Temporal Association Between Reported Use of Psychoactive Substances and Cognitive Function in Individuals With Multiple Sclerosis.

Objective: The study aimed to examine same-day within-person associations between psychoactive substance use and cognitive function in people with multiple sclerosis (MS) using ecological momentary assessment.

Design: This secondary analysis used data collected over 14 days from people with MS.

Setting: Community.

Participants: Ambulatory adults with MS (N=257).

Interventions: Not applicable.

Main outcome measures: Participants completed daily ecological momentary assessment via smartphone, reporting use of psychoactive substances (alcohol, cannabis, opioids, nicotine, and caffeine) and perceived cognitive function. Objective cognitive performance was assessed using the Dot Memory Test (working memory) and Symbol Search Tests (processing speed).

Results: Of the 274 enrolled participants, 257 completed the 14-day monitoring phase, yielding over 14,000 assessments with >76% completion across measures. At the between-person level, no significant associations were observed between average substance use and cognitive outcomes. However, within-person analyses revealed that caffeine use was associated with better perceived cognitive function (B=-3.31; P<.001) and faster processing speed (B=-32.58; P=.01). Cannabis use predicted worse perceived cognitive function (B=3.38; P=.049) and alcohol use was linked to poorer working memory performance (B=0.05; P=.02). No significant within-person effects were found for nicotine or opioid use.

Conclusions: Caffeine may produce short-term cognitive benefits, whereas cannabis and alcohol are related to negative cognitive effects. Findings highlight the importance of developing personalized, evidence-based guidance for people with MS who may consume psychoactive substances for symptom management, recreation, or other reasons.