humulene and Multiple-Sclerosis

Previous studies have shown that tetrahydrocannabinol (THC), the main psychoactive component of cannabis, can impair cognitive abilities. There is also some evidence that cannabidiol (CBD), the most abundant non-intoxicating constituent of cannabis, can attenuate these effects. The purpose of this study was to investigate the effects of THC:CBD oromucosal spray (with equal parts THC and CBD) on cognition compared with control conditions in human studies.. A systematic literature search was performed on four major bibliographic databases. Studies were included in the present review if they evaluated the cognitive effects of THC:CBD oromucosal spray compared with a control condition.. Ten studies were identified (7 on patients with multiple sclerosis, 1 on those with Huntington, and 2 on healthy volunteers) with 510 participants in total. There was considerable heterogeneity among the studies in terms of dose and duration of administration. All studies have used an equal or nearly equal dose of THC and CBD.. Although the results across studies were somewhat inconsistent, most evidence revealed that there is no significant difference between THC:CBD oromucosal spray and control treatments in terms of cognitive outcomes. However, more trials are needed with longer follow-up periods, and dose considerations, particularly comparing lower and higher doses of the spray.

Topics: Cannabidiol; Cannabis; Cognition; Dronabinol; Drug Combinations; Humans; Multiple Sclerosis

As far as 80% of people diagnosed with multiple sclerosis (MS) experience disabling symptoms in the course of the disease, such as spasticity and neuropathic pain. As first-line symptomatic therapy is associated with important adverse reactions, cannabinoids have become increasingly popular among patients with MS. This review intends to provide an overview of the evidence of the role of cannabinoids in treating symptoms related to MS and to encourage further research on this matter.. To date, the evidence supporting the role of cannabis and its derivatives in alleviating the MS-related symptoms comes only from studies on experimental models of demyelination. To the best of our knowledge, relatively few clinical trials inquired about the therapeutic effects of cannabinoids on patients with MS, with variable results.. We conducted a literature search through PubMed and Google Scholar from the beginning until 2022. We included articles in English describing the latest findings regarding the endocannabinoid system, the pharmacology of cannabinoids, and their therapeutic purpose in MS.. Evidence from preclinical studies showed that cannabinoids can limit the demyelination process, promote remyelination, and have anti-inflammatory properties by reducing immune cell infiltration of the central nervous system in mice with experimental autoimmune encephalomyelitis. Moreover, it has been established that experimental autoimmune encephalomyelitis mice treated with cannabinoids experienced a significant reduction of symptoms and slowing of the disease progression. Given the complexity of human immune and nervous systems, cannabinoids did not have the anticipated effects on human subjects. However, data obtained from clinical trials showed some beneficial results of cannabinoids as a single or as add-on therapy in reducing the spasticity and pain related to MS.. Considering their various mechanisms of action and good tolerability, cannabinoids remain an interesting therapy for spasticity and chronic pain related to MS.

Topics: Animals; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Encephalomyelitis, Autoimmune, Experimental; Humans; Mice; Models, Theoretical; Multiple Sclerosis; Muscle Spasticity; Neuralgia

Multiple sclerosis (MS) is a chronic demyelinating disease which leads to sensory, motor, autonomic, and cognitive symptoms. Cannabis is a common way for persons with MS (pwMS) to seek symptomatic therapy. Given the capacity for both cannabis and MS to cause cognitive impairment, it is important to determine whether there is any negative impact when the two co-occur. The objective of this systematic review was to evaluate the effects of cannabis and medicinal cannabinoid products on cognition in pwMS in order to provide guidance to clinicians and enable them to make evidence-based recommendations regarding cannabis and cannabinoid products.. A systematic review was carried out searching common keyword combinations for cannabis and MS across five databases, producing 840 unique articles, 18 of which were included in a qualitative synthesis.. Aggregate data from existing studies to date highlight potential impairments from chronic whole-plant cannabis use in commonly affected cognitive domains in multiple sclerosis, including attention and working memory, and to a lesser extent, visual memory, verbal memory, and executive function. Results also suggest that in the short-term, medicinal cannabinoid preparations do not significantly impair cognition and may even ameliorate cognitive symptoms in the context of obtrusive MS disease. The findings are limited by disparities in detail of cannabis use data reported across whole-plant cannabis publications.. Existing literature on co-occurrence of cannabis use and MS lacks high quality evidence to recommend for or against cannabis and cannabinoid therapies for pwMS based on cognitive effects. Existing data suggest that cognition may be differentially impacted in pwMS depending on the type of product, the duration of use, and the indication. Future studies on whole-plant cannabis require comprehensive cannabis use data reporting including frequency, dosing, duration, and type of cannabis product. Future studies on medicinal cannabinoid products should be long-term to assess the effects of chronicity.

Topics: Cannabinoids; Cannabis; Cognition; Executive Function; Humans; Multiple Sclerosis

Spasticity and chronic neuropathic pain are common and serious symptoms in people with multiple sclerosis (MS). These symptoms increase with disease progression and lead to worsening disability, impaired activities of daily living and quality of life. Anti-spasticity medications and analgesics are of limited benefit or poorly tolerated. Cannabinoids may reduce spasticity and pain in people with MS. Demand for symptomatic treatment with cannabinoids is high. A thorough understanding of the current body of evidence regarding benefits and harms of these drugs is required.. To assess benefit and harms of cannabinoids, including synthetic, or herbal and plant-derived cannabinoids, for reducing symptoms for adults with MS.. We searched the following databases from inception to December 2021: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), CINAHL (EBSCO host), LILACS, the Physiotherapy Evidence Database (PEDro), the World Health Organisation International Clinical Trials Registry Platform, the US National Institutes of Health clinical trial register, the European Union Clinical Trials Register, the International Association for Cannabinoid Medicines databank. We hand searched citation lists of included studies and relevant reviews.. We included randomised parallel or cross-over trials (RCTs) evaluating any cannabinoid (including herbal Cannabis, Cannabis flowers, plant-based cannabinoids, or synthetic cannabinoids) irrespective of dose, route, frequency, or duration of use for adults with MS.. We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane Risk of bias 2 tool for parallel RCTs and crossover trials. We rated the certainty of evidence using the GRADE approach for the following outcomes: reduction of 30% in the spasticity Numeric Rating Scale, pain relief of 50% or greater in the Numeric Rating Scale-Pain Intensity, much or very much improvement in the Patient Global Impression of Change (PGIC), Health-Related Quality of Life (HRQoL), withdrawals due to adverse events (AEs) (tolerability), serious adverse events (SAEs), nervous system disorders, psychiatric disorders, physical dependence.. We included 25 RCTs with 3763 participants of whom 2290 received cannabinoids. Age ranged from 18 to 60 years, and between 50% and 88% participants across the studies were female.  The included studies were 3 to 48 weeks long and compared nabiximols, an oromucosal spray with a plant derived equal (1:1) combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (13 studies), synthetic cannabinoids mimicking THC (7 studies), an oral THC extract of Cannabis sativa (2 studies), inhaled herbal Cannabis (1 study) against placebo. One study compared dronabinol, THC extract of Cannabis sativa and placebo, one compared inhaled herbal Cannabis, dronabinol and placebo. We identified eight ongoing studies. Critical outcomes • Spasticity: nabiximols probably increases the number of people who report an important reduction of perceived severity of spasticity compared with placebo (odds ratio (OR) 2.51, 95% confidence interval (CI) 1.56 to 4.04; 5 RCTs, 1143 participants; I. Compared with placebo, nabiximols probably reduces the severity of spasticity in the short-term in people with MS. We are uncertain about the effect on chronic neurological pain and health-related quality of life. Cannabinoids may increase slightly treatment discontinuation due to AEs, nervous system and psychiatric disorders compared with placebo. We are uncertain about the effect on drug tolerance. The overall certainty of evidence is limited by short-term duration of the included studies.

Topics: Activities of Daily Living; Adolescent; Adult; Analgesics; Cannabinoids; Cannabis; Chronic Pain; Dronabinol; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Neuralgia; Plant Extracts; Quality of Life; Young Adult

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Topics: Alzheimer Disease; Analgesics; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Glaucoma; Humans; Multiple Sclerosis; Parkinson Disease; Proteome; Proteomics; Schizophrenia

Although the recreational cannabis use is expressive worldwide, the literature about medical potential of cannabis extracts, including its anti-inflammatory properties, remains inconclusive.. We screened all articles, published on the PubMed database, on inflammatory mediators and any information about cannabis use from 1980 to March 2019.. Six studies were included, and the main findings were as follows: (i) among healthy volunteers and cannabis users, cannabinoids seemed to decrease the inflammatory response, thus decreasing the immune response, which led to a higher risk of infections; (ii) among patients with multiple sclerosis, cannabinoids seemed to have little impact on the inflammatory markers' levels.. Although cannabis use can produce immune inflammatory suppression in healthy people, this effect is not robust enough to change inflammatory mediators' levels in situations of highly dysfunctional inflammatory activation. Nevertheless, the impact of cannabinoids in clinical outcomes of these conditions remains to be determined.

Topics: Analgesics; Cannabis; Humans; Inflammation Mediators; Multiple Sclerosis

A growing body of preclinical evidence indicates that certain cannabinoids, including cannabidiol (CBD) and synthetic derivatives, may play a role in the myelinating processes and are promising small molecules to be developed as drug candidates for management of demyelinating diseases such as multiple sclerosis (MS), stroke and traumatic brain injury (TBI), which are three of the most prevalent demyelinating disorders. Thanks to the properties described for CBD and its interesting profile in humans, both the phytocannabinoid and derivatives could be considered as potential candidates for clinical use. In this review we will summarize current advances in the use of CBD and other cannabinoids as future potential treatments. While new research is accelerating the process for the generation of novel drug candidates and identification of druggable targets, the collaboration of key players such as basic researchers, clinicians and pharmaceutical companies is required to bring novel therapies to the patients.

Topics: Brain Injuries, Traumatic; Cannabidiol; Cannabinoids; Cannabis; Demyelinating Diseases; Humans; Multiple Sclerosis; Stroke

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Cannabidiol; Cannabinoids; Cannabis; Cartilage Diseases; Cytokines; Diabetes Mellitus, Type 1; Dronabinol; Humans; Immunomodulation; Lupus Erythematosus, Systemic; Mice; Multiple Sclerosis; Th17 Cells

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

Cannabis has been used for thousands of years in many cultures for the treatment of several ailments including pain. The benefits of cannabis are mediated largely by cannabinoids, the most prominent of which are tetrahydrocannabinol (THC) and cannabidiol (CBD). As such, THC and/or CBD have been investigated in clinical studies for the treatment of many conditions including neuropathic pain and acute or chronic inflammation. While a plethora of studies have examined the biochemical effects of purified THC and/or CBD, only a few have focused on the effects of full-spectrum cannabis plant extract. Accordingly, studies using purified THC or CBD may not accurately reflect the potential health benefits of full-spectrum cannabis extracts. Indeed, the cannabis plant produces a wide range of cannabinoids, terpenes, flavonoids, and other bioactive molecules which are likely to contribute to the different biological effects. The presence of all these bioactive molecules in cannabis extracts has garnered much attention of late especially with regard to their potential role in the treatment of neuropathic pain associated with multiple sclerosis.. Literature review was performed to further understand the effect of clinically used full-spectrum cannabis extract in patients with multiple sclerosis.. Herein, the current knowledge about the potential beneficial effects of existing products of full-spectrum cannabis extract in clinical studies involving patients with multiple sclerosis is extensively reviewed. In addition, the possible adverse effects associated with cannabis use is discussed along with how the method of extraction and the delivery mechanisms of different cannabis extracts contribute to the pharmacokinetic and biological effects of full-spectrum cannabis extracts.Herein, the current knowledge about the potential beneficial effects of existing products of full-spectrum cannabis extract in clinical studies involving patients with multiple sclerosis is extensively reviewed. In addition, the possible adverse effects associated with cannabis use is discussed along with how the method of extraction and the delivery mechanisms of different cannabis extracts contribute to the pharmacokinetic and biological effects of full-spectrum cannabis extracts.

Topics: Analgesics; Anti-Inflammatory Agents; Cannabinoids; Cannabis; Humans; Multiple Sclerosis; Neuralgia; Plant Extracts

Despite the fact that the risk versus benefit of smoking cannabis has not been extensively studied, many individuals with multiple sclerosis are smoking cannabis to reduce their pain intensity and spasticity. The lack of information about inhaled cannabis might be attributed to the fact that most trials focus on orally administered cannabis. Given the fact that the administration of cannabis via inhalation is known to rapidly deliver cannabinoids with a higher total bioavailability than what can be achieved through oral or buccal routes, it is important to understand the clinical trials conducted using smoked cannabis on patients with multiple sclerosis.. We sought to discuss the relevant literature about the safety and efficacy of smoked cannabis in multiple sclerosis patients in order to further understand the risks and benefits of this potential therapy for this patient population.. The current knowledge about the potential effects of smoked cannabis on treating neuropathic pain associated with multiple sclerosis is reviewed. In addition, we discuss the possible adverse effects associated with smoking cannabis and we suggest safer as well as new effective inhaled cannabis formulations for the treatment of neuropathic pain associated with multiple sclerosis.

Topics: Administration, Inhalation; Cannabis; Cognitive Dysfunction; Humans; Marijuana Smoking; Medical Marijuana; Multiple Sclerosis; Neuralgia

Cannabis ( Cannabis sativa) is the most widely used illicit drug in the world, with an estimated 192 million users globally. The main psychoactive component of cannabis is (-)- trans-Δ

Topics: Cannabis; Chronic Pain; Dronabinol; Humans; Medical Marijuana; Multiple Sclerosis; Nausea

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

In recent years, the media and scientists have shown increased interest in cannabis-based drugs.. Background information about cannabis-based drugs and their mechanism of action as well as discussion of possible applications as supportive therapy or in palliative medicine, respectively, are presented.. The recent literature was examined and evaluated.. In many medical fields, we do not have sufficient evidence for the efficacy of cannabinoids. In German pharmaceutical legislation, the use of nabiximols for the treatment of intermediate to severe, therapy-resistant spasticity in multiple sclerosis is the only approved indication for cannabis-based drugs. Furthermore, in view of the current evidence cannabinoids, combined with established treatments and as part of an individual therapeutic attempt, can be used for neuropathic pain, cancer-associated pain and human immunodeficiency virus (HIV)-related cachexia.. In most cases, today's assessment of cannabinoids relies on studies that are classified as low evidence. Therefore, further studies which involve more participants and evaluate long-term effects are needed.

Topics: Cannabinoids; Cannabis; Humans; Medical Marijuana; Multiple Sclerosis

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

Topics: Cannabinoids; Cannabis; Endocannabinoids; Humans; Medical Marijuana; Multiple Sclerosis; Neurons; Phytotherapy

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

Although extracts from the cannabis plant have been used medicinally for thousands of years, it is only within the last 2 decades that our understanding of cannabinoid physiology and the provision of evidence for therapeutic benefit of cannabinoids has begun to accumulate. This review provides a background to advances in our understanding of cannabinoid receptors and the endocannabinoid system, and then considers how cannabinoids may help in the management of multiple sclerosis (MS). The relative paucity of treatments for MS-related symptoms has led to experimentation by patients with MS in a number of areas including the use of cannabis extracts. An increasing amount of evidence is now emerging to confirm anecdotal reports of symptomatic improvement, particularly for muscle stiffness and spasms, neuropathic pain and sleep and bladder disturbance, in patients with MS treated with cannabinoids. Trials evaluating a role in treating other symptoms such as tremor and nystagmus have not demonstrated any beneficial effects of cannabinoids. Safety profiles of cannabinoids seem acceptable, although a slow prolonged period of titration improves tolerability. No serious safety concerns have emerged. Methodological issues in trial design and treatment delivery are now being addressed. In addition, recent experimental evidence is beginning to suggest an effect of cannabinoids on more fundamental processes important in MS, with evidence of anti-inflammation, encouragement of remyelination and neuroprotection. Trials are currently under way to test whether cannabinoids may have a longer term role in reducing disability and progression in MS, in addition to symptom amelioration, where indications are being established.

Topics: Animals; Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Clinical Trials as Topic; Humans; Multiple Sclerosis; Receptors, Cannabinoid

For some years a mixture of anecdotal report and data from animal models have implied a potential role for cannabis-based medicines in ameliorating a variety of symptoms of multiple sclerosis. Only recently however have large randomised controlled trials (RCTs) examined these potential effects rigorously. At present the results of RCTs have lacked a coherent message to the prescribing clinician and reasons for such heterogeneity in cannabinoid trials are discussed.

Topics: Cannabinoids; Cannabis; Humans; Multiple Sclerosis; Phytotherapy; Randomized Controlled Trials as Topic

Cannabis therapy has been considered an effective treatment for spasticity, although clinical reports of symptom reduction in multiple sclerosis (MS) describe mixed outcomes. Recently introduced therapies of combined Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts have potential for symptom relief with the possibility of reducing intoxication and other side effects. Although several past reviews have suggested that cannabinoid therapy provides a therapeutic benefit for symptoms of MS, none have presented a methodical investigation of newer cannabinoid treatments in MS-related spasticity. The purpose of the present review was to systematically evaluate the effectiveness of combined THC and CBD extracts on MS-related spasticity in order to increase understanding of the treatment's potential effectiveness, safety and limitations.. We reviewed MEDLINE/PubMed, Ovid, and CENTRAL electronic databases for relevant studies using randomized controlled trials. Studies were included only if a combination of THC and CBD extracts was used, and if pre- and post-treatment assessments of spasticity were reported.. Six studies were systematically reviewed for treatment dosage and duration, objective and subjective measures of spasticity, and reports of adverse events. Although there was variation in the outcome measures reported in these studies, a trend of reduced spasticity in treated patients was noted. Adverse events were reported in each study, however combined TCH and CBD extracts were generally considered to be well-tolerated.. We found evidence that combined THC and CBD extracts may provide therapeutic benefit for MS spasticity symptoms. Although some objective measures of spasticity noted improvement trends, there were no changes found to be significant in post-treatment assessments. However, subjective assessment of symptom relief did often show significant improvement post-treatment. Differences in assessment measures, reports of adverse events, and dosage levels are discussed.

Topics: Cannabis; Humans; Multiple Sclerosis; Muscle Spasticity; Phytotherapy; Plant Extracts

Topics: Cannabis; Complementary Therapies; Dietary Supplements; Electromagnetic Fields; Humans; Multiple Sclerosis; Physical Therapy Modalities; Phytotherapy

Multiple sclerosis (MS) is a neurodegenerative disease that is characterised by repeated inflammatory/demyelinating events within the central nervous system (CNS). In addition to relapsing-remitting neurological insults, leading to loss of function, patients are often left with residual, troublesome symptoms such as spasticity and pain. These greatly diminish "quality of life" and have prompted some patients to self-medicate with and perceive benefit from cannabis. Recent advances in cannabinoid biology are beginning to support these anecdotal observations, notably the demonstration that spasticity is tonically regulated by the endogenous cannabinoid system. Recent clinical trials may indeed suggest that cannabis has some potential to relieve, pain, spasms and spasticity in MS. However, because the CB(1) cannabinoid receptor mediates both the positive and adverse effects of cannabis, therapy will invariably be associated with some unwanted, psychoactive effects. In an experimental model of MS, and in MS tissue, there are local perturbations of the endocannabinoid system in lesional areas. Stimulation of endocannabinoid activity in these areas either through increase of synthesis or inhibition of endocannabinoid degradation offers the positive therapeutic potential of the cannabinoid system whilst limiting adverse events by locally targeting the lesion. In addition, CB(1) and CB(2) cannabinoid receptor stimulation may also have anti-inflammatory and neuroprotective potential as the endocannabinoid system controls the level of neurodegeneration that occurs as a result of the inflammatory insults. Therefore cannabinoids may not only offer symptom control but may also slow the neurodegenerative disease progression that ultimately leads to the accumulation of disability.

Topics: Animals; Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Clinical Trials as Topic; Disease Models, Animal; Endocannabinoids; Humans; Multiple Sclerosis; Quality of Life; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2

Disabling tremor or ataxia is common in multiple sclerosis (MS) and up to 80% of patients experience tremor or ataxia at some point during their disease. A variety of treatments are available, ranging from pharmacotherapy or stereotactic neurosurgery to neurorehabilitation.. To assess the efficacy and tolerability of both pharmacological and non-pharmacologic treatments of ataxia in patients with MS.. The following electronic resources were searched: Cochrane MS Group trials register (June 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2006), National Health Service National Research Register (NRR) including the Medical Research Council Clinical Trials Directory (Issue 2, 2006), MEDLINE (January 1996 to June 2006), and EMBASE (Jan 1988 to June 2006). Manual searches of bibliographies of relevant articles, pertinent medical and neurology journals and abstract books of major neurology and MS conferences (2001-2006) were also performed. Direct communication with experts and drug companies was sought.. Blinded, randomised trials which were either placebo-controlled or which compared two or more treatments were included. Trials testing pharmacological agents must have had both participant and assessor blinding. Trials testing surgical interventions or effects of physiotherapy, where participants could not have been blinded to the treatment, must have had independent assessors who were blinded to the treatment. Cross-over trials were included.. Three independent reviewers extracted data and the findings of the trials were summarised. A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed.. Ten randomised controlled trials met the inclusion criteria. Six placebo-controlled studies (pharmacotherapy) and four comparative studies (one stereotactic neurosurgery and three neurorehabilitation) were reviewed. No standardised outcome measures were used across the studies. In general, pharmacotherapies were unrewarding and data on neurosurgery or rehabilitation is insufficient to lead to a change in practice.. The absolute and comparative efficacy and tolerability of pharmacotherapies to treat ataxia in MS are poorly documented and no recommendations can be made to guide prescribing. Although studies on neurosurgery and neurorehabilitation showed promising results, the absolute indications for treating with those methods cannot be developed. Standardised, well validated measures of ataxia and tremor need to be developed and employed in larger randomised controlled trials with careful blinding.

Topics: Ataxia; Baclofen; Cannabis; Humans; Multiple Sclerosis; Muscle Relaxants, Central; Phytotherapy; Randomized Controlled Trials as Topic; Thalamus

Despite effective conventional therapies for multiple sclerosis (MS), many people with MS explore complementary and alternative medicine (CAM) therapies for their symptoms. Common CAM therapies that people use include dietary modification, nutritional and herbal supplementation, and mind-body therapies. There is a revival of interest among MS researchers about the therapeutic potential of low-fat diet and essential fatty acid supplementation in MS. The efficacy of specific vitamin supplementation remains unclear. Recently, cannabis and yoga have been studied in more controlled studies and have provided evidence that they may have some benefit. The research on CAM therapies in MS is still exploratory, but considering peoples' interest and common use of these therapies, further research in this area is clearly warranted.

Topics: Bee Venoms; Cannabis; Complementary Therapies; Diet; Dietary Supplements; Ginkgo biloba; Humans; Multiple Sclerosis; Plant Preparations; Risk Factors; Treatment Outcome; Yoga

Most MS patients use unconventional therapies, usually as complementary measures in addition to the conventional treatment. Only a few adequate clinical trials exist in this field. By definition, the efficacy of these therapies is unproven. Moreover, the possible risks are also largely unknown. Some therapies rely on rational pathophysiological considerations, other must be regarded as potentially harmful. The influence of diet on MS is unproven. Possibly, unsaturated fatty acids are beneficial. However, a few randomized trials yielded inconclusive results. Long-term supplementation of Vitamin D is associated with a decreased MS incidence. There is, however, insufficient evidence for an influence of Vitamin D on the course of the disease. Because of the high prevalence of osteoporosis in MS patients, prophylaxis with Vitamin D and Calcium is widely accepted. The effects of various minerals, selenium, antioxidant compounds, fish oil or vitamins remain speculative. Many patients use cannabis to alleviate spasticity and pain. Small series indicated positive effects, but randomized trials were negative for spasticity. However, many patients report subjective improvement under cannabis even if their objective parameters remain unchanged. Hyperbaric oxygenation was the subject of several small studies with heterogeneous results which, overall, do not support its use. Generally, physical therapies are perceived as an established therapy for MS. Short-term effects are probable, whereas the possible favourable long-term effects are unclear.

Topics: Cannabis; Complementary Therapies; Dietary Supplements; Fatty Acids, Omega-3; Humans; Hyperbaric Oxygenation; Multiple Sclerosis; Physical Therapy Modalities; Phytotherapy; Vitamins

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

An increasing body of evidence suggests that cannabinoids have beneficial effects on the symptoms of multiple sclerosis, including spasticity and pain. Endogenous molecules with cannabinoid-like activity, such as the "endocannabinoids", have been shown to mimic the anti-inflammatory properties of cannabinoids through the cannabinoid receptors. Several studies suggest that cannabinoids and endocannabinoids may have a key role in the pathogenesis and therapy of multiple sclerosis. Indeed, they can down regulate the production of pathogenic T helper 1-associated cytokines enhancing the production of T helper 2-associated protective cytokines. A shift towards T helper 2 has been associated with therapeutic benefit in multiple sclerosis. In addition, cannabinoids exert a neuromodulatory effect on neurotransmitters and hormones involved in the neurodegenerative phase of the disease. In vivo studies using mice with experimental allergic encephalomyelitis, an animal model of multiple sclerosis, suggest that the increase of the circulating levels of endocannabinoids might have a therapeutic effect, and that agonists of endocannabinoids with low psychoactive effects could open new strategies for the treatment of multiple sclerosis.

Topics: Animals; Autoimmune Diseases of the Nervous System; Cannabinoid Receptor Modulators; Cannabis; Central Nervous System Diseases; Endocannabinoids; Humans; Multiple Sclerosis

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

Topics: Cannabis; Humans; Multiple Sclerosis; Muscle Spasticity; Plants, Medicinal; Randomized Controlled Trials as Topic

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

Although cannabis has been used as a medicine for several centuries, the therapeutic properties of cannabis preparations (essentially haschich and marijuana) make them far most popular as a recreational drugs.. Scientific studies on the effects of cannabis were advanced considerably by the identification in 1964 of cannabinoid D9-tetrahydrocannadinol (THC), recognized as the major active constituent of cannabis. Cloning of the centrally located CB1 receptor in 1990 and the identification of the first endogenous ligand of the CB1 receptor, anandamide, in 1992 further advanced our knowledge.. Progress has incited further research on the biochemistry and pharmacology of the cannabinoids in numerous diseases of the central nervous system. In the laboratory animal, cannabinoids have demonstrated potential in motion disorders, demyelinizing disease, epilepsy, and as anti-tumor and neuroprotector agents. Several clinical studies are currently in progress, but therapeutic use of cannabinoids in humans couls be hindered by undesirable effects, particularly psychotropic effects. CB1 receptor antagonists also have interesting therapeutic potential.

Topics: Amidohydrolases; Calcium Channels; Cannabis; Humans; Huntington Disease; Multiple Sclerosis; Neuroprotective Agents; Parkinson Disease; Phytotherapy; Protein-Tyrosine Kinases; Receptor, Cannabinoid, CB1; Tourette Syndrome

Multiple sclerosis is a common human demyelinating disease of the central nervous system (CNS), and it is thought to involve autoimmune responses to CNS myelin antigens. Current symptomatic therapies for multiple sclerosis are in some cases ineffective and may have a high risk of serious side effects. This has led some multiple sclerosis patients to self-medicate with cannabis, which anecdotal evidence suggests may be beneficial in controlling symptoms such as spasticity, pain, tremor and bladder dysfunction. In support of these claims, results from experimental studies have suggested that cannabinoid-based treatments may be beneficial in a wide number of diseases. Furthermore, recent research in animal models of multiple sclerosis has demonstrated the efficacy of cannabinoids in controlling disease-induced symptoms such as spasticity and tremor, as well as in ameliorating the severity of clinical disease. However, these initially promising results have not yet been fully translated into the clinic. Although cannabinoid treatment of multiple sclerosis symptoms has been shown to be both well tolerated and effective in a number of subjective tests in several small-scale clinical trials, objective measures demonstrating the efficacy of cannabinoids are still lacking. Currently, a number of large-scale phase III clinical trials are under way to further elucidate the use of cannabinoids in the symptomatic treatment of multiple sclerosis. This review highlights the recent advances in our understanding of the endocannabinoid system, discusses both the experimental and clinical evidence for the use of cannabinoids to treat multiple sclerosis and explores possible future strategies of cannabinoid therapy in multiple sclerosis.

Topics: Animals; Cannabinoids; Cannabis; Clinical Trials, Phase III as Topic; Cross-Over Studies; Double-Blind Method; Humans; Japan; Multicenter Studies as Topic; Multiple Sclerosis; Phytotherapy; Randomized Controlled Trials as Topic; Receptors, Cannabinoid

There has been renewed interest in the therapeutic applications of cannabis, and people, particularly those with multiple sclerosis, claim that it may offer benefit in symptom control. Cannabis exerts many of its effects because it taps into an endogenous cannabinoid system. Recent advances have begun to shine light on the biology of this system and may support some of the anecdotal medical claims. The problem with cannabis as a drug is that both the positive and negative aspects are largely the work of the same receptor. However, it may be possible to avoid these through modulation of the endogenous system. Cannabinoids provide a novel therapeutic target, not only for controlling symptoms, but also slowing disease progression through inhibition of neurodegeneration, which is the cause of accumulating irreversible disability.

Topics: Animals; Cannabinoids; Cannabis; Humans; Multiple Sclerosis; Receptors, Cannabinoid; Receptors, Drug

This review gives insight into the potential therapeutical role of cannabinoids in neurology. Preclinical data are presented which could give a rationale for the clinical use of cannabinoids in the fields of multiple sclerosis, spasticity, epilepsy, movement disorders, and neuroprotection after traumatic head injury or ischemic stroke. Besides, clinical data (case reports, open-label and randomised controlled studies) dealing with the therapeutical use of cannabinoids in these fields are reported and discussed. At present, clinical data are insufficient to recommend the use of cannabinoids in any neurological disease as standard therapy. Several questions still have to be answered (which cannabinoid? which way of administration? stimulation of endogenous cannabinoids? separation between desired and undesired effects?), and controlled studies are still needed to clarify the potential therapeutical role of cannabinoids in neurology.

Topics: Analgesics; Cannabinoids; Cannabis; Clinical Trials as Topic; Humans; Multiple Sclerosis; Nervous System Diseases; Pain Management; Parkinsonian Disorders; Phytotherapy

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

There is a growing amount of evidence to suggest that cannabis and individual cannabinoids may be effective in suppressing certain symptoms of multiple sclerosis and spinal cord injury, including spasticity and pain. Anecdotal evidence is to be found in newspaper reports and also in responses to questionnaires. Clinical evidence comes from trials, albeit with rather small numbers of patients. These trials have shown that cannabis, Delta(9)-tetrahydrocannabinol, and nabilone can produce objective and/or subjective relief from spasticity, pain, tremor, and nocturia in patients with multiple sclerosis (8 trials) or spinal cord injury (1 trial). The clinical evidence is supported by results from experiments with animal models of multiple sclerosis. Some of these experiments, performed with mice with chronic relapsing experimental allergic encephalomyelitis (CREAE), have provided strong evidence that cannabinoid-induced reductions in tremor and spasticity are mediated by cannabinoid receptors, both CB(1) and CB(2). Endocannabinoid concentrations are elevated in the brains and spinal cords of CREAE mice with spasticity, and in line with this observation, spasticity exhibited by CREAE mice can be ameliorated by inhibitors of endocannabinoid membrane transport or enzymic hydrolysis. Research is now needed to establish whether increased endocannabinoid production occurs in multiple sclerosis. Future research should also be directed at obtaining more conclusive evidence about the efficacy of cannabis or individual cannabinoids against the signs and symptoms of these disorders, at devising better modes of administration for cannabinoids and at exploring strategies that maximize separation between the sought-after therapeutic effects and the unwanted effects of these drugs.

Topics: Animals; Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Clinical Trials as Topic; Dronabinol; Humans; Multiple Sclerosis

Review commissioned in 1996 by the Department of Health (DOH).. Assess therapeutic profile of cannabis and cannabinoids.. Medline search, references supplied by DOH and others, and personal communications.. Cannabis and some cannabinoids are effective anti-emetics and analgesics and reduce intra-ocular pressure. There is evidence of symptom relief and improved well-being in selected neurological conditions, AIDS and certain cancers. Cannabinoids may reduce anxiety and improve sleep. Anticonvulsant activity requires clarification. Other properties identified by basic research await evaluation. Standard treatments for many relevant disorders are unsatisfactory. Cannabis is safe in overdose but often produces unwanted effects, typically sedation, intoxication, clumsiness, dizziness, dry mouth, lowered blood pressure or increased heart rate. The discovery of specific receptors and natural ligands may lead to drug developments. Research is needed to optimise dose and route of administration, quantify therapeutic and adverse effects, and examine interactions.

Topics: Analgesics, Non-Narcotic; Appetite; Cannabinoids; Cannabis; Epilepsy; Government Agencies; Humans; Legislation, Drug; Male; Multiple Sclerosis; Nausea; Phytotherapy; United Kingdom

The use of crude marijuana for herbal medicinal applications is now being widely discussed in both the medical and lay literature. Ballot initiatives in California and Arizona have recently made crude marijuana accessible to patients under certain circumstances. As medicinal applications of pure forms of delta-9-tetrahydrocannabinol (THC) and crude marijuana are being considered, the most promising uses of any form of THC are to counteract the nausea associated with cancer chemotherapy and to stimulate appetite. We evaluated the relevant research published between 1975 and 1996 on the medical applications, physical complications, and legal precedents for the use of pure THC or crude marijuana. Our review focused on the medical use of THC derivatives for nausea associated with cancer chemotherapy, glaucoma, stimulation of appetite, and spinal cord spasticity. Despite the toxicity of THC delivered in any form, evidence supports the selective use of pure THC preparations to treat nausea associated with cancer chemotherapy and to stimulate appetite. The evidence does not support the reclassification of crude marijuana as a prescribable medicine.

Topics: Appetite Stimulants; Cannabis; Dronabinol; Glaucoma; Humans; Multiple Sclerosis; Muscle Spasticity; Nausea; Neoplasms

The effect of nutrition and dietary supplements as environmental factors has been suggested as possible factors affecting both disease risk and progression in on the course of multiple sclerosis with complex genetic-risk profiles. This study was aimed to assess regulation of surface-membrane enzymes such as Delta-6-desaturase (FADS2), secretory Phospholipase A2(sPLA2) by hemp seed and evening primrose oils as well as Hot-natured dietary intervention in relapsing remitting multiple sclerosis (RRMS) patients.. In this double blind, randomized trial, 100 RRMS patients with Extended disability status score (EDSS)<6 were allocated into 3 groups: "Group A" who received co-supplemented hemp seed and evening primrose oils along with advised Hot nature diet; "Group B", who received olive oil; "Group C", who received the co-supplemented oils. Clinically EDSS and functional score as well as biochemical parameters [blood cells polyunsaturated fatty acid (PUFA), FADS2, sPLA2] were assessed at baseline and after 6 months.. Mean follow-up was 180±2.9SD days (N=65, 23 M and 42 F aged 34.25±8.07 years with disease duration 6.80±4.33 years). There was no significant difference in studies parameters at baseline. After 6 months, significant improvements in EDSS and functional score were found in the groups A and C while EDSS and pyramidal score showed significant increase in group B. Alteration of biochemical parameters showed improvement in groups A and C whereas there was worsening condition for group B after the intervention.. The co-supplemented hemp seed and evening primrose oils with Hot nature diet can have beneficial effects in improving clinical symptoms and signs in RRMS patients which were confirmed by regulation of surface-membrane enzymes.

Topics: Adult; Cannabis; Double-Blind Method; Fatty Acid Desaturases; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Multiple Sclerosis; Oenothera biennis; Phospholipases A2, Secretory; Plant Oils; Seeds

It is unknown whether diets with a high dietary total antioxidant capacity (TAC) can modify oxidative stress, low-grade inflammation, or liver dysfunction, all of which are risk factors for multiple sclerosis disease. This study assesses alanine amino-transferase (ALT), aspartate-aminotransferase (AST) and gamma-glutamyl transferase (GGT) activities in MS patients treated with co-supplemented hemp seed and evening primrose oils as well as Hot-nature diet and the therapeutic potential this intervention.. In this double blind, randomized trial, 100 MS patients with EDSS<6 were allocated into 3 groups: "group A", who received co-supplemented hemp seed and evening primrose oils with advised Hot-nature diet; "group B",who received olive oil; and "group C", who received the co-supplemented oils. Clinically, EDSS as well as serum level of liver enzymes (GGT, AST, and ALT) were assessed at baseline and after 6 months.. Mean follow-up was 180±2.9 SD days (N=65, 23 M and 42 F aged 34.25±8.07 years with disease duration of 6.80±4.33 years). There was no significant difference in the study parameters at baseline. Serum levels of liver enzymes (GGT, AST, and ALT) were serially monitored. Intervention was associated with liver function alteration in three groups. Significance decreased in EDSS score and the levels of liver enzymes were found in groups A and C, whereas elevated serum liver enzymes and EDSS score were observed in group B after the intervention.. Selecting foods according to their Total antioxidant capacity such as co-supplemented hemp seed and evening primrose oils with Hot-nature diet affects antioxidant intake and can have beneficial effects on improving EDSS score and activity of liver enzymes in RRMS patients.

Topics: Adolescent; Adult; Cannabis; Double-Blind Method; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Liver; Male; Middle Aged; Multiple Sclerosis; Oenothera biennis; Plant Oils; Seeds; Young Adult

Multiple sclerosis (MS) is the most chronic and inflammatory disorder. Because of limited efficacy and adverse side effects, identifying novel therapeutic and protective agents is important. This study was aimed to assess the potential therapeutic effects of hemp seed and evening primrose oils as well as Hot-nature dietary intervention on RRMS patients.. In this double blind, randomized trial, 100 MS patients with EDSS<6 were allocated into 3 groups: "Group A" who received co-supplemented hemp seed and evening primrose oils with advised Hot-nature diet, "Group B" who received olive oil, "Group C" who received the co-supplemented oils. Mizadj, clinically EDSS and relapse rate as well as immunological factors (IL-4, IFN-γ and IL-17) were assessed at baseline and after 6 months.. Mean follow-up was 180±2.9 SD days (N=65, 23 M and 42 F aged 34.25±8.07 years with disease duration 6.80±4.33 years). There was no significant difference in studies parameters at baseline. After 6 months, significant improvements in Mizadj, EDSS and relapse rate were found in the groups A and C, while the group B showed a border significant decrease in relapse rate. Immunological parameters showed improvement in groups A and C, whereas there was worsening condition for group B after the intervention.. The co-supplemented hemp seed and evening primrose oils with Hot-nature diet have beneficial effects in improving of clinical score in RRMS patients which were confirmed by immunological findings.

Topics: Adult; Cannabis; Cytokines; Diet; Double-Blind Method; Fatty Acids, Unsaturated; Female; Humans; Inflammation; Iran; Male; Medicine, Traditional; Metabolic Networks and Pathways; Multiple Sclerosis; Oenothera biennis; Phytotherapy; Plant Extracts; Plant Oils; Seeds

Spasticity is a common and poorly controlled symptom of multiple sclerosis. Our objective was to determine the short-term effect of smoked cannabis on this symptom.. We conducted a placebo-controlled, crossover trial involving adult patients with multiple sclerosis and spasticity. We recruited participants from a regional clinic or by referral from specialists. We randomly assigned participants to either the intervention (smoked cannabis, once daily for three days) or control (identical placebo cigarettes, once daily for three days). Each participant was assessed daily before and after treatment. After a washout interval of 11 days, participants crossed over to the opposite group. Our primary outcome was change in spasticity as measured by patient score on the modified Ashworth scale. Our secondary outcomes included patients' perception of pain (as measured using a visual analogue scale), a timed walk and changes in cognitive function (as measured by patient performance on the Paced Auditory Serial Addition Test), in addition to ratings of fatigue.. Thirty-seven participants were randomized at the start of the study, 30 of whom completed the trial. Treatment with smoked cannabis resulted in a reduction in patient scores on the modified Ashworth scale by an average of 2.74 points more than placebo (p < 0.0001). In addition, treatment reduced pain scores on a visual analogue scale by an average of 5.28 points more than placebo (p = 0.008). Scores for the timed walk did not differ significantly between treatment and placebo (p = 0.2). Scores on the Paced Auditory Serial Addition Test decreased by 8.67 points more with treatment than with placebo (p = 0.003). No serious adverse events occurred during the trial.. Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity. Future studies should examine whether different doses can result in similar beneficial effects with less cognitive impact.

Topics: Adult; Cannabis; Cognition; Cross-Over Studies; Fatigue; Female; Humans; Male; Marijuana Smoking; Middle Aged; Multiple Sclerosis; Muscle Spasticity; Musculoskeletal Pain; Phytotherapy; Plant Preparations; Treatment Outcome; Walking

Pain, spasticity, tremor, spasms, poor sleep quality, and bladder and bowel dysfunction, among other symptoms, contribute significantly to the disability and impaired quality of life of many patients with multiple sclerosis (MS). Motor symptoms referable to the basal ganglia, especially paroxysmal dystonia, occur rarely and contribute to the experience of distress. A substantial percentage of patients with MS report subjective benefit from what is often illicit abuse of extracts of the Cannabis sativa plant; the main cannabinoids include delta-9-tetrahydrocannabinol (delta9-THC) and cannabidiol. Clinical trials of cannabis plant extracts and synthetic delta9-THC provide support for therapeutic benefit on at least some patient self-report measures. An illustrative case is presented of a 52-year-old woman with MS, paroxysmal dystonia, complex vocal tics, and marijuana dependence. The patient was started on an empirical trial of dronabinol, an encapsulated form of synthetic delta9-THC that is usually prescribed as an adjunctive medication for patients undergoing cancer chemotherapy. The patient reported a dramatic reduction of craving and illicit use; she did not experience the "high" on the prescribed medication. She also reported an improvement in the quality of her sleep with diminished awakenings during the night, decreased vocalizations, and the tension associated with their emission, decreased anxiety and a decreased frequency of paroxysmal dystonia.

Topics: Adult; Cannabis; Dronabinol; Female; Hallucinogens; Humans; Male; Marijuana Abuse; Multiple Sclerosis; Nocturnal Paroxysmal Dystonia; Phytotherapy; Tics

Cannabinoids have been suggested as possessing immunomodulatory properties, and cannabinoid receptors are present on leucocytes. Clinically, there is some evidence that cannabinoids may be therapeutically useful in treating multiple sclerosis, which is generally believed to be an autoimmune condition. This paper reports data derived from the Cannabinoids in MS (CAMS) study, which was the largest randomized controlled trial yet conducted to evaluate the therapeutic efficacy of cannabinoids. We found no evidence for cannabinoid influence on serum levels of interferon (IFN)-gamma, interleukin (IL)-10, IL-12 or C-reactive protein as measured using enzyme-linked immunosorbent assay (ELISA), in comparison to control values. Mitogenic stimulation experiments also failed to demonstrate any significant reduction in percentage of CD3+, IFN-gamma producing cells after exposure to cannabinoids in vivo, although numbers were small. Further work is needed to establish the functional significance of cannabinoid receptors on immune cells.

Topics: C-Reactive Protein; Cannabinoids; Cannabis; Cells, Cultured; Cytokines; Double-Blind Method; Dronabinol; Female; Humans; Immunologic Factors; Interferon-gamma; Interleukin-10; Interleukin-12; Male; Middle Aged; Multiple Sclerosis; Phytotherapy; Plant Oils

To test the effectiveness and long term safety of cannabinoids in multiple sclerosis (MS), in a follow up to the main Cannabinoids in Multiple Sclerosis (CAMS) study.. In total, 630 patients with stable MS with muscle spasticity from 33 UK centres were randomised to receive oral Delta(9)-tetrahydrocannabinol (Delta(9)-THC), cannabis extract, or placebo in the main 15 week CAMS study. The primary outcome was change in the Ashworth spasticity scale. Secondary outcomes were the Rivermead Mobility Index, timed 10 metre walk, UK Neurological Disability Score, postal Barthel Index, General Health Questionnaire-30, and a series of nine category rating scales. Following the main study, patients were invited to continue medication, double blinded, for up to 12 months in the follow up study reported here.. Intention to treat analysis of data from the 80% of patients followed up for 12 months showed evidence of a small treatment effect on muscle spasticity as measured by change in Ashworth score from baseline to 12 months (Delta(9)-THC mean reduction 1.82 (n = 154, 95% confidence interval (CI) 0.53 to 3.12), cannabis extract 0.10 (n = 172, 95% CI -0.99 to 1.19), placebo -0.23 (n = 176, 95% CI -1.41 to 0.94); p = 0.04 unadjusted for ambulatory status and centre, p = 0.01 adjusted). There was suggestive evidence for treatment effects of Delta(9)-THC on some aspects of disability. There were no major safety concerns. Overall, patients felt that these drugs were helpful in treating their disease.. These data provide limited evidence for a longer term treatment effect of cannabinoids. A long term placebo controlled study is now needed to establish whether cannabinoids may have a role beyond symptom amelioration in MS.

Topics: Administration, Oral; Adolescent; Adult; Analgesics, Non-Narcotic; Cannabis; Disabled Persons; Double-Blind Method; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Placebos; Plant Extracts; Severity of Illness Index; Treatment Outcome

Disabling tremor is common in patients with multiple sclerosis (MS). Data from animal model experiments and subjective and small objective studies involving patients suggest that cannabis may be an effective treatment for tremor associated with MS. To our knowledge, there are no published double-blind randomized controlled trials of cannabis as a treatment for tremor in MS patients.. The authors conducted a randomized double-blind placebo-controlled crossover trial to examine the effect of oral cannador (cannabis extract) on 14 patients with MS with upper limb tremors. There were eight women and six men, with a mean age of 45 years and mean Expanded Disability Status Scale score of 6.25. Patients were randomly assigned to receive each treatment and the doses escalated over a 2-week period before each assessment. The primary outcome was change on a tremor index, measured using a validated tremor rating scale. The study was powered to detect a functionally significant 50% improvement in the tremor index. Secondary outcomes included accelerometry, an ataxia scale, spiral drawing, finger tapping, and nine-hole pegboard test performance.. Analysis of the data showed no significant improvement in any of the objective measures of upper limb tremor with cannabis extract compared to placebo. Finger tapping was faster on placebo compared to cannabis extract (p < 0.02). However, there was a nonsignificant trend for patients to experience more subjective relief from their tremors while on cannabis extract compared to placebo.. Cannabis extract does not produce a functionally significant improvement in MS-associated tremor.

Topics: Administration, Oral; Adult; Cannabis; Cross-Over Studies; Disability Evaluation; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fingers; Humans; Male; Middle Aged; Multiple Sclerosis; Plant Extracts; Psychomotor Performance; Treatment Outcome; Tremor

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

The authors conducted a randomized, double-blind, placebo-controlled, twofold crossover study in 16 patients with MS who presented with severe spasticity to investigate safety, tolerability, and efficacy of oral Delta(9)-Tetrahydrocannabinol (THC) and Cannabis sativa plant extract. Both drugs were safe, but adverse events were more common with plant-extract treatment. Compared with placebo, neither THC nor plant-extract treatment reduced spasticity. Both THC and plant-extract treatment worsened the participant's global impression.

Topics: Administration, Oral; Cannabinoids; Cannabis; Cross-Over Studies; Double-Blind Method; Dronabinol; Health Status; Humans; Middle Aged; Multiple Sclerosis; Muscle Spasticity; Muscle Tonus; Pain Measurement; Plant Extracts; Sample Size; Treatment Outcome

Topics: Cannabinoids; Cannabis; Humans; Multiple Sclerosis

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

Although cannabis has become an increasingly common method for pain management among people with multiple sclerosis (PwMS), there is a dearth of knowledge regarding the types of cannabis products used as well as the characteristics of cannabis users. The current study aimed to (1) describe the prevalence of cannabis use and the routes of administration of cannabis products in adults with an existing chronic pain condition and MS, (2) to examine differences in demographic and disease-related variables between cannabis users and non-users, and (3) to examine differences between cannabis users and non-users in pain-related variables, including pain intensity, pain interference, neuropathic pain, pain medication use, and pain-related coping.. Secondary analysis of baseline data from participants with multiple sclerosis (MS) and chronic pain (N = 242) enrolled in an RCT comparing mindfulness-based cognitive therapy (MBCT), cognitive-behavioral therapy (CBT), and usual care for chronic pain. Statistical methods included t-tests, Mann-Whitney tests, chi-square tests, and Fisher's exact tests to assess for differences in demographic, disease-related, and pain-related variables between cannabis users and non-users.. The current study identified factors that may intersect with cannabis use for pain management and adds to our current knowledge of the types of cannabis products used by PwMS. Future research should continue to investigate trends in cannabis use for pain management, especially as the legality and availability of products continue to shift. Additionally, longitudinal studies are needed to examine the effects of cannabis use on pain-related outcomes over time.

Topics: Adult; Cannabis; Chronic Pain; Humans; Medical Marijuana; Middle Aged; Multiple Sclerosis; Neuralgia

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

The extent of medical cannabis use by people with multiple sclerosis (MS) in Canada has not been evaluated for more than a decade since recreational cannabis was legalized. Legalization provided an avenue for those to whom legal cannabis was previously inaccessible to access it as an alternative therapy. Our objective was to evaluate the prevalence of medical cannabis use by Canadians with MS, the reasons it is used, adverse effects, as well as the context surrounding how it is obtained and where users learned about it.. An anonymous questionnaire was distributed to prospective participants through various channels. The questionnaire included questions about participant characteristics and quality of life, their MS, and their medical cannabis use. It also employed two validated patient-reported outcome measures, the PDDS and the MSQOL-54.. Completed questionnaires were submitted by 344 individuals. Among respondents, 215/344 (64.5%) reported having used medical cannabis at least once, and 180 (52.3%) reported still currently using it. Based on disease and quality of life data, we found that respondents with more severe or progressive forms of MS were more likely to have tried medical cannabis. Medical cannabis was used most by current and former users to treat sleep problems (84.2%), pain (80.0%), and spasticity (68.4%), while the most reported adverse effects were drowsiness (57.2%), feeling quiet/subdued (48.8%), and difficulty concentrating (28.4%). Most current and former users obtained their cannabis from a legal, reliable source (76.1%) and many (74%) learned about medical cannabis from someone other than a healthcare provider.. This study showed that nearly two-thirds of survey respondents, comprised of Canadians living with MS, have tried medical cannabis at least once and that those with a greater disease burden were more likely to have tried it. Users reported that cannabis is moderately to highly effective in treating several symptoms and that adverse effects are not generally severe, nor are they the main factor driving medical cannabis cessation. Our results support the need for more research examining medical cannabis use in MS and for evidence-based resources to be publicly available for those exploring it as a potential therapy.

Topics: Canada; Cannabis; Cross-Sectional Studies; Humans; Medical Marijuana; Multiple Sclerosis; Prospective Studies; Quality of Life

Topics: Cannabis; Humans; Medical Marijuana; Multiple Sclerosis; Muscle Spasticity

Topics: Analgesics; Cannabis; Humans; Multiple Sclerosis; Surveys and Questionnaires

The use of cannabis as medical therapy to treat chronic pain and spasticity in patients with multiple sclerosis (MS) is increasing. However, the evidence on safety when initiating treatment with medical cannabis oils is limited. The aim of this study was to investigate the safety of sublingual medical cannabis oils in patients with MS.. In this prospective observational safety study 28 patients with MS were treated with medical cannabis oils (THC-rich, CBD-rich and THC+CBD combined products) and were followed during a titration period of four weeks. Patients were evaluated at treatment start (Visit 1) and after four weeks treatment (Visit 2). At each visit neurological examination (Expanded Disability Status Scale - EDSS), ambulation (Timed 25-Foot Walk Test - T25FWT), routine blood tests, plasma cannabinoids, dexterity (9-Hole Peg Test - 9-HPT) and processing speed (Symbol Digit Modalities Test - SDMT) were tested. Adverse events (AEs) and tolerability were reported at Visit 2. Secondary, efficacy of medical cannabis on pain, spasticity and sleep disturbances were measured by numeric rating scale (NRS-11) each day during the 4-week treatment period.. During treatment with cannabis preparations containing 10-25 mg/mL THC, the most common AEs were dry mouth, drowsiness, dizziness and nausea of mild to moderate degree. Two patients experienced pronounced symptoms with excessive dreaming and drowsiness, respectively, which led to treatment stop during the titration. Three serious adverse events (SAE) were reported but were not associated with the treatment. Mean doses of THC and CBD were 4.0 mg and 7.0 mg, respectively, and primarily administered as a once-daily evening dose. Furthermore, pain decreased from a median NRS score of 7 to 4, (p = 0.01), spasticity decreased from a median NRS score of 6 to 2.5 (p = 0.01) and sleep disturbances decreased from a median NRS score of 7 to 3 (p < 0.001). No impairment in disability, ambulation, dexterity or processing speed was observed.. Treatment with medical cannabis oils was safe and well tolerated, and resulted in a reduction in pain intensity, spasticity and sleep disturbances in MS patients. This suggests that medical cannabis oils can be used safely, especially at relatively low doses and with slow titration, as an alternative to treat MS-related symptoms when conventional therapy is inadequate.

Topics: Cannabidiol; Cannabis; Dronabinol; Humans; Medical Marijuana; Multiple Sclerosis; Muscle Spasticity; Oils

To survey the pattern and benefits of medical cannabis use (MCU) in a cross section of persons with multiple sclerosis (PWMS).. One hundred and fifteen subjects completed a 36-question survey online or on paper which queried aspects of their use of cannabis, including frequency of use, effect on symptoms, and changes in their use of prescription medications, as well asa number of key demographic variables such as age, gender, disease duration and clinical course, etc. All subjects were treated at a multiple sclerosis (MS) clinic in Connecticut and enrolled in the Connecticut Medical Marijuana Program (CTMMP).. Self-reported benefit from cannabis use for two or more symptoms of MS was associated with relapsing remitting MS (RRMS) vs progressive (PMS) (OR 3.043, 95% CI 1.026-9.028, p=0.038) and less benefit for two or more symptoms for those who required a wheelchair vs. those who ambulated without assistance (OR .246, 95% CI .195-.797, p=0.016). General benefit from cannabis use was reported for mood disorders (p<0.001), insomnia (p<0.001), sensory symptoms, including pain (p<0.001), and muscle cramps and spasms (p<0.001). Furthermore, benefit was also significantly associated with symptom severity in the case of insomnia (OR 9.735, 95% CI 2.751-34.445, p<0.001), and cramps and spasms (OR 5.234, 95% CI 1.261-21.729, p=0.014). A significant proportion of respondents had stopped or reduced prescription medications (86% vs. 55%, p<0.001) as a function of finding cannabis more effective than prescription medications. These included opioids, benzodiazepines, muscle relaxers and other pain medications.. MCU among PWMS can lead to the reduction or discontinuation of several categories of prescription medications for symptoms of MS. Persons reporting the most benefit from MCU tended to have a milder form of MS with less disability, in contrast to previous studies. This study confirms the benefit of cannabis in several common MS symptoms, extending these findings to show that benefit can be related to baseline severity of some symptoms.

Topics: Cannabis; Humans; Medical Marijuana; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Surveys and Questionnaires

The use of cannabis to treat some symptoms of neurological diseases, including multiple sclerosis (MS), has increased worldwide. We aimed to assess the use of cannabis in patients with MS (PwMS) from Argentina, its reasons and patients' perceptions on the management of MS symptoms. Additionally, we assessed their association with socio-demographic and clinical aspects.. A cross-sectional online survey that included 281 PwMS from Argentina was conducted. Screening instruments: Demographics and clinical data, health-related QoL (MS Impact Scale-29), Fatigue Severity Scale, The Hospital Anxiety and Depression Scale, sleep disorders, physical disability (self-administrated Expanded Disability Status Scale) and medical or recreational cannabis use were evaluated. A logistic regression model was carried out.. Current users (cannabis was used within the past year) was reported in 34.2% and former users (had tried cannabis but not used it within the past year) in 22.7%. Daily cannabis use was reported in 31.3% (current + former users) of the studied cohort, 41.9% started their use after MS diagnosis and 54.3% of them had never discussed about cannabis use with their neurologist. Recreational use was reported in 47.5%. Younger (age below 30 years) PwMS (OR = 2.39, p = 0.03), presence of chronic pain (OR = 2.42, p = 0.002) and current alcohol intake (OR = 3.33, p = 0.001) were predictors of current cannabis use in our multivariate model.. A high prevalence of use of cannabis in PwMS from Argentina was observed. Demographic, symptoms and lifestyle factors predict cannabis use. Identifying the presence and severity of these conditions would contribute to a better MS management and treatment.

Topics: Adult; Argentina; Cannabis; Cross-Sectional Studies; Humans; Multiple Sclerosis; Quality of Life

With widespread moves toward legalization of cannabis, increasing numbers of people with multiple sclerosis (pwMS) are using the drug. Emerging MS-related data show that cannabis can cause or exacerbate cognitive dysfunction.. To understand why people with MS continue using cannabis despite adverse cognitive consequences. It was hypothesized that lack of awareness, a component of metacognition, could explain this decision, in part.. Forty pwMS who smoked cannabis almost daily were assigned by odd-even case number selection to either a cannabis continuation (CC) or cannabis withdrawal (CW) group. Both groups were followed for 28 days. All participants completed, at baseline and day 28, the brief repeatable battery of neuropsychological tests (BRNB) in MS for measures of processing speed, memory and executive function; Modified fatigue impact scale (mFIS) for self-report indices of cognitive functioning.. No significant baseline differences between the groups on the BRNB and mFIS. At day 28, significant improvement within group was seen on all measures of the BRNB, but only in the CW group (p = .0001 for all indices). A repeat measure ANOVA did not find any significant group (CC vs. CW) × time (baseline and day 28) interactions for the self-report cognitive measures on the mFIS. Cannabis abstainers did report less ability to function away from home. All 19 participants in the CW group reverted to using cannabis on study completion despite being informed individually of their cognitive improvement.. The inability of pwMS to accurately appraise their memory and executive function can help explain, in part, why they continue to smoke cannabis despite objective evidence of the deleterious cognitive side effects of this behavior.

Topics: Cannabis; Cognition; Cognitive Dysfunction; Humans; Multiple Sclerosis; Neuropsychological Tests

Evidence supports that cannabinoids reduce self-reported spasticity and neuropathic pain in people with MS (PwMS), and legal access to cannabis for medical and recreational use continues to rise. However, there are limited data regarding patterns of cannabis use and perceived benefits of cannabis among PwMS in the US. This study describes the prevalence of cannabis use, routes of administration, perceived benefit of cannabis for MS, and characteristics associated with cannabis use and perception of benefit among a population of PwMS living in two states where cannabis is legal for both medical and recreational use.. A survey about treatments used by PwMS, focusing on complementary and alternative medicine (CAM), was sent to PwMS living in Oregon and Southwest Washington. This survey included questions about current and past cannabis use, route of cannabis administration, and perceived benefits, as well as personal demographics.. Of the 1188 returned surveys, 1000 had at least 75% complete survey responses and also completed the questions about current and past cannabis use. Thirty percent (n=303) of respondents reported currently using cannabis, 21% (n=210) used in the past but not currently, and 49% (n=487) had never used cannabis. Among current users, rates of use by smoking, vaping, topicals, tinctures and oils, or edibles were similar (35-46%), and most (59%) reported using multiple routes of administration. Most (64-78%, varying by route) current and past users reported cannabis being very or somewhat beneficial for their MS. The odds of current cannabis use were higher in PwMS who: 1) were younger (OR 2.24 [95% CI 1.39-3.61] for those age 18-40 compared with age >60]; 2) had lower household income (OR 3.94 [95% CI 2.55-6.09] with annual income <$25k compared with those with >$100k); 3) had secondary progressive MS (OR 1.77 [95% CI 1.07-2.92]); and 4) had more than minimal MS disability (OR 2.05 [95% CI 1.03-4.10] for those using a walker compared to those with none/minimal disability). The odds of perceiving cannabis as beneficial for MS were higher in: 1) younger individuals (OR 5.61 [95% CI 2.62-11.98] for those age 18-40 compared with age >60); 2) those with lower household income (OR 3.35 [95% CI 1.65-6.80] with annual income <$25k compared with those with >$100k), 3) those not currently using disease modifying therapies (OR 2.32 [95% CI 1.30-4.13]), and 4) those with the greatest disability (OR 17.96; [95% CI 2.00-161.22]).. In this survey, 30% of PwMS reported currently using cannabis for their MS, mostly by multiple routes of administration, and most of these people report this being helpful for their MS. People who were younger, had lower household income, had progressive disease, and had more than minimal disability were more likely to use cannabis and report it was beneficial for their MS. People who were not using disease modifying therapies were also more likely to report benefit from cannabis use.

Topics: Adolescent; Adult; Cannabis; Cross-Sectional Studies; Humans; Multiple Sclerosis; Oregon; Washington; Young Adult

Growing evidence supports that cannabinoids relieve MS-related spasticity but little is known about cannabis use among people with MS (PwMS) and spasticity.. To characterize cannabis use among PwMS and spasticity.. As part of baseline data collection for a spasticity intervention trial in Oregon, PwMS and self-reported spasticity answered questions about cannabis use.. 54% reported ever using cannabis and 36% currently use. 79% use multiple routes of administration, 58% use at least daily. 79% find cannabis helpful for spasticity and 26% use cannabis and prescribed oral antispasticity medications.. Many PwMS and spasticity use cannabis and report it helps their spasticity.

Topics: Adult; Aged; Aged, 80 and over; Cannabinoid Receptor Modulators; Cannabis; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Muscle Spasticity; Plant Preparations; Self-Management; Treatment Outcome

Mouse model of multiple sclerosis (MS) is used for the inflammatory demyelinating disease. Rapamycin (RAPA) may contribute to the reduction of inflammatory responses to experimental autoimmune encephalomyelitis (EAE). Due to its adverse side effects, identifying new therapeutic agents is important. We investigated the transcriptional effects of evening primrose/hemp seed oil (EP/HS oil) compared to RAPA on the expression of immunological factors genes in spleen cells of EAE mouse models. We firstly induced EAE mice by injection of myelin oligodendrocyte glycoprotein (MOG). Then, the EAE mice treated and untreated with EP/HS oil were evaluated and compared with naïve mice. The spinal cords were examined histologically. The immunological factors including genes expression of the regulatory-associated protein of mammalian target of rapamycin (RAPTOR), regulatory-associated companion of mammalian target of rapamycin (RICTOR), interferon (IFN)-γ, interleukin (IL)-10, signal transducer and activator of transcription factors (STAT3), forkhead box P3 (FOXP3), and IL-17 of splenocytes were evaluated by real time-polymerase chain reaction (RT-PCR). The data showed that EP/HS oil was able to reduce the severity of EAE and inhibited the development of the disease. EP/HS oil treatment significantly inhibited the expression of RAPTOR, IFN-γ, IL-17, and STAT3 genes and promoted the expression of RICTOR, IL-10, and FOXP3 genes. In conclusion, the EP/HS oil is likely to be involved in transcription of factors in favor of EAE improvement as well as participating in remyelination in the EAE spinal cord and that it suggests to be effective in therapeutic approaches for MS.

Topics: Animals; Cannabis; Cytokines; Disease Models, Animal; Drug Therapy, Combination; Encephalomyelitis, Autoimmune, Experimental; Female; Forkhead Transcription Factors; gamma-Linolenic Acid; Humans; Linoleic Acids; Linseed Oil; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Oenothera biennis; Plant Oils; Regulatory-Associated Protein of mTOR; Seeds; Sirolimus; Spleen

Democratization of the cannabis consumption and its derivatives incite patients to ask ever more for medical cannabinoid prescriptions, especially in the context of chronic pain. Its use is only validated in certain limited cases, in particular spasticity linked to multiple sclerosis and refractory epilepsies. All other prescriptions require a special request to the OFSP. Moreover, cannabinoid intake may produce several dose-dependent side effects that require a close monitoring with a slow and gradual initiation of its dosage. In the absence of clear medical evidence, many other mechanisms of action need to be investigated with ongoing and future studies to clarify their indication.. La démocratisation de la consommation de cannabis et de ses dérivés pousse les patients à être de plus en plus demandeurs de prescriptions de cannabis à usage médical, d’autant plus dans le cadre de douleurs chroniques. Il convient alors de rappeler que son utilisation n’est validée que dans certains cas restreints, notamment dans la spasticité liée à la sclérose en plaques et les épilepsies réfractaires. Toute autre prescription nécessite une demande spéciale à l’Office fédéral de la santé publique. Par ailleurs, la prise de cannabinoïdes étant liée à nombre d’effets secondaires dose-dépendants, son administration nécessite une surveillance rapprochée et une initiation lente et progressive. En l’absence d’évidence médicale claire, il reste de nombreuses pistes encore à développer pour cibler leur indication.

Topics: Analgesics; Cannabinoids; Cannabis; Chronic Pain; Humans; Multiple Sclerosis

Topics: Cannabis; Cognition; Humans; Magnetic Resonance Imaging; Moon; Multiple Sclerosis

Topics: Cannabis; Empathy; Humans; Multiple Sclerosis

Many potentially modifiable risk factors for MS are investigated. It is not known, however, if these factors also apply to MS-related cognitive impairment (CI), a frequent consequence of MS.. The aim of our study was to assess risk factors for CI in MS patients, focusing on environmental exposures, lifestyle and comorbidities.. We included MS patients referring to MS Centers in Florence and Barletta between 2014 and 2017. Neuropsychological performance was assessed through the Rao's battery and Stroop test, cognitive reserve (premorbid intelligence quotient-IQ) was evaluated using the National Adult Reading Test (NART). Potential risk factors were investigated through a semi-structured questionnaire.. 150 patients were included. CI was detected in 45 (30%) subjects and was associated with older age (p<0.005), older age at MS onset (p = 0.016), higher EDSS score (p<0.005), progressive disease course (p = 0.048) and lower premorbid IQ score (p<0.005). As for risk factors, CI was related with lower physical activity in childhood-adolescence (p<0.005). In women, hormonal therapy resulted to be protective against CI (p = 0.041). However, in the multivariable analysis, the only significant predictors of CI were older age (p<0.05; OR 1.06, 95% CI 1.02-1.10) and lower premorbid IQ (p<0.05; OR 0.93, 95% CI: 0.88-0.98). Removing IQ from the model, CI was associated with higher EDSS (p = 0.030; OR 1.25, 95% CI 1.02-1.53) and, marginally, previous physical activity (p = 0.066; OR 0.49, 95% CI: 0.23-1.05).. Our findings suggest that physical activity in childhood-adolescence could be a contributor to cognitive reserve building, thus representing a potential protective factors for MS-related CI susceptible to preventive strategies.

Topics: Adult; Cannabis; Cognitive Dysfunction; Cognitive Reserve; Disease Progression; Exercise; Female; Humans; Intelligence Tests; Life Style; Male; Middle Aged; Multiple Sclerosis; Neuropsychological Tests; Risk Factors; Smoking; Wechsler Scales

Topics: Animals; Cannabidiol; Cannabis; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Glatiramer Acetate; Immunosuppressive Agents; Mice; Multiple Sclerosis; Plant Extracts

Use of cannabis to alleviate multiple sclerosis (MS)-related symptoms is increasing. Due to strict regulations, only a minority of MS patients receive cannabis-based prescription drugs. The extent of recreational and medical cannabis use among Danes with MS is unknown. Our aim was to evaluate the prevalence of illegal and legal use of cannabis in MS patients, as well as reasons for use and perceived adverse effects.. An anonymous questionnaire was sent to all 3606 patients at the Danish Multiple Sclerosis Center, Rigshospitalet, University of Copenhagen. The questionnaire included questions about sociodemographic factors, clinical characteristics and medical or recreational cannabis use.. Questionnaires were completed by 2244/3606 (62%), of which 2009 questionnaires from patients with MS or clinical isolated syndrome (CIS) were valid for analysis. Forty-nine percent (980/2009) had used cannabis at least once. Cannabis was used within the past year (current user) by 21%, and only 21% of those received prescribed cannabis-based medicine. Recreational use was reported by 17%. The primary reasons for use were to alleviate pain (61%), spasticity (52%) and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%) and dizziness (13%). Almost half (44%) of the non-cannabis users would consider use of cannabis to alleviate MS symptoms if the drug was legalized.. This study shows that illegal cannabis use is common among Danes with MS as only 21% of the current cannabis users received prescribed cannabis-based medicine. Current cannabis users reported high efficacy in relieving pain, spasticity and sleep disturbances. In addition, only mild to moderate severity of adverse effects were reported. To the best of our knowledge, this is the most comprehensive survey of cannabis use among MS patients.

Topics: Adult; Cannabis; Cross-Sectional Studies; Denmark; Female; Humans; Illicit Drugs; Male; Marijuana Smoking; Medical Marijuana; Middle Aged; Multiple Sclerosis; Surveys and Questionnaires; Young Adult

Currently, a combination of marijuana cannabinoids including delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is used as a drug to treat muscle spasticity in patients with Multiple Sclerosis (MS). Because these cannabinoids can also suppress inflammation, it is unclear whether such patients benefit from suppression of neuroinflammation and if so, what is the mechanism through which cannabinoids act. In the currently study, we used a murine model of MS, experimental autoimmune encephalomyelitis (EAE), to study the role of gut microbiota in the attenuation of clinical signs of paralysis and inflammation caused by cannabinoids. THC + CBD treatment attenuated EAE and caused significant decrease in inflammatory cytokines such as IL-17 and IFN-γ while promoting the induction of anti-inflammatory cytokines such as IL-10 and TGF-β. Use of 16S rRNA sequencing on bacterial DNA extracted from the gut revealed that EAE mice showed high abundance of mucin degrading bacterial species, such as Akkermansia muciniphila (A. muc), which was significantly reduced after THC + CBD treatment. Fecal Material Transfer (FMT) experiments confirmed that THC + CBD-mediated changes in the microbiome play a critical role in attenuating EAE. In silico computational metabolomics revealed that LPS biosynthesis, a key component in gram-negative bacteria such as A. muc, was found to be elevated in EAE mice which was confirmed by demonstrating higher levels of LPS in the brain, while treatment with THC + CBD reversed this trend. EAE mice treated with THC + CBD also had significantly higher levels of short chain fatty acids such as butyric, isovaleric, and valeric acids compared to naïve or disease controls. Collectively, our data suggest that cannabinoids may attenuate EAE and suppress neuroinflammation by preventing microbial dysbiosis seen during EAE and promoting healthy gut microbiota.

Topics: Animals; Cannabidiol; Cannabinoids; Cannabis; Cytokines; Disease Models, Animal; Dronabinol; Dysbiosis; Encephalomyelitis, Autoimmune, Experimental; Female; Gastrointestinal Microbiome; Inflammation; Interferon-gamma; Interleukin-17; Mice; Mice, Inbred C57BL; Multiple Sclerosis; RNA, Ribosomal, 16S

Topics: Cannabinoids; Cannabis; Humans; Medical Marijuana; Multiple Sclerosis; Muscle Spasticity; Nausea; Neuralgia; Vomiting

Topics: Cannabinoids; Cannabis; Humans; Multiple Sclerosis; Muscle Spasticity; Needs Assessment

Cannabis has been used for medicinal purpose for thousands of years; however the positive and negative effects of cannabis use in Parkinson's disease (PD) and Multiple Sclerosis (MS) are mostly unknown. Our aim was to assess cannabis use in PD and MS and compare results of self-reported assessments of neurological disability between current cannabis users and non-users.. An anonymous web-based survey was hosted on the Michael J. Fox Foundation and the National Multiple Sclerosis Society webpages from 15 February to 15 October 2016. The survey collected demographic and cannabis use information, and used standardized questionnaires to assess neurological function, fatigue, balance, and physical activity participation. Analysis of variance and chi-square tests were used for the analysis.. The survey was viewed 801 times, and 595 participants were in the final data set. Seventy-six percent and 24% of the respondents reported PD and MS respectively. Current users reported high efficacy of cannabis, 6.4 (SD 1.8) on a scale from 0 to 7 and 59% reported reducing prescription medication since beginning cannabis use. Current cannabis users were younger and less likely to be classified as obese (P < 0.035). Cannabis users reported lower levels of disability, specifically in domains of mood, memory, and fatigue (P<0.040).. Cannabis may have positive impacts on mood, memory, fatigue, and obesity status in people with PD and MS. Further studies using clinically and longitudinally assessed measurements of these domains are needed to establish if these associations are causal and determine the long-term benefits and consequences of cannabis use in people with PD and MS.

Topics: Adult; Affect; Aged; Cannabis; Disabled Persons; Fatigue; Female; Humans; Internet; Male; Marijuana Smoking; Medical Marijuana; Memory; Memory Disorders; Middle Aged; Mood Disorders; Multiple Sclerosis; Obesity; Parkinson Disease; Surveys and Questionnaires

The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea and inflammation. Current research is inspecting the use of cannabis for many diseases, including multiple sclerosis, epilepsy, dystonia, and chronic pain. In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and:pain and diarrhea in Crohn's disease. Despite their therapeutic potential, cannabinoids are not free of side effects including psychosis, anxiety, paranoia, dependence and abuse. Controlled clinical studies investigating the therapeutic potential of cannabis are few and small, whereas pressure for expanding cannabis use is increasing. Currently, as long as cannabis is classified as an illicit drug and until further controlled studies are performed, the use of medical cannabis should be limited to patients who failed conventional better established treatment.

Topics: Cannabis; Chronic Pain; Crohn Disease; Diarrhea; Drug and Narcotic Control; Epilepsy; Humans; Inappropriate Prescribing; Inflammation; Israel; Medical Marijuana; Multiple Sclerosis; Phytotherapy; Psychoses, Substance-Induced; Substance-Related Disorders

Canada has the highest incidence of MS worldwide. Anecdotal evidence reveals that people with MS smoke, ingest or vaporize cannabis for a multiplicity of reasons. With the legal situation in relation to use currently in flux, we undertook a study investigating patterns of use amongst people with MS and their attitudes towards the drug.. A consecutive sample of people with MS (n=246) attending a neurology (n=118) and a neuropsychiatry (n=107) clinic was enrolled and asked to complete a questionnaire containing demographic, disease and cannabis related variables.. There is a wide acceptance of cannabis within the MS patient community. One in five people currently use the drug for reasons that differ between neuropsychiatry and neurology clinics. Use could potentially more than double if the drug were legalized.

Topics: Canada; Cannabis; Female; Health Knowledge, Attitudes, Practice; Humans; Incidence; Legislation, Drug; Male; Marijuana Smoking; Middle Aged; Multiple Sclerosis; Phytotherapy

Topics: Cannabidiol; Cannabis; Dronabinol; Drug Combinations; Humans; Multiple Sclerosis; Muscle Spasticity; Parasympatholytics; Plant Extracts

Topics: Adolescent; Appetite; Biomedical Research; Cannabis; Child; Colorado; Confounding Factors, Epidemiologic; Dronabinol; Humans; Marijuana Abuse; Marijuana Smoking; Medical Marijuana; Multiple Sclerosis; Netherlands; New Zealand; Prevalence; Schizophrenia; Seizures; Sweden; Young Adult

Topics: Animals; Canada; Cannabidiol; Cannabinol; Cannabis; China; Dronabinol; Drug and Narcotic Control; Drug Approval; Drug Combinations; Endocannabinoids; Herbal Medicine; History, 16th Century; History, 17th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; History, Medieval; Humans; Medical Marijuana; Multiple Sclerosis; New Orleans; Phytotherapy; Plant Extracts; Plants, Medicinal; 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

Multiple Sclerosis (MS) is a global concern disease leading to a progressive, chronic and demyelinating condition, affecting the central nervous system (CNS). The pathology has an inflammatory/autoimmune origin; nevertheless, neuronal cell death mechanisms are not to be underestimated. The present study was designed to test the effects of intraperitoneal administration of cannabidiol (CBD), the main non-psychotropic cannabinoid of Cannabis sativa (CS), in an experimental model of MS. The aim is to evaluate the capability of CBD administration to thwart the cascade of mediators involved in MS-induced apoptosis.. Experimental Autoimmune Encephalomyelitis (EAE) was induced by immunization with myelin oligodendroglial glycoprotein (MOG)35-55 peptide in mice. After immunization, mice were observed daily for signs of EAE and weight loss. Disease signs were evaluated using a standardized scoring system.. Immunohistochemical and Western blot assessments of key apoptotic markers reveal that CBD treatment is able to avoid Fas pathway activation, phospho-ERK p42/44 and cleaved caspase-3 triggering as well as alterations in mitochondrial permeability due to Bax/Bcl-2 unbalance. Moreover, CBD interferes with p53-p21 axis activation. As results, the absence of tissue apobody formation in spinal cord tissues of EAE-mice treated with CBD was established. Most of therapeutic properties of CS are currently ascribed to the psychotropic effects of phenylterpenoid delta-9 tetrahydrocannabinol.. We have demonstrated that, alone, purified CBD possesses an anti-apoptotic power against the neurodegenerative processes underlying MS development. This represents an interesting new profile of CBD that could lead to its introduction in the clinical management of MS.

Topics: Animals; Apoptosis; Cannabidiol; Cannabis; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Male; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Phytotherapy; Plant Extracts

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

Cannabinoids affect immune responses in ways that may be beneficial for autoimmune diseases. We sought to determine whether chronic Cannabis use differentially modulates a select number of immune parameters in healthy controls and individuals with multiple sclerosis (MS cases). Subjects were enrolled and consented to a single blood draw, matched for age and BMI. We measured monocyte migration isolated from each subject, as well as plasma levels of endocannabinoids and cytokines. Cases met definition of MS by international diagnostic criteria. Monocyte cell migration measured in control subjects and individuals with MS was similarly inhibited by a set ratio of phytocannabinoids. The plasma levels of CCL2 and IL17 were reduced in non-naïve cannabis users irrespective of the cohorts. We detected a significant increase in the endocannabinoid arachidonoylethanolamine (AEA) in serum from individuals with MS compared to control subjects, and no significant difference in levels of other endocannabinoids and signaling lipids irrespective of Cannabis use. Chronic Cannabis use may affect the immune response to similar extent in individuals with MS and control subjects through the ability of phytocannabinoids to reduce both monocyte migration and cytokine levels in serum. From a panel of signaling lipids, only the levels of AEA are increased in individuals with MS, irrespective of Cannabis use or not. Our results suggest that both MS cases and controls respond similarly to chronic Cannabis use with respect to the immune parameters measured in this study.

Topics: Adult; Arachidonic Acids; Cannabinoids; Cannabis; Case-Control Studies; Cell Movement; Chemokine CCL2; Cross-Sectional Studies; Endocannabinoids; Female; Humans; Interleukin-17; Male; Marijuana Smoking; Monocytes; Multiple Sclerosis; Polyunsaturated Alkamides

To evaluate the effect of a Cannabis sativa extract enriched in cannabidiol (CBD) botanic drug substance (BDS) and pure CBD, on bladder contractility in vitro. Cannabis based-medicines, including CBD-enriched extracts, have been shown to reduce urinary urgency, incontinence episodes, frequency, and nocturia in patients with multiple sclerosis.. Strips were cut from male Wistar rats and the human bladder body and placed in organ baths containing Krebs solution. Contractions were induced by electrical field stimulation, acetylcholine, KCl, and α,β-methylene adenosine triphosphate.. CBD BDS significantly reduced the contractions induced by acetylcholine, but not those induced with electrical field stimulation, KCl, or α,β-methylene adenosine triphosphate in the isolated rat bladder. The inhibitory effect of CBD BDS was not significantly modified by the cannabinoid or opioid receptor antagonists or by modulators of calcium levels, but it was increased by ruthenium red and capsazepine, 2 transient receptor potential vanilloid type-1 blockers. In humans, CBD BDS and pure CBD significantly reduced acetylcholine-induced contractions, an effect that was not changed by the transient receptor potential vanilloid type-1 blockers.. Our data have suggested that CBD BDS reduces cholinergic-mediated contractility and that this effect is modulated by transient receptor potential vanilloid type-1 in rats but not in humans. CBD is the chemical ingredient of CBD BDS responsible for such activity. If confirmed in vivo, such results could provide a pharmacologic basis to explain, at least in part, the efficacy of Cannabis medicines in reducing incontinence episodes in patients with multiple sclerosis.

Topics: Acetylcholine; Animals; Cannabidiol; Cannabis; Cholinergic Agonists; Humans; In Vitro Techniques; Male; Multiple Sclerosis; Muscle Contraction; Muscle, Smooth; Plant Extracts; Rats; Rats, Wistar; Urinary Bladder; Urinary Incontinence

Topics: Cannabis; Humans; Multiple Sclerosis; Muscle Spasticity; Phytotherapy

While neuropsychological deficits have been reported in healthy individuals who use street cannabis, data in patients with multiple sclerosis (MS) are lacking. Given that MS is associated with cognitive deterioration, the aim of this study was to determine the neuropsychological effects of cannabis use in this population.. Two groups, each of 25 patients with MS (cannabis users and nonusers), were administered the Minimal Assessment of Cognitive Function in MS battery of neuropsychological tests, the Hospital Anxiety and Depression Scale (HADS), and the Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID-I). Group-matching and regression analysis were used to control for the effects of age, sex, education, premorbid intelligence, disability, and disease course and duration on cognitive function.. Cannabis users performed significantly more poorly than nonusers on measures of information processing speed, working memory, executive functions, and visuospatial perception. They were also twice as likely as nonusers to be classified as globally cognitively impaired. There were no between-group differences on the HADS measures of depression and anxiety or lifetime SCID-I psychiatric diagnoses.. This cross-sectional study provides empirical evidence that prolonged use of inhaled or ingested street cannabis in patients with MS is associated with poorer performance on cognitive domains commonly affected in this population. Whatever subjective benefits patients may derive from using street cannabis (e.g., pain and spasticity relief) should be weighed against the associated cognitive side effects.

Topics: Adolescent; Adult; Aged; Cannabis; Cognition; Cognition Disorders; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Neuropsychological Tests; Phytotherapy; Plant Preparations; Prospective Studies; Psychiatric Status Rating Scales; Young Adult

Topics: Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Drug Approval; Drug Combinations; Humans; Multiple Sclerosis; Muscle Spasticity; Parasympatholytics; Plant Extracts

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

In the present work, we report repeated out-of-body experiences (OBEs) in a patient with tetraplegia and severe somatosensory loss due to multiple sclerosis and predominant involvement of the cervical spinal cord. OBEs were experienced on a daily basis and induced by cannabis treatment that was started for severe spasticity with painful cramps and cloni. In order to investigate the link between OBEs and mental own-body imagery, the patient was asked to imagine himself in the position and visual perspective that is generally reported during OBEs, using front- and back-facing schematic human stimuli. Performance was measured before and after cannabis consumption. First, our data reveal that the patient was less accurate for back-facing than front-facing stimuli. This was found before and after cannabis consumption and is the opposite pattern to what is generally observed in healthy participants and in our control subjects (who did not use cannabis). We refer to this as lesion effect and argue that this relative facilitation for stimuli reflecting the position and visual perspective that is generally reported during OBEs might be due to recurrent and spontaneous own-body transformations during the patient's frequent OBEs. Secondly, we found a cannabis effect, namely a performance improvement in the back-facing condition while performance in the front-facing condition remained unchanged, after cannabis administration. We argue that cannabis administration may interfere with own-body imagery when reflecting the actual body position and only when associated with brain damage. Based on these data we propose an extended neurological model for own-body illusions including multisensory and sensorimotor mechanisms, cannabis consumption, and cortical and subcortical processing.

Topics: Body Image; Cannabis; Humans; Imagination; Male; Middle Aged; Multiple Sclerosis; Muscle Spasticity; Neuropsychological Tests; Photic Stimulation; Phytotherapy; Quadriplegia; Self Concept; Visual Perception

Topics: Cannabis; Cognition Disorders; Humans; Multiple Sclerosis; Psychiatry

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

Topics: Cannabis; Humans; Marijuana Smoking; Mental Disorders; Multiple Sclerosis; Plant Extracts

A significant minority of patients with multiple sclerosis (MS) use cannabis, yet no study has examined the possible effects on mentation. Here, we report the emotional and cognitive correlates of street cannabis use in patients with MS.. A sample of 140 consecutive patients with MS were interviewed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Axis I disorders (SCID-IV) from which details of cannabis use were recorded. Cognition was assessed using the Neuropsychological Battery for MS supplemented with the Symbol Digit Modalities Test (SDMT), an index of information processing speed, working memory, and sustained attention.. Ten subjects (7.7%) were defined as current cannabis users based on use within the last month. Compared to non-cannabis users (n = 130), they were younger (p = 0.001). Each of the 10 current cannabis users was matched on demographic and disease variables to four subjects with MS who did not use cannabis (total control sample n = 40). Group comparisons revealed that the proportion of patients meeting DSM-IV criteria for a psychiatric diagnosis was higher in cannabis users (p = 0.04). In addition, on the SDMT, cannabis users had a slower mean performance time (p = 0.006) and a different pattern of response compared to matched controls (group x time interaction; p = 0.001).. Inhaled cannabis is associated with impaired mentation in patients with multiple sclerosis, particularly with respect to cognition. Future studies are required to clarify the direction of this relationship.

Topics: Adult; Cannabis; Cognition Disorders; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Male; Marijuana Smoking; Middle Aged; Multiple Sclerosis; Neuropsychological Tests

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

Little is known about the extent and patterns of cannabis use in people with multiple sclerosis (MS).. MS patients attending neurology outpatient clinics at two hospitals in London and one in Kent, UK completed a questionnaire.. Questionnaires were completed by 254/337 (75%) MS patients. Forty-three per cent had used cannabis at some stage (ever users). Of these, 68% (75/110) had used cannabis to alleviate symptoms of MS (MS-related cannabis use). Forty-six (18%) had used cannabis in the last month (current users), of whom 12% (31/254) had used it for symptom relief. Being married or having a long-term partner, tobacco smokers and increasing disability were independent risk factors for MS-related cannabis use. Compared to patients who could walk unaided, cannabis use was more likely in those who were chair-bound (adjusted OR 2.47; 1.10-5.56) or only able to walk with an aid (adjusted OR 1.56; 0.90-3.60). Pain and spasms were common reasons for cannabis use. Seventy-one per cent of individuals who had never used cannabis said they would try the drug if it were available on prescription.. A large proportion of MS patients had tried cannabis for symptom control, however current use was small. A subgroup with greater disability appears to derive some symptomatic benefit.

Topics: Adult; Aged; Cannabis; Drug Utilization; Female; Humans; Male; Marijuana Abuse; Middle Aged; Multiple Sclerosis; Phytotherapy; Plant Preparations; Risk Factors; Surveys and Questionnaires

Topics: Canada; Cannabidiol; Cannabis; Dronabinol; Drug Approval; Drug Combinations; Humans; Multiple Sclerosis; Neuralgia; Phytotherapy; Plant Extracts

Topics: Cannabinoids; Cannabis; Humans; Multiple Sclerosis; Substance-Related Disorders

Topics: Animals; Canada; Cannabis; Dronabinol; Drug and Narcotic Control; Drug Utilization; Epilepsy; Humans; Kindling, Neurologic; Multiple Sclerosis; Phytotherapy; Plant Preparations; Public Opinion; 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

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

The majority of patients with multiple sclerosis (MS) develop troublesome lower urinary tract symptoms (LUTS). Anecdotal reports suggest that cannabis may alleviate LUTS, and cannabinoid receptors in the bladder and nervous system are potential pharmacological targets. In an open trial we evaluated the safety, tolerability, dose range, and efficacy of two whole-plant extracts of Cannabis sativa in patients with advanced MS and refractory LUTS. Patients took extracts containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD; 2.5 mg of each per spray) for eight weeks followed by THC-only (2.5 mg THC per spray) for a further eight weeks, and then into a long-term extension. Assessments included urinary frequency and volume charts, incontinence pad weights, cystometry and visual analogue scales for secondary troublesome symptoms. Twenty-one patients were recruited and data from 15 were evaluated. Urinary urgency, the number and volume of incontinence episodes, frequency and nocturia all decreased significantly following treatment (P <0.05, Wilcoxon's signed rank test). However, daily total voided, catheterized and urinary incontinence pad weights also decreased significantly on both extracts. Patient self-assessment of pain, spasticity and quality of sleep improved significantly (P <0.05, Wilcoxon's signed rank test) with pain improvement continuing up to median of 35 weeks. There were few troublesome side effects, suggesting that cannabis-based medicinal extracts are a safe and effective treatment for urinary and other problems in patients with advanced MS.

Topics: Adult; Cannabidiol; Cannabis; Dose-Response Relationship, Drug; Dronabinol; Drug Administration Schedule; Follow-Up Studies; Humans; Medical Records; Middle Aged; Multiple Sclerosis; Pilot Projects; Plant Extracts; Sensation; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder; Urinary Bladder, Neurogenic; Urinary Incontinence; Urination; Urodynamics

Topics: Administration, Oral; Affect; Appetite; Cannabidiol; Cannabinoids; Cannabis; Clinical Trials, Phase III as Topic; Double-Blind Method; Dronabinol; Humans; Multiple Sclerosis; Muscle Spasticity; Neuralgia; Plant Extracts; Reflex, Abnormal; Safety; Sleep; Switzerland; Treatment Outcome; United Kingdom

Cannabinoids can modulate the function of immune cells. We here present the first human in vivo study measuring immune function in 16 MS patients treated with oral cannabinoids. A modest increase of TNF-alpha in LPS-stimulated whole blood was found during cannabis plant-extract treatment (p=0.037), with no change in other cytokines. In the subgroup of patients with high adverse event scores, we found an increase in plasma IL-12p40 (p=0.002). The results suggest pro-inflammatory disease-modifying potential of cannabinoids in MS.

Topics: Adjuvants, Immunologic; Administration, Oral; Adult; Cannabinoids; Cannabis; Confidence Intervals; Cross-Over Studies; Dronabinol; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Phytotherapy; Plant Extracts

Topics: Cannabis; Humans; Multiple Sclerosis; Phytotherapy; Plant Preparations

Multiple sclerosis (MS) is one of the most common neurological diseases affecting young adults. The prevalence of MS in Alberta has been described as among the highest reported in the world, estimated at 217 per 100,000. Numerous anecdotal reports, and a few small empirical investigations have suggested that cannabis use may relieve the symptom experience of those with MS. The present study was undertaken to describe cannabis use by this patient group. Information on peoples' beliefs, practices and experiences related to use were investigated.. A questionnaire was mailed to a sample of 780 adults with MS in southern Alberta, Canada.. Completed questionnaires were returned by 420/673 eligible subjects (response rate 62%). Mean sample age was 48 years and 75% were women. Respondents ranged from mildly to severely impaired. The majority of respondents (96%) was aware cannabis was potentially therapeutically useful for MS and most (72%) supported legalization for medicinal purposes. Forty-three percent had tried cannabis at some point in their lives, 16% for medicinal purposes. Symptoms reported to be ameliorated included anxiety/depression, spasticity and chronic pain. Reasons given for not trying cannabis were the fact that it is an illegal substance, concern about side effects and lack of knowledge on how to obtain it.. Subjective improvements in symptom experience were reported by the majority of people with MS who currently use cannabis. Further evaluation of this substance is warranted.

Topics: Adult; Attitude to Health; Cannabis; Female; Humans; Legislation, Drug; Male; Middle Aged; Multiple Sclerosis; Phytotherapy; Plant Preparations; Surveys and Questionnaires; Treatment Outcome

Topics: Cannabis; Glaucoma; HIV Infections; Humans; Jurisprudence; Multiple Sclerosis; Phytotherapy; Practice Patterns, Physicians'; Supreme Court Decisions; United States

Cannabis is under clinical investigation to assess its potential for medicinal use, but the question arises as to whether there is any advantage in using cannabis extracts compared with isolated Delta9-trans-tetrahydrocannabinol (Delta9THC), the major psychoactive component. We have compared the effect of a standardized cannabis extract (SCE) with pure Delta9THC, at matched concentrations of Delta9THC, and also with a Delta9THC-free extract (Delta9THC-free SCE), using two cannabinoid-sensitive models, a mouse model of multiple sclerosis (MS), and an in-vitro rat brain slice model of epilepsy. Whilst SCE inhibited spasticity in the mouse model of MS to a comparable level, it caused a more rapid onset of muscle relaxation, and a reduction in the time to maximum effect compared with Delta9THC alone. The Delta9THC-free extract or cannabidiol (CBD) caused no inhibition of spasticity. However, in the in-vitro epilepsy model, in which sustained epileptiform seizures were induced by the muscarinic receptor agonist oxotremorine-M in immature rat piriform cortical brain slices, SCE was a more potent and again more rapidly-acting anticonvulsant than isolated Delta9THC, but in this model, the Delta9THC-free extract also exhibited anticonvulsant activity. Cannabidiol did not inhibit seizures, nor did it modulate the activity of Delta9THC in this model. Therefore, as far as some actions of cannabis were concerned (e.g. antispasticity), Delta9THC was the active constituent, which might be modified by the presence of other components. However, for other effects (e.g. anticonvulsant properties) Delta9THC, although active, might not be necessary for the observed effect. Above all, these results demonstrated that not all of the therapeutic actions of cannabis herb might be due to the Delta9THC content.

Topics: Animals; Anticonvulsants; Brain; Cannabis; Chromatography, High Pressure Liquid; Disease Models, Animal; Dronabinol; Epilepsy; Membrane Potentials; Mice; Multiple Sclerosis; Phytotherapy; Plant Preparations; Rats

Topics: Acquired Immunodeficiency Syndrome; Cannabis; Crime; Drug and Narcotic Control; Epilepsy; Evidence-Based Medicine; Humans; Marijuana Abuse; Multiple Sclerosis; Neoplasms; Ontario; Patient Advocacy

Topics: Cannabis; Humans; Male; Multiple Sclerosis; Nystagmus, Pathologic

Topics: Canada; Cannabis; Drug and Narcotic Control; Drug Therapy; Fees, Pharmaceutical; Humans; Multiple Sclerosis

Topics: Cannabis; Consumer Organizations; HIV Infections; Humans; Multiple Sclerosis; Neoplasms; Referral and Consultation

In 1998, Washington State passed a law, Initiative 692 (I-692), that gives individuals who are charged with possession of marijuana for medical purposes a possible affirmative defense. The law lets these individuals provide a note from their doctor or a copy of their medical records stating they have a condition that may benefit from the use of marijuana. I-692 does not legalize the medical use of marijuana and does not affect Federal law, which makes obtaining, possessing, and growing marijuana illegal. The Washington law limits the amount of marijuana a patient can possess to a 60-day supply and defines the conditions for which medical marijuana may be used. These conditions include HIV, cancer, multiple sclerosis, and epilepsy.

Topics: Cannabis; Epilepsy; Glaucoma; HIV Infections; Humans; Legislation, Drug; Multiple Sclerosis; Muscle Spasticity; Neoplasms; Pain, Intractable; United States

Topics: Cannabis; Clinical Trials as Topic; Drug and Narcotic Control; Humans; Marijuana Smoking; Multiple Sclerosis; Plants, Medicinal; United Kingdom

The Gay and Lesbian Medical Association (GLMA) issued a statement on May 19, 1995, announcing its support of clinical trials of the therapeutic uses of marijuana. The U.S. Department of Health and Human Services has continued to resist permitting clinical trials of marijuana despite evidence that it can relieve symptoms of cancer, multiple sclerosis, and glaucoma. According to Dr. Alvin Novick, head of GLMA's AIDS Task Force, the Clinton Administration is being asked to not let its political fears blind it to the positive and legitimate scientific research designed to alleviate the suffering of thousands of AIDS patients.

Topics: Acquired Immunodeficiency Syndrome; Cannabis; Clinical Trials as Topic; Glaucoma; Humans; Multiple Sclerosis; Neoplasms; Organizations, Nonprofit; United States

Topics: Cannabis; Humans; Multiple Sclerosis

The chronic motor handicaps of a 30-year-old multiple sclerosis patient acutely improved while he smoked a marihuana cigarette. This effect was quantitatively assessed by means of clinical rating, electromyographic investigation of the leg flexor reflexes and electromagnetic recording of the hand action tremor. It is concluded that cannabinoids may have powerful beneficial effects on both spasticity and ataxia that warrant further evaluation.

Topics: Adult; Ataxia; Cannabinoids; Cannabis; Humans; Male; Multiple Sclerosis; Muscle Spasticity