sex-related differences in prescription patterns and clinical outcomes in medical cannabis patients with chronic pain

Sex-Related Prescription Patterns and Clinical Outcomes in Medical Cannabis Treatment for Chronic Pain 

Despite the still-limited use of medical cannabis products as a routine treatment option – largely thanks to a relative lack of clinical evidence supporting their efficacy – a growing number of clinicians and patients prescribing this treatment for chronic pain conditions. In fact, chronic pain is now the most commonly-reported condition associated with medical cannabis use globally.  

Cannabis Sativa L. has been used medicinally for thousands of years, with many historical examples of its use for pain management. The use of medical cannabis products was commonplace in Western medicine right up until the early 20th century; however, this gradually began to decline until the outright prohibition of the plant was announced with the introduction of the Misuse of Drugs Act in 1971. Since, then, though, a growing number of countries have again begun to recognise the medicinal and therapeutic potential of this diverse plant, with law reforms continuing to sweep across the globe. These reforms have given many vulnerable people access to high-quality, safe medical cannabis products for use across a number of clinical indications – the most common being chronic pain. 

A recent observational study aimed to assess patient-reported outcome measures (PROMs) in a cohort of adult chronic pain patients in Bogotá, Colombia.  

Medical Cannabis and Pain 

A growing number of studies, paired with observational, anecdotal, and historical evidence, suggests that cannabis derivatives – the most well-known being THC and CBD – may reduce pain in humans. It is believed that this is likely achieved through their interaction with the endocannabinoid system (ECS) a modulatory receptor and protein system that is expressed throughout the central nervous and immune systems. This system is believed to play a significant role in many human physiological, behavioural, immunological, and metabolic functions – including the perception of nociception (pain). 

Design and Methods of the Study 

For this observational study, researchers identified eligible participants using the medical records of patients receiving treatment with cannabis-based medical products (CBMPs) at the ILANS-Zerenia clinic in Bogotá between May and September 2021. At follow-up visits, patients were encouraged to respond to a short PROMs questionnaire designed to monitor the degree of clinical improvement, as well as the occurrence of side effects.  

Patients were first asked to describe the primary symptom for which they were receiving medical cannabis treatment, which products they were using, and whether or not they had experienced improvement in their primary symptom. Next, participants were asked to rate their current illness score on a scale of 0-100 in relation to their pre-treatment baseline score (0 = no improvement; 100 = “total improvement of primary symptom”). Finally, participants were asked if they had experienced any side effects in relation to the initiation of medical cannabis treatment. 

For answers relating to a 0-100 scale, answers were separated into four groups representing degree of improvement: residual (0-10); slight (20-40); moderate (50-70); and robust (80-100). PROMs were then analysed by sex of the patient; prescribed CBMPs (four oral products with varying concentrations of CBD and THC were available to prescribers); and duration of treatment at the time of completing the PROMs questionnaire. 

Results of the Study 

A total of 2,761 completed the PROMs questionnaire for at least one follow-up consultation, of which, 2,161 (78.3%) reported “chronic pain” as their primary symptom. Forty-nine PROMs results were excluded from review due to inconsistencies between their PROMs questionnaire and their medical records. Therefore, a total of 2,112 patients were included in the study, a majority of which were female (76.1%) with an average age of 58.7 years. Participants who reported experiencing chronic pain were diagnosed in mainly three categories: (i) unspecified pain; (ii) diseases of the musculoskeletal system and connective tissue; and (iii) nervous system diseases.  

Most prescribed CBMPs 

Of the four CBMPs available to prescribers, the chemotype-1 formulation (FM-001), containing only THC, and the epidyolex-like formulation (FM-004) containing only CBD were only marginally used. The majority of prescriptions (99%) were filled using chemotype-3 formulation (FM-003) containing primarily CBD And the chemotype-2 or balanced composition (FM-002). These findings demonstrate a general preference for low-THC and balanced CBD:THC preparations as an introductory CBMP.  

The average dose of THC consumed by patients treated with FM-002 ranged between 9.4 and 17.4 mg per day, and the average dose of CBD on patients treated with FM-003 ranged from 25.6 to 48.5 mg per day. 

Notably, most patients (especially females) initiated their treatment with a CBD-predominant product. However, the use of this formulation diminished over time which was partially due to participants switching chemotypes from FM-003 to FM-002. 

Patient-reported pain measures 

A majority of participants reported some degree of improvement in their chronic pain following the initiation of medical cannabis treatment. The average improvement score was 54.7% and the patient responses to the single assessment numeric evaluation suggested a clinical improvement of 70%.  

Due to extremely low prescription rates of two of the cannabis formulations (FM-001 and FM-004), the researchers focused their analysis on in the results reported for FM-002 and FM-003. They found that, with both CBMPs, more than 75% of patients reported either a moderate or robust reduction in chronic pain. Analysis failed to identify statistically significant differences between chemotypes, patient sex, or duration of treatment. However, female patients reported a steady improvement in pain control while males reported less benefit in the first four weeks. Overall, females reported the most pronounced improvement in chronic pain (29%) with FM-002 between 4 and 12 weeks of treatment.  

Adverse Events 

Most of this patient sample (71.7%) did not report significant adverse side effects associated with medical cannabis treatment. The most commonly reported side effects tended to be mild and included somnolence (13%), dizziness (8.1%), and dry mouth (4.3%). Serious side effects requiring hospitalisation or medical intervention were not reported. Overall, somnolence (drowsiness) was the most commonly reported side effect for both males and females who were treated with the THC-containing chemotype FM-002. Furthermore, the CBD:THC balanced chemotype FM-003 was associated with lower incidence of side effects. This may support growing evidence that CBD may be able to reduce unwanted side effects associated with THC administration. 

Sex-Related Prescription Bias 

Interestingly, the researchers identified a significant sex-bias in the rate of prescription for the two most commonly used CBMPs. According to the data collected in this study, female patients were more likely to begin and continue treatment using the CBD-predominant formulation (FM-003). The researchers consider that this may be due to perceived additional benefits that are commonly associated with CBD – namely its potential anxiolytic properties: Females present consistently higher prevalence rates of anxiety disorders compared to males, which may explain a higher rate of CBD-predominant CBMPs among female patients.  

Conclusions 

In conclusion to the analysis of these data, the researchers note that oral medical cannabis formulations may represent a valuable option as an adjunctive therapy for the management of chronic pain. It is also noted that, while there is a lack of medical guidelines and clinical evidence around the use of medical cannabis in this capacity, real-world evidence – such as that collected in this study – can be useful to inform future practices in CBMP selection and dosing.  

The researchers note that their findings are well-aligned with those reported from similar clinical populations, including in long-standing medical cannabis access programs such as in Israel and Canada.