Involvement of CB1 cannabinoid receptors in methamphetamine-related decision-making and social behavior deficits

Methamphetamine (METH) abuse is associated with profound cognitive and behavioral impairments, notably in decision-making and social interaction. Emerging evidence suggests the endocannabinoid system, particularly CB1 receptors (CB1Rs), plays a modulatory role in these processes. This study investigated whether pharmacological modulation of CB1Rs can alter METH-induced deficits in decision-making, social behavior, and anxiety in a rodent model. Adult male Wistar rats were administered METH and treated with either a CB1R agonist WIN55,212-2 (WIN; 3 mg/kg; i.p) or antagonist (Rimonabant;1 mg/kg; i.p.). Behavioral assessments included effort-based decision-making via the Y-maze barrier task, social behavior tests, and anxiety evaluation using the elevated plus maze. METH exposure significantly reduced high-reward choices in effort-based tasks and impaired multiple domains of social behavior. It also induced anxiety-like behaviors. Rimonabant treatment partially reversed these effects, improving decision-making performance, enhancing social interactions, and reducing anxiety-related responses. In contrast, WIN did not significantly alleviate METH-induced behavioral impairments. CB1R antagonism via Rimonabant may mitigate METH-induced cognitive and social deficits, underscoring the therapeutic potential of targeting the endocannabinoid system in stimulant-related neuropsychiatric disorders. These findings highlight CB1R antagonists as promising agents for future interventions in METH addiction and its associated behavioral disruptions. Not applicable.