Few Well Done Studies Support Medical Use of Cannabis

MedicalResearch.com Interview with:
Penny F. Whiting, PhD
School of Social and Community Medicine, University of Bristol
The National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West at University Hospitals, Bristol NHS Foundation Trust, Bristol UK
Kleijnen Systematic Reviews Ltd, Escrick, York, United Kingdom

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Whiting: Cannabis is one of the most popular recreational drugs – only tobacco, alcohol and caffeine are more popular. It can result in an alteration to mood and a feeling of “high”. An estimated 141 million people use cannabis worldwide – this is equivalent to 2.5% of the world’s population. Cannabis has a long history of use for the relief of a wide variety of medical symptoms. There is evidence of its use for medical purposes going back to early Egyptian times. The pen-ts’ao ching the world’s oldest herbal book includes reference to cannabis as medicine for rheumatic pain, constipation, disorders of the female reproductive system, and malaria amongst others, this herbal book also contains the first reference to cannabis as a psychoactive drug. However, its use is controversial as it has been included as a controlled drug in the United Nations Single Convention on Narcotic Drugs since 1961, and the use of cannabis is illegal in most countries.

Medical cannabis (or medical marijuana) refers to the use of cannabis or cannabinoids (any compound, natural or synthetic, that can mimic the actions of plant-derived cannabinoids) as medical therapy to treat disease or alleviate symptoms, this is different from CBD oil that also has been found to help with certain medical conditions, click to see details about CBD oil. Some countries have legalised medicinal-grade cannabis to chronically ill patients but in others its use remains illegal even for medicinal purposes. Canada and the Netherlands have government-run programmes where specialised companies supply quality controlled herbal cannabis. There are different strains of cannabis can help with aliments, those who are interested in finding out more about a list of low odor strains by GreenBudGuru.com might be interested in visiting or doing some research to find out more. These programmes have been running since 2001 and 2003 respectively. In the US around half of the states have introduced laws to permit the medical use of cannabis; other countries have similar laws.

Kleijnen Systematic Reviews Ltd (see below) were commissioned by the Swiss Federal Office of Public Health to conduct a systematic review for the effects and adverse events of medical cannabis to inform policy decision making. Systematic reviews are studies of studies that offer a systematic approach to reviewing and summarising evidence. They follow a defined structure to identify, evaluate and summarise all available evidence addressing a particular research question. We were asked to focus on the following ten indications which were of particular interest to our commissioners: nausea and vomiting due to chemotherapy, patients with HIV/AIDS, chronic pain, spasticity in patients with multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, and Tourette’s syndrome. We only included randomised trials, the most robust design for evaluating the effects of an intervention. We included almost 80 trials (nearly 6500 participants). We had most evidence for chronic pain (28 trials), nausea and vomiting due to chemotherapy (28 trials) and spasticity due to MS or paraplegia (14 trials) with less than five studies included for each of the other indications and none for depression. With the exception of the nausea and vomiting due to chemotherapy population, studies general compared cannabinoids to placebo with only single studies for each indication comparing cannabinoid with an active comparator. In the nausea and vomiting population the majority of studies compared cannabinoids to an active comparator, most commonly prochlorperazine.

Most trials reported greater improvement in symptoms with cannabinoids compared to control groups, however, these did not always reach statistical significance. Cannabinoids were also associated with a greater risk of short term adverse events, including serious adverse events. Common adverse events included dizziness, dry mouth, nausea, fatigue, sleepiness, and euphoria. Overall we found that there was moderate quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity and low-quality evidence to suggest that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep quality, and Tourette syndrome. When determining the quality of the evidence we considered the risk of bias in trials, the consistency of the evidence across the trials, the directness of the evidence (was the trials research question directly applicable to our review question), and the precision of the evidence.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Whiting: We have used the same robust evidence based methods to evaluate the effects of medical cannabis (cannabinoids) as we would apply to any other intervention. It is important that all interventions are judged according to the same standards and that the potential benefits and adverse effects of cannabinoids are considered in light of the evidence and are not clouded by the issues around the legal status of cannabis. As systematic reviewers, we have provided a summary of the available evidence which clinicians and policy makers can now use this to make recommendations for practice.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Whiting: Further large, well conducted, randomised controlled trials are needed to confirm the effects of cannabinoids, particularly on weight gain in patients with HIV/AIDS, depression, sleep disorders, anxiety disorder, psychosis, glaucoma, and Tourette syndrome are required. We only found two studies that evaluated cannabis and so further trials evaluating cannabis itself are also required.

Two main challenges faced by our review were the poor reporting and lack of standardised outcome measures. Future trials therefore need to adhere to CONSORT reporting standards and report outcome data in a form that can be incorporated into meta-analyses. Poor reporting made it difficult to assess the risk of bias in the included trials and to extract appropriate numerical data for inclusion in meta-analyses (statistical combination of data from primary studies to give an estimate of the effect across all studies). Lack of standardised outcomes meant that included trials reported a wide variety of outcomes measured in different ways making it very difficult to combine data in a meaningful way. Future studies need to assess relevant outcomes (including disease-specific endpoints, quality of life, and adverse events) using standardised outcome measures at similar time points to ensure inclusion in meta-analyses.

Kleijnen Systematic Reviews Ltd (KSR Ltd)

Staff at KSR Ltd have many years of experience in preparing systematic reviews and health technology assessments of therapeutic, screening and diagnostic interventions. Such reviews have been used to support policy making, local decision making about commissioning health services, fourth hurdle processes (such as for NICE in the UK, or for IQWiG in Germany), and guideline development. We have extensive experience in all these areas and our names appear as authors on numerous journal publications, technology assessment reports for NICE, systematic reviews for IQWiG, health technology assessment reports, and guidelines.

KSR Ltd has also been appointed as a “Centre of Excellence” for Technology Assessment Reviews (TARs) by the National Institute for Health Research (NIHR). In this capacity we are involved in providing TARs for national UK NHS decision-making bodies and policy customers, such as the National Institute for Health and Care Excellence (NICE). Such TARs are most commonly produced to inform NICE Appraisal Committee guidance on the use of new and existing medicines, treatments and procedures within the NHS in England and Wales.

Citation:

Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA.2015;313(24):2456-2473. doi:10.1001/jama.2015.6358.

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Penny F. Whiting, PhD, School of Social and Community Medicine, University of Bristol, & The National Institute for Health Research Collaboration for Leadership in Applied Health (2015). Few Well Done Studies Support Medical Use of Cannabis

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