Medicinal cannabis for treating post-traumatic stress disorder and comorbid depression: real-world evidence.

BACKGROUND: Cannabis-based medicinal products (CBMPs) are increasingly being used to treat post-traumatic stress disorder (PTSD), despite limited evidence of their efficacy. PTSD is often comorbid with major depression, and little is known about whether comorbid depression alters the effectiveness of CBMPs. AIMS: To document the prevalence of depression among individuals seeking CBMPs to treat PTSD and to examine whether the effectiveness of CBMPs varies by depression status. METHOD: Data were available for 238 people with PTSD seeking CBMP treatment (5.9% of the treatment-seeking sample) and 3-month follow-up data were available for 116 of these. Self-reported PTSD symptoms were assessed at treatment entry and at 3-month follow-up using the PTSD Checklist - Civilian Version (PCL-C). The probable presence of comorbid depression at treatment entry was assessed using the nine-item Patient Health Questionnaire (PHQ-9). Additional data included sociodemographic characteristics and self-reported quality of life. RESULTS: In total, 77% met screening criteria for depression, which was associated with higher levels of PTSD symptomatology (mean 67.8 v. 48.4, F(1,236) = 118.5, P < 0.001) and poorer general health, quality of life and sleep. PTSD symptomatology reduced substantially 3 months after commencing treatment (mean 58.0 v. 47.0, F(1,112) = 14.5, P < 0.001), with a significant interaction (F(1,112) = 6.2, P < 0.05) indicating greater improvement in those with depression (mean difference 15.3) than in those without (mean difference 7). CONCLUSIONS: Depression is common among individuals seeking CBMPs to treat PTSD and is associated with greater symptom severity and poorer quality of life. Effectiveness of CBMPs for treating PTSD does not appear to be impaired in people with comorbid depression.

Feasibility of a cannabidiol-dominant cannabis-based medicinal product for the treatment of long COVID symptoms: A single-arm open-label feasibility trial.

AIMS: To conduct a single-arm open-label feasibility trial of the safety and tolerability of a full-spectrum cannabidiol (CBD)-dominant cannabis-based medicinal product for treating the symptoms of long COVID. METHODS: The treatment phase ran for a total of 21 weeks, followed by ~3 weeks without the study drug. Participants received up to 3 mL of MediCabilis 5% CBD Oil (50 mg CBD/mL, <2 mg δ-9-tetrahydrocannabinol/mL) per day orally. Monthly patient-reported outcome measures of common symptoms and daily self-report of symptoms were collected via a smartphone app. Key measures of heart rate, activity, sleep and oxygen saturation were assessed using wearable technology. RESULTS: Twelve (1 male, 11 female) individuals diagnosed with long COVID were recruited into the trial. All participants adhered to the treatment protocol for the duration of the study and there were no serious adverse events. Response rates for the research assessments were high with over 90% completion of patient-reported outcome measures and daily self-report. CONCLUSION: The study drug was safe and well-tolerated, demonstrating feasibility of CBD-dominant cannabis-based medicinal products in individuals diagnosed with long COVID. However, there were limitations in research design related to recruitment strategy demonstrating a lack of feasibility in the approach implemented in this study. Future work with larger samples and incorporating a control group are required to test the efficacy of this treatment.

The value of real world evidence: The case of medical cannabis.

Randomised controlled trials (RCTs) have long been considered the gold standard of medical evidence. In relation to cannabis based medicinal products (CBMPs), this focus on RCTs has led to very restrictive guidelines in the UK, which are limiting patient access. There is general agreement that RCT evidence in relation to CBPMs is insufficient at present. As well as commercial reasons, a major problem is that RCTs do not lend themselves well to the study of whole plant medicines. One solution to this challenge is the use of real world evidence (RWE) with patient reported outcomes (PROs) to widen the evidence base. Such data increasingly highlights the positive impact medical cannabis can have on patients' lives. This paper outlines the value of this approach which involves the study of interventions and patients longitudinally under medical care. In relation to CBMPs, RWE has a broad range of advantages. These include the study of larger groups of patients, the use of a broader range and ratio of components of CBMPs, and the inclusion of more and rarer medical conditions. Importantly, and in contrast to RCTs, patients with significant comorbidities-and from a wider demographic profile-can also be studied, so providing higher ecological validity and increasing patient numbers, whilst offering significant cost savings. We conclude by outlining 12 key recommendations of the value of RWE in relation to medical cannabis. We hope that this paper will help policymakers and prescribers understand the importance of RWE in relation to medical cannabis and help them develop approaches to overcome the current situation which is detrimental to patients.

Characteristics of People Seeking Prescribed Cannabinoids for the Treatment of Chronic Pain: Evidence From Project Twenty 21.

Background: Prescribed cannabinoids are now legal in the UK and increasingly being used for a variety of conditions, with one of the most frequent conditions being chronic pain. This paper describes the characteristics of individuals seeking prescribed cannabinoids for the treatment of chronic pain in Project Twenty 21, a UK based real world data registry of prescribed cannabis patients. Method: By 1st November 2021 data were available for 1,782 people who had sought treatment with medical cannabis as part of Project Twenty 21. The most common diagnosis among this cohort was chronic pain with 949 (53.5%) of the cohort reporting a primary condition related to chronic pain. Medical and self-report data on the characteristics of these patients, their health status and type/s of cannabinoid/s prescribed are summarized in this report. Results: Of the 949 people reporting chronic pain as a primary condition 54.7% were male and their average age was 42.0 years (range = 18-84). Patients reported a low quality of life and high levels of comorbidity: people reported an average of 4.6 comorbid conditions with the most common comorbid conditions including anxiety, depression, insomnia and stress. A range of cannabinoid products were prescribed with the most common products being classified as high THC flower (48.5%). The majority of patients also reported using at least one other prescribed medication (68.7%). Conclusions: Consistent with findings in other national and international databases, chronic pain was the most common primary condition in this real world study of prescribed cannabinoids. There was considerable variation in the types of chronic pain, comorbid pathology and in the characteristics of products being prescribed to treat these conditions. Together, this evidence supports the utility of real world evidence, as opposed to clinical trial approaches to studying the potential benefits of prescribed cannabinoids in treating chronic pain.

Cannabinoids and the endocannabinoid system in fibromyalgia: A review of preclinical and clinical research.

Characterised by chronic widespread musculoskeletal pain, generalised hyperalgesia, and psychological distress, fibromyalgia (FM) is a significant unmet clinical need. The endogenous cannabinoid system plays an important role in modulating both pain and the stress response. Here, we appraise the evidence, from preclinical and clinical studies, for a role of the endocannabinoid system in FM and the therapeutic potential of targeting the endocannabinoid system. While many animal models have been used to study FM, the reserpine-induced myalgia model has emerged as perhaps the most translatable to the clinical phenotype. Inhibition of fatty acid amide hydrolase (FAAH) has shown promise in preclinical studies, ameliorating pain- and anxiety-related behaviour . Clinically, there is evidence for alterations in the endocannabinoid system in patients with FM, including single nucleotide polymorphisms and increased levels of circulating endocannabinoids and related N-acylethanolamines. Single entity cannabinoids, cannabis, and cannabis-based medicines in patients with FM show promise therapeutically but limitations in methodology and lack of longitudinal studies to assess efficacy and tolerability preclude the current recommendation for their use in patients with FM. Gaps in the literature that warrant further investigation are discussed, particularly the need for further development of animal models with high validity for the multifaceted nature of FM, balanced studies to eliminate sex-bias in preclinical research, and ultimately, better translation between preclinical and clinical research.

Current controversies in medical cannabis: Recent developments in human clinical applications and potential therapeutics.

Knowledge about the therapeutic potential of medical cannabis has greatly improved over the past decade, with an ever-increasing range of developments in human clinical applications. A growing body of scientific evidence supports the use of medical cannabis products for some therapeutic indications, whilst for others, the evidence base remains disputed. For this narrative review, we incorporate areas where the current evidence base is substantial, such as intractable childhood epilepsy and multiple sclerosis, as well as areas where the evidence is still controversial, such as PTSD and anxiety. We provide a high-level summary of current developments using findings from recent major reviews, as well as real world evidence (RWE), including global database registries and other patient reported outcomes (PROs). On the one hand, our strongest empirical data supports the use of cannabis-based medicinal products (CBMPs) for conditions with relatively small patient numbers. Yet on the other hand, the conditions, where the highest patient numbers present, often have debatable clinical evidence but good RWE, incorporating PROs of 1000s of patients. The discord between PROs and the respective strength of the evidence from randomised controlled trials (RCTs) highlights the urgent need for further research. The scientific literature examining the efficacy of medical cannabis for many conditions is still developing, whilst large numbers of patients globally have been successfully using medical cannabis to treat a broad range of conditions. We conclude on the importance of systematically developing RWE databases to supplement RCTs and to bridge the current evidence gaps.

A multi criteria decision analysis (MCDA) for evaluating and appraising government policy responses to non medical heroin use.

BACKGROUND: Globally, non-medical heroin use is generating significant public health and social harms, and drug policy about heroin is a controversial field that encompasses many complex issues. Policy responses to illegal heroin markets have varied from militarized eradication of the opium poppy and harsh punishment of users, to more tolerant harm reduction approaches with decriminalized possession and use. METHODS: This paper reports the outcomes of a multi-criteria decision analysis (MCDA) on four generic regulatory regimes of heroin: prohibition, decriminalisation, state control and free market. Invited experts on drug harms, addiction, criminology and drug policy developed a comprehensive set of 27 policy outcome criteria against which these drug policy regimes were assessed. RESULTS: State control of heroin was identified as the preferred policy option although other policy regimes scored better on specific outcome criteria. The free market model scored better than decriminalisation, with absolute prohibition scoring worst on every criterium. The ranking of the regimes was robust to variations in the criterion-specific weights. CONCLUSION: The implications of these findings for the development of future policy responses to heroin and opioids generally are discussed in detail. Despite increasing overdose deaths and an opioid epidemic in North America, prohibition remains the predominant policy approach to heroin regulation at present. It is hoped that the current paper adds to the discussion of finding a valid regulatory alternative.

So near yet so far: why won't the UK prescribe medical cannabis?

Although cannabis-based products for medicinal use are now legal in the UK, it is still challenging for patients to gain access, and only very few National Health Service prescriptions have been written to date. This paper attempts to make sense of why the UK lags behind so many other countries which also have legalised medical cannabis. From consulting with parents and patients, prescribers, pharmacists and decision-makers it seems that there are a series of distinct barriers to prescribing that need to be overcome in order to improve patient access to medical cannabis in the UK. These include concerns about the perceived lack of scientific evidence. To alleviate these concerns, we highlight the importance of patient-centred approaches including patient-reported outcomes, pharmacoepidemiology and n=1 trials, which can contribute to the development of the evidence base for medical cannabis. We hope that this paper will help policymakers and prescribers understand the challenges to prescribing and so help them develop approaches to overcome the current situation which is detrimental to patients.

Medical cannabis in the UK: From principle to practice.

BACKGROUND: In the UK, medical cannabis was approved in November 2018, leading many patients to believe that the medicine would now be available on the NHS. Yet, to date, there have been only 12 NHS prescriptions and less than 60 prescriptions in total. In marked contrast, a recent patient survey by the Centre for Medical Cannabis (Couch, 2020) found 1.4 m people are using illicit cannabis for medical problems. AIMS: Such a mismatch between demand and supply is rare in medicine. This article outlines some of the current controversies about medical cannabis that underpin this disparity, beginning by contrasting current medical evidence from research studies with patient-reported outcomes. OUTCOMES: Although definite scientific evidence is scarce for most conditions, there is significant patient demand for access to medical cannabis. This disparity poses a challenge for prescribers, and there are many concerns of physicians when deciding if, and how, to prescribe medical cannabis which still need to be addressed. Potential solutions are outlined as to how the medical profession and regulators could respond to the strong demand from patients and families for access to medical cannabis to treat chronic illnesses when there is often a limited scientific evidence base on whether and how to use it in many of these conditions. CONCLUSIONS: There is a need to maximise both clinical research and patient benefit, in a safe, cautious and ethical manner, so that those patients for whom cannabis is shown to be effective can access it. We hope our discussion and outlines for future progress offer a contribution to this process.

An Evaluation of Regulatory Regimes of Medical Cannabis: What Lessons Can Be Learned for the UK?

This paper evaluates current regulatory regimes of medical cannabis using peer-reviewed and grey literature as well as personal communications. Despite the legalization of medical cannabis in the UK in November 2018, patients still lack access to the medicine, with fewer than 10 NHS prescriptions having been written to date. We look at six countries that have been at the forefront of prescribing medical cannabis, including case studies of the three largest medical cannabis markets in the EU: Germany, Italy, and the Netherlands. Canada, Israel and Australia add global examples. These countries have a more successful history of prescribing medical cannabis than the UK. Their legislations are outlined and numbers of medical cannabis prescriptions are provided to give an indication of how successful their regulatory regime has been in providing patient access. Evaluating countries' medical cannabis regulations allows us to offer implications for lessons to be learned for the development of a successful medical cannabis regime in the UK.

A new approach to formulating and appraising drug policy: A multi-criterion decision analysis applied to alcohol and cannabis regulation.

BACKGROUND: Drug policy, whether for legal or illegal substances, is a controversial field that encompasses many complex issues. Policies can have effects on a myriad of outcomes and stakeholders differ in the outcomes they consider and value, while relevant knowledge on policy effects is dispersed across multiple research disciplines making integrated judgements difficult. METHODS: Experts on drug harms, addiction, criminology and drug policy were invited to a decision conference to develop a multi-criterion decision analysis (MCDA) model for appraising alternative regulatory regimes. Participants collectively defined regulatory regimes and identified outcome criteria reflecting ethical and normative concerns. For cannabis and alcohol separately, participants evaluated each regulatory regime on each criterion and weighted the criteria to provide summary scores for comparing different regimes. RESULTS: Four generic regulatory regimes were defined: absolute prohibition, decriminalisation, state control and free market. Participants also identified 27 relevant criteria which were organised into seven thematically related clusters. State control was the preferred regime for both alcohol and cannabis. The ranking of the regimes was robust to variations in the criterion-specific weights. CONCLUSION: The MCDA process allowed the participants to deconstruct complex drug policy issues into a set of simpler judgements that led to consensus about the results.