Daily Temporal Associations Between Use of Psychoactive Substances and Fatigue, Pain, Stress, and Depressive Symptoms in People with Multiple Sclerosis

Arch Phys Med Rehabil. 2026 Feb 1:S0003-9993(26)00035-3. doi: 10.1016/j.apmr.2026.01.014. Online ahead of print.

ABSTRACT

OBJECTIVES: To examine daily within-person associations between symptoms reported by people with multiple sclerosis (MS) and psychoactive substance use using ecological momentary assessment (EMA).

DESIGN: This secondary analysis used EMA data collected four times daily for 14 days at baseline, 1-year, and 2-year follow-ups.

SETTING: Community PARTICIPANTS: Ambulatory adults with MS (N= 258).

MAIN OUTCOME MEASURES: Participants completed daily EMAs via smartphone, reporting use of psychoactive substances and symptoms. Psychoactive substance use (alcohol, caffeine, nicotine, cannabis, opioids) was assessed dichotomously (yes/no). Momentary symptoms, including fatigue, pain, stress, and depressive symptoms, were assessed using brief self-report measures. Mixed-effects logistic regression models assessed lagged associations between symptoms and subsequent substance use; multilevel models examined the reverse direction.

RESULTS: Momentary increases in stress predicted lower odds of alcohol use. Higher average pain was linked to reduced alcohol use and increased opioid use. Substance use also predicted symptoms: alcohol, nicotine, and cannabis were associated with greater fatigue, while caffeine predicted reduced fatigue. Cannabis was linked to higher momentary pain, and opioids to higher average pain. Alcohol was associated with reduced stress, whereas caffeine predicted increased stress.

CONCLUSIONS: MS symptoms and psychoactive substance use are dynamically and bidirectionally related. These findings improve understanding of how individuals with MS use substances for symptom regulation, which may lead to both beneficial and adverse outcomes.

PMID:41633444 | DOI:10.1016/j.apmr.2026.01.014