Both CB1 blocking and CB2 activation reduced cocaine reward in mice
CB1 receptor antagonism and CB2 receptor agonism both reduced cocaine-induced behavioral sensitization and place preference in mice, with opposite receptor roles.
Quick Facts
What This Study Found
CB1 antagonist AM251 inhibited acquisition and expression of cocaine sensitization and conditioned place preference (CPP). CB2 agonist JWH133 similarly inhibited both sensitization and CPP, with effects reversed by CB2 antagonist AM630. Both drugs prevented cocaine-induced hippocampal neuronal activation (c-Fos), suggesting converging mechanisms despite acting on different receptors.
Key Numbers
AM251 inhibited sensitization at 0.3-3 mg/kg and CPP at 10 mg/kg; JWH133 inhibited both at 0.3-3 mg/kg; effects reversed by CB2 antagonist AM630 (5 mg/kg).
How They Did This
Animal study in male Swiss mice using CB1 antagonist AM251 and CB2 agonist JWH133 in cocaine-induced behavioral sensitization and conditioned place preference models, with c-Fos immunohistochemistry.
Why This Research Matters
This study shows that the endocannabinoid system modulates cocaine reward through two independent receptor pathways, potentially doubling the number of therapeutic targets for cocaine addiction.
The Bigger Picture
That CB1 antagonism and CB2 agonism both reduce cocaine reward through different mechanisms suggests the endocannabinoid system offers multiple potential intervention points for stimulant addiction.
What This Study Doesn't Tell Us
Animal study in mice; synthetic cannabinoid agents not available clinically; only male mice used (sex differences unknown); acute dosing paradigm may not reflect chronic treatment.
Questions This Raises
- ?Would combined CB1 antagonist + CB2 agonist produce additive anti-cocaine effects?
- ?Could these targets work for other stimulant addictions?
Trust & Context
- Key Stat:
- Two independent cannabinoid receptor targets both reduced cocaine reward
- Evidence Grade:
- Preliminary: animal study with synthetic compounds; no human clinical data.
- Study Age:
- Published 2020.
- Original Title:
- The roles of cannabinoid CB1 and CB2 receptors in cocaine-induced behavioral sensitization and conditioned place preference in mice.
- Published In:
- Psychopharmacology, 237(2), 385-394 (2020)
- Database ID:
- RTHC-02692
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
How do cannabinoid receptors affect cocaine addiction?
CB1 and CB2 receptors have opposite roles but both pathways can be targeted to reduce cocaine reward: blocking CB1 or activating CB2 each independently reduced cocaine-seeking behavior in mice.
Could this lead to a cocaine addiction treatment?
Potentially. Having two independent cannabinoid targets doubles the options for drug development, but these are early animal findings needing human validation.
Read More on RethinkTHC
- cannabis-dependence-physical-psychological-addiction-science
- cannabis-perception-vs-evidence-gap
- cannabis-use-disorder-test
- cross-addiction-quit-weed-start-drinking
- is-weed-addictive
- is-weed-addictive-science
- quitting-weed-and-alcohol
- rehab-for-weed-addiction-necessary
- signs-of-cannabis-use-disorder
- weed-vape-pen-addiction
Cite This Study
https://rethinkthc.com/research/RTHC-02692APA
Lopes, Jadna B; Bastos, Juliana R; Costa, Rayssa B; Aguiar, Daniele C; Moreira, Fabrício A. (2020). The roles of cannabinoid CB1 and CB2 receptors in cocaine-induced behavioral sensitization and conditioned place preference in mice.. Psychopharmacology, 237(2), 385-394. https://doi.org/10.1007/s00213-019-05370-5
MLA
Lopes, Jadna B, et al. "The roles of cannabinoid CB1 and CB2 receptors in cocaine-induced behavioral sensitization and conditioned place preference in mice.." Psychopharmacology, 2020. https://doi.org/10.1007/s00213-019-05370-5
RethinkTHC
RethinkTHC Research Database. "The roles of cannabinoid CB1 and CB2 receptors in cocaine-in..." RTHC-02692. Retrieved from https://rethinkthc.com/research/lopes-2020-the-roles-of-cannabinoid
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.