A year and a half after the Food and Drug Administration (FDA) changed its opinion on cannabis-based pharmaceuticals, the European Commission has followed suit. In September, 2019 GW Pharmaceuticals announced it had marketing approval for Epidyolex, a cannabis-derived pharmaceutical developed for the treatment of seizure disorders (Lennox‑Gastaut syndrome and Dravet syndrome) for patients two years of age and older.
Alongside the approval of GW Pharmaceuticals’ Epidiolex in the US, cannabinoid medicines are the new frontier of epilepsy drugs hitting markets today.
These hard-won regulatory approvals in two of the most critical global markets, the US and the EU, have legitimized cannabis-based medicines like never before. Research of cannabinoids for the treatment of seizure disorders are some of the most advanced areas of cannabis research, surpassing research of cannabis for mood disorders and chronic pain.
Pharmaceutical preparations of cannabinoids, plus growing patient access to medical cannabis programs, are opening up an entirely new world of treatment options for patients with seizure disorders.
For researchers, it must feel like they have caught a wave of positive forward momentum. Every day there is a new scientific breakthrough, new studies launching, and new regulatory approvals. What does the future hold for cannabinoid therapy for the treatment of epilepsy and seizure disorders?
The Potential of Cannabinoid Medicine: 50 Percent Reduction in Seizure Frequency
According to their analysis of the available body of study, cannabinoids, and specifically CBD, has the potential to reduce seizure activity by over 50 percent in some patients. The vast majority of the studies included within their systematic review worked exclusively with CBD, and with patients who had treatment-resistant types of seizure disorders. Two out of the six randomized control trials found more than 50 percent reduction in seizures. Roughly 48.5 percent of patients within 17 of the observational studies (470 patients total) experienced similar positive declines in seizure activity.
A significant secondary outcome noted by Stockings and Zagic et al. was complete seizure freedom, as reported by roughly eight percent of patients from 14 of the observational studies. The systematic review concluded, “In many cases, there was qualitative evidence that cannabinoids reduced seizure frequency in some patients, improved other aspects of the patients’ quality of life and were generally well tolerated with mild-to-moderate AEs.”
As the authors evaluated from the randomized control trials and observational studies, patients receiving CBD, as opposed to a placebo, “had a small but significant increase in the risk of experiencing any [adverse events].” These included reports of drowsiness, diarrhea, and changes in appetite.
Perhaps surprisingly, there is a much more robust body of literature focused on cannabinoids for the treatment of intractable forms of epilepsy among children. Because the research has thus far been skewed towards minors, the authors were much more confident in their assessment of the safety profile, tolerability, and efficacy of CBD for use among children than for applications among adults.
Improvements to Quality of Life Measures, Beyond Seizure Reductions
Conjunctive therapy with CBD-based medicines may also improve quality of life, independent of the effects on seizure severity and frequency. A study published in the Journal of Epilepsy and Behavior, in conjunction with a state of Alabama-funded UAB CBD program, explored these impacts among 53 adult patients. Participants all had treatment-resistant forms of epilepsy, which had failed to respond to at least four antiseizure drugs. Some cases had also failed to respond to surgical interventions.
Between participant enrolment and the one-year follow up, the authors noted “statistically significant improvements” to total seizure counts. Using three separate measures to explore quality of life (QOLIE-89, POMS, AEP), the study also determined equally as significant changes in quality of life.
After one year of treatment with a CBD-based pharmaceutical, the researchers found, on average, a 60 percent decrease in seizure severity and substantial decreases in frequency. Using the QOLIE-89 scoring system, they saw a 10 point increase between enrolment and the end of the study, so remarkable the researchers explained, “The observed improvements were not only statistically but may also be clinically significant.”
CBD and other Cannabis Extracts Effective, Compared to Placebo
In the most extensive systematic review and meta-analysis to date, the researchers behind “Efficacy and adverse event profile of cannabidiol and medicinal cannabis for treatment-resistant epilepsy: Systematic review and meta-analysis” came to a few notable conclusions.
The first, “CBD treatments were effective compared with placebo,” is perhaps not surprising to patients with treatment-resistant forms of epilepsy already experiencing the anticonvulsant activities. What was perhaps more remarkable? The efficacy of CBD was “regardless of the dose administered.”
Another exciting discovery was the relatively comparable levels of adverse events between CBD-based treatments and those containing measurable levels of THC. Interestingly, in studies using broader-spectrum cannabis extract (which contained low-levels of THC), the side effects were minimal with “notable efficacy” in the treatment of the seizure disorder.
According to this data analysis, the most commonly reported side effects from either CBD or extracts with low THC levels were diarrhea, drowsiness, and appetite loss. The most severe adverse events included drowsiness and increased seizure activity in some cases. Tolerability of CBD extract or cannabis extract was more favorable with longer-term treatments, as compared to short-term protocols, suggesting “a time-dependent evolution of CBD treatment of epilepsy in terms of the [adverse event] profile.”
Improved Accessibility and Clarity on Therapeutic Value
With the recent approvals of cannabis-based drugs for treatment-resistant epilepsy by both the FDA and the European Commission, cannabis is increasingly viewed by patients and healthcare providers as a legitimate treatment option.
Finally, thanks to GW Pharmaceuticals and other global drug companies, cannabinoids are reaching advanced stages of research, including clinical trials. These have been sorely missing in the fight for legalization. The study and subsequent approval of cannabis-based pharmaceuticals have unintentionally had positive benefits for medical cannabis as a whole. In a way, the study of cannabis for the treatment of epilepsy has helped improve global access to medical cannabis and a shift in public opinion of the plant.
Between expanding medical cannabis programs and the support of federal regulators, cannabis is no longer simply seen as fringe medicine. Cannabis is now a legitimate tool for patients battling treatment-resistant forms of epilepsy.