A new 2026 study reports that (+)-trans-cannabidiol [(+)-CBD] acts as an agonist at human CB2 cannabinoid receptors, activating a major receptor of the endocannabinoid system involved in immune and inflammatory signaling.

Researchers found that (+)-CBD produced a strong, concentration-dependent CB2 response, reaching roughly 90% of the maximum effect produced by the reference cannabinoid agonist CP55940. Additional testing indicated that the compound acts through the receptor’s primary, or orthosteric, binding site.

The findings show that different molecular forms of cannabidiol can interact with cannabinoid receptors in very different ways. The researchers conclude that (+)-CBD may deserve further study in CB2-sensitive disease states, adding another layer to our understanding of how cannabinoid chemistry can influence the human endocannabinoid system.

“(-)-trans-Cannabidiol ((-)-CBD) is a principal phytocannabinoid from Cannabis sativa. (-)-CBD has complex pharmacology but is a relatively weak inhibitor of CB₁ and CB₂ receptor signaling. Cannabidiol has two chiral centres and thus four stereoisomers. (+)-trans-CBD ((+)-CBD) has a higher affinity than (-)-CBD at CB₁ and CB₂, but its pharmacodynamic effects at these receptors are incompletely described.

We examined the activity of (+)-CBD at human CB₁ and CB₂ receptors using a fluorescence-based assay of membrane potential in AtT20 cells stably expressing CB₁ or CB₂ receptors.

(+)-CBD produced a rapid, concentration-dependent hyperpolarization in CB₂-expressing cells (pEC₅₀ 6.63 ± 0.08) with a maximal effect 90% of the response to CP55940. The CB₂ response was blocked by pertussis toxin pretreatment and competitively inhibited by the CB₂ antagonist AM630 (Schild slope 1.1 ± 0.1). (+)-CBD was a low-efficacy, low-potency CB₁ agonist and inhibited somatostatin-receptor effects at high concentrations (10-30 μM). (+)-CBD had no effect on the membrane potential of AtT20 wild-type cells. In silico modeling of ligand interactions with CB₂ indicated that (+)-CBD but not (-)-CBD formed an H-bond with Ser285, a residue crucial for agonist activation of CB₂.

Our data suggests (+)-CBD acted as a CB₂ agonist via the orthosteric binding site on the receptor. Synthetic CBD, including (+)-CBD, has previously been administered in clinical trials, presumably without consideration of its potential CB₂ agonist activity.

Given the relative safety of (-)-CBD in people, (+)-CBD may be a useful drug to explore CB₂-sensitive disease states.”

https://pubmed.ncbi.nlm.nih.gov/42745361

“This study emphasizes the importance of understanding the molecular actions of the enantiomers of chiral cannabinoids. Although the safety of (+)-CBD cannot simply be assumed to be the same as (−)-CBD, the identification of (+)-CBD as a robust CB2 agonist suggests that (+)-CBD may be worth exploring as a therapeutic agent in chronic inflammatory conditions or other diseases where CB₂ activation may prove beneficial.”

https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.70325