Specific Cannabinoid Compositions Associated with Analgesic Response and Adverse Events in Chronic Pain Patients

Specific Cannabinoid Compositions Associated with Analgesic Response and Adverse Events in Chronic Pain Patients

While access remains limited in many countries, medical cannabis is slowly becoming an increasingly utilised treatment option for patients around the world with chronic pain.

In the UK, the National Institute of Health and Care Excellence (NICE) currently recommends the use of cannabis in cases of treatment-resistant epilepsy, spasticity in multiple sclerosis, and nausea and vomiting associated with chemotherapy. However, cannabis-based medicines may also be prescribed through private clinics for a much wider range of indications, including chronic pain.

Chronic pain conditions represent a significant proportion of medical cannabis prescriptions globally, however, evidence regarding short- and long-term efficacy and adverse events (AEs) of different cannabis components is still limited.

A recent study aimed to identify patterns of phytocannabinoid compositions associated with medical cannabis treatment response and related AEs.

Design and Methods of the Study

This was a multi-centre, prospective, long-term observational study carried out between December 2015 and October 2019. For the study period, participants were directed to complete a study questionnaire at baseline, before medical cannabis treatment, and at five follow-up times (one, three, six, nine, and twelve months following treatment initiation).

Meanwhile, phytocannabinoids of most clinically administered cannabis chemovars of all approved cultivators in Israel (where the study was held).

Questionnaire Design

The questionnaire was completed online using secure survey technology. The baseline questionnaire included demographic questions as well as questions to gauge average weekly pain intensity scores (0-10) which were determined as the study’s primary outcome measure.

At follow-up intervals, the questionnaires included questions to collect data on medical cannabis treatment characteristics, including administration route(s), monthly dose, medical cannabis cultivar name(s), and adverse events (AEs) which the patients attributed directly to medical cannabis treatment. The researchers also utilised reports on the incidence of central nervous system, gastrointestinal and psychological MC-related AEs.

The researchers selected only patients who had provided full data on the medical cannabis chemovar consumed via inhalation to avoid comparisons between different administration routes. A total of 501 and 321 patients at month 1 and month 12, respectively, were qualified for this study analysis.

Results of the Study

The study identified no significant differences in patients’ demographics and pain aetiologies. Between month 1 and month 12, the total monthly dose of medical cannabis at month 12 was significantly higher than at month 1.

Data from month 1 questionnaires showed that only two patients (<1%) consumed 30g of medical cannabis per month, with most patients (>99%) consuming 20g per month. At month 12, the variance of doses increased, with 91 (28%) consuming 20g  per month, 184 (57%) consuming 30g per month and 46 patients (14%) consuming 40g per month.

Furthermore, the researchers observed a significant change in the number of different cultivars consumed simultaneously per month. Data collected from the short-term follow-up questionnaires revealed that patients were consuming one or more of 59 different cultivars. Data from the long-term follow-up, however, showed that patients consumed one or more of 76 different cultivars.

For all of these different cultivars, all of the phytocannabinoid concentrations were identified. Total tetrahydrocannabinol (THC) concentrations ranged from 0.29% to 19.57% while total cannabidiol (CBD) concentrations ranged between 0.02% and 14.56%.

Assessing Phytocannabinoid Profiles

Medical cannabis can often be complicated due to the wide variety of available cultivars and the possibility of consuming more than one cultivar in varying dose in the same month. In this study, this produced 180 and 189 unique combinations at month 1 and month 12, respectively. Furthermore, each patient consumed the varying doses of each cultivar, resulting in a unique profile of phytocannabinoid compositions per patient.

Therefore, the researchers were unable to assess the effects of single specific medical cannabis cultivars on treatment response and safety. However, for each individual patient, the monthly phytocannabinoids consumption was calculated – for example, for each patient that consumed three different cultivars, the single values of each cannabinoid from each cultivar were totalled to determine a single value per month.

Patients were then grouped by their similarities in monthly dose consumption (only phytocannabinoids with a minimum average monthly dose of 0.1g were included) to assess the differences between groups both in rates of treatment response and adverse events at month 1 and month 12.


The researchers observed that some groups of phytocannabinoids were associated with either less or more adverse event rates. However, an association between phytocannabinoids profile and analgesic response was not identified. The authors of this study conclude that this study demonstrates that the clinical treatment response of pain reduction was similar for all phytocannabinoid compositions.

The data collected through this study suggests that there was a similar treatment response rate between patients consuming high-THC, high-CBD, and balanced chemovars. This conclusion is supported by a cross-sectional Dutch study of around 100 patients (mostly with chronic pain), which also identified no difference between THC-dominant and CBD-dominant cultivars in daily dose or symptoms alleviation.

However, the researchers suggest that the fact that participating patients chose their medical cannabis cultivars at their own discretion, followed by a period of trial and error, the similar rates of treatment success between phytocannabinoid composition groups could be a result of patients’ personal choice that are not based on pain reduction. Afterall, the treatment of pain is often more complex than simply reducing pain intensity, with factors such as quality of life, sleep quality, depression, anxiety, and disability all playing an important role.

Furthermore, the researchers did find that specific phytocannabinoid compositions were associated with significantly higher treatment-related AEs rates than other compositions. However, these adverse events could not be attributed to solely CBD or THC monthly doses, with other minor cannabinoids playing a role in the prevalence of AEs.

The authors of this study conclude that the composition of other cannabinoids, beyond THC and CBD, within full-spectrum medical cannabis preparations are important in deciding the best treatment for an individual.