Cannabidiol Exerts Anticonvulsant Effects Alone and in Combination with Δ9-THC through the 5-HT1A Receptor in the Neocortex of Mice

Bibliographic Details
Title: Cannabidiol Exerts Anticonvulsant Effects Alone and in Combination with Δ9-THC through the 5-HT1A Receptor in the Neocortex of Mice
Authors: Yasaman Javadzadeh, Alexandra Santos, Mark S. Aquilino, Shanthini Mylvaganam, Karolina Urban, Peter L. Carlen
Source: Cells, Vol 13, Iss 6, p 466 (2024)
Publisher Information: MDPI AG, 2024.
Publication Year: 2024
Collection: LCC:Cytology
Subject Terms: drug resistant epilepsy, cannabinoids, serotonin, 5-HT1A receptor, electrophysiology, cannabidiol (CBD), Cytology, QH573-671
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2073-4409
Relation: https://www.mdpi.com/2073-4409/13/6/466; https://doaj.org/toc/2073-4409
DOI: 10.3390/cells13060466
Access URL: https://doaj.org/article/25e28b919c8a4bdf862adde674c16db9
Accession Number: edsdoj.25e28b919c8a4bdf862adde674c16db9
Database: Directory of Open Access Journals
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More Details
ISSN:20734409
DOI:10.3390/cells13060466
Published in:Cells
Language:English