THC, CBD and minor cannabinoid CBDV differently modulate hippocampal neurons firing.
Giulia Tomagra, Nikita Gandlevskiy, Elena Rosso, Monica Bonardi, Arianna Binello, Valentina Carabelli, Alessandro Barge
Neurotoxicology May 1, 2025 Peer reviewed DOI: 10.1016/j.neuro.2025.04.004 via PubMed
Summary
Cannabis sativa extracts and standard cannabinoids were tested on cultured hippocampal neurons. THC, alone or combined with CBD, significantly decreased spontaneous firing. CBD alone had no effect. CBDV, a non-psychoactive cannabinoid, reversed the firing suppression caused by THC+CBD and, when given alone, increased firing. All effects returned to normal within 24 hours. The findings highlight CBDV's potential to counteract THC's inhibitory impact on neuronal activity.
Study at a glance
| Design | experimental study |
|---|---|
| Population | cultured hippocampal neurons |
| Key finding | CBDV reversed the inhibition of neuronal firing caused by THC and CBD and increased firing when administered alone. |
Abstract
Cannabis sativa L. presents a very complex composition that includes several secondary metabolites besides the two main compounds, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Many of these minor cannabinoids are still under investigation and are arousing increasing interest for their biological effects and potential therapeutic roles. Cannabis sativa extracts, either properly purified and enriched with cannabinoids, were tested here on the neuronal activity, by monitoring the spontaneous firing rate and the bursts generation of cultured hippocampal neurons. In particular, we focused on the combined effect of THC, CBD and cannabidivarin (CBDV), a non-psychoactive homologue of CBD whose side chain has two fewer carbon atoms, and their related standard compounds. We found that standard THC, recognised for its psychoactive impact and side effects including anxiety and paranoia, significantly decreased the spontaneous firing discharge of cultured hippocampal neurons, whether applied alone or in combination with standard CBD at comparable concentrations. In contrast, the firing activity did not exhibit any significant alterations when CBD was administered alone. When C. sativa extracts were tested, we found that CBDV was able to reverse the inhibition of the firing discharge caused by the mixture of THC and CBD. Furthermore, when administered alone, CBDV significantly increased the firing discharge of hippocampal neurons. In all tested conditions, the effects exerted by standard compounds or extracts were restored to control conditions after 24 hours from administration. Overall, these data unravel a novel action of CBDV in reverting the detrimental effect exerted by the THC+CBD on neuronal firing activity.