Minor Cannabinoids: Pharmacological Effects

In a recent study, the activity of eight cannabinoids and their effects on cannabinoid 1 (CB₁) and CB₂ receptors were evaluated.[1] 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)

Tetrahydrocannabivarin (THCV)

• 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

Cannabidivarin (CBDV)

• 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

Cannabigerol (CBG)

• Weak partial agonist at both CB₁ and CB₂ receptors
• Small effect on pain and anxiety relief at high doses

Cannabichromene (CBC)

• 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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Reference

1. Zagzoog A, et al. “In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa.” Sci Rep. 2020;10:20405.