Medical marijuana (MM) policies are changing rapidly, and the consequences of MM use for individuals who seek access to it are unknown. At the time of this submission, 25 states as well as the District of Columbia have legalized MM, and following this policy change, it is likely that individuals who either have not used marijuana in the past, or who have used marijuana occasionally for recreational purposes, will start to use marijuana medicinally for the first time. Once these individuals receive MM cards, they will have increased access to marijuana as well as societal permission because of perceived medical benefit. Increased access to marijuana may lead to escalation of use and possible marijuana-related harms; as recreational marijuana use has been associated with adverse heath outcomes such as cannabis use disorders (CUD), neurocognitive impairments, and brain-based changes, it is critical to study whether MM patients will experience similar effects. To address these timely and clinically important questions, we propose to conduct a randomized, longitudinal study of MM that will: (1) characterize the impact of MM on indices of addiction, such as CUD, escalation of use, tolerance, and withdrawal among those who stop using, (2) assess, via dosing diaries, the effect of MM use patterns on use of other medications, and perception of underlying disease symptomatology, (3) characterize the impact of MM on neurocognitive performance, including executive function, memory, attention, and decision-making and (4) examine evidence for impact of MM on brain structure and function. We propose to enroll 200 adults with no current CUD or heavy marijuana use (e.g. weekly or less frequent), who express interest in obtaining MM cards to use MM to treat pain, insomnia, anxiety, and/or depression, the most common conditions for which MM is used. Participants will be randomly assigned to either an active MM arm (n = 100) in which they can obtain MM cards without delay, or to a waitlist control arm (WLC) (n = 100), in which they are asked to wait 3 months before obtaining a card. Participants will be assessed at baseline, regularly for 3 months, and at a 6-month and 1-year follow-up for MM use behaviors, development of CUD, perception of disease symptomatology, and neurocognitive performance. Participants will be incentivized to keep detailed dosing diaries, via smartphone apps, to record how much MM was used each day, other medications used, and daily ratings of pain, sleep quality, and mood. Urine collected at each visit will be assessed with quantitative assays for cannabis metabolites. In the MM group, MRI scans will be collected at baseline and at 1 year, to longitudinally investigate possible brain changes associated with MM use. The proposed project will fill a critical gap in our knowledge, at a significant time when cannabis is being legalized for ‘medical’ use with little known about effects of MM on disease symptoms, addictions, neurocognition or brain...