Pharmacological Treatments for Methamphetamine Use Disorder: Current Status and Future Targets
Summary & key facts
This paper reviews what medicines have been tested to treat methamphetamine use disorder in animals and people. The authors say there are still no approved drugs that reliably cut cravings or help people stop using meth. Some medicines helped in animal tests but did not lower meth use in people, while other drugs might help with meth-related psychosis or thinking problems. The paper also points to new drug targets that work in animals but need human trials, and it recommends studying sex differences and genes that might change who responds to treatment.
- Methamphetamine use and overdose deaths have risen a lot since the mid-2010s, which is why finding treatments is urgent.
- Right now there are no approved medicines that clearly reduce cravings or lead to long-term abstinence from methamphetamine.
- Several drugs showed promise in animal studies but did not produce lasting reductions in meth use in people; examples tested in humans include modafinil, some antipsychotic medicines, and baclofen.
- Some medications that did not cut meth use might still help with other problems caused by meth, such as psychosis-like symptoms or thinking and memory problems; examples mentioned are atomoxetine and varenicline.
- New types of drugs reduce meth's reinforcing effects in animal tests. These include drugs that block the vesicular monoamine transporter 2 (a protein that helps store brain chemicals), drugs that change glutamate signaling (a common brain chemical), and drugs that activate trace amine-associated receptors (a different brain receptor).
- Those new drug types have not yet been proven in people; clinical trials are needed to see if they actually treat methamphetamine use disorder.
- The authors recommend future studies pay more attention to biological sex differences and to using genetic information to predict who will respond to which treatments.
Abstract
The illicit use of the psychostimulant methamphetamine (METH) is a major concern, with overdose deaths increasing substantially since the mid-2010s. One challenge to treating METH use disorder (MUD), as with other psychostimulant use disorders, is that there are no available pharmacotherapies that can reduce cravings and help individuals achieve abstinence. The purpose of the current review is to discuss the molecular targets that have been tested in assays measuring the physiological, the cognitive, and the reinforcing effects of METH in both animals and humans. Several drugs show promise as potential pharmacotherapies for MUD when tested in animals, but fail to produce long-term changes in METH use in dependent individuals (eg, modafinil, antipsychotic medications, baclofen). However, these drugs, plus medications like atomoxetine and varenicline, may be better served as treatments to ameliorate the psychotomimetic effects of METH or to reverse METH-induced cognitive deficits. Preclinical studies show that vesicular monoamine transporter 2 inhibitors, metabotropic glutamate receptor ligands, and trace amine-associated receptor agonists are efficacious in attenuating the reinforcing effects of METH; however, clinical studies are needed to determine if these drugs effectively treat MUD. In addition to screening these compounds in individuals with MUD, potential future directions include increased emphasis on sex differences in preclinical studies and utilization of pharmacogenetic approaches to determine if genetic variances are predictive of treatment outcomes. These future directions can help lead to better interventions for treating MUD.