Therapeutic use of cannabis and cannabinoids: benefits and risks.

Societal issues and policy implications related to the use of cannabinoids, cannabis, and cannabis-based medicines for pain management.

Ensuring access to safe, effective, and affordable cannabis-based medicines.

Cannabis and cannabinoids have been used medically and recreationally for thousands of years and recently there has been a growing body of research in this area. With increased access now that medical marijuana is available in many jurisdictions, patients and providers want to know more about the evidence for benefits and risks of cannabinoid use. This paper provides an overview of the available cannabinoid-based formulations, a summary of the highest quality evidence for the use of cannabinoids for treating spasticity and pain associated with multiple sclerosis (MS), and a discussion of possible dosing regimens based on information from these studies. Two recent high-quality systematic reviews concluded that the only strong evidence for medical marijuana in neurological disorders was for reducing the symptoms of patient-reported spasticity and central pain in MS and that the only complementary and alternative medicine (CAM) intervention in MS with strong supportive evidence was cannabinoids. Based on this review, they concluded that nabiximols (Sativex oral spray), oral cannabis extract (OCE), and synthetic tetrahydrocannabinol (THC) are probably effective at reducing patient-reported symptoms of spasticity in people with MS, but OCE and synthetic THC were not found to be effective for reducing physician-administered measures of spasticity. In addition, nabiximols, OCE, and synthetic THC are probably effective at reducing MS-related pain. Cannabinoids were generally well-tolerated. However, cannabis use has been associated with an increased risk of psychosis and schizophrenia in at-risk individuals, there is growing evidence that cannabis can increase the risk for cardiovascular diseases, including myocardial infarction (MI), hypertension, heart failure, and stroke, and a recently recognized adverse effect of cannabis is cannabinoid hyperemesis syndrome. The medical use of cannabinoids remains controversial. While cannabinoids have been studied for a variety of neurologic disorders, there is strongest evidence to indicate benefits in treatment of spasticity and neuropathic pain in multiple sclerosis. Although the best dose for an individual remains uncertain, most participants in the studies discussed in this paper used between 20 and 40mg of THC a day in divided doses. Adverse events in studies were generally more common in the groups using cannabinoid products but serious adverse events were rare and cannabis products were generally well-tolerated. Cannabis use does appear to be associated with increased risk of certain adverse events, including psychosis, cardiovascular diseases, and cannabinoid hyperemesis syndrome.

The debate regarding therapeutic use of cannabis is being confused by a lack of distinction between therapeutic and social use of cannabis. Separate consideration of therapeutic and social use would enable strategies to minimise any negative social impact of therapeutic use. For therapeutic use of cannabis to be considered on its own merits, greater emphasis needs to be placed on scientific evidence of therapeutic efficacy. At present the evidence is limited, it mostly relates to the use of synthetic cannabinoids, and much of it fails to compare cannabis with the best therapies available for the conditions of interest. Claims of therapeutic efficacy tend to be based on opinion and anecdote rather than the results of controlled studies. Further research is needed to clarify the potential therapeutic benefits, to enable claims of therapeutic use to be objectively assessed and to enable informed decisions to be made about the relative risks and benefits for any individual using cannabis for therapeutic purposes. Further research is required to clarify the efficacy of pure, synthetic cannabinoids compared to cannabis, the most effective route of administration, and the importance of delivering a known dose. The most likely value of cannabis is as an adjunct, rather than a replacement for, current medical approaches. The potential therapeutic benefits of cannabis will be greatest for those conditions where long-term cannabis use, with its attendant health risks, is not an issue and where the patient has the capacity to titrate dose against symptoms. There is sufficient evidence of potential therapeutic benefit to justify the facilitation of further research.

Cannabinoids and the Coronavirus.

There is an increasing interest in the therapeutic use of cannabis worldwide, with a number of cannabinoid-derived drugs currently approved by the Food and Drug Administration (FDA) for certain indications. This study was conducted via a printed questionnaire and aimed to explore the attitudes and knowledge regarding the therapeutic use of cannabis and cannabinoids among community pharmacists residing in Amman, Jordan. The results revealed a neutral to low agreement level regarding the medical usefulness of cannabis; however, a higher agreement level was observed for FDA-approved cannabinoid-derived drugs. The majority of the participants reported that they did not learn enough regarding cannabinoids, do not adequately remember what they have learned, and do not actively look for information after graduation. The average percentages of correct identification of cannabis/cannabinoid FDA-approved drug indications, common adverse effects, interacting drugs, and cautions/contraindications were 40.6%, 53%, 49.4%, and 57.3%, respectively, with an overall correct identification rate of 51.1% of the participants. In conclusion, the results indicate an inadequate level of knowledge with a significant room for improvement regarding the various aspects of cannabinoid pharmacology.

BackgroundAlthough cannabis and cannabinoids are widely used with therapeutic purposes, their claimed efficacy is highly controversial. For this reason, medical cannabis use is a broad field of research that is rapidly expanding. Our objectives are to identify, characterize, appraise, and organize the current available evidence surrounding therapeutic use of cannabis and cannabinoids, using evidence maps.MethodsWe searched PubMed, EMBASE, The Cochrane Library and CINAHL, to identify systematic reviews (SRs) published from their inception up to December 2017. Two authors assessed eligibility and extracted data independently. We assessed methodological quality of the included SRs using the AMSTAR tool. To illustrate the extent of use of medical cannabis, we organized the results according to identified PICO questions using bubble plots corresponding to different clinical scenarios.ResultsA total of 44 SRs published between 2001 and 2017 were included in this evidence mapping with data from 158 individual studies. We extracted 96 PICO questions in the following medical conditions: multiple sclerosis, movement disorders (e.g. Tourette Syndrome, Parkinson Disease), psychiatry conditions, Alzheimer disease, epilepsy, acute and chronic pain, cancer, neuropathic pain, symptoms related to cancer (e.g. emesis and anorexia related with chemotherapy), rheumatic disorders, HIV-related symptoms, glaucoma, and COPD. The evidence about these conditions is heterogeneous regarding the conclusions and the quality of the individual primary studies. The quality of the SRs was moderate to high according to AMSTAR scores.ConclusionsEvidence on medical uses of cannabis is broad. However, due to methodological limitations, conclusions were weak in most of the assessed comparisons. Evidence mapping methodology is useful to perform an overview of available research, since it is possible to systematically describe the extent and distribution of evidence, and to organize scattered data.

BackgroundDespite growing interest in the therapeutic use of cannabis to manage chronic pain, only limited data that address these issues are available. In recent years, a number of nations have introduced specific laws to allow patients to use cannabis preparations to treat a variety of medical conditions. In 2015, the Italian government authorized the use of cannabis to treat several diseases, including chronic pain generally, spasticity in multiple sclerosis, cachexia and anorexia among AIDS and cancer patients, glaucoma, Tourette syndrome, and certain types of epilepsy. We present the first snapshot of the Italian experience with cannabis use for chronic pain over the initial year of its use.MethodsThis is a retrospective case series analysis of all chronic pain patients treated with oral or vaporized cannabis in six hubs during the initial year following the approval of the new Italian law (December 2015 to November 2016). We evaluated routes of administration, types of cannabis products utilized, dosing, and effectiveness and safety of the treatment.ResultsAs only one of the six centers has extensively used cannabinoids for intractable chronic pain (614 patients of 659), only the population from Azienda Ospedaliero Universitaria Pisana (Pisa) was considered. Cannabis tea was the primary mode of delivery, and in almost all cases, it was used in association with all the other pain treatments. Initial and follow-up cannabinoid concentrations were found to vary considerably. At initial follow-up, 76.2% of patients continued the treatment, and <15% stopped the treatment due to side effects (none of which were severe).ConclusionWe present the first analysis of Italian clinical practice of the use of cannabinoids for a large variety of chronic pain syndromes. From this initial snapshot, we determined that the treatment seems to be effective and safe, although more data and subsequent trials are needed to better investigate its ideal clinical indication.

PC-FACS

Introduction and objective: Therapy with the use of "medical marijuana" is becoming more and more popular with patients, who often perceive it as a more natural and safe form of treatment. It is also more and more boldly considered by physicians in the pediatric population, especially when standard methods of pharmacotherapy prove insufficient. The following review focuses on the possibilities of using cannabis preparations in children with drug-resistant epilepsy, autism spectrum disorders and spasticity. It also draws attention to the possible side effects and risks of unjustified use of medical marijuana. State of knowledge: In the pediatric population, high efficacy and a favorable safety profile have been proven so far in the treatment of epileptic seizures associated with Lennox-Gastaut syndrome and Dravet syndrome, and for the treatment of epileptic seizures in tuberous sclerosis complex, (TSC) . Although the therapy has been approved only for the above-mentioned indications, high hopes are also placed on the use of cannabinoids to treat the symptoms of other diseases and disorders, including spasticity and autism spectrum disorders. Conclusions: The research carried out so far gives hope for the possibility of using medical marijuana in other indications as well, as its use correlates with the reduction of i.a. symptoms of spasticity or autism spectrum disorders. At the same time, further studies are needed to assess the balance of benefits and potential risks of the therapy. Since recreational cannabis use in youth is known to be associated with serious adverse events, and medical cannabis use has a relatively strong placebo effect, decisions about its use should always be made carefully and based on scientific evidence.

Momentum grows for medical use of cannabis

This review is to summarize most recent evidence published in the last 18 months on medical and recreational use of cannabis and cannabinoids in relation to anxiety, depression (unipolar and bipolar), and dysregulation of emotions as part of posttraumatic stress disorders (PTSD) and emotionally instable personality disorders. It also covers the investigation of endocannabinoids as potential biomarkers in these conditions. This is important with increasing medicinal use of cannabinoids and growing social tolerance towards recreational cannabis use. There is some recent evidence suggesting cannabinoids, cannabidiol or cannabidiol-enriched cannabis preparations have anxiolytic properties. In addition, depression may be worsened by cannabis use, however, randomized controlled trials (RCT) are lacking. New evidence also suggests that cannabidiol or cannabidiol-enriched cannabis use for PTSD and emotion regulation can induce hyporesponse to fear and stress. Further, several lines of evidence point to the endocannabinoid system as a key player in some of the reviewed disorders, in particular anxiety and PTSD. The most recent evidence for a therapeutic use of cannabinoids in the reviewed conditions is weak and lacking well designed RCTs. However, there is some indication of the role of the endocannabinoid system in these conditions that warrant further studies.

This article summarizes pharmacological and nonpharmacological therapies for cannabinoid hyperemesis syndrome (CHS) that may be utilized in the emergency department (ED). CHS is an increasingly common condition in the ED characterized by cyclic vomiting and abdominal pain in the setting of excessive consumption of cannabis or cannabinoid use. Symptoms are usually alleviated by hot baths or showers, but when they persist patients often present to the ED. Emergency medicine pharmacists should be able to recognize the common presentation of CHS and assist with treatment of these patients in the ED. There is a paucity of data regarding the most effective pharmacotherapy for CHS, but cessation of cannabis use is accepted as the quintessential cure. Common therapies for CHS include dopamine antagonists such as haloperidol and droperidol, conventional antiemetics such as ondansetron and metoclopramide, and topical capsaicin. Opioids and benzodiazepines should not be used as first-line therapy for CHS.

The therapeutic use of cannabis and cannabis-based medicines raises safety concerns for patients, clinicians, policy-makers, insurers, researchers and regulators. Although the efficacy of cannabinoids is being increasingly demonstrated in randomized controlled trials, most safety information comes from studies of recreational use. We performed a systematic review of safety studies of medical cannabinoids published over the past 40 years to create an evidence base for cannabis-related adverse events and to facilitate future cannabis research initiatives. We critically evaluated the quality of published studies with a view to identifying ways to improve future studies. A total of 321 articles were eligible for evaluation. After excluding those that focused on recreational cannabis use, we included 31 studies (23 randomized controlled trials and 8 observational studies) of medical cannabis use in our analysis. In the 23 randomized controlled trials, the median duration of cannabinoid exposure was 2 weeks (range 8 hours to 12 months). A total of 4779 adverse events were reported among participants assigned to the intervention. Most (4615 [96.6%]) were not serious. Of the 164 serious adverse events, the most common was relapse of multiple sclerosis (21 events [12.8%]), vomiting (16 events [9.8%]) and urinary tract infection (15 events [9.1%]). The rate of nonserious adverse events was higher among participants assigned to medical cannabinoids than among controls (rate ratio [RR] 1.86, 95% confidence interval [CI] 1.57-2.21); the rates of serious adverse events did not differ significantly between these 2 groups (RR 1.04, 95% CI 0.78-1.39). Dizziness was the most commonly reported nonserious adverse event (714 events [15.5%]) among people exposed to cannabinoids. Short-term use of existing medical cannabinoids appeared to increase the risk of nonserious adverse events. The risks associated with long-term use were poorly characterized in published clinical trials and observational studies. High-quality trials of long-term exposure are required to further characterize safety issues related to the use of medical cannabinoids.

Cyclic vomiting attacks associated with chronic cannabis use were virtually unknown until 25 years ago. Following legalization of cannabis for recreational use in North America and the resulting increase in high-potency cannabis use, the prevalence of cannabis-related cyclic vomiting in emergency departments was increasing at an alarming rate. In the ROME-IV criteria, cannabis-induced cyclic vomiting is now defined as cannabinoid hyperemesis syndrome (CHS). This review is intended to provide information on the current state of knowledge on CHS, as an increase in CHS cases is also to be expected in Germany following the partial legalization of cannabis for recreational use.Scoping review on the diagnosis, complications, treatment options and prognosis of CHSCannabis-related cyclic vomiting attacks are better known in emergency medicine than in general medicine and addiction medicine. Young adults are often affected. A reliable differentiation between CHS and the nosologically related cyclic vomiting syndrome (CVS) - in which 30% of those affected also use cannabis chronically - is only possible by establishing remission during at least 6 months of abstinence. For this reason, mixed forms of CVS and CHS are usually seen in emergency departments (suspicious CHS), sometimes with masked life-threatening comorbidities. Severe vomiting can also lead to serious complications. Common antiemetics are often ineffective. Hot showers and baths (diagnostic secondary criterion in ROM-IV) and haloperidol (up to 5 mg i.m.) can acutely alleviate the severe vomiting. Rubbing the abdomen with 0.075-0.1% capsaicin cream also helps, but less quickly. After several cyclical CHS clusters, the individual threshold for their occurrence decreases continuously (chronification): Cannabis relapses, even at low doses, lead to stronger and longer cyclic CHS clusters than experienced before (sensitization).CHS is nosologically classified in ROME-IV as a specific variant of CVS, but it is also a specific and mostly a severe cannabis-related disorder. As full remission and cure (full remission for at least 5 years) can only be achieved through sustained abstinence from cannabis, suspected CHS presents an interdisciplinary challenge for various medical disciplines, consultation/liaison psychiatry and addiction support systems.