Bidirectional associations between cannabis use, oddball performance and P3 event-related potential

Importance

Cannabis use remains prevalent in youth despite concerns regarding its potential impact on cognitive function. Unraveling whether the association between cannabis use and cognition is partially due to preexisting differences or primarily related to use is vital to understanding underlying mechanisms.

Objective

To estimate the longitudinal association between cannabis initiation and cognitive trajectories, indexed by task performance and P3 event-related potential (ERP), and to estimate whether baseline cognition is associated with cannabis initiation.

Design

Data were analyzed from the ongoing longitudinal Collaborative Study on the Genetics of Alcoholism (COGA) cohort, which was followed up approximately every 2-5 years from 2004 to 2025.

Setting

6 sites across the United States.

Participants

Adolescent and young adult offspring of past COGA participants and control families who reported on their cannabis use and who had Visual Oddball (VOP) performance and P3 ERP data (N=4814; 52.4% female, 68.4% white) were grouped based on the timing of cognitive data collection relative to cannabis initiation into Pre-onset (n=2,449; ≥1 assessment) and Post-onset (n=998; ≥3 assessments) subsamples.

Main Outcomes and Measures

VOP measures include performance accuracy (%), reaction times (ms), and P3 amplitude (μV) and latency (ms) during target trials. Cannabis measures included lifetime use of cannabis (i.e., ever used) and age at first use.

Results

High P3 amplitude, and prolonged P3 latency and reaction time were associated with a reduced hazard of cannabis initiation (All Hazards Ratio, [H.R.s]< 0.91, p’s<.008). Following initiation, cannabis use was associated with steeper declines in P3 amplitude (b=-0.29, p=0.02) and stabilized reaction time (b=0.35; p=0.005). Steeper decline in P3 amplitude (i.e., slope) was associated with greater cannabis progression (e.g., Cannabis Use Disorder, Odds Ratio, [O.R.]=2.34, p<.001), whereas steeper decline in reaction time was associated with reduced progression (O.R.=.79, p=.002).

Conclusion

Baseline P3 indices and reaction time were associated with cannabis initiation, while cannabis use was associated with subsequent changes in P3 amplitude and reaction time trajectories. These findings indicate that accelerated neurodevelopment may modify the likelihood of cannabis initiation which, in turn, may further contribute to neurocognitive changes that deepen cannabis involvement.

Key Points