Anti-seizure Effects of Cannabinoids May Benefit Some Neurological Disorders But Not Others, Review Study Says

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Despite the promising anti-seizure effects of cannabinoids in children with Dravet syndrome and Lennox-Gastaut syndrome, more research is needed to understand how these compounds work and their potential benefits for other neurological disorders, according to a study.

The study, “Safety, efficacy, and mechanisms of action of cannabinoids in neurological disorders,” was published in The Lancet Neurology.

“Extracts of cannabis have been used to treat human diseases for thousands of years, but the isolation of biologically active cannabinoids and identification of their targets of action in humans, coupled with changing regional legislation regarding cannabis prohibition, have led to great interest in cannabinoid treatments among both patients and clinicians,” the investigators wrote.

Since the discovery of their effects on the central nervous system (CNS, consisting of the brain, brainstem, and cerebellum), cannabinoids have been particularly sought after for the treatment of neurological disorders, including multiple sclerosis (MS), different forms of epilepsy, dementia, attention deficit hyperactivity disorder, and Huntington’s disease.

Based on promising results from several Phase 3 clinical trials, in 2018 the U.S. Food and Drug Administration approved Epidiolex, the first plant-derived cannabidiol medication that has been shown to reduce the frequency of epileptic seizures in children with Dravet syndrome and Lennox-Gastaut syndrome, two rare forms of epilepsy that fail to respond to treatment with conventional anti-epileptic drugs.

Marketed by Greenwich Biosciences, a subsidiary company of GW Pharmaceuticals, Epidiolex is a purified liquid formulation of plant-derived cannabis that is supplied as a 100 mg/mL strawberry-flavored oral solution in a sesame oil base.

Since then, more clinical trials have been launched to assess the anti-seizure properties of cannabidiol for other forms of epilepsy, including in patients with seizures associated with tuberous sclerosis complex (NCT02544763) and in children with infantile spasms, another rare form of epilepsy (NCT03421496).

In addition, alternative cannabidiol formulations are being tested, including Zynerba Pharmaceuticals‘ Zygel (ZYN002), a cannabidiol gel formulation, for adults with drug-resistant focal epilepsy (ACTRN12616000510448).

The anti-seizure effect of cannabidavarin, another cannabinoid compound, in combination with other anti-epileptic medications is also being tested in a randomized, placebo-controlled Phase 2 clinical trial (NCT02369471).

Despite their promising anti-seizure effects on different forms of epilepsy, cannabinoids’ effects on the control of pain and muscle tightness (spasticity) in patients with MS have been more controversial, which “might suggest that only a subset of patients will benefit from treatment with cannabinoids,” the researchers wrote.

Nevertheless, nabiximols — a mixture of cannabidiol and Δ⁹tetrahydrocannabinol — have already been approved for the treatment of spasticity in MS patients in several countries worldwide, including Brazil, Canada, Norway, Denmark, Iceland, Finland, the U.K., Germany, Poland, Austria, Italy, Spain, Switzerland, Turkey, Israel, Australia, and New Zealand.

Unfortunately in other neurological disorders, such as Huntington’s disease, attention deficit hyperactivity disorder, and dementia, cannabinoids failed to improve patients’ cognitive, motor, or behavioral clinical outcomes. Other trials are currently ongoing to assess the effects of cannabinoids for other neurological disorders, including fragile X syndrome (NCT03614663) and Tourette syndrome (NCT03087201).

“(F)urther studies are needed to determine if the anti-seizure effects of cannabidiol extend to other forms of epilepsy, to overcome pharmacokinetic (how the body processes a drug) challenges with oral cannabinoids, and to uncover the exact mechanisms by which cannabidiol or other exogenous and endogenous cannabinoids exert their therapeutic effects,” the researchers wrote.

“Additionally, more studies are also needed to determine long-term safety, especially the effect on brain development,” they concluded.