I RECENTLY wrote about a “true life drama”: the struggling family of a disabled child who rejected conventional medicine fell into the arms of the organised antivaccination movement and treated his seizures with unregulated cannabis oil, supplied by a deregistered doctor. The child has cerebral palsy, microcephaly and epilespy, and is fed via a percutaenous tube. In the comments section, we discussed how families are vulnerable to charlatans who offer simple solutions – especially where medicine doesn’t “have all the answers”.
In the same issue of MJA Insight there was an article reporting a study of the efficacy of cannabidiol (CBD) in controlling seizures in the rare genetic disorder severe myoclonic epilepsy of infancy, known as Dravet syndrome. This syndrome – difficult to control with conventional anti-epileptics – has become a focus for the campaign for the so-called “medical cannabis”.
As I said in the comments section, the push to take advantage of the potential therapeutic effects of cannabis extracts has become muddied by the campaign to legalise recreational use. As potential prescribers, it is important for all of us to be as informed as possible about the various aspects of this debate: clinical, social and legal.
Like the opium poppy, the plant Cannabis sativa contains a mix of plant chemicals with physiologically active – including psychoactive – properties. Like morphine, cannabis can alleviate a range of symptoms and cause a range of side effects. Both can be used and misused, both are prone to habituation and addiction.
Like most so-called “medicinal herbs”, raw plant material is chemically and structurally very complex. The potentially beneficial compounds may be packaged together with toxic ones, or bound to fibrous material. The amount of the desirable chemicals varies from plant to plant – genetically, regionally and according to season. It is for this reason that herbal medicine developed into modern pharmaceutical medicine – where active ingredients are purified and standardised to maximise both safety and efficacy.
In cannabis plants, there is a wide variation in content of the two main active compounds. Tetrahydrocannabinol is responsible for most of the psychotropic effects and is also the constituent that promotes misuse. In the United States, it is sometimes prescribed as an extract – or analogue – for the treatment of nausea and appetite stimulation in oncology patients, and for control of spasticity in multiple sclerosis. In heavy regular use, it may also stimulate the bizarre syndrome of cyclical vomiting, where patients spend hours under a hot shower to relieve their distress .
The other major compound ( CBD) has been the focus of research for treatment-resistant epilepsy. As this article explains, human studies so far have been poorly conducted and have shown mixed results.
So, back to the study in Dravet syndrome that I mentioned above – published in May 2017 in the New England Journal of Medicine. The trial was funded by GW Pharmaceuticals, and the company was responsible for the trial design, trial management, site monitoring, trial pharmacovigilance, data analysis and statistical analysis, as well as preparation and provision of both the active CBD product and placebo. One hundred and twenty subjects with Dravet syndrome, aged between 2 to 18 years, and whose seizures were poorly controlled on their current treatment, were enrolled. In a randomised double-blind design, either CBD or placebo were added to their regime, with treatment spanning 14 weeks. The study found a reduced median seizure frequency in the CBD treatment group from 12.4 to 5.9 with CBD, compared with a decrease from 14.9 to 14.1 for placebo (adjusted median difference −22.8 percentage points; 95% confidence interval, −41.1 to −5.4; P = 0.01). CBD was also associated with a higher rate of adverse events, including diarrhoea, vomiting, fatigue, pyrexia, somnolence and abnormal results on liver function tests. However, there is also good evidence of improved seizure control in patients with Dravet Syndrome with the addition of the newer drug topiramate.
Findings like these have fueled the community campaign for “medicinal cannabis”, with proponents frequently campaigning for the use of the whole plant, homegrown, as “herbal medicine”. Outrageous claims have been made – well beyond the plant’s pharmacological potential – for cures for everything from cancer to Alzheimer disease. Growers and users are emphasising the “natural”, “herbal” aspects of the whole plant, invoking conspiracies about Big Pharma. This is a thinly-disguised bid for liberalisation of recreational use.
The “war on drugs” narrative has certainly complicated this discussion, and there are legitimate discussions to be had about the relative harms of different recreational substances. I won’t explore these here. What we do have, though, is a precedent for the prescribed use of restricted plant-derived substances: the narcotics.
While the use of potent narcotics is restricted in the community, morphine is a mainstay of pain treatment in both acute and chronic care and at the end of life. Morphine isn’t medicine in the sense that it cures pathology – but it provides much-needed symptomatic relief, while also often producing side effects.
Prescribed cannabis extracts and derivatives may legitimately sit alongside the narcotics in our pharmacological toolbox – especially at the end of life. Some people with treatment-resistant seizures may well benefit from the addition of CBD.
As experts in therapeutics, it is essential that we are familiar with the evidence – what is known, what is plausible and what is not. In that way, we can make good use of the evidence-based effects, anticipate and manage side effects and debunk the multitude of myths. I would urge readers to explore the references in this article, and continue to explore further.
Dr Sue Ieraci is a specialist emergency physician with 30 years’ experience in the public hospital system. Her particular interests include policy development and health system design, and she has held roles in medical regulation and management. She is an executive member of Friends of Science in Medicine.
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