In a recent study, the activity of eight cannabinoids and their effects on cannabinoid 1 (CB1) and CB2 receptors were evaluated. The study, published in Scientific Reports, assessed the effect of certain cannabinoids on cells (in vitro) and a mouse model (in vivo).
Assays were used to screen cannabinoids against each other and a reference compound to assess their activity. The researchers found that all cannabinoids displayed some level of activity at CB1 or CB2 receptor sites in cell culture assays, in addition to different effects on behavior.
Tetrahydrocannabinolic acid (THCA)
- Greater affinity (strength of binding) toward the CB2 receptor
- Pain-relieving effects, as well as reduced motor activity, at lower doses (3mg/kg) and anti-anxiety effects at higher doses (10mg/kg)
- Agonist/partial agonist (increases activity) at CB1 and CB2 receptors
- Loss of motion and hypothermia at high doses, and pain-relieving and anti-anxiety effects, as well as reduced motor activity, at both high and low doses
Cannabidiolic acid (CBDA)
- Partial agonism at CB2 receptor
- Notable effects on reducing anxiety and motor activity
- Affinity for the CB2 receptor
- No significant in vivo response, though previous reports have linked this cannabinoid with anticonvulsant effects at higher doses than tested
- Weak partial agonist at both CB1 and CB2 receptors
- Small effect on pain and anxiety relief at high doses
- Partial agonist at both CB1 and CB2 receptors with great potency at CB2 receptors
- Small effect on pain and motor activity
The data uncovered in the study supports the growing school of thought that it’s important to understand the pharmacology of lesser-abundant cannabinoids and the receptors they interact with to fully grasp the pharmacology of cannabis-derived molecules.
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- Zagzoog A, et al. “In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa.” Sci Rep. 2020;10:20405.