Sigma-1 receptors: potential therapeutic targets for substance use disorders

Abstract

Substance use disorders are a prominent issue within the United States that must be addressed given the high prevalence, economic cost, and negative health consequences of these medical conditions. Current treatments are inadequate due to the limited success of behavioral therapies and the lack of pharmacological interventions geared towards preventing the neuroplastic changes initiated by substances of abuse that lead to addiction. Sigma-1 receptors represent promising pharmacological targets for treatment of substance use disorders involving cocaine and methamphetamine use. A review of recent studies suggests that sigma-1 receptors contribute to the underlying mechanisms of action utilized by cocaine. Yet the use of sigma-1 receptor antagonists shows promising results of mitigating the physiological effects induced by cocaine. In contrast to cocaine, sigma-1 receptors have yet to be linked to the underlying mechanisms of action utilized by methamphetamine. However studies indicate that the use of sigma-1 receptors agonists creates a neuroprotective effect against the physiological effects induced by methamphetamine. Currently the pharmacological targeting of sigma-1 receptors is not utilized to treat substance use disorders. A review of literature was conducted in order to elucidate the mechanistic role that sigma-1 receptors play in mediating the physiological effects induced by cocaine and methamphetamine that lead to addiction. Using this information, the potential use of sigma-1 receptors as therapeutic targets was discussed in order to provide insight about the benefits and limitations of utilizing such an intervention as treatment for substance use disorders involving cocaine and methamphetamine use.