In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa
A. Zagzoog, Kawthar A. Mohamed, H. J. J. Kim, Eunhyun D. Kim, Connor Frank, T. Black, P. D. Jadhav, L. Holbrook, R. Laprairie
Scientific Reports November 23, 2020 DOI: 10.1038/s41598-020-77175-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro and in vivo preclinical pharmacology study Peer reviewed |
|---|---|
| Population | Chinese hamster ovary (CHO) cells stably expressing human CB1R or CB2R, and C57BL/6 mice |
| Interventions | cannabidiol (CBD) cannabidiolic acid (CBDa) cannabidivarin (CBDV) cannabigerol (CBG) cannabichromene (CBC) |
| Topics | Cannabis |
| Key points | Many of the eight phytocannabinoids tested showed partial agonist activity at CB1R and/or CB2R in cell assays, and mice displayed responses often associated with CB1R activation, such as catalepsy, hypothermia, anti-nociception, hypolocomotion, and anxiolysis. The authors contend these findings support cannabinoid receptor-dependent pharmacology for less-abundant phytocannabinoids. |
Abstract
The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆9-THC is known to bring about the ‘high’ associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing these receptors and in C57BL/6 mice in an attempt to better understand their pharmacodynamics. Specifically, ∆9-THC, ∆9-tetrahydrocannabinolic acid (∆9-THCa), ∆9-tetrahydrocannabivarin (THCV), CBD, cannabidiolic acid (CBDa), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC) were evaluated. Compounds were assessed for their affinity to receptors, ability to inhibit cAMP accumulation, βarrestin2 recruitment, receptor selectivity, and ligand bias in cell culture; and cataleptic, hypothermic, anti-nociceptive, hypolocomotive, and anxiolytic effects in mice. Our data reveal partial agonist activity for many phytocannabinoids tested at CB1R and/or CB2R, as well as in vivo responses often associated with activation of CB1R. These data build on the growing body of literature showing cannabinoid receptor-dependent pharmacology for these less-abundant phytocannabinoids and are critical in understanding the complex and interactive pharmacology of Cannabis-derived molecules.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 8
- THC, CBD and minor cannabinoid CBDV differently modulate hippocampal neurons firing. Neurotoxicology May 1, 2025
- Tetrahydrocannabivarin (THCV) Dose Dependently Blocks or Substitutes for Tetrahydrocannabinol (THC) in a Drug Discrimination Task in Rats Biomolecules September 18, 2025
- Side-Chain Homologs of Δ9-THC, Δ8-THC, and HHC Reveal Pathway Bias at CB1R and CB2R Cannabinoid Receptors. Molecular Neurobiology August 20, 2026
- Therapeutic potential of phytocannabinoids in depression and cognitive dysfunction: Evidence from preclinical models. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie May 1, 2026
- Evaluation of cannabimimetic effects of selected minor cannabinoids and Terpenoids in mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry June 8, 2024
and 3 more in the library