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What Affects the Likelihood of Experiencing an Adverse Event with Medical Cannabis?

Published: 07/12/2023

While medical cannabis products are increasingly prescribed for patients with chronic health conditions in the UK and internationally, many physicians remain cautious about prescribing. This hesitance is often attributed to a lack of available evidence regarding their safety and a lack of confidence in their ability to counsel patients on its benefit-risk balance.

In recent years, a growing body of evidence has aimed to assess the therapeutic potential of cannabis and its derivatives in a wide range of settings. As such there are now licensed medical cannabis products for treatment-resistant epilepsy, multiple sclerosis-associated spasticity, and chemotherapy-induced nausea and vomiting.

Medical cannabis, like any medication, can be associated with potential adverse events (AEs). These can be attributable to tetrahydrocannabinol (THC) or cannabidiol (CBD), the method of administration, or indeed the interaction between medical cannabis and other co-prescribed medications.

While many studies have investigated the potential adverse events associated with cannabis, many of these have focused on synthetic pharmaceutical cannabinoids or purified extracts. In contrast, the majority of patients in clinical practice are prescribed unlicensed medical cannabis products. Following the legalisation of medical cannabis in Canada, the Quebec Cannabis Registry was established in 2014 to collect province-wide, real-world data on the use and safety of medical cannabis as it was authorised.

A recent study aimed to use this data to describe AE reports related to medical cannabis collected over a period of up to three years following initial authorisation and enrolment in the Quebec Cannabis Registry.

Design and Methods of the Study

Access to medical cannabis in the province of Quebec was conditional on enrolment in the Quebec Cannabis Registry, a prospective, non-comparative registry of adult (age ≥ 18 years) patients who initiated medical cannabis, as directed by a physician. Enrolment in the registry started in May 2015 and ended in October 2018, when recreational cannabis was legalised in Canada. Patients were followed for up to year with follow-up ending when either the patient discontinued medical cannabis, loss to follow-up, or end of data collection (May 2019).

Follow-up visits were recorded approximately every three months for the first two years and then at least once per year in the third year. At baseline, the prescribing physician recorded mode of administration, type of cannabis, cannabinoid ratios, and number of products authorised. The physician also reported the primary indication for medical cannabis use.

At follow-up visits, physicians recorded the occurrence of AEs since the last visit, in addition to information regarding their medical cannabis recommendation. However, in practice, as physicians were required to fill individual AE reports, only moderate and severe AEs were collected. This largely included AEs that required stopping MC and actively managing sequela.

The following contraindications for THC use were assessed: unstable cardiopathy, personal or family history of psychosis, and pregnancy/breastfeeding status. The following circumstances, which may present relative contraindications for the use of THC, were also assessed: history of physical or sexual abuse, concurrent active mood or anxiety disorders, and schizophrenia.

Results of the Study

There were 2,991 patients included in the registry. Of these, 759 (25.4%) were still present at one year, 197 (6.6%) at two years, and only three completed all three years of follow-up. Follow-up ended between October 2018 and May 2019 for 585 patients still in the study. Otherwise, 1981 patients (66.2%) were lost to follow-up, and 425 patients or investigators ended the study for reasons such as lack of effectiveness (n = 132, 4.4%), non-compliance (n = 112, 3.7%), unable to afford cannabis (n = 57, 1.9%), adverse events (n = 32, 1.1%), or other/not specified (n = 92, 3.1%).

Throughout follow-up, 108 patients (3.6%) experienced at least one moderate or severe AE. In total, 32 patients exited the study due to an AE, of which 23 completed an AE report, altogether describing 41 AEs. The three most reported adverse events categorised using system organ classes were nervous system disorders, psychiatric disorders, and gastrointestinal disorders.

Patients who experienced AEs in these system organ classes tended to be older than the overall population and were more frequently using opioids, benzodiazepines, and anti-epileptic drugs, which the authors note may magnify the burden of some of these common side effects or induce a positive or negative pharmacodynamic drug interaction.

Patients experiencing AEs were more frequently using medical cannabis for pain than the overall population (60.2% vs 53.3%). The authors note that patients experiencing pain may use several classes of medications concurrently and administer their pain medications more regularly and in larger doses. This may explain why these patients experienced AEs more frequently in the present study.

The presence of a mental health disorder at baseline was not associated with the occurrence of AEs – a factor that is traditionally considered a risk factor for medical cannabis (MC) associated AEs.

The authors note that no safety concerns were identified in the registry, although notable differences in AE profile between modes of administration and cannabinoid content ratios may need to be considered by healthcare providers. The findings of this study warrant further work to identify and manage risk factors for AEs to maintain a favourable benefit-risk balance in the use of medical cannabis products.

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