Squirrel monkeys successfully discriminated the cannabinoid antagonist rimonabant from vehicle, providing a new tool for studying how cannabinoid receptor blockade feels subjectively.
Behavioral pharmacologists, cannabinoid researchers, and drug development scientists.
THC blocked the rimonabant discrimination, confirming CB1 mechanism
What the researchers 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.
Why it 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 numbers in context
Squirrel monkeys discriminated rimonabant from vehicle in a dose-dependent manner; THC blocked the rimonabant discrimination.
How the study worked
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.
What this study cannot 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.
How to read the evidence
Preliminary: animal behavioral pharmacology study with small sample size.
When this study was published
Published 2016.
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 Rimonabant was once marketed for obesity but withdrawn due to psychiatric side effects.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.
Questions still open
- Could newer, more selective CB1 antagonists avoid the psychiatric side effects seen with rimonabant while retaining therapeutic benefits?
Common questions
What is drug discrimination?
What happened to rimonabant?
Read the original research
Cannabinoid Antagonist Drug Discrimination in Nonhuman Primates.
The Journal of pharmacology and experimental therapeutics, 372(1), 119-127
Citation
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
Explore the wider topic
- How THC Affects Your Amygdala: The Brain's Threat Detector and Cannabis
- The Anandamide Connection: Your Body's Natural Bliss Molecule
- How Long for Cannabinoid Receptors to Return to Normal
- Physical vs Psychological Cannabis Dependence: What Science Actually Shows
- Cannabis and the Developing Brain: What Every Teenager (and Parent) Should Know
- The Gap Between Cannabis Perception and Science: Why What We Believe Outpaces What We Know
- Cannabis Use Disorder: Am I Addicted? Self-Assessment Guide
- Why Can't I Enjoy Anything Without Weed? The Science Behind It
- Cross-Addiction After Quitting Weed: When One Habit Replaces Another
- Dopamine Recovery After Quitting Weed: What the Science Says
- The Endocannabinoid System Explained Simply: What It Does and Why It Matters
- Your Endocannabinoid System Explained: Why Withdrawal Happens
- Is Weed Addictive? What the Research Actually Shows
- Is Cannabis Addictive? What the DSM-5 and Brain Science Say
- Your Nervous System After Quitting Weed: Fight or Flight
- Quitting Weed and Alcohol Together: What to Know About Dual Cessation
- Is Rehab Necessary for Weed? An Honest Assessment
- Signs You May Have Cannabis Use Disorder: An Honest Self-Assessment
- Using Weed Under 18: What It Does to Your Developing Brain
- What THC Does to Your Brain: Why Withdrawal Happens
- THC and Your Prefrontal Cortex: What Cannabis Does to Your Decision-Making Brain
- Weed, Cortisol, and Stress: What Cannabis Does to Your Stress Hormones
- Weed and Memory: What the Science Says About THC and Your Hippocampus
- Weed and Motivation: Is Amotivational Syndrome Real?
- Weed and Your Nervous System: What THC Actually Does to Your Brain and Body
- How Weed Rewires Your Reward System (And How to Reset It)
- Weed Vape Pen Addiction: Why Vaping Makes It Harder to Quit