Primates can learn to distinguish between cannabinoid receptor activation and blockade
Squirrel monkeys successfully discriminated the cannabinoid antagonist rimonabant from vehicle, providing a new tool for studying how cannabinoid receptor blockade feels subjectively.
Quick Facts
What This Study Found
Squirrel monkeys were trained to discriminate rimonabant (a CB1 antagonist/inverse agonist) from vehicle in a drug discrimination paradigm. The discrimination was dose-dependent and could be blocked by THC, confirming it was mediated through CB1 receptors.
Key Numbers
Squirrel monkeys discriminated rimonabant from vehicle in a dose-dependent manner; THC blocked the rimonabant discrimination.
How They Did This
Drug discrimination study in squirrel monkeys using a two-lever food-reinforced operant procedure. Animals were trained to discriminate rimonabant from vehicle across multiple dose levels.
Why This Research Matters
Drug discrimination procedures reveal how substances "feel" to animals, providing insight into subjective effects. Establishing that cannabinoid blockade produces discriminable effects helps researchers study the endocannabinoid system and potential therapeutic applications of antagonists.
The Bigger Picture
Understanding how cannabinoid receptor blockade is perceived is relevant for developing potential treatments. Rimonabant was once marketed for obesity but withdrawn due to psychiatric side effects. Better understanding its subjective effects could inform safer drug development.
What This Study Doesn't Tell Us
Animal study with a small number of primates; subjective effects in monkeys may not directly translate to human experience. Rimonabant is no longer marketed for clinical use.
Questions This Raises
- ?Could newer, more selective CB1 antagonists avoid the psychiatric side effects seen with rimonabant while retaining therapeutic benefits?
Trust & Context
- Key Stat:
- THC blocked the rimonabant discrimination, confirming CB1 mechanism
- Evidence Grade:
- Preliminary: animal behavioral pharmacology study with small sample size.
- Study Age:
- Published 2016.
- Original Title:
- Cannabinoid Antagonist Drug Discrimination in Nonhuman Primates.
- Published In:
- The Journal of pharmacology and experimental therapeutics, 372(1), 119-127 (2020)
- Authors:
- Kangas, Brian D(4), Zakarian, Ani S, Vemuri, Kiran(7), Alapafuja, Shakiru O, Jiang, Shan, Nikas, Spyros P, Makriyannis, Alexandros, Bergman, Jack
- Database ID:
- RTHC-02641
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is drug discrimination?
A behavioral method where animals learn to press different levers depending on whether they received a drug or placebo. It reveals whether a substance produces distinct internal cues or "feelings."
What happened to rimonabant?
Rimonabant was approved in Europe for obesity treatment but was withdrawn in 2008 due to increased risk of depression and suicidal ideation.
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Cite This Study
https://rethinkthc.com/research/RTHC-02641APA
Kangas, Brian D; Zakarian, Ani S; Vemuri, Kiran; Alapafuja, Shakiru O; Jiang, Shan; Nikas, Spyros P; Makriyannis, Alexandros; Bergman, Jack. (2020). Cannabinoid Antagonist Drug Discrimination in Nonhuman Primates.. The Journal of pharmacology and experimental therapeutics, 372(1), 119-127. https://doi.org/10.1124/jpet.119.261818
MLA
Kangas, Brian D, et al. "Cannabinoid Antagonist Drug Discrimination in Nonhuman Primates.." The Journal of pharmacology and experimental therapeutics, 2020. https://doi.org/10.1124/jpet.119.261818
RethinkTHC
RethinkTHC Research Database. "Cannabinoid Antagonist Drug Discrimination in Nonhuman Prima..." RTHC-02641. Retrieved from https://rethinkthc.com/research/kangas-2020-cannabinoid-antagonist-drug-discrimination
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.