Blocking CB1 receptors (with rimonabant) and activating CB2 receptors (with JWH-133) both reduced cocaine's rewarding properties and motor-stimulant effects in rats, through opposing but complementary cannabinoid mechanisms.
Read this if you're interested in how the cannabinoid system could be targeted to treat cocaine addiction.
CB2 activation abolished cocaine-induced vertical activity and reduced reward learning
What the researchers found
The CB1 antagonist rimonabant (3 mg/kg) decreased both the learning and expression of cocaine-induced place preference and reduced cocaine's stimulant effects on movement. The CB2 agonist JWH-133 (10 mg/kg) produced similar effects, also reducing cocaine place preference and abolishing cocaine-induced vertical activity.
JWH-133's effects were specifically through CB2 receptors, as they were reversed by the CB2 antagonist AM630. The study found that CB1 and CB2 receptors appear to have opposite roles in regulating cocaine's effects: blocking CB1 or activating CB2 both reduced cocaine reward, suggesting these are complementary pharmacological strategies.
Importantly, JWH-133 inhibited cocaine-related behaviors both during learning and during expression of already-learned associations, suggesting it could potentially help both prevention and treatment.
Why it matters
Cocaine addiction lacks effective pharmacological treatments. This study identifies two cannabinoid-based strategies, CB1 blockade and CB2 activation, that both reduce cocaine reward in animals. CB2 agonists are particularly interesting because they do not produce the psychiatric side effects associated with CB1 antagonists.
The numbers in context
Rimonabant 3 mg/kg: reduced acquisition and expression of cocaine CPP, decreased motor activity. JWH-133 10 mg/kg: reduced acquisition and expression of cocaine CPP, abolished vertical activity. AM630 5 mg/kg: reversed JWH-133 effects (confirming CB2 mechanism). Cocaine dose: 20 mg/kg.
How the study worked
Conditioned place preference (cocaine reward), conditioned motor activity, and open-field activity tests in rats. The CB1 antagonist rimonabant and CB2 agonist JWH-133 were administered at various time points to assess effects on acquisition and expression of cocaine conditioning. AM630 (CB2 antagonist) was used to confirm receptor specificity.
What this study cannot tell us
Animal study using conditioned place preference, which models drug reward but not the full complexity of human addiction. Rimonabant was withdrawn from market due to psychiatric effects, limiting its clinical relevance. JWH-133 has not been tested in humans for cocaine addiction. The doses and timing may not translate directly to clinical use.
How to read the evidence
Controlled animal study with appropriate pharmacological controls (receptor antagonist reversal). Well-designed but preclinical.
When this study was published
Published in 2017. CB2 agonists as addiction treatments remain under investigation.
The bigger picture
The cannabinoid system modulates cocaine's rewarding effects through two receptor types with opposite roles. This creates multiple pharmacological angles for treating cocaine addiction. CB2 agonists may be particularly promising because they lack the reward-related effects of CB1 manipulation, making them safer for addiction treatment.
Questions still open
- Would CB2 agonists reduce cocaine craving and relapse in humans? Could combined CB1 blockade and CB2 activation produce additive effects? Are peripherally restricted CB1 antagonists (avoiding psychiatric effects) still effective against cocaine reward?
Common questions
Could cannabinoid drugs treat cocaine addiction?
Does cannabis itself reduce cocaine cravings?
Read the original research
Attenuation of Cocaine-Induced Conditioned Place Preference and Motor Activity via Cannabinoid CB2 Receptor Agonism and CB1 Receptor Antagonism in Rats.
The international journal of neuropsychopharmacology, 20(3), 269-278
Citation
Delis, Foteini; Polissidis, Alexia; Poulia, Nafsika; Justinova, Zuzana; Nomikos, George G; Goldberg, Steven R; Antoniou, Katerina. (2017). Attenuation of Cocaine-Induced Conditioned Place Preference and Motor Activity via Cannabinoid CB2 Receptor Agonism and CB1 Receptor Antagonism in Rats.. The international journal of neuropsychopharmacology, 20(3), 269-278. https://doi.org/10.1093/ijnp/pyw102
Explore the wider topic
- Physical vs Psychological Cannabis Dependence: What Science Actually Shows
- The Gap Between Cannabis Perception and Science: Why What We Believe Outpaces What We Know
- Cannabis Use Disorder: Am I Addicted? Self-Assessment Guide
- Cross-Addiction After Quitting Weed: When One Habit Replaces Another
- Is Weed Addictive? What the Research Actually Shows
- Is Cannabis Addictive? What the DSM-5 and Brain Science Say
- 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
- Weed Vape Pen Addiction: Why Vaping Makes It Harder to Quit