PROJECT SUMMARY/ABSTRACT Lagging behind rapid changes to state laws, societal views, and medical practice is the scientific investigation of cannabis's impact on the human brain. As recently as March of 2017, 28 states and the District of Columbia had enacted legislation that facilitates using cannabis to treat various medical conditions, including chronic pain, neuropathic pain, and pain related to cancer treatment options (e.g., chemotherapy). Yet, the analgesic properties of cannabis are not well understood. Convergent evidence points to neurotransmitter system disruptions among cannabis users, including gamma-Aminobutyric acid (GABA) and glutamate, in brain regions related to pain processing. Functional magnetic resonance imaging (fMRI) is one of the most powerful non-invasive ways to investigate the neurobiological systems that support psychological processes such as perceiving pain. Indeed, a modest literature on pain has linked somatosensory pain perception to the anterior cingulate cortex (ACC). Moreover, a recent meta-analysis of functional neuroimaging studies – a manuscript on which the applicant served as primary author – found that cannabis use was associated with reduced activation throughout the ACC among users. Given the disruption of neurotransmitter systems among cannabis users, including GABA and glutamate, an important challenge facing the field is to determine how cannabis- related changes in behavior and neural activation during pain processing are linked to changes in subservient neurochemistry. Functional magnetic resonance spectroscopy (fMRS) can be used to address this challenge by measuring neurotransmitter fluctuations associated with cannabis-related differences in behavior and neural activation between cannabis-using and non-cannabis-using subjects. Using fMRS to examine somatosensory pain perception is well supported, however, studies extending this approach to cannabis users are lacking. Moreover, most fMRS investigations have been performed using lower magnetic field strengths (i.e., 3T, or less), likely limiting abilities to effectively detect neurotransmitter fluctuations. Given the paucity of studies involving fMRS, and given the potential to examine neurotransmitter fluctuations during pain processing among cannabis users via fMRS, our overall goals are to examine the neurochemical correlates that may support cannabis-related differences in pain perception between users and non-users. To accomplish these goals, we propose to implement fMRS at a greater magnetic field strength (i.e., 7T) during somatosensory pressure- based pain among cannabis-using and non-cannabis-using subjects, using an MR-compatible pressure-based pain apparatus.