Cannabinoid use is enhanced by stress and changes conditioned stress responses

Area of Science:

• Neuroscience
• Psychopharmacology
• Behavioral Science

Background:

• Post-traumatic stress disorder (PTSD) frequently co-occurs with substance use disorders.
• Cannabis is commonly used by PTSD patients, but its effects on stress-related responses are debated.
• Existing literature shows mixed results on whether cannabis use alleviates or intensifies stress-associated conditioned stimuli (stress-CS) responses.

Purpose of the Study:

• To investigate how cannabis use impacts responsivity to stress-associated conditioned stimuli (stress-CS) in a rat model.
• To determine if self-administration of cannabinoids (delta-9-tetrahydrocannabinol + cannabidiol; THC+CBD) alters conditioned stress responses and coping behaviors.

Main Methods:

• Rats were exposed to acute stress in the presence of an odor stress-CS.
• Following stress, rats self-administered THC+CBD for 15 days.
• Reinstatement of THC+CBD seeking was tested using the stress-CS or a novel odor (stress-NS), followed by behavioral analysis of coping mechanisms and spine morphology in the nucleus accumbens.

Main Results:

• Surprisingly, the novel odor (stress-NS) reinstated THC+CBD seeking, an effect mitigated by N-acetylcysteine.
• The stress-CS inhibited THC+CBD-CS induced reinstatement, and altered active/passive coping behaviors.
• THC+CBD self-administration prevented stress-CS-induced spine head expansion in the nucleus accumbens core, suggesting altered cue salience.

Conclusions:

• Cannabis (THC+CBD) self-administration significantly altered the salience of environmental cues in rats.
• Neutral cues promoted active behaviors (drug seeking, burying), while stress-CS shifted behavior towards passive coping (immobility).
• These findings suggest that cannabis use may exacerbate conditioned stress responses in individuals with PTSD.