Depression is one of the most common mental health conditions, with approximately one in five people affected by at least one period of clinical depression in their lifetime. The condition can have a significant impact on patient health-related quality of life (HRQoL). Reductions in HRQoL can be linked to depressive symptoms themselves, as well as additional impacts on social, occupational, and cognitive functioning. Furthermore, poor HRQoL has been linked to an increased risk of resistance to treatment and an inability to perform occupational and social activities.
Current Treatments for Depression
Treatment options for depression typically include the use of antidepressant medications and therapy. However, while antidepressant medications are widely used, their efficacy is often debated. For example, a recent meta-analysis confirmed that second-generation antidepressants were more effective for treating depressive symptoms than placebo, but effect sizes were mostly modest and response rates were relatively low at around 50%. Furthermore, the efficacy of antidepressants is more marked in individuals with severe depression, however, for those with mild-moderate depression severity the effects appear to be less strong.
In recent years, second-generation antidepressants have largely replaced tricyclic antidepressants due to improved tolerability. Nonetheless, adverse effects (AEs) remain a significant issue, as highlighted by dropout rates among patients administered second-generation antidepressants compared to placebo in randomised controlled trials (RCTs). There is therefore a clinical need for effective and tolerable alternative therapies for depression.
Medical Cannabis and Depression
Recent research has focused on identifying alternative targets, aside from monoamine reuptake inhibitors, for depression therapies. One potential target is the endocannabinoid system (ECS), a system comprising cannabinoid receptors, enzymes, and endogenous cannabinoids (endocannabinoids). Cannabinoid receptors (specifically, CB1 receptors) have been found in abundance in the brain, where they play a significant role in the release of neurotransmitters. In the central nervous system (CNS), CB2 receptors have also been proposed to play a role in neuroprotection and regulation of emotional behaviour.
Common cannabis compounds, CBD and THC, interact with the endocannabinoid systems in a number of ways. For example, CBD has been found to increase levels of the endocannabinoids anandamide and increase constitutive activation of CB1 receptors.
Various studies have reported the changes in changes in depression symptoms as a secondary outcome of medical cannabis; however, there remains a paucity of high-quality clinical evidence in this area. Observational studies have also produced conflicting results. While some have concluded that CBMPs do not affect depression symptoms, others suggest they could improve depression symptoms. With a view to addressing these conflicting findings, the authors of a recent study analysed real-world data from the UK Medical Cannabis Registry to assess multiple domains of HRQoL outcomes and the incidence of AEs in patients with depression.
Data Collection for the UK Medical Cannabis Registry
The UK Medical Cannabis Registry, which has been managed by Sapphire Medical Clinics since 2019, is the first UK patient registry to collect data regarding CBMP prescription formulations, patient demographics, patient-reported outcome measures (PROMs) and AEs. The current analysis assessed data from patients with a primary diagnosis of depression who have received a medical cannabis prescription.
Patient-Reported Outcome Measures (PROMs)
The data assessed in this study was reported electronically by patients or contemporaneously by clinicians during initial clinical consultations. Primary outcome measures were changes in PROMs from baseline to 1-, 3-, and 6-month follow-up. Secondary outcomes were the incidence and severity of AEs. PROMs were measured using the Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder 7 (GAD-7), EQ-5D-5L, Single-Item Sleep Quality Scale (SQS), and Patient Global Impression of Change (PGIC).
The PHQ-9 is a 9-item numerical rating scale (NRS) that assesses the presence and severity of depression. It scores nine symptoms of depression depending on how often they are experienced by the patient on a scale of 0 (not at all) to 3 (nearly every day). These scores are used to generate a total score ranging from 0 to 27 which can be used to determine mild (≥5), moderate (≥10), moderately severe (≥15), or severe (≥20) depression.
The EQ-5D-5L is the HRQoL measure recommended by the National Institute for Health and Care Excellence (NICE). The SQS utilises a numerical rating scale rating from 0 (terrible) to 10 (excellent) to assess sleep quality over the past 7 days. GAD-7 evaluates seven aspects of generalised anxiety by the number of days they were experienced in the past fortnight. The PGIC assesses perceived change since starting care at Sapphire Clinics in terms of activity limitations, symptoms, emotions, and overall quality of life, through two parts.
Results of Analysis
A total of 129 patients were included in the final analysis, including 107, 72, and 34 patients who had completed PROMs at 1, 3, and 6 months, respectively. The majority of patients (n= 115; 89.1%) were either current or ex-users of recreational cannabis; 72 patients (55.8%) were on antidepressant medication at the time of data extraction (11 patients were on two antidepressant medications).
Patients were prescribed either vaporised dry flower preparations (47.3%), oral/sublingual oils (16.3%) or both (25.6%). The median daily initial THC dose was 120 mg (100.0 – 200.0 mg) and the median daily initial CBD dose was 5.5 mg (0.0 – 100.0 mg).
Health-Related Quality of Life (HRQoL)
The initiation of care was associated with statistically significant improvements in PHQ-9, GAD-7, and SQS scores at 1, 3, and 6 months. Clinically significant reductions (≥5) were observed in approximately 50% of patients across all follow-ups. Furthermore, all EQ-5D-5L usual activity and anxiety/depression subscores, and the EQ-5D-5L Index Vale were also sustained at 6 months. However, the exact causality of these effects remains unclear.
Subgroup analysis also revealed that patients with baseline anxiety experienced greater PHQ-9 improvements at 1 and 3 months. This was likely due to the overlap between the symptoms of anxiety and depression. Improvement in PHQ-9 was also greater among current or ex-cannabis users compared with cannabis naïve patients.
Adverse Events (AEs)
Eighteen patients (14%) reported a total of 153 adverse events. The most commonly reported AEs were fatigue (n=14; 10.9%) and insomnia (n=13; 10.1%). The majority of AEs were mild or moderate (87%) and there were no reported incidents of life-threatening or disabling adverse events. There was no significant association between the occurrence of adverse events and THC or CBD dose.
Conclusions
The data collected through the UKMCR and assessed in this study indicate that initiation of care could be associated with changes in depression symptoms; however, the authors note that there are limitations to this study design which mean that a causal relationship cannot be proven. Nonetheless, the results indicate that initiation of care was associated with improvements in anxiety, sleep quality, and overall HRQoL. The authors recommend that future studies focus on controlled observational studies or pilot trials to determine the potential of CBMPs for depression.
