Both CB1 blockade and CB2 activation reduced cocaine's rewarding and stimulant effects in rats
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- CB2 activation abolished cocaine-induced vertical activity and reduced reward learning
- Evidence Grade:
- Controlled animal study with appropriate pharmacological controls (receptor antagonist reversal). Well-designed but preclinical.
- Study Age:
- Published in 2017. CB2 agonists as addiction treatments remain under investigation.
- Original Title:
- Attenuation of Cocaine-Induced Conditioned Place Preference and Motor Activity via Cannabinoid CB2 Receptor Agonism and CB1 Receptor Antagonism in Rats.
- Published In:
- The international journal of neuropsychopharmacology, 20(3), 269-278 (2017)
- Authors:
- Delis, Foteini, Polissidis, Alexia, Poulia, Nafsika, Justinova, Zuzana, Nomikos, George G, Goldberg, Steven R, Antoniou, Katerina
- Database ID:
- RTHC-01366
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Could cannabinoid drugs treat cocaine addiction?
This animal study suggests two possible approaches: blocking CB1 receptors or activating CB2 receptors. Both reduced cocaine's rewarding effects in rats. CB2 agonists are considered more promising because they avoid the psychiatric side effects associated with CB1 blockers like rimonabant.
Does cannabis itself reduce cocaine cravings?
This study used specific receptor-targeted drugs, not cannabis itself. Cannabis contains THC, which activates CB1 (the opposite of what helped here). The findings suggest that targeted cannabinoid pharmacology, rather than whole-plant cannabis, would be needed for cocaine addiction treatment.
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Cite This Study
https://rethinkthc.com/research/RTHC-01366APA
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
MLA
Delis, Foteini, et al. "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, 2017. https://doi.org/10.1093/ijnp/pyw102
RethinkTHC
RethinkTHC Research Database. "Attenuation of Cocaine-Induced Conditioned Place Preference ..." RTHC-01366. Retrieved from https://rethinkthc.com/research/delis-2017-attenuation-of-cocaineinduced-conditioned
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.