Abstract
The cannabis plant exerts its pharmaceutical activity primarily by the binding of cannabinoids to two G protein-coupled cannabinoid receptors, CB1 and CB2. The role that cannabis terpenes play in this activation has been considered and debated repeatedly, based on only limited experimental results. In the current study we used a controlled in-vitro heterologous expression system to quantify the activation of CB1 receptors by sixteen cannabis terpenes individually, by tetrahydrocannabinol (THC) alone and by THC-terpenes mixtures. The results demonstrate that all terpenes, when tested individually, activate CB1 receptors, at about 10–50% of the activation by THC alone. The combination of some of these terpenes with THC significantly increases the activity of the CB1 receptor, compared to THC alone. In some cases, several fold. Importantly, this amplification is evident at terpene to THC ratios similar to those in the cannabis plant, which reflect very low terpene concentrations. For some terpenes, the activation obtained by THC- terpene mixtures is notably greater than the sum of the activations by the individual components, suggesting a synergistic effect. Our results strongly support a modulatory effect of some of the terpenes on the interaction between THC and the CB1 receptor. As the most effective terpenes are not necessarily the most abundant ones in the cannabis plant, reaching “whole plant” or “full spectrum” composition is not necessarily an advantage. For enhanced therapeutic effects, desired compositions are attainable by enriching extracts with selected terpenes. These compositions adjust the treatment for various desired medicinal and personal needs.
| Original language | English |
|---|---|
| Article number | 115548 |
| Pages (from-to) | 115548 |
| Journal | Biochemical Pharmacology |
| Volume | 212 |
| DOIs | |
| State | Published - Jun 2023 |
Bibliographical note
Funding Information:This research was supported by the Bazelet group and by research grant to YBC from the Open University of Israel.
Funding Information:
We thank Prof. Ken Mackie, Indiana University, Bloomington, Indiana for kindly providing the CB1 receptor construct. We thank Prof. Amiram Goldblum for his thorough review of the manuscript. FUNDING, This research was supported by the Bazelet group and by research grant to YBC from the Open University of Israel. AUTHOR CONTRIBUTION, NR and AME designed the research, performed data analysis and wrote the manuscript. DBZ prepared the materials and contributed to research plan. DHS performed data analysis and contributed to manuscript preparation. EMD provided clinical practicable input. MT and AD performed the experiments. YBC designed the research, performed the experiments and the data analysis and wrote the manuscript. All authors reviewed and approved the final version of the manuscript.
Publisher Copyright:
© 2023 The Author(s)
Keywords
- Cannabinoid Receptor Agonists
- Cannabinoids/pharmacology
- Cannabis/chemistry
- Dronabinol/pharmacology
- Hallucinogens
- Receptor, Cannabinoid, CB1
- Receptor, Cannabinoid, CB2
- Terpenes/pharmacology