Among 149 young adult marijuana users, those who both used marijuana frequently (past 30 days) and reported using it to cope with negative emotions had the highest levels of anxious arousal, agoraphobic cognitions, and worry. This pattern held after accounting for cigarettes, alcohol, and years of marijuana use. No similar interaction was found for depressive symptoms, suggesting the link is specific to anxiety rather than depression.
Caffeine co-administered with THC produced minimal changes in subjective effects, performance, or metabolism, though signals for perceived driving impairment were observed. In contrast, CBD co-administered with THC and caffeine increased outcomes associated with abuse liability and performance impairment versus THC alone. CBD also increased plasma THC and 11-OH-THC concentrations. These data provide the first direct assessment of pharmacodynamic and pharmacokinetic effects of THC and caffeine co-administered in humans, emphasizing the importance of considering full cannabinoid profiles and drug combinations in regulatory decision-making.