Cannabis-based Medicines Research Articles

Perspectives on Cannabis-Based Therapy of Multiple Sclerosis: A Mini-Review.

The consistency, efficacy, and safety of cannabis-based medicines have been demonstrated in humans, leading to the approval of the first cannabis-based therapy to alleviate spasticity and pain associated with multiple sclerosis (MS). Indeed, the evidence supporting the therapeutic potential of cannabinoids for the management of pathological events related to this disease is ever increasing. Different mechanisms of action have been proposed for cannabis-based treatments in mouse models of demyelination, such as Experimental Autoimmune Encephalomyelitis (EAE) and Theiler’s Murine Encephalomyelitis Virus-Induced Demyelinating Disease (TMEV-IDD). Cells in the immune and nervous system express the machinery to synthesize and degrade endocannabinoids, as well as their CB1 and CB2 receptors, each mediating different intracellular pathways upon activation. Hence, the effects of cannabinoids on cells of the immune system, on the blood-brain barrier (BBB), microglia, astrocytes, oligodendrocytes and neurons, potentially open the way for a plethora of therapeutic actions on different targets that could aid the management of MS. As such, cannabinoids could have an important impact on the outcome of MS in terms of the resolution of inflammation or the potentiation of endogenous repair in the central nervous system (CNS), as witnessed in the EAE, TMEV-IDD and toxic demyelination models, and through other in vitro approaches. In this mini review article, we summarize what is currently known about the peripheral and central effects of cannabinoids in relation to the neuroinflammation coupled to MS. We pay special attention to their effects on remyelination and axon preservation within the CNS, considering the major questions raised in the field and future research directions.

The Role of Cannabidiol (CBD) in Chronic Pain Management: An Assessment of Current Evidence.

Given the growing challenges in chronic pain management coupled with the ongoing consequences of the opioid epidemic, pain management practitioners are looking into more effective, innovative, and safer alternatives to treat pain. Cannabis-based medicine had been described for hundreds of years but only recently have we seen the more scientific, evidence-based approach to its use, and ongoing investigations continue to explore its potential medical benefits. While historically more attention has been paid to the psychoactive component of the cannabis plant Δ9-tetrahydrocannabinol (THC), there have been fewer scientific studies on the medical use of the cannabidiol (CBD) - a non-psychoactive component of the cannabis plant. By examining recent literature, we investigated the use of CBD and its potential role in pain management. Since there are currently no approved pharmaceutical products that contain CBD alone for the management of pain, this review focused on nabiximols (which is a combined product of THC/CBD in a 1:1 ratio) as the only pharmaceutical product available that contains CBD and is being used for the management of pain. It is difficult to definitely attribute the therapeutic properties to CBD alone since it is always administered with THC. Based on the available literature, it is difficult to make a recommendation for the use of CBD in chronic pain management. It is also important to note that there are many CBD products currently availableas supplements, but these products are non-pharmaceuticals and lack the appropriate clinicalstudies to support their efficacy claims.

Adherence to Consolidated Standards of Reporting Trials (CONSORT) Guidelines for Reporting Safety Outcomes in Trials of Medical Cannabis and Cannabis-based Medicines for Chronic Noncancer Pain: A Systematic Review.

Current treatments for chronic pain have limited effectiveness and tolerability. With growing interest in the potential of cannabinoids, there is a need to inform risk-benefit considerations. Thus, this focused systematic review assesses the quality of safety assessment and reporting in chronic noncancer pain cannabinoid trials. The protocol for this review has been published, and, registered in PROSPERO. We searched MEDLINE, Embase, The Cochrane Library, Scopus, and PsychINFO for double-blind, placebo-controlled, randomized controlled trials of cannabinoids for chronic pain, with a primary outcome related to pain. The primary review outcome is adherence to the 2004 Consolidated Standards of Reporting Trials (CONSORT) Harms extension. Secondary outcomes included type, reporting method, frequency and severity of adverse events (AEs), trial participant withdrawals, and reasons for withdrawals. In total, 43 studies (4436 participants) were included. Type of cannabinoid (number of studies) included nabiximols (12), dronabinol (8), nabilone (7), oral cannabis extract preparations (5), smoked tetrahydrocannabinol (5), vaporized tetrahydrocannabinol (3), novel synthetic cannabinoids (2), sublingual cannabis extract preparations (1). The median CONSORT score was 7. On average, 3 to 4 recommendations of the CONSORT guidelines were not being met in trials. Seventeen trials did not provide their method of AE assessment, 14 trials did not report on serious AEs and, 7 trials provided no quantitative data about AEs. Better harms assessment and reporting are needed in chronic pain cannabinoid trials. Improvements may be achieved through: expanded education/knowledge translation increased research regulation by ethics boards, funding agencies and journals, and greater emphasis on safety assessment and reporting throughout research training.

A Scoping Review on Clinical Trials of Pain Reduction With Cannabis Administration in Adults.

Indications of cannabis use are numerous although the indication to relief pain remains a major research interest and clinical application. Studies investigating the effect of herbal cannabis and cannabis-based medicine on neuropathic, non-neuropathic pain, acute pain and experimentally induced pain were reviewed. A search was performed in PubMed and Cochrane library for articles published in English between January 1, 2000 and May 8, 2020. The search terms used were related to cannabis and pain in adults. We identified 34 studies, of which 30 were randomized controlled clinical trials (RCTs). Varying effects were identified from the RCTs, and as expected more promising effects from non-RCTs. Cannabis-based medications were found most effective as an adjuvant therapy in refractory multiple sclerosis, and weak evidence was found to support the treatment of cancer pain especially in advanced stages. Chronic rheumatic pain showed promising results. Adverse events of cannabis-based treatment were found to be more frequent with tetrahydrocannabinol herbal strains compared to other cannabis-derived products.

Cannabinoids as an Emerging Therapy for Posttraumatic Stress Disorder and Substance Use Disorders.

Posttraumatic Stress Disorder (PTSD) is a leading psychiatric disorder that mainly affects military and veteran populations but can occur in anyone affected by trauma. PTSD treatment remains difficult for physicians because most patients with PTSD do not respond to current pharmacological treatment. Psychotherapy is effective, but time consuming and expensive. Substance use disorder is often concurrent with PTSD, which leads to a significant challenge for PTSD treatment. Cannabis has recently received widespread attention for the potential to help many patient populations. Cannabis has been reported as a coping tool for patients with PTSD and preliminary legalization data indicate Cannabis use may reduce the use of more harmful drugs, such as opioids. Rigorous clinical studies of Cannabis could establish whether Cannabis-based medicines can be integrated into treatment regimens for both PTSD and substance use disorder patients.

Treatment of Gilles de la Tourette Syndrome with Cannabis-Based Medicine: Results from a Retrospective Analysis and Online Survey.

Introduction: Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder that is characterized by motor and vocal tics and psychiatric comorbidities, including attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive behavior/disorder (OCB/OCD). From anecdotal reports and preliminary controlled studies, it is suggested that cannabis-based medicine (CBM) may improve tics and comorbidities in adults with GTS. This study was designed to further investigate efficacy and safety of CBM in GTS and specifically compare effects of different CBM. Materials and Methods: First, we performed a retrospective data analysis including all those adult patients seen at our clinic, who had used CBM for the treatment of GTS at some time. All these patients were asked to complete an online survey (second study part) to receive more detailed data about treatment with CBM. Results: From medical records, we identified 98 patients who had used CBM (most often street cannabis followed by nabiximols, dronabinol, medicinal cannabis) for the treatment of GTS: Of the 38 patients who were able to judge, 66% preferred treatment with medicinal cannabis, 18% dronabinol, 11% nabiximols, and 5% street cannabis. Altogether, CBM resulted in a subjective improvement of tics (of about 60% in 85% of treated cases), comorbidities (55% of treated cases, most often OCB/OCD, ADHD, and sleeping disorders), and quality of life (93%). The effects of CBM appear to persist in the long term. Adverse events occurred in half of the patients, but they were rated as tolerable. Dosages of all CBM varied markedly. Patients assessed cannabis (with a preference for tetrahydrocannabinol [THC]-rich strains) as more effective and better tolerated compared with nabiximols and dronabinol. These data were confirmed by results obtained from the online survey (n=40). Conclusion: From our results, it is further supported that CBM might be effective and safe in the treatment of tics and comorbidities at least in a subgroup of adult patients with GTS. In our sample, patients favored THC-rich cannabis over dronabinol and nabiximols, which might be related to the entourage effect of cannabis. However, several limitations of the study have to be taken into considerations such as the open uncontrolled design and the retrospective data analysis.

Benefits and harms of medical cannabis: a scoping review of systematic reviews

BackgroundThere has been increased interest in the role of cannabis for treating medical conditions. The availability of different cannabis-based products can make the side effects of exposure unpredictable. We sought to conduct a scoping review of systematic reviews assessing benefits and harms of cannabis-based medicines for any condition.MethodsA protocol was followed throughout the conduct of this scoping review. A protocol-guided scoping review conduct. Searches of bibliographic databases (e.g., MEDLINE®, Embase, PsycINFO, the Cochrane Library) and gray literature were performed. Two people selected and charted data from systematic reviews. Categorizations emerged during data synthesis. The reporting of results from systematic reviews was performed at a high level appropriate for a scoping review.ResultsAfter screening 1975 citations, 72 systematic reviews were included. The reviews covered many conditions, the most common being pain management. Several reviews focused on management of pain as a symptom of conditions such as multiple sclerosis (MS), injury, and cancer. After pain, the most common symptoms treated were spasticity in MS, movement disturbances, nausea/vomiting, and mental health symptoms. An assessment of review findings lends to the understanding that, although in a small number of reviews results showed a benefit for reducing pain, the analysis approach and reporting in other reviews was sub-optimal, making it difficult to know how consistent findings are when considering pain in general. Adverse effects were reported in most reviews comparing cannabis with placebo (49/59, 83%) and in 20/24 (83%) of the reviews comparing cannabis to active drugs. Minor adverse effects (e.g., drowsiness, dizziness) were common and reported in over half of the reviews. Serious harms were not as common, but were reported in 21/59 (36%) reviews that reported on adverse effects. Overall, safety data was generally reported study-by-study, with few reviews synthesizing data. Only one review was rated as high quality, while the remaining were rated of moderate (n = 36) or low/critically low (n = 35) quality.ConclusionsResults from the included reviews were mixed, with most reporting an inability to draw conclusions due to inconsistent findings and a lack of rigorous evidence. Mild harms were frequently reported, and it is possible the harms of cannabis-based medicines may outweigh benefits.Systematic review registrationThe protocol for this scoping review was posted in the Open Access (https://ruor.uottawa.ca/handle/10393/37247).

Cannabis-Based Medicines and Medical Cannabis in Rheumatic Diseases: A Treasure Chest or Pandora’s box

Interest in cannabinoids as a therapy in rheumatic diseases has grown exponentially. With legalization of medical and recreational cannabis in many jurisdictions worldwide, patients have easier access and opportunity to explore medicinal use. We report on the evidence for effect of cannabinoids in rheumatic diseases and critically address the current challenges surrounding use. Preclinical study of cannabinoids points to an effect on pain and inflammation, fundamental features of rheumatic diseases. The findings of the few randomized controlled trials (RCTSs) of cannabis-based medicines in rheumatic diseases are limited by short study duration, small study samples, and methodology flaws. There are no RCTs of medical cannabis in rheumatic diseases. Therefore, current guidelines mostly recommend against use of any cannabinoid product for rheumatology patients. Even with limited clinical evidence, patients are increasingly showing interest in cannabis. Rheumatologists must be diligent in exploring other established treatment options prior to a trial of cannabinoids in any form. Cannabis holds potential as a treasure chest for rheumatic disease treatment, but with true effect and risks largely unknown and requiring study. Governments’ move to legalize medical cannabis has bypassed the established procedures of drug approval and opened Pandora’s box.

Living with a Hope of Survival Is Challenged by a Lack of Clinical Evidence: An Interview Study among Cancer Patients Using Cannabis-Based Medicine.

Background: There is an increasing focus among cancer patients on the use of cannabis-based medicine (CBM) as a supplement to conventional palliative care. However, physicians are reluctant to engage in dialog with the patients as clinical evidence is lacking. As a result, the patients are often left alone to rely on their own judgment in purchasing CBM products on the illegal market. Objective: Our study aimed to collect information from CBM treatment-experienced cancer patients receiving palliative care regarding treatment decision rationale and outcome. Design: A qualitative interview study using thematic analysis was performed. Setting/Participants: A total of 20 informants took part in individual interviews. Results: To the question addressing the main rationale for starting CBM treatment, all 20 patients responded that they carried a hope that cannabis would have a curative effect on the cancer disease. Most patients reported relief of symptoms, such as insomnia, anxiety, nausea, and pain, after initiation of CBM treatment, but this outcome was perceived as less of a focus in comparison to hope of a cure. Conclusion: This study contributes with knowledge from the perspective of the cancer patient in palliative care regarding the decision behind the use of CBM. There seems to be striving for surviving cancer based on the rationale that cannabis may constitute curative properties. Relief of symptoms is perceived as a secondary reason for treatment. This knowledge is essential in the dialog between the health professional and the cancer patient about the use of CBM products for treatment.

MEDICAL CANNABIS USE: EXPLORING THE PERCEPTIONS AND EXPERIENCES OF OLDER ADULTS WITH CHRONIC CONDITIONS

The past decade has witnessed an increased interest in the therapeutic properties of cannabis, and a growing body of research illustrates the varied uses of cannabis-based medicines for diverse symptoms, syndromes, disorder and both acute and chronic conditions, many of which are associated with advanced age (Lucas et. al, 2016). While the use of medical cannabis is on the rise in the older adult population (Kaskie et. al, 2017), more research is needed to advance the discourse on medical cannabis. With this study, we investigate older adult’s perceptions and experiences of medical cannabis use to treat and/or manage chronic conditions, specifically as a substitute for prescription drugs. Our findings suggest that older adults are open to medical cannabis as an alternative to pharmaceutical. Additionally, narratives revealed that users are hopeful that medical cannabis will provide relief with regard to the management of symptoms and relief of pain. Participants discussed their awareness and ability to manage issues related to stigma both from their primary care providers as well as family and friends. Furthermore, older adults described the frustrations with a lack of education, awareness, and support with dosing. Findings are presented as an interpretation of the participants’ perceptions of their medical cannabis use. Implications for putting medical cannabis use into everyday practice as well as policy implications are considered.

Study protocol for a randomised, double-blind, placebo-controlled study evaluating the Efficacy of cannabis-based Medicine Extract in slowing the disease pRogression of Amyotrophic Lateral sclerosis or motor neurone Disease: the EMERALD trial

IntroductionAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no known cure and with an average life expectancy of 3–5 years post diagnosis. The use of complementary medicine such as...

Cannabinoids in the treatment of rheumatic diseases: Pros and cons.

Medical cannabis is being increasingly used in the treatment of rheumatic diseases because, despite the paucity of evidence regarding its safety and efficacy, a growing number of countries are legalising its use for medical purposes in response to social pressure. Cannabinoids may be useful in the management of rheumatic disorders for two broad reasons: their anti-inflammatory and immunomodulatory activity, and their effects on pain and associated symptoms. It is interesting to note that, although a wide range of medications are available for the treatment of inflammation, including an ever-lengthening list of biological medications, the same is not true of the treatment of chronic pain, a cardinal symptom of many rheumatological disorders. The publication of systematic reviews (SR) concerning the use of cannabis-based medicines for chronic pain (with and without meta-analyses) is outpacing that of randomised controlled trials. Furthermore, narrative reviews of public institution are largely based on these SRs, which often reach different conclusions regarding the efficacy and safety of cannabis-based medicines because of the lack of high-quality evidence of efficacy and the presence of indications that they may be harmful for patients. Societal safety concerns about medical cannabis (e.g. driving risks, workplace safety and pediatric intoxication) must always be borne in mind, and will probably not be addressed by clinical studies. Medical cannabis and cannabis-based medicines have often been legalised as therapeutic products by legislative bodies without going through the usual process of regulatory approval founded on the results of traditional evidence-based studies. This review discusses the advantages and limitations of using cannabis to treat rheumatic conditions.

Cannabis-based medicines for chronic pain management

The medicinal use of cannabis has recently become the focus of much medical, as well as political, attention. This reality of growing use but limited evidence creates unique dilemmas for the prescribing clinician. The purpose of this review is to explore current evidence and gaps in knowledge and offer some practical considerations. There is robust preclinical data regarding the relevance of the endocannabinoid system to many pain-relevant processes. However, evidence to support cannabis-based medicines clinical use is still lacking. The best evidence to date is in managing neuropathic pain, although whether effects are clinically significant remains undetermined. However, the safety profile of cannabinoids seems favorable, especially by comparison to other medications used for pain control. The endocannabinoid system is undoubtedly a new and exciting pharmaceutical target for chronic pain management, but transition from preclinical to clinical studies has so far proved difficult. Although it is reasonable to consider cannabinoids for otherwise unresponsive pain, care should be taken in frail clinical populations. As this has become a socioeconomic and political issue in which agendas often take precedence over due diligence, there is a pressing need for unbiased empirical data and high quality evidence to better inform prescribers and patients.

Cannabinoids and Pain Management: an Insight into Recent Advancements

This review discusses the recent advancements in research on Cannabinoids’ role in pain, including its use in cancer pain, neuropathic pain, fibromyalgia, headache, visceral pain, postoperative and failed back pain management, and concurrent use with opioids. Current research suggests that a potential role exists for medical cannabis in pain management, although research shows varied effectiveness by the type of pain. Moreover, its coadministration with opioids may result in reduced opioid requirements. Patients with neuropathic pain, cancer pain, and migraine headache may benefit from the analgesic effects of a cannabis-based medicine (CBM), but not necessarily patients with chronic abdominal pain. Equivocal results were shown in fibromyalgia and postoperative orthopedic pain. Interestingly, the opioid-sparing properties of CBM make it an attractive option for pain management. However, the scale and quality of studies conducted are limited. Further research is necessary to establish recommendation guidelines for medical cannabis in pain management.

Medicinal cannabis and cannabis-based medication: an appeal to physicians, journalists, health insurances, and politicians for their responsible handling

Since the adoption of the law of March 6, 2017, any German physician can prescribe medical cannabis flowers and cannabis-based magistral and finished medicinal products. No specific indications for prescriptions are provided in the law. The statutory health insurance companies bear the costs once an application for cost coverage has been approved by the Medical Service of the Health Funds. The German associations of psychiatry (child, adolescents, and adults), neurology, palliative care, addictology, and pain medicine are watching these developments in the media, politics, and medical world with concern due to: the option to prescribe cannabis flowers despite the lack of sound evidence and against the recommendations of the German Medical Association; the lack of distinction between medical cannabis flowers and cannabis-based magistral and finished medical products; the indiscriminately positive reports on the efficacy of cannabis-based medicines for chronic pain and mental disorders; the attempts by the cannabis industry to influence physicians; the increase in potential indications by leaders of medical opinion paid by manufacturers of cannabis-based medicines. The medical associations make the following appeal to journalists: To report on the medical benefits and risks of cannabis-based medicines in a balanced manner. To physicians: to prescribe cannabis-based medicines with caution; to prefer magistral and finished medicinal products over cannabis flowers. To politicians: to consider data according to the standards of evidence-based medicine when making decisions and provide financial support for medical research into cannabis-based medicines.

A protocol for the systematic review and meta-analysis of studies in which cannabinoids were tested for antinociceptive effects in animal models of pathological or injury-related persistent pain.

Introduction:The International Association for the Study of Pain has established a global task force to comprehensively investigate the use of cannabinoids and cannabis-based medicines for pain management. This systematic review, the first in this field, will assess the preclinical literature that investigates the antinociceptive effects of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators in animal models of tissue damage, inflammation, or neuropathy.Methods:A systematic electronic search of 3 online databases will identify relevant studies in which cannabinoids, cannabis-based medicines, and endocannabinoid system modulators have been tested in animal models of injury-related or pathological persistent pain. Data will be extracted for pain-associated behavioural outcomes, study design, and the reporting of measures to avoid bias. Standardised mean difference meta-analysis will be used to provide summary estimates of efficacy, with the effects of study quality and study design explored using stratified meta-analysis.Perspective:The evaluation of the preclinical evidence will quantify the antinociceptive effects of cannabinoids on pain behaviour in animal models of pathological pain in an effort to quantify the presence and prevalence of analgesic efficacy. It will also provide an understanding of the strengths and weaknesses of the preclinical field and inform an agenda for future research.

Cannabis-based medicines for chronic pain: indications, selection of drugs, effectiveness and safety : Experiences of pain physicians in Saarland

There are uncertainties among physicians with respect to the indications, selection of drugs, effectiveness and safety of cannabis-based medicines for chronic pain. All statutory health insurance pain physicians in Saarland were asked to complete aself-developed questionnaire assessing their experiences with cannabis-based medicines, which they prescribed between 10 March 2017 and 30 November 2018 for adult patients with chronic cancer and non-cancer pain. All statutory health insurance pain physicians participated in the survey and 13 out of 20reported having prescribed cannabis-based medicines. The most frequent reasons for prescriptions in 136 patients (1.9% of the patients of the institutions) were failure of established treatment (73%) and desire of the patient (63%). In 35% of patients the type of pain was nociceptive, in 34% neuropathic, in 29% nociceptive and neuropathic and in 13% nociplastic. Dronabinol was prescribed for 95% of the patients and 71% were responders (clinically relevant reduction of pain or of other symptoms). In 29% of patients treatment was terminated due to either a lack of efficacy or adverse events. Statutory health insurance pain physicians in Saarland were reluctant to prescribe cannabis-based medicines. Dronabinol was effective and well-tolerated in the majority of the highly selected patients.

Illegal cannabis use is common among Danes with multiple sclerosis

BackgroundUse 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. MethodsAn 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. ResultsQuestionnaires 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. ConclusionThis 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.

Efficacy, tolerability and safety of cannabis-based medicines for cancer pain

The importance of medical cannabis and cannabis-based medicines for cancer pain management needs to be determined. Asystematic literature search until December 2018 included CENTRAL, PubMed, SCOPUS and trial registers. Randomised controlled trials (RCTs) investigating medical cannabis and/or pharmaceutical cannabinoids for pain control in cancer patients with astudy duration of at least 2weeks and asample size of at least 20participants per study arm were included. Clinical outcomes comprised efficacy (pain intensity, patient impression of improvement, combined responder, sleep problems, psychological distress, opioid maintenance and breakthrough dosage), tolerability (dropout rate due to adverse events) and safety (nervous system, psychiatric and gastrointestinal side effects; serious adverse events). The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Five RCTs with oromucosal nabiximols or tetrahydrocannabinol (THC) including 1534 participants with moderate and severe pain despite opioid therapy were identified. Double blind period of the RCTs ranged between 2 and 5weeks. Four studies with aparallel design and 1333 patients were available for meta-analysis. The quality of evidence was very low for all comparisons. Oromucosal nabiximols and THC did not differ from placebo in reducing pain, sleep problems, opioid dosages and in the frequency of combined responder, serious adverse events and psychiatric disorders side effects. The number of patients who reported to be much or very much improved was higher with oromucosal nabiximols and THC than with placebo (number needed to treat for an additional benefit 16; 95% confidence interval [CI] 8 to infinite). The dropout rates due to adverse events (number needed to treat for an additional harm [NNTH]:20; 95% CI 11-100), the frequency of nervous system (NNTH:10; 95% CI 7-25) and of gastrointestinal side effects (NNTH:11; 95% CI 7-33) was higher with oromucosal nabiximols and THC than with placebo. Very low quality evidence suggests that oromucosal nabiximols and THC have no effect on pain, sleep problems and opioid consumption in patients with cancer pain with insufficient pain relief from opioids. The complete manuscript is written in English.

Cannabinoids, cannabis, and cannabis-based medicine for pain management: a protocol for an overview of systematic reviews and a systematic review of randomised controlled trials.

Pain is an experience that affects many people worldwide and is associated with higher mortality and lower quality of life. Cannabinoid, cannabis, and cannabis-based medicines (CBMs) are thought to reduce pain, but a proliferation of different products has led to variability in trials, creating a challenge when determining the assessment of efficacy in systematic reviews. We will conduct 2 systematic reviews commissioned by the International Association for the Study of Pain Task Force on the use of cannabinoids, cannabis, and CBMs for pain management: first, an overview review of systematic reviews to summarise the evidence base and second, a systematic review of randomised controlled trials of cannabinoids, cannabis, and CBMs. In these reviews we will determine the harm and benefit of CBM from the current literature and will interpret the findings in light of the quality of evidence and reviews included. We will search online databases and registries in any language for systematic reviews and randomised controlled trials. We will include studies that evaluate any cannabinoid or CBM vs any control for people with acute and chronic pain. Our primary outcomes for both reviews are the number of participants achieving (1) a 30% and (2) 50% reduction in pain intensity, (3) moderate improvement, and (4) substantial improvement. A number of secondary outcome measures will also be included. We will assess risk of bias and quality of evidence. We will analyse data using fixed and random effect models, with separate comparators for cannabis and CBMs. Prospero ID (CRD42019124710; CRD42019124714).