Stress increases cocaine use in both sexes, but the cannabinoid system plays different roles in males versus females
Repeated stress enhanced cocaine self-administration equally in male and female rats, but blocking CB1 receptors reduced cocaine intake through different mechanisms in each sex.
Quick Facts
What This Study Found
Footshock stress increased cocaine self-administration in both sexes. In males, CB1 antagonism only reduced cocaine intake in rats with combined stress-and-cocaine history. In females, rimonabant reduced cocaine intake even without stress history, with stressed females sensitive to both doses tested.
Key Numbers
Cocaine dose: 0.5 mg/kg/infusion. Rimonabant doses: 1 and 3 mg/kg. Females showed stress-specific front-loading behavior. Both rimonabant doses effective in stressed females.
How They Did This
Male and female Sprague-Dawley rats self-administered cocaine during sessions with or without footshock stress. CB1 receptor antagonist rimonabant administered systemically at two doses (1 and 3 mg/kg).
Why This Research Matters
Stress is a major driver of drug relapse, and sex differences in addiction mechanisms are increasingly recognized. The cannabinoid system mediates stress-cocaine interactions differently in males and females.
The Bigger Picture
This adds to growing evidence that addiction biology differs meaningfully between sexes. The endocannabinoid system appears more broadly involved in cocaine-taking in females, regardless of stress.
What This Study Doesn't Tell Us
Rat models may not fully translate to human cocaine use disorder. Only one stress paradigm tested. Systemic rimonabant affects the whole body.
Questions This Raises
- ?Would CB1 receptor modulators be more effective for treating cocaine addiction in women than men?
- ?What brain circuits mediate the sex-specific CB1R effects?
Trust & Context
- Key Stat:
- CB1 receptor blockade reduced cocaine intake in stressed males only, but in females both with and without stress history
- Evidence Grade:
- Well-designed animal study with appropriate controls and both sexes, but limited to one stress paradigm.
- Study Age:
- 2025 publication.
- Original Title:
- Repeated footshock stress enhances cocaine self-administration in male and female rats: Role of the cannabinoid receptor 1.
- Published In:
- Physiology & behavior, 293, 114840 (2025)
- Authors:
- Gaulden, Andrew D(2), Tepe, Erin A(2), Sia, Eleni(2), Rollins, Sierra S, McReynolds, Jayme R
- Database ID:
- RTHC-06516
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Why does the cannabinoid system matter for cocaine addiction?
The endocannabinoid system modulates stress responses and reward circuits. When stress enhances drug-seeking, cannabinoid signaling appears to be recruited as a mediator.
What does this mean for treating cocaine addiction differently in men and women?
Targeting the cannabinoid system might be effective for cocaine addiction in women more broadly, while in men it might be most useful when stress is driving drug use. These are animal findings needing human validation.
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Cite This Study
https://rethinkthc.com/research/RTHC-06516APA
Gaulden, Andrew D; Tepe, Erin A; Sia, Eleni; Rollins, Sierra S; McReynolds, Jayme R. (2025). Repeated footshock stress enhances cocaine self-administration in male and female rats: Role of the cannabinoid receptor 1.. Physiology & behavior, 293, 114840. https://doi.org/10.1016/j.physbeh.2025.114840
MLA
Gaulden, Andrew D, et al. "Repeated footshock stress enhances cocaine self-administration in male and female rats: Role of the cannabinoid receptor 1.." Physiology & behavior, 2025. https://doi.org/10.1016/j.physbeh.2025.114840
RethinkTHC
RethinkTHC Research Database. "Repeated footshock stress enhances cocaine self-administrati..." RTHC-06516. Retrieved from https://rethinkthc.com/research/gaulden-2025-repeated-footshock-stress-enhances
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.