Post-Traumatic Stress Disorder – more commonly referred to as PTSD – is a common condition that usually occurs following exposure to trauma. The condition is characterised by several, often debilitating, symptoms that can significantly affect the patient’s personal and professional endeavours and general health-related quality of life (HRQoL). Such symptoms may manifest as flashbacks, trigger avoidance, hyperarousal, depressive symptoms, and nightmares.
Current Treatment Options for PTSD
PTSD is a relatively common condition, believed to affect between 5% and 10% of the population in their lifetimes. Furthermore, PTSD is often associated with other psychiatric disorders and physical health conditions. As such, effective treatment options are an important area for development in order to improve patient outcomes and limit related socio-economic costs.
Currently, psychotherapy is at the centre of PTSD management, despite unclear long-term effectiveness. Evidence suggests that selective serotonin reuptake inhibitors (SSRIs), which are commonly prescribed for PTSD management, are not appropriate first-line agents for promoting sustained symptom improvement. SSRIs may carry particular side effects in PTSD outcomes, including agitation, which may be linked to the presence of hyperarousal as a common symptom.
Other pharmacological treatments that may be prescribed include prazosin, an alpha-1 adrenoceptor antagonist, trazodone, a serotonin receptor antagonist and reuptake inhibitor, and agomelatine, a melatonin antagonist, though the efficacy of these products also remains unclear. Therefore, there is a clear need for PTSD therapies that offer long-term symptom relief with minimal side effects.
Medical Cannabis and PTSD
There is a growing interest in the potential of medical cannabis for a variety of conditions and ailments, including PTSD. The UK, in addition to many other countries around the world, has now rescheduled medical cannabis. Under current UK legislation, medical cannabis can be prescribed by specialist clinicians to patients with PTSD who have failed to respond to appropriate licensed therapies. Despite the growing availability of medical cannabis treatment, there remains a paucity of clinical evidence regarding the efficacy of cannabis-based medical products (CBMPs).
Current evidence on CBMPs for PTSD is largely conflicting and difficult to synthesise due to the use of selective cohorts, methodological heterogeneity, and underpowered studies. For example, while some studies have reported significantly reduced symptom severity, improved sleep and minimal adverse events, one longitudinal observational study reported that medical cannabis “worsened violent behaviour and substance use disorders.”
There is, therefore, a clear need for further research to address these disparities. Real-world evidence is a valuable resource for determining the safety and efficacy of CBMPs for relevant conditions, such as PTSD. The UK Medical Cannabis Registry was developed to collect prospective data regarding outcome measures for patients receiving CBMP prescriptions in the UK. A recent analysis of this data aimed to assess the clinical outcomes of PTSD patients who have received medical cannabis treatment.
Data Collection for the UK Medical Cannabis Registry
The UK Medical Cannabis Registry (UKMCR), 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 adverse events (AEs). The current analysis assessed data from patients with PTSD who have received a medical cannabis prescription.
Patient-Reported Outcome Measures (PROMs)
Data collected includes demographic information, prior cannabis use, and prescription and dosage details. Data 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 Impact of Events Scale-Revised (IES-R), Single-Item Sleep Quality Scale (SQS), Generalised Anxiety Disorder-7 (GAD-7) and Patient Global Impression of Change (PGIC).
The IES-R is a 22-item questionnaire rating how distressing post-trauma difficulties had been in the past week, on a scale from 0 (not at all) to 4 (extremely). Questions relate to three key PTSD symptom groups: hyperarousal, avoidance, and intrusions. A score of 24-32 signifies clinical concern for partial PTSD, 33 is considered a probable cut-off for PTSD diagnosis, and scores above 37 are at a severity that has demonstrated physiological effects, such as inducing immunosuppression.
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 generalized anxiety by the number of days they were experienced in the past fortnight. The PGIC assesses perceived change since starting treatment in terms of activity limitations, symptoms, emotions, and overall quality of life, through two parts.
Adverse Events (AEs)
Adverse events were recorded following the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE). This method allows for comprehensive reporting and grading comparable to other studies. The severity of AEs is graded using unique clinical descriptions specific to each AE. Patients were prompted to report AEs during the completion of their PROMs; clinicians can also update any AEs reported during clinical consultations.
Results of Analysis
A total of 162 patients were identified for analysis in the current study. The recorded incidence of the six further comorbidities was anxiety/depression (n=108; 66.67%), arthritis (n= 16, 9.88%), endocrine dysfunction (n= 7, 4.47%), epilepsy (n= 3, 1.85%), and hypertension (n= 7, 4.32%). Seventy-one (43.83%) patients had a secondary indication for CBMP prescription, of which anxiety was the most common (n = 39, 24.07%). Tertiary indications were present for 42 (25.93%) participants and largely consisted of depression (n = 18, 11.11%) and insomnia (n = 10, 6.17%).
Health-Related Quality of Life (HRQoL)
Statistically significant improvements were seen in all domains of the IES-R, and both GAD7 and SQS, at all lengths of follow-up. The EQ-5D-5L index score and both ‘usual activities’ and ‘anxiety and/or depression’ subscales also improved significantly at all follow-ups. Furthermore, PROMs identified improvements in the ‘self-care’ and ‘pain and discomfort’ subscales seen at 1- and 3-month follow-up and the ‘mobility’ subscale at 3-month follow-up.
IES-R data reported improvements in PTSD symptoms across all follow-ups. At 3- and 6-month follow-ups, IES-R scores neared the 33-point threshold for PTSD diagnosis, compared to baseline scores of above 50, supporting previous findings in this area. Changes in anxiety were indicated through improvements in both the GAD-7 and EQ-5D-5L ‘anxiety and depression’ subscale. This is an important finding as anxiety is a common comorbidity of PTSD.
Changes in sleep quality were also reported. This is particularly important finding as “sleep quality has been identified as both a predicting factor of PTSD development and a perpetuating factor that impacts overall outcomes.”
A total of 220 AEs were reported across the patient sample (20.37%) – the majority of which were either mild (n=100; 61.73%) or moderate (n=90; 55.56%) in severity; no life-threatening or disabling events were reported. The most commonly reported AEs were insomnia and fatigue (n=20; 12.35%), followed by headache (n=15; 9.26%), dry mouth (n=15; 9.26%), and concentration impairment (n=14; 8.64%).
The authors of the current analysis conclude that current data from the UK Medical Cannabis Registry indicates an associated change “in PTSD-specific HRQoL, sleep, and anxiety outcomes at up to 6-month follow-up.” Reported adverse events were in line with evidence from similar patient cohorts. While this study has several limitations, including the subjectivity of PROMs, the authors suggest that the current findings can serve to inform future randomised placebo-controlled trials to better assess the safety and efficacy of medical cannabis for the treatment of PTSD.