PubMed: Cannabidiol Exerts Anticonvulsant Effects Alone and in Combination with delta(9)-THC through the 5-HT1A Receptor in the Neocortex of Mice

PubMed: Cannabidiol Exerts Anticonvulsant Effects Alone and in Combination with delta(9)-THC through the 5-HT1A Receptor in the Neocortex of Mice

Cells. 2024 Mar 7;13(6):466. doi: 10.3390/cells13060466.

ABSTRACT

Cannabinoids have shown potential in drug-resistant epilepsy treatment; however, we lack knowledge on which cannabinoid(s) to use, dosing, and their pharmacological targets. This study investigated (i) the anticonvulsant effect of Cannabidiol (CBD) alone and (ii) in combination with Delta-9 Tetrahydrocannabinol (Δ9-THC), as well as (iii) the serotonin (5-HT)1A receptor’s role in CBD’s mechanism of action. Seizure activity, induced by 4-aminopyridine, was measured by extracellular field recordings in cortex layer 2/3 of mouse brain slices. The anticonvulsant effect of 10, 30, and 100 µM CBD alone and combined with Δ9-THC was evaluated. To examine CBD’s mechanism of action, slices were pre-treated with a 5-HT1A receptor antagonist before CBD’s effect was evaluated. An amount of ≥30 µM CBD alone exerted significant anticonvulsant effects while 10 µM CBD did not. However, 10 µM CBD combined with low-dose Δ9-THC (20:3 ratio) displayed significantly greater anticonvulsant effects than either phytocannabinoid alone. Furthermore, blocking 5-HT1A receptors before CBD application significantly abolished CBD’s effects. Thus, our results demonstrate the efficacy of low-dose CBD and Δ9-THC combined and that CBD exerts its effects, at least in part, through 5-HT1A receptors. These results could address drug-resistance while providing insight into CBD’s mechanism of action, laying the groundwork for further testing of cannabinoids as anticonvulsants.

PMID:38534310 | DOI:10.3390/cells13060466

https://pubmed.ncbi.nlm.nih.gov/38534310/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240327132335&v=2.18.0.post9+e462414 March 27, 2024 10:00 am