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Related Concept Videos

Chemotherapy-Induced Nausea and Vomiting: Cannabinoids01:21

Chemotherapy-Induced Nausea and Vomiting: Cannabinoids

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Tetrahydrocannabinol (THC) is a phytocannabinoid that primarily interacts with the CB1 receptor, a type of G protein-coupled receptor (GPCR) predominantly in and around the chemoreceptor trigger zone (CTZ) and emetic center. THC also blocks the serotonin receptor activity in the dorsal vagal complex (DVC) by inhibiting serotonin release. THC exerts its anti-emetic effects through these interactions, which are beneficial for patients undergoing chemotherapy.
Two synthetic agonists of THC,...
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Cannabinoids Activate Monoaminergic Signaling to Modulate Key C. elegans Behaviors.

Mitchell D Oakes1, Wen Jing Law1, Tobias Clark1

  • 1Department of Biological Sciences, University of Toledo, Toledo, Ohio 43606.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
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Summary

Cannabinoids from cannabis activate conserved signaling pathways in C. elegans, modulating pain and feeding behaviors. This research reveals how cannabinoids interact with neurotransmitter systems, offering insights into potential therapeutic applications.

Keywords:
C. eleganscannabinoidmonoamineneuromodulationnociception

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Genetics

Background:

  • Cannabis sativa, or marijuana, is recognized for its psychoactive and potential medicinal properties.
  • Understanding cannabinoid signaling is crucial for exploring therapeutic benefits, yet cellular studies yield conflicting results.
  • The nematode Caenorhabditis elegans offers a genetically tractable whole-animal model for studying complex biological systems.

Purpose of the Study:

  • To investigate the conserved cannabinoid signaling system in C. elegans.
  • To elucidate the mechanisms by which cannabinoids modulate monoaminergic signaling.
  • To explore the potential of C. elegans as a model for studying cannabinoid effects on behavior.

Main Methods:

  • Utilized C. elegans to study the effects of endogenous cannabinoid receptor agonists, 2-arachidonoylglycerol (2-AG) and anandamide (AEA).
  • Investigated pathways involving the cannabinoid-like receptor NPR-19, the octopamine receptor OCTR-1, and the serotonin receptor SER-4.
  • Employed genetic manipulation (e.g., npr-19-null animals) and receptor expression (human CB1) to confirm receptor orthology and pathway function.

Main Results:

  • 2-AG and AEA activate a canonical cannabinoid receptor in C. elegans, inhibiting nociception and feeding via NPR-19.
  • Cannabinoid signaling modulates nociception and locomotion through an NPR-19-independent pathway involving OCTR-1 and SER-4.
  • Demonstrated direct activation of OCTR-1 by 2-AG and enhanced SER-4 signaling by increased endogenous serotonin.

Conclusions:

  • A conserved cannabinoid signaling system exists in C. elegans, analogous to mammalian systems.
  • Cannabinoids directly and indirectly modulate monoaminergic signaling (octopaminergic and serotonergic).
  • C. elegans serves as a valuable model for dissecting cannabinoid signaling and its impact on behavior and potential therapeutic targets.