ABSTRACT Background: The use of cannabis is growing in older adults but there is very limited high quality information on the acute effects of cannabinoids in healthy older adults. As the legalization of cannabis continues to increase globally, the age range of individuals using cannabis across the lifespan continues to expand, and the aging population continues to increase. Recent statistics indicate an increase in recreational cannabis use by 75% and higher use of medical cannabis in older adults compared to younger adults3,4. As the baby boomer generation grows older and the legal status of cannabis changes globally, the use of cannabis by older individuals is projected to continue to grow5. The acute effects of cannabis in older individuals could be different due to important age-related cognitive and physiological differences. First, the target of THC, the endocannabinoid (eCB) system, changes across the lifespan. Second, age-related reductions in cognitive reserve could make older adults more susceptible to the cognitive-impairing effects of cannabinoids. Third, the aging brain may be less reward-driven6. Fourth, given the cardiovascular risks of cannabinoids7, age-related reductions in cardiovascular reserve could place older adults at greater cardiovascular risk. Finally, age-related changes in metabolism8 could impact the response to cannabinoids. Hypotheses: Increasing age will confer greater vulnerability to THC-induced cognitive impairments, anxiogenic effects, and cardiovascular effects but are less vulnerability to its rewarding effects. Increasing age will confer greater vulnerability to THC-induced deficits in electrophysiological indices of information processing including. Pilot data: Older (>50 years old, n = 4) adults are more vulnerable to the acute memory-impairing and anxiogenic effects of THC than younger adults (<25 years, n = 5). Methods: In this double-blind, placebo-controlled, hybrid fixed-order/randomized, single test day laboratory study 60 adults ( 21 years) will receive 0 (placebo) and 0.03 mg/kg of intravenous THC over 20 minutes. Cognitive function (memory, attention, etc.) and proximal measures of attention and information processing (EEG measures, including P300, ASSR, and neural noise) will be tested after the administration of THC/placebo. Subjective effects, perceptual alterations, vital signs, objective measures of information processing (EEG), and blood for PK will be collected before and after the administration of THC.