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Drug dependence, abuse, and addiction are complex phenomena that can precipitate various abnormal states. Physical dependence refers to a state of pharmacological adaptation to a drug. This adaptation often results in tolerance—a reduced response to the drug after repeated administrations. When the drug use is abruptly stopped, withdrawal symptoms occur due to the body's need to readjust from the pharmacologically induced imbalance. However, tolerance and withdrawal symptoms do not...

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Updated: Nov 14, 2025

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

Published on: January 22, 2016

Targeting mGlu₅ for Methamphetamine Use Disorder.

Johannes Petzold¹, Karen K Szumlinski², Edythe D London³

¹Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, CA, USA; Department of Psychiatry and Psychotherapy, Carl Gustav Carus School of Medicine, TU Dresden, Dresden, Germany.

Pharmacology & Therapeutics

|March 11, 2021

Summary

This summary is machine-generated.

New therapeutic approaches are needed for methamphetamine use disorder. Targeting the Group-I metabotropic glutamate receptor 5 (mGlu5) with allosteric modulators shows promise for treating addiction.

Keywords:

Addiction Allosteric modulators Glutamate Group-I metabotropic glutamate receptors Medication development Stimulants

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Area of Science:

Neuroscience
Pharmacology
Addiction Research

Background:

Methamphetamine use disorder (MUD) has severe consequences, with no FDA-approved treatments.
Methamphetamine disrupts forebrain function, particularly involving the Group-I metabotropic glutamate receptor 5 (mGlu5).

Purpose of the Study:

To explore the potential of mGlu5 allosteric modulators as novel therapeutics for MUD.
To investigate the role of mGlu5 in methamphetamine-induced behavioral and cognitive disruptions.

Main Methods:

Review of preclinical animal studies and clinical trial data for mGlu5 modulators.
Analysis of mGlu5 receptor localization and function in the context of methamphetamine exposure.

Main Results:

Negative allosteric modulators of mGlu5 reduce methamphetamine's rewarding effects in animal models.
Positive allosteric modulators of mGlu5 show antipsychotic, anxiolytic, and learning-facilitating properties in preclinical studies.
mGlu5 modulators may ameliorate methamphetamine-induced cognitive deficits.

Conclusions:

mGlu5 allosteric modulators represent a promising therapeutic strategy for MUD.
Further clinical research is essential to validate mGlu5-targeted treatments for methamphetamine addiction.