Semi-Synthesis of Dimeric Cannabidiol Derivatives and Evaluation of their Affinity at Neurological Targets.
Zachary Stryker, Jorge I Castillo-Arellano, Stephen J Cutler, Michael D Wyatt, Francisco León
Journal of Natural Products February 28, 2025 DOI: 10.1021/acs.jnatprod.4c01174 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical chemistry study (synthesis and in vitro receptor screening) Peer reviewed |
|---|---|
| Intervention | CBD/Δ8-THC heterodimers |
| Measures | GIRK channel activation assay |
| Topics | CBD |
| Key points | The synthesized CBD and Δ8-THC homodimers and CBD/Δ8-THC heterodimers were generally more active at 5-HT2B and sigma 2 receptors, with Ki values ranging from 0.6 to 8.7 μM. The authors present this as early evidence that the dimers may serve as novel chemical entities for exploring receptor function and may have bivalent, bitopic, or dual mechanisms of action. |
Abstract
Cannabidiol (CBD) is a natural product associated with a wide range of biological and therapeutic activities. Despite the widespread cultural acceptance of CBD as a medicinal agent, much remains to be determined regarding its precise mechanism(s) of action in treating multiple conditions. CBD has been shown to promiscuously interact with several neurological targets with varying affinities. To expand the chemical space of phytocannabinoids and develop novel chemical compounds, we have designed and synthesized a series of CBD and Δ8-THC homodimers, and CBD/Δ8-THC heterodimers. The capacity of the dimers to interact with a panel of CNS targets was explored along with the capacity to activate CB1 receptors, as measured by a GIRK channel activation assay. In the panel screen, the dimers were shown to be generally more active toward 5-HT2B and sigma 2 receptors with a range of Ki values from 0.6 to 8.7 μM. These findings provide early evidence that this new class of dimers can serve as novel chemical entities to explore receptor function and the potential for these dimers to have bivalent, bitopic, or dual mechanisms of action.