Multiple sclerosis patients face daily decisions about substances that could either support or undermine their already-compromised cognitive abilities. Understanding which substances help versus harm could reshape treatment approaches for the 2.8 million people worldwide living with this debilitating neurological condition. Real-time tracking of 257 MS patients over two weeks revealed striking same-day effects of common psychoactive substances on cognitive performance. Caffeine consumption consistently enhanced both subjective cognitive function and objective processing speed, with participants performing significantly faster on symbol search tasks after caffeine use. Conversely, cannabis use degraded perceived cognitive abilities, while alcohol consumption specifically impaired working memory as measured by dot memory tests. Nicotine and opioids showed no measurable cognitive impact within the study timeframe. These findings challenge the conventional wisdom that substance effects in neurological disease mirror those in healthy populations. The cognitive benefits of caffeine appear amplified in MS patients, potentially due to the inflammatory component of the disease that caffeine's anti-inflammatory properties may counteract. The cannabis findings are particularly relevant given increasing medical marijuana use among MS patients for symptom management. This research suggests a complex risk-benefit calculation where cannabis may relieve physical symptoms while simultaneously compromising cognitive function. The methodology represents a significant advance in neurological research, using ecological momentary assessment to capture real-world substance effects rather than relying on laboratory conditions that poorly reflect daily life with MS.