The behavioral pharmacology and therapeutic potential of lorcaserin for substance use disorders

Substance abuse is serious public health problem for which there are few effective pharmacotherapies. Traditional strategies for drug development have focused on antagonists to block the abuse-related effects of a drug at its site of action, and agonists to replace/mimic the effects of the abused substance. However, recent efforts have targeted receptors, such as serotonin (5-HT)₂ receptors, that can indirectly modulate dopamine neurotransmission with the goal of developing a pharmacotherapy that might be effective at reducing the abuse-related effects of drugs more generally. Lorcaserin is a 5-HT_2C receptor-preferring agonist that is approved by the US Food and Drug Administration for the treatment of obesity. Mounting evidence from preclinical and clinical studies suggests that lorcaserin might also be effective at reducing the abuse-related effects of drugs with different pharmacological mechanisms (e.g., cocaine, heroin, ethanol, and nicotine). Lorcaserin represents a promising and important first step towards the development a new class of pharmacotherapies that have the potential to dramatically improve the treatment of substance abuse. This article will review the behavioral pharmacology of 5-HT_2C receptor-preferring agonists, with a focus on lorcaserin, and evaluate the preclinical evidence supporting the development of lorcaserin for treating substance abuse. This article is part of the Special Issue entitled ‘Psychedelics: New Doors, Altered Perceptions’.