A Critical Evaluation of Terpenoid Signaling at Cannabinoid CB1 Receptors in a Neuronal Model

In addition to phytocannabinoids, cannabis contains terpenoids that are claimed to have a myriad of effects on the body. We tested a panel of five common cannabis terpenoids, myrcene, linalool, limonene, α-pinene and nerolidol, in two neuronal models, autaptic hippocampal neurons and dorsal root gan...

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Published in:Molecules (Basel, Switzerland) Switzerland), 2022-09, Vol.27 (17), p.5655
Main Authors: Dvorakova, Michaela, Wilson, Sierra, Corey, Wesley, Billingsley, Jenna, Zimmowitch, Anaëlle, Tracey, Joye, Straiker, Alex, Mackie, Ken
Format: Article
Language:English
Subjects:
2-Arachidonoylglycerol
cannabinoid
Cannabinoid CB1 receptors
Cannabinoids
Cannabis
CB1
Cell receptors
Cellular signal transduction
Chemical properties
Diglycerides
Dorsal root ganglia
Enzymes
G protein-coupled receptor
Hippocampus
Limonene
Linalool
Marijuana
Nerolidol
Neurons
Physiological aspects
Physiological research
Physiology
terpene
Terpenes
terpenoid
Tetrahydrocannabinol
THC
Transient receptor potential proteins
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Summary:In addition to phytocannabinoids, cannabis contains terpenoids that are claimed to have a myriad of effects on the body. We tested a panel of five common cannabis terpenoids, myrcene, linalool, limonene, α-pinene and nerolidol, in two neuronal models, autaptic hippocampal neurons and dorsal root ganglion (DRG) neurons. Autaptic neurons express a form of cannabinoid CB1 receptor-dependent retrograde plasticity while DRGs express a variety of transient receptor potential (TRP) channels. Most terpenoids had little or no effect on neuronal cannabinoid signaling. The exception was nerolidol, which inhibited endocannabinoid signaling. Notably, this is not via inhibition of CB1 receptors but by inhibiting some aspect of 2-arachidonoylglycerol (2-AG) production/delivery; the mechanism does not involve reducing the activity of the 2-AG-synthesizing diacylglycerol lipases (DAGLs). Nerolidol was also the only terpenoid that activated a sustained calcium response in a small (7%) subpopulation of DRGs. In summary, we found that only one of five terpenoids tested had notable effects on cannabinoid signaling in two neuronal models. Our results suggest that a few terpenoids may indeed interact with some components of the cannabinoid signaling system and may therefore offer interesting insights upon further study.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27175655