How Cannabis Use May Generalize Stress Responses Through Brain Changes in Rats

THC+CBD self-administration followed by withdrawal caused male rats to show stress-coping behaviors in response to a neutral stimulus unrelated to the original stressor. This generalization was linked to astrocyte retraction from synapses and decreased Synapsin-I density in the nucleus accumbens core. Effects were observed only in males.

Rats were restraint-stressed with an associated odor (stress-CS), then self-administered THC+CBD for 10 days followed by 10 days of withdrawal. Stress responses to the conditioned and neutral odors were measured in a defensive burying task. Brain changes were assessed via in vivo zymography and confocal microscopy.

Cannabis use disorder and PTSD frequently co-occur. Understanding how cannabinoid exposure might alter brain circuits involved in stress generalization could point to new treatment targets for both conditions.

The finding that cannabinoid exposure can cause stress responses to spread beyond their original triggers mirrors a key feature of PTSD. The sex-specific nature of these effects adds to growing evidence that cannabis affects male and female brains differently.

Animal study results may not translate directly to humans. The THC+CBD combination and dosing may not reflect typical human consumption patterns. Only examined one brain region. The sex difference mechanism was not fully explained.