The evidence behind medical cannabis – where are we now?

We have seen that there is early promise for medical cannabis in the clinical setting, but there is currently not enough high-quality clinical data to support further guidance.

Dr Daniel Couch | Medical Lead at the Centre for Medicinal Cannabis

Medical cannabis is unlike any other drug, new or old.  If I were to tell you that a drug prescribed since the 19th century now had a new disease target (such as aspirin recently being recommended for the prevention of some inherited bowel cancers) there would be little fanfare from the public.  There are no advocacy groups celebrating or calling for the wider use of aspirin.  Similarly, if I told you that there was a completely novel drug, recently developed with early evidence that it could be lifesaving or life changing there would be little public debate over it should be prescribed or even developed. Society generally adopts new medicines if they’re safe for use, if they work and if they’re affordable.

But then there’s medical cannabis, its numerous derivatives and combinations, and its synthetic substitutes. 

Medical cannabis has been used for centuries for its symptomatic effects, but it is unlike other medicines derived from “natural” origins.  Unlike aspirin, derived originally from the willow tree, morphine from poppies, and digoxin, a widely used heart medication, from foxglove, serious academic attention into how cannabis exerts its effects and how it could be clinically applied was effectively embargoed until the second half of the twentieth century.  Even after 1950, when academic papers exploring the science of cannabis begin to propagate, it remains a niche research area.  Seventy years on this body of research has grown, but slowly.  There is now a body of scientific and clinical research surrounding medical cannabis, although this is modest, perhaps because there are comparatively few academics in the field.  

One complicating matter for medical cannabis is its street availability.

People began noticing as early as during the Napoleonic wars that the recreational use of cannabis harboured symptomatic relief, and hence the colloquial use of cannabis in addition to the recreational has persisted to today.  Because of this and in opposition to the study of other drugs, where development of new therapeutics is left to academics and industry, patients have since been doing research of their own.  Last year a study from the Centre for Medicinal Cannabis estimated that around 1.4 million adults in the UK use recreational cannabis for the relief of symptoms from a diagnosed medical condition.  The majority of these sourced their cannabis from the street, rather than through a specialist clinician.  This leaves medical cannabis in a delicate and difficult position. On one hand we have academic research gradually and carefully elucidating where medical cannabis could be clinically useful, when it is safe to use and in what way. On the other we have public advocates vitriolically supporting its use and passionately calling for increased prescribing to what they see as a viable medicine.  The prevailing argument is that if sought through a pharmaceutical rather than recreational route reliance on criminal networks would be diminished and provide patients access to safer, more reliable medicines. 

In the middle lies the clinical relationship between patient and doctor. 

How can they jointly decide if any of the available preparations of medical cannabis are suitable for a condition when contemporary best medical care has failed?  How can they decide if they are safe and effective from the incomplete but growing clinical evidence?  No doctor wants to see their patient suffering through indecision, but likewise the mantra of “do no harm” must persist and in the absence of sufficient safety data many clinicians feel uncomfortable in prescribing unknowns to their patients.  In the UK the National Institute of Health and Care Excellence (NICE) assess the clinical evidence and safety profiles of novel medicines and provide recommendations on this basis to the NHS in context with the heath economic benefit of their prescription.  It is no secret that NICE guidance is sacrosanct amongst the majority of prescribers in the NHS.   This guidance provides a backstop for doctors in the event of adverse clinical incidents and represents the gates to the wider prescribing of any particular medication for an indication.  

In November 2019 NICE released long awaited guidance for the prescribing of cannabis-based medicines.  On review of the existing clinical evidence NICE recommended the use of nabilone for intractable chemotherapy induced nausea and vomiting, a trial of THC:CBD spray for spasticity in multiple sclerosis, and CBD for Dravet and Lennox-Gastaut epilepsy syndromes.  In this guidance these medicines can only be prescribed when others contemporary medications have failed, and only in the context of specialist practice with multi-disciplinary support. For some this guidance was long-awaited and well received, however many patients and clinicians were found frustrated by the conservative nature of the guidance and disappointed the NICE did not go further.  The underlying factor in this guidance is that NICE must produce recommendations based solely on the highest quality clinical evidence.  In the medical cannabis arena this evidence is still in a period of growth with many questions unanswered, but we can briefly review where evidence does and does not exist.

Three thorough reviews of the clinical evidence summarise the data well 1,2,3. Perhaps the most studied condition is spasticity in MS.  There is early evidence of good standard that THC and nabiximols benefit the relief of spasticity in this case though unfortunately, the evidence provided did not give data on the long-term effects and interestingly from the 14 controlled trials improvement was seen in patient reported measures, rather than those reported by the clinician.  There is also evidence from these studies that THC and nabiximols may help in the relief of pain in MS, however the data behind these conclusions was of limited benefit. Epilepsy has also been investigated, but the available data suffers from a significant risk of bias in the published studies.   This allowed NICE recommendation only for the relatively rare childhood epilepsy Dravet and Lennox-Gastaut syndromes.  Again, we await appropriately powered and well-conducted trials to determine if cannabis-based medicines can be of clinical benefit in the treatment of adult epilepsy after early promising, if unreliable data. In addition, there is also perhaps the most successful trials investigating the use of cannabis-based medicines for chemotherapy induced nausea and vomiting.  In 28 studies of 1772 patients trialling nabilone, dronabinol and nabiximols, against placebo or prochlorperazine, meta-analysis showed an odds ratio of 3.82 favouring cannabinoids over placebo, enough to justify NICE guidance.  Outside of the research supporting this, data has been published surrounding insomnia, chronic and acute pain, and glaucoma.  Unfortunately, although the data around chronic pain is of moderate quality none was insufficient to support further NICE recommendation.  Additionally, there is low quality evidence that cannabinoids increase appetite and weight gain in HIV/AIDS, improve sleep, improve ticks in Tourette’s syndrome, and may relieve anxiety, depression and psychosis, but not of sufficient quality to be confident of their clinical effects. 

So where now from here?

We have seen that there is early promise for medical cannabis in the clinical setting, but there is currently not enough high-quality clinical data to support further guidance.  Positive data alone is not enough, it must be free from bias so that we may unequivocally comment on its effectiveness and safety.  It would seem though that the urgent clinical data is unlikely to be forthcoming when examining the historical trend of medical cannabis research and perhaps a more cohesive research strategy should be adopted.