CBD and cognition in epilepsy
Cognitive dysfunction is common in epilepsy patients. Its causes are multiple, and it can take the form of mental slowness, memory difficulties, attention deficit, or all three.
Recently, cannabidiol (CBD) has demonstrated efficacy in treatment of epilepsy itself. We have written about this in other blog posts. Highly purified, plant-derived CBD has been approved for several years in the treatment of Dravet syndrome and Lennox-Gastaut syndrome, two forms of the disease. Its action appears to be independent of the two known neural receptor sites for cannabinoids, though it is known to antagonize CB1 action at low concentrations. It may target the orphan G protein-coupled receptor GPR55, where it reduces Glut exocytosis and dampens neuronal excitability, which is not active at baseline conditions. It may also control seizures by regulating levels of adenosine. Other targets in epilepsy might be 5HT receptors, coupled with Gi/o proteins, or GABAA receptors, or voltage-gated sodium channels or vanilloid type 1 TRP channels. There are other candidate loci of action even beyond these.
CBD also has demonstrated beneficial action on aspects of cognitive function, about which we have written elsewhere too. This should be no surprise, either. The endocannabinoid system is dysfunctional in disorders as varied as depression and schizophrenia. In suicide victims, for example, stimulation of [35S]GTPγS binding, activation of Gα protein subunits, and inhibition of adenylyl cyclase by the cannabinoid agonist WIN55,212-2 show that CB1 receptor-stimulated is clearly implicated.
The natural question to ask at this point is what effect CBD has on cognition in patients using the drug in epilepsy treatment. This would be useful to know both from the standpoint of efficacy and of overall tolerability in the long term.
A recent study (Epilepsy Behav 2019 Aug;97:105-110), part of an ongoing open-label safety study, has examined this. An open-label study is one in which treatment information is not withheld from participants, a common feature of ongoing, or ‘extension’, studies, in which data-gathering continues beyond their original termination dates.
In this particular study, conducted at the University of Alabama, Birmingham, 27 adults with treatment-resistant epilepsy underwent standardized cognitive testing at pre-CBD administration baseline and at one-year follow-up. Testing measured aspects of working memory, episodic memory, executive function, processing speed, and language.
At baseline, cognitive test performance was below average. In longitudinal analysis there was no significant group change across any of the testing scales. Of the seven individual assessments used, no scores changed with any statistical significance. There was no correlation either between the cognitive scores and CBD dosing. Interestingly, such changes in cognitive test performance that did occur did not associate with change in seizure severity.
These findings show that at the cognitive level, long-term administration of pharmaceutical grade CBD in patients with treatment-resistant epilepsy is well-tolerated, eliciting no undesired effects.
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The foregoing is a report on trends and developments in the cannabinoid industry. No product described herein is intended to diagnose, treat, cure or prevent any disease or syndrome.