plant-derived tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray is approved for spasticity in multiple sclerosis refractory to conventional treatment in 21 EFIC chapters. Plant-derived THC (dronabinol) is approved for some palliative care conditions in four EFIC chapters. Synthetic THC analogue (nabilone) is approved for chemotherapy-associated nausea and vomiting refractory to conventional treatment in four EFIC chapters'. Eight EFIC chapters' countries have an exceptional and six chapters an expanded access programme for medical cannabis. German and Israeli pain societies recommend the use of cannabis-based medicines as third-line drug therapies for chronic pain within a multicomponent approach. Conversely, the German medical association and a team of finish experts and officials do not recommend the prescription of medical cannabis due to the lack of high-quality evidence of efficacy and the potential harms.. There are marked differences between the countries represented in EFIC in the approval and availability of cannabis-based products for medical use. EFIC countries are encouraged to collaborate with the European Medicines Agency to publish a common document on cannabis-based medicines.. There are striking differences between European countries in the availability of plant-derived and synthetic cannabinoids and of medical cannabis for pain management and for symptom control in palliative care and in the covering of costs by health insurance companies or state social security systems.

Topics: Antiemetics; Antineoplastic Agents; Cannabidiol; Cannabinoid Receptor Agonists; Chronic Pain; Dronabinol; Drug Approval; Drug Combinations; Europe; Germany; Humans; Israel; Medical Marijuana; Multiple Sclerosis; Muscle Spasticity; Nausea; Pain Management; Palliative Care; Societies, Medical; Surveys and Questionnaires; Vomiting

In The Netherlands, pharmaceutical-grade cultivated cannabis is distributed for medicinal purposes as commissioned by the Ministry of Health. Few studies have thus far described its therapeutic efficacy or subjective (adverse) effects in patients. The aims of this study are to assess the therapeutic satisfaction within a group of patients using prescribed pharmaceutical-grade cannabis and to compare the subjective effects among the available strains with special focus on their delta-9-tetrahydrocannabinol and cannabidiol content. In a cross-sectional and natural design, users of pharmaceutical-grade cannabis were investigated with questionnaires. Medical background of the patients was asked as well as experienced therapeutic effects and characteristics of cannabis use. Subjective effects were measured with psychometric scales and used to compare among the strains of cannabis used across this group of patients. One hundred two patients were included; their average age was 53 years and 76% used it for more than a year preceding this study. Chronic pain (53%; n = 54) was the most common medical indication for using cannabis followed by multiple sclerosis (23%; n = 23), and 86% (n = 88) of patients (almost) always experienced therapeutic satisfaction when using pharmaceutical cannabis. Dejection, anxiety, and appetite stimulation were found to differ among the 3 strains of cannabis. These results show that patients report therapeutic satisfaction with pharmaceutical cannabis, mainly pain alleviation. Some subjective effects were found to differ among the available strains of cannabis, which is discussed in relation to their different tetrahydrocannabinol/cannabidiol content. These results may aid in further research and critical appraisal for medicinally prescribed cannabis products.

Topics: Adult; Aged; Aged, 80 and over; Cannabidiol; Cannabis; Chronic Pain; Cross-Sectional Studies; Dronabinol; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Netherlands; Patient Satisfaction; Phytotherapy; Plant Preparations; Psychometrics; Surveys and Questionnaires; Treatment Outcome; Young Adult

Certain types of nonpsychoactive cannabinoids can potentiate glycine receptors (GlyRs), an important target for nociceptive regulation at the spinal level. However, little is known about the potential and mechanism of glycinergic cannabinoids for chronic pain treatment. We report that systemic and intrathecal administration of cannabidiol (CBD), a major nonpsychoactive component of marijuana, and its modified derivatives significantly suppress chronic inflammatory and neuropathic pain without causing apparent analgesic tolerance in rodents. The cannabinoids significantly potentiate glycine currents in dorsal horn neurons in rat spinal cord slices. The analgesic potency of 11 structurally similar cannabinoids is positively correlated with cannabinoid potentiation of the α3 GlyRs. In contrast, the cannabinoid analgesia is neither correlated with their binding affinity for CB1 and CB2 receptors nor with their psychoactive side effects. NMR analysis reveals a direct interaction between CBD and S296 in the third transmembrane domain of purified α3 GlyR. The cannabinoid-induced analgesic effect is absent in mice lacking the α3 GlyRs. Our findings suggest that the α3 GlyRs mediate glycinergic cannabinoid-induced suppression of chronic pain. These cannabinoids may represent a novel class of therapeutic agents for the treatment of chronic pain and other diseases involving GlyR dysfunction.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cannabidiol; Cell Line; Chronic Pain; Dinoprostone; Humans; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Neuralgia; Nuclear Magnetic Resonance, Biomolecular; Protein Structure, Tertiary; Rats; Rats, Sprague-Dawley; Receptors, Glycine