Cannabidiol, or CBD as it is commonly known, has been a compound of medical interest since its discovery in 1940. However, CBD has been the subject of particular interest in recent years as studies have shown its potential as a treatment option for epilepsy, particularly in those with associated childhood epilepsy syndromes.
Epidyolex (Epidiolex in the USA), a medicinal preparation of CBD has now been approved for use in the UK for adults and children above the age of two. While many people have heard about the potential of CBD in reducing seizure and symptoms in epileptic children, little publicity has been given to how CBD can impact on adult epilepsy patients.
A recent study aimed to determine the effect of CBD on the quality of life (QOL) of a sample of adult patients diagnosed with treatment-resistant forms of epilepsy. The open-label study enrolled 53 patients, measuring quality of life – based on several controls – at baseline and after one year of treatment.
The Aims and Methods of the Study
A number of studies have revealed the potential of CBD in reducing the frequency and severity of epileptic seizures. Treatment-resistant epilepsy is generally associated with reduced QOL as symptoms are extremely difficult to manage, often resulting in extremely high seizure frequency as well as negative effects on mental health, physical functioning, and social activity. While CBD treatment has been associated with improved QOL in epilepsy patients, it remains unclear if such improvements are independent of improvements in seizure control.
The authors of this study hypothesised that “QOL would improve independent of changes in seizure frequency (SF) or severity, mood, or adverse events.” A sample of adult treatment-resistant epilepsy patients was gathered for an open-label study of purified CBD (Epidyolex).
Measuring Quality of Life in Epilepsy Patients
Current literature demonstrates that QOL in patients with epilepsy worsens with increased seizure frequency and severity. In addition, mood (such as anxiety and depression), longer duration of seizures, and adverse events are significant predictors of poor ratings in quality of life. In order to assess quality of life in epilepsy patients, a number of methods have been developed.
This study used the Quality of Life in Epilepsy-89 (QOLIE-89) instrument to measure QOL in participants. QOLIE-89 is a validated measure which is frequently used in clinical trials of antiseizure drugs (ADSs).
The 89-item QOLIE assessment and the Profile of Mood States (POMS) – a 5-item questionnaire widely used to assess mood – were used to determine the QOL scores of participating patients following their enrolment into the study. The Adverse Events profile (AEP), a 19-item, validated questionnaire used to assess adverse events related to seizure medications, was also used.
Patients were then started on an initial CBD dose of 5mg/kg/day with the dose increasing incrementally by 5mg/kg/day every two weeks until seizure control was reached or tolerability at in-person visits to a maximum of 50mg/kg/day. Changes in CBD dose changes were determined by detailed seizure calendars (which were began three months prior to the beginning of the study) kept by participants or carers and reported side effects.
Results of the Study
A total of 53 participants completed enrolment and qualifying follow-up visits (either 1 year or early study termination visit). Seven of these patients withdrew from the trial due to a lack of efficacy.
Data from the participants’ enrolment analysis showed a correlation between age and QOLIE-89 scores. Patients aged <25 tended to produce lower QOLIE-89 scores at enrolment while patients in higher age categories were associated with higher QOLIE-89 scores.
Over the course of the study, statistically significant improvements in total seizure counts were observed. At enrolment, 28.3% of participants reported over 50 seizures every two weeks compared with 13.2% at one year. Further, over 30% of the sample had 14-50 seizures every two weeks. This was reduced to 24.5% of patients at follow-up. Patients who experienced less than 14 seizures every two weeks rose from 41.5% at enrolment to 62.3% at follow-up.
These results support the results from previous studies, indicating that CBD can be an effective add-on therapy to reduce seizure frequency in epilepsy patients.
Researchers also found that QOLIE-89 scores improved significantly in participants from enrolment to follow-up. The mean QOLIE-89 score at enrolment was 49.4, indicating relatively low quality of life. In comparison, the mean QOLIE-89 score at one year or study termination was 57.
The authors of this study point out that this improvement of close to 10 points represents not only a statistically significant, but also perhaps a clinically significant, positive change.
The results of POMS Total Mood Disturbance (TMD) and AEP scores were also positive. Mean POMS TMD scores were seen to fall 9.7 points, indicating a reduction in mood disturbance throughout the study period. POMS TMD at follow-up was the only other variable in the model that had an independent and negative association with QOLIE-89 at follow-up, indicating that mood problems are associated with lower quality of life, after accounting for other factors.
Further, mean AEP scores also saw a reduction of 5.8 points between enrolment and follow-up. This indicates that CBD may have a statistically significant positive effect on the occurrence of adverse events associated with antiseizure drugs. Again, these results support the findings of some previous studies.
The authors conclude that these findings support their primary hypothesis – that “QOL would improve independent of changes in seizure frequency (SF) or severity, mood, or adverse events.” This study has demonstrated that CBD is associated with both statistically and clinically significant increases in QOL among adult treatment-resistant epilepsy patients.
While CBD appears to approve patient outcome for a number of measures (QOL, mood, seizure frequency and severity, and adverse events), these changes appear to be largely independent of each other. While the results of this open-label study are promising, the authors note that more controlled studies – i.e. with comparison against a placebo – are needed to support the current evidence.