Characterization of the Behavioral and Molecular Effects of Acute Exposure to the Fourth-Generation Synthetic Cannabinoid, 5F-EDMB-PICA, in Male Mice of Different Age Groups

Adolescents and young adults are using synthetic cannabinoids at increasing rates, and the use of synthetic cannabinoids (SCs) carries significant medical and psychiatric risks. Although studies have been conducted to preliminarily explore the pharmacological effects of the fourth-generation synthetic cannabinoid 5F-EDMB-PICA (ethyl 2-(1-(5-fluoropentyl)-1 H-indole-3-carboxamido)-3,3-dimethylbutyrate), there is still a lack of research addressing its deleterious effects in mice of different age groups. We investigated the effects of 5F-EDMB-PICA on multiple aspects of emotional functioning, locomotor performance, and cognitive functioning in adolescent and young adult mice by determining the affinity of 5F-EDMB-PICA for cannabinoid receptors in conjunction with behavioral experiments and transcriptomic analyses. Acute 5F-EDMB-PICA administration disrupted anxiety regulation, motor control, and spatial memory in mice of different age groups; accompanying hippocampal transcriptomic screens further pinpointed candidate genes that may mediate these deficits. This study establishes the molecular network of synthetic cannabinoid neurological harms, provides key gene expression profiles for subsequent in-depth analysis of the harm mechanisms, and also provides more data support for future control of cannabinoids.