Effects of cannabidiol on fear conditioning in anxiety disorders: decreased threat expectation during retention, but no enhanced fear re-extinction.

RATIONALE: Preclinical research suggests that pharmacologically elevating cannabinoid levels may attenuate fear memory expression and enhance fear extinction. OBJECTIVES: We studied the effects of cannabidiol (CBD) on fear memory expression and fear re-extinction in 69 patients with panic disorder with agoraphobia or with social anxiety disorder. Moderation by sex, diagnosis, and serotonergic antidepressant (AD) use was explored. METHODS: A cued fear conditioning paradigm was applied before the first treatment session with 300 mg CBD/placebo augmented exposure therapy. Study medication was administered orally preceding 8 weekly sessions. Fear acquisition and suboptimal extinction took place prior to the first medication ingestion (T0). After the first medication ingestion (T1), we investigated effects on fear memory expression at retention and fear re-extinction. Subjective fear, shock expectancy, skin conductance, and startle responses to conditioned (CS+) and safety stimulus (CS-) were measured. RESULTS: Across the sample, CBD reduced shock expectancy at retention under low and ambiguous threat of shock, but fear re-extinction at T1 was unaffected by CBD. However, in AD users, re-extinction of subjective fear was impaired in the CBD condition compared to placebo. In female AD users, CBD interfered with safety learning measured with fear-potentiated startle. CONCLUSIONS: The current findings provide no evidence for enhanced fear re-extinction by CBD. However, CBD acutely decreased threat expectation at retention, without affecting other indices of fear. More studies are needed to elucidate possible interactions with AD use and sex, as well as potential effects of CBD on threat expectancies.

Trajectories of fear learning in healthy participants are able to distinguish groups that differ in individual characteristics, chronicity of fear and intrusions.

BACKGROUND AND OBJECTIVES: Studies on the development and treatment of anxiety disorders mostly focus on the comparison of predefined groups. An alternative approach is to use data-driven latent class growth analyses (LCGA) to determine differentiation between groups based on particular mechanistic factors. This study validated the use of LCGA on responses in a compact fear conditioning task and whether specific characteristics are associated with maladaptive fear learning trajectories. METHODS: Healthy subjects (N = 300) completed a fear conditioning task that included uninstructed and instructed acquisition and extinction phases. Subjective fearfulness and US expectancy were used as outcome measures. Latent classes in the responses to the CS+ (coupled with a scream) and the CS- (control stimulus) were determined based on trajectories across the experimental phases. State and trait anxiety were measured during testing, and return of fear and intrusions were measured one and six weeks later. RESULTS: Fear learning trajectories of poor extinction in responding to the CS+ and generalization of fear to the CS- were associated with higher state and trait anxiety. Individuals belonging to these trajectories reported more intrusions, fear and had higher US expectancy ratings after 1 week. LIMITATIONS: Only 56% of participants completed the six weeks follow-up measures. CONCLUSION: Fear learning trajectories are associated with individual characteristics, return of fear and intrusions. Next, this task will be implemented in clinical practice to assess its predictive power for the extent to which patients benefit from exposure treatments.