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.
Regular cannabis users who self-administered commercially available edible products experienced increased intoxication and elation, decreased tension, and no change in paranoia two hours after use. Those who consumed a CBD-dominant product reported less intoxication than those who used a THC-only or THC+CBD product. Participants who used a THC+CBD product consumed less THC and had lower plasma THC levels than those using a THC-only product, yet reported similar positive and psychotomimetic effects. Psychotomimetic effects were very low across all conditions. The findings suggest that edible products containing CBD may allow experienced users to achieve desired effects with lower THC exposure, potentially reducing harm.
Cannabis flower with both THC and CBD produces similar positive effects but less paranoia and anxiety than THC-dominant cannabis. In a naturalistic at-home study, 159 regular cannabis users were randomly assigned to one of three chemovars: THC-dominant (24% THC, 1% CBD), THC+CBD (9% THC, 10% CBD), or CBD-dominant (1% THC, 23% CBD). Plasma samples showed those using the CBD-dominant or THC+CBD chemovars had significantly less THC and more CBD than those using the THC-dominant chemovar. The THC+CBD chemovar yielded similar positive subjective effects but significantly less paranoia and anxiety compared to the THC-dominant chemovar, suggesting potential harm reduction from CBD.