TAAR1 agonists for the treatment of stimulant use disorder

The National Institute on Drug Abuse awarded Psychogenics Inc. $398,947 on June 15, 2026, under the Drug Use and Addiction Research Programs (CFDA 93.279) to conduct preclinical evaluation of two novel molecules as potential pharmacotherapies for cocaine use disorder.

Psychogenics will evaluate the compounds' effects in behavioral models of cocaine self-administration and stress-induced reinstatement of drug-seeking behavior. The work includes testing both molecules' ability to reduce cocaine infusions under a fixed ratio schedule of reinforcement, then evaluating the most effective molecule in stress-induced reinstatement assays to assess whether it can prevent relapse triggered by stress after a drug-free period. If single-dose efficacy is demonstrated, Psychogenics will examine whether effects persist with repeated administration and will assess whether the compounds also modify food reinforcement to determine selectivity for drug versus non-drug reinforcers.

Work is performed in Paramus, New Jersey, with a period of performance ending May 31, 2027. The award is a project grant, the assistance type used by NIDA to support substance use research leading to new prevention, diagnosis, and treatment approaches.

Abstract

Cocaine use disorder (CUD) is a serious public health concern in the united states. Approximately 0.5% of the US population have CUD, and these people are more prone to death, particularly by overdose, suicide, and cardiovascular events. CUD treatment focuses on psychological therapies, which are expensive and only moderately effective. There are no approved medications for CUD, thus identifying novel pharmacotherapies for this disorder is an important unmet need. The long-term goal of this project is to bring to market a safe and effective pharmaceutical drug treatment that leverages novel mechanisms of action to reduce cocaine use and improve abstinence. We have discovered two molecules featuring different mechanisms of action that may plausibly be effective in treating CUD. The current project will evaluate these two compounds for their effects in behavioral models evaluating cocaine- and non-drug-related reinforcement, and stress-induced reinstatement of drug-seeking behavior. Specifically, we will evaluate the ability of these two molecules to reduce the number of cocaine infusions in cocaine self-administration studies based on a fixed ratio schedule of reinforcement. We will then evaluate the most effective molecule in a stress-induced reinstatement assay, which evaluates the ability of the compound to prevent a relapse induced by stress after a drug-free period. If our compound is effective with a single dose, we will examine whether IT remains effective at suppressing stress-induced reinstatement after repeated administration. Finally, we will evaluate whether the effects of the compound also modify the reinforcing value of food in a fixed ratio schedule of reinforcement. The resulting data will help US understand to what extent the effects of the compound are selective for drug and non-drug reinforcers.