Investigational cannabinoids in seizure disorders, what have we learned thus far?

ABSTRACT

Introduction:The anticonvulsant activity of cannabinoids attracted much attention in the last decade. Cannabinoids that are currently investigated with the intention of making them drugs for the treatment of epilepsy are cannabidiol, cannabidivarin, Δ9-tetrahydrocannabivarin, and Δ9-tetrahydrocannabinolic acid.

Areas covered:In this review, the authors look at the results of preclinical and clinical studies with investigational cannabinoids. Relevant literature was searched for in MEDLINE, SCOPUS, EBSCO, GOOGLE SCHOLAR, and SCINDEX databases.

Expert opinion: Preclinical studies confirmed anticonvulsant activity of cannabidiol and cannabidivarin in a variety of epilepsy models. While the results of clinical trials with cannabidivarin are still awaited, cannabidiol showed clear therapeutic benefit and good safety in patients with therapy-resistant seizures associated with Dravet syndrome and in patients with Lennox–Gastaut syndrome who have drop seizures. However, the full therapeutic potential of cannabinoids in treatment-resistant epilepsy needs to be investigated in the near future.

KEYWORDS:

• Cannabidiol
• cannabidivarin
• treatment-resistant epilepsy
• Dravet syndrome
• Lennox–Gastaut syndrome

Article highlights

• There are four investigational cannabinoids: cannabidiol, cannabidivarin, Δ9-tetrahydrocannabivarin, and Δ9-tetrahydrocannabinolic acid

• Both cannabidiol and cannabidivarin were clearly protective against seizures in a variety of preclinical models of epilepsy; Δ9-tetrahydrocannabivarin and Δ9-tetrahydrocannabinolic acid are not tested yet

• Cannabidiol demonstrated clear efficacy against treatment-resistant seizures in clinical trials on patients with Dravet and Lennox–Gastaut syndromes

• Cannabidiol also demonstrated good safety in clinical trials to date

• Results of phase II clinical trials of cannabidivarin in patients with treatment-resistant focal seizures are about to be published in close future

• There is significant potential of cannabidiol in other types of treatment-resistant seizures that should be explored in future preclinical and clinical trials

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article was partially funded by the Grant No 175007, from Serbian Ministry of Education, Science and Technological Development.