Metabotropic Glutamate Receptor 5 as a Potential Biomarker of the Intersection of Trauma and Cannabis Use

Abstract

Background Metabotropic glutamate receptor 5 (mGlu5) dysregulation has been implicated in the pathophysiology of trauma-related psychopathology, and there are direct interactions between the endocannabinoid and glutamatergic systems. However, relationships between cannabis use (CU) and mGlu5 have not been directly investigated in trauma-related psychopathology. Methods Using positron emission tomography (PET) with [18F]FPEB, we examined relationships between CU status and mGlu5 availability in vivo in a cross-diagnostic sample of individuals with trauma-related psychopathology(N = 55). Specifically, we tested whether mGlu5 availability in frontolimbic regions of interest (ROIs; dlPFC, OFC, vmPFC, amygdala, hippocampus) differed as a function of CU status. Results Past year CU (n = 22) was associated with 18.97-19.12% higher mGlu5 availability in frontal and 14.24-16.55% higher in limbic ROIs relative to participants with no recent CU. Similarly, past month/monthly CU (n = 16) was associated with higher mGlu5 availability in frontal (18.05-20.62%) and limbic (15.53-16.83%) ROIs. mGlu5 availability in the OFC and amygdala was negatively associated with depressive symptoms in the past year CU group. In both CU groups, exploratory analyses showed negative correlations between mGlu5 availability and sadness across all ROIs, and with perceptions of worthlessness, and past failures (r’s = -.46-.66, p’s = .006-.033) in the vmPFC. Participants with CU reported lower mean depressive symptoms (p’s = .019-.031) relative to those without CU. Conclusions These findings have substantial implications for our understanding of interactions between CU and glutamatergic neurotransmission in trauma-related psychopathology, underscoring the need for treatment development efforts to consider the effects of CU in this population.