Δ⁹‐Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats

Abstract

-THCV (0.025-2.5 mg/kg) on pentylenetetrazole (PTZ)-induced seizures in adult rats were also assessed. Results: After induction of stable spontaneous epileptiform activity, acute D 9 -THCV application ( ‡20 lM) significantly reduced burst complex incidence and the amplitude and frequency of paroxysmal depolarizing shifts (PDSs). Furthermore, slices pretreated with 10 lM D 9 -THCV prior to induction of epileptiform activity exhibited significantly reduced burst complex incidence and PDS peak amplitude. In radioligand-binding experiments, -THCV exerts antiepileptiform and anticonvulsant properties, actions that are consistent with a CB1 receptor-mediated mechanism and suggest possible therapeutic application in the treatment of pathophysiologic hyperexcitability states.

Convulsions Associated with the Use of a Synthetic Cannabinoid Product

“…When extensively tested, spice products have been found to have one or multiple synthetic cannabinoids, but as expected, not co-existant phytocannabinoids [17]. The phytocannabinoids in marijuana include the major psychoactive component, Δ-9-THC [18], and various non-psychoactive cannabinoids including cannabinol, cannibidiol, and Δ-9-tetrahydrocannabivarin (THCV) [19,20]. Although animal studies have provided conflicting results (proconvulsant and anticonvulsant) on the effect of Δ-9-THC depending on the model used [12], cannabidiol and its derivatives has been found to be consistently anticonvulsant in animal models [12,21,22] and in limited human trials [23,24].…”

“…Although animal studies have provided conflicting results (proconvulsant and anticonvulsant) on the effect of Δ-9-THC depending on the model used [12], cannabidiol and its derivatives has been found to be consistently anticonvulsant in animal models [12,21,22] and in limited human trials [23,24]. Δ-9-THCV was also recently demonstrated to exert anticonvulsant properties [20]. Although we did not specifically exclude the presence of the anticonvulsant phytocannabinoids in the product used by our patient, the confirmed absence of Δ-9-THCwould make their presence seem extremely unlikely.…”

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

“…These effects could be useful in spinocerebellar ataxias, a pharmacologically untreatable group of hyperexcitability disorders, although preclinical in vivo animal studies in this specific therapeutic area have yet to be undertaken (347). The inhibitory effects of the compound could also be useful in epilepsy, and indeed, ⌬ 9 -THCV produces antiepileptiform and anticonvulsant properties (346). Administered daily for 14 days to 6-hydroxydopamine-lesioned rats, it alleviates the symptoms associated with PD by blocking CB1 receptors at low doses, and induces neuroprotection (284).…”

Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study

“…D 9 -Tetrahydrocannabivarin (THCV) is a naturally occurring analog of THC, but with different pharmacological effects. It is has been reported to behave as both a CB 1 /CB 2 agonist and/or a CB 1 / CB 2 -neutral antagonist (20)(21)(22)(23)(24), probably dose-dependent, with agonism observed at high doses and antagonism at low doses (19). However, there is little evidence of CB 1 agonism in vivo compared with the observed in vivo effects of THC at similar doses.…”