Childhood adverse experiences associate with reduced brain CB1 endocannabinoid receptor availability in healthy controls and patients with first-episode psychosis

Multiple childhood adverse events (≥2 before age 16) are associated with lower CB1R availability in temporo-limbic brain regions, with the largest effects in the amygdala (η²=0.37).

• Why it matters: The endocannabinoid system is dysregulated in first-episode psychosis, but how developmental adversity may imprint this system in humans is not well understood.
• What they did: Using [18F]FMPEP-d2 PET, CB1R binding was quantified as metabolite-corrected distribution volumes (VT) across 13 ROI in 15 first-episode psychosis patients and 20 healthy controls, with ACE categorized as simple (0–1) or multiple (≥2).
• The result: In an rmANOVA, ACE showed a significant association with regional CB1R VT (p<0.001), with group (p=0.027) and sex*group interaction (p=0.018), supporting that early adversity relates to adult ECS availability in both groups.