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Background <p>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.</p> Methods <p>Adult male Wistar rats were administered METH and treated with either a CB1R agonist WIN55,212-2 (WIN; 3&#xa0;mg/kg; i.p) or antagonist (Rimonabant;1&#xa0;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.</p> Results <p>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.</p> Conclusion <p>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.</p> Clinical trial number <p>Not applicable.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月23日

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  • Tahoora Mousavi,
  • Nadia Hatami,
  • Saba Niknamfar,
  • Mahshid Naseri,
  • Raheleh Rafaiee,
  • Seyedeh Masoumeh Seyedhosseini Tamijani,
  • Mohammad Saleh Ranaiy,
  • Hamed Ghazvini

摘要

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Clinical trial number

Not applicable.