Chronic stress enhanced fear memories in adolescent female rats, and CB1 receptor activation reduced fear recall but impaired the ability to permanently extinguish those fears.
PTSD researchers, clinicians treating trauma, and women considering cannabis for anxiety or PTSD.
CB1 activation: reduced fear recall but impaired extinction
What the researchers found
Chronic mild stress enhanced trace fear conditioning (episodic fear memories) in adolescent female rats. The CB1 agonist ACEA reduced fear during memory recall in both stressed and non-stressed females, but it either had no effect on or impaired both short-term and long-term fear extinction. For contextual fear, ACEA had opposite effects on extinction depending on stress history.
Why it matters
This has direct implications for using medical cannabis to treat PTSD in women. While CB1 activation reduced acute fear responses, it may actually impair the therapeutic process of fear extinction that underlies exposure-based PTSD treatments.
The numbers in context
ACEA dose: 0.1 mg/kg. CMS enhanced trace fear conditioning vs controls. ACEA reduced baseline freezing during recall. ACEA impaired long-term contextual extinction in stressed females while facilitating it in non-stressed controls.
How the study worked
Adolescent female Sprague-Dawley rats underwent chronic mild unpredictable stress, then were tested on hippocampal-dependent trace and contextual fear conditioning. CB1 agonist ACEA (0.1 mg/kg) was administered before memory recall or acquisition.
What this study cannot tell us
Preprint (bioRxiv), not yet peer-reviewed. Only female rats were tested (no direct male comparison in this study, but references prior male data). The synthetic CB1 agonist ACEA may not perfectly mimic THC effects.
How to read the evidence
Preprint study (not yet peer-reviewed) with only female rats, limiting broader conclusions.
When this study was published
2026 preprint.
The bigger picture
Women are diagnosed with PTSD at roughly twice the rate of men, yet most cannabis-PTSD research uses male animals. These sex-specific findings suggest the endocannabinoid system may function differently in female stress responses, which could affect treatment outcomes.
Questions still open
- Could cannabis use impair the effectiveness of exposure therapy for PTSD in women? Do the sex differences in CB1 effects translate to human clinical populations?
Common questions
Can cannabis help with PTSD in women?
Why study only females?
Read the original research
Effects of chronic mild stress and CB1 receptor activation on hippocampal-dependent fear conditioning in female adolescent rats.
bioRxiv : the preprint server for biology
Citation
Reich, Christian G; Ferraro, Angelica; Wig, Philip; Amada, Nicole; Weiss, Michael S. (2026). Effects of chronic mild stress and CB1 receptor activation on hippocampal-dependent fear conditioning in female adolescent rats.. bioRxiv : the preprint server for biology. https://doi.org/10.64898/2026.02.13.705785
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