CB1 receptor antagonism and CB2 receptor agonism both reduced cocaine-induced behavioral sensitization and place preference in mice, with opposite receptor roles.
Addiction researchers, pharmacologists developing cannabinoid-based treatments, and neuroscientists.
Two independent cannabinoid receptor targets both reduced cocaine reward
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
What this study cannot 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.
How to read the evidence
Preliminary: animal study with synthetic compounds; no human clinical data.
When this study was published
Published 2020.
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.
Questions still open
- Would combined CB1 antagonist + CB2 agonist produce additive anti-cocaine effects? Could these targets work for other stimulant addictions?
Common questions
How do cannabinoid receptors affect cocaine addiction?
Could this lead to a cocaine addiction treatment?
Read the original research
The roles of cannabinoid CB1 and CB2 receptors in cocaine-induced behavioral sensitization and conditioned place preference in mice.
Psychopharmacology, 237(2), 385-394
Citation
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
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