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. 2025 Jan 31.
doi: 10.1007/s00213-025-06748-4. Online ahead of print.

Acute and chronic cannabis vapor exposure produces immediate and delayed impacts on phases of fear learning in a sex specific manner

Savannah H M Lightfoot #  1   2 , Andrei S Nastase #  1   2 , Gabriela Costa Lenz Cesar  3 , Catherine Hume  1   4 , Renaud C Gom  1   2 , G Campbell Teskey  1   4 , Matthew N Hill  5   6   7
Affiliations

Acute and chronic cannabis vapor exposure produces immediate and delayed impacts on phases of fear learning in a sex specific manner

Savannah H M Lightfoot et al. Psychopharmacology (Berl). .

Abstract

Rationale: Current treatment options for PTSD have unreliable efficacy, with many individuals unable to achieve complete remission. Cannabis and cannabinoids that act through the endogenous cannabinoid (endocannabinoid) system to help promote trauma recovery by means of enhanced extinction learning are potential therapeutic, pharmacological candidates. Using a preclinical model of translationally-relevant cannabis administration in rodents, we examined the impact of cannabis exposure on aversive memory.

Objectives: Our study investigated the effects of acute cannabis exposure prior to (1) fear conditioning and (2) fear extinction, as well as (3) chronic cannabis exposure prior to fear conditioning, on the behavioural representations of fear memory dynamics in a Pavlovian auditory conditioning paradigm.

Methods: Male and female Sprague Dawley rats were acutely or chronically exposed to THC-dominant cannabis extract or vehicle vapor as described above. We then assessed both passive (freezing) and active (darting) fear behaviours during conditioning, extinction, retrieval, and spontaneous recovery.

Results: Acute cannabis exposure prior to conditioning had no immediate effects on fear acquisition, but impaired fear recall in females 24 h later and prevented spontaneous recovery of conditioned fear following a two-week retrieval test in both male and female rats. Acute cannabis exposure prior to extinction training impaired extinction in females while enhancing extinction acquisition in males. Finally, chronic THC exposure prior to fear conditioning initially potentiated fear responses, predominately in females, but produced no differences in spontaneous recovery in a two-week retrieval test.

Conclusions: Cannabis exposure has complex dynamics on fear memory, however, acute cannabis exposure prior to fear learning appears to result in destabilization of the fear memory long term, which could have potential implications for PTSD.

Keywords: Acute; Auditory fear conditioning; Cannabis; Chronic; Extinction; Spontaneous recovery.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no conflict of interest.

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