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 DOI: 10.1016/j.neuro.2025.04.004 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Cultured hippocampal neurons |
| Topics | Cannabis CBD |
| Keywords | C. sativa Cannabidivarin Hippocampal neurons Mea |
| Citations | 3 |
| Key findings | Cannabidivarin (CBDV) reversed the inhibition of spontaneous firing discharge caused by the combination of THC and CBD in cultured hippocampal neurons 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.
Comparable studies
Other experimental studies on CBD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity Healthy volunteers experienced with cannabis but not regular users | 2019 | Within-subjects experimental design | n = 17 |
| Pharmacological characterization of cannabidiol as a negative allosteric modulator of the 5-HT2A receptor. HEK 293 cells and rat primary cortical neurons | 2025 | Laboratory study | |
| Placebo Effects of Edible Cannabis: Reported Intoxication Effects at a 30-Minute Delay Participants | 2017 | Within-subjects experimental design | n = 20 |
| Acute and Extended Anxiolytic Effects of Cannabidiol in Cannabis Flower: A Quasi-Experimental ad libitum Use Study Participants with anxiety symptoms who were not using cannabis or who used cannabis... | 2024 | Nonequivalent control group quasiexperimental design | n = 300 |
| Baseline affective symptomatology moderates acute subjective effects of high potency THC and CBD cannabis concentrates. Cannabis users (48% female; mean age 29.87 years) | 2023 | Exploratory experimental study with ad libitum naturalistic use | n = 54 |