PROJECT SUMMARY/ABSTRACT Changes in the legal landscape of cannabis have occurred simultaneously with increases in use among adults. Research efforts have focused on examining consequences of use, however, characterizing the impact of cannabis abstinence on health among regular cannabis users is also a relevant public health concern. Few research studies have compared cognition or psychiatric disorder symptoms between abstinent cannabis users, using contingency management (CM), to individuals in a control condition (monitoring), which does not require changes in cannabis use. The current study aims to extend the findings to an older population, for a longer period of cannabis abstinence, and to examine all cognitive domains. Thus, the first aim is to test the impact of cannabis abstinence for 6 weeks (42 days) on memory, attention, processing speed, language, and executive function (EFs) on adults, who are between 31 to 47 years old. The second aim is to explore how cannabis abstinence effects psychiatric disorder symptoms. The third aim (exploratory) is to examine how genetic risk for various psychiatric disorder symptoms by environment (cannabis abstinence versus continued use) interactions impact cognition. The proposed study is novel in that we will use experimental manipulation to create discordance in cannabis use among monozygotic (MZ) twin pairs. This research design will require significantly fewer resources than large-scale randomized controlled trials because the use of MZ twin pairs requires a smaller sample size and is still sufficiently powered to detect small effects. Fifty identical twin pairs (N=100), who are concordant on cannabis use, will be recruited from the Colorado Twin Registry, which have all been genotyped. Each twin, within a twin pair, will be randomly assigned to either CM, incentive-based protocol to promote abstinence, or control, no changes in cannabis use requested, for 42 days. Participants will be assessed across 42 days on measures of cognition and psychiatric disorder symptoms (baseline, day 14, day 28, and day 42). The method proposed in this project could be used to understand other outcomes from cannabis abstinence (e.g., physical health) or abstinence from other substances. The aims of the research project map on to the training goals: 1) clinical trial methodology, 2) longitudinal statistical analysis, and 3) behavioral genetics. Experts in clinical trial methodology, longitudinal statistical analysis, and behavioral genetics, will guide the research and training program. The team of researchers consists of Drs. John Hewitt and Christian Hopfer (primary mentors, training aim 3), Drs. Susan Mikulich-Gilbertson (mentor, training aim 2) and Naomi Friedman (consultant, training aim 2), Drs. Randi Schuster (co-mentor, training aim 1), Paula Riggs, and Kent Hutchison (consultants, training aim 1). Each training aim consists of one-on-one meetings with mentors or consultants, workshops, courses, seminars, spec...