From laboratory models to small human trials, a new review examines whether popular metabolic drugs can help curb alcohol, nicotine and drug use, and highlights how many clinical trials remain.

Potential role of GLP-1 receptor agonists in substance use disorders – a systematic review. Image credit: VectorMine / Shutterstock

In a recent study published in the journal Frontiers of pharmacologyresearchers investigated the potential role of glucagon-like peptide-1 (GLP-1) receptor agonist (R.A.) in the treatment of substance use disorders (foam).

Substance use disorders and the rationale for GLP-1-based treatments

foam It represents a significant public health concern and is characterized by limited treatment efficacy and high recurrence rates. GLP-1 R.A.originally developed for type 2 diabetes (T2D) and obesity have emerged as promising candidates for treating addiction. Beyond its appetite suppressing and blood sugar lowering effects, GLP-1 R.A. It exerts neuroprotective and anti-inflammatory effects in the central nervous system. nervous system and gut-related immune-inflammatory signaling GLP-1 receptor.

Research scope and purpose

In this study, researchers systematically evaluated the treatment potential of: GLP-1 R.A. in Sud process. First, a comprehensive search was conducted across the Web of Science, Scopus, PubMed, Cochrane Central Register, Embase, and PsycINFO databases to identify randomized controlled trials (RCT), preclinical studies, and clinical trials with control groups. After deduplication, titles and abstracts were screened and full text reviewed.

Study selection and data extraction

Relevant data including study characteristics, sample details, intervention details, outcomes, and statistical methods were extracted from eligible studies. The Cochrane risk of bias tool was used to assess study quality. Evidence from clinical and preclinical studies was narratively synthesized due to heterogeneity in study design, intervention, and outcome measurement.

Summary of included studies

The search strategy yielded 2,869 records. Of these, 41 studies met the inclusion criteria through database searches and one additional eligible clinical study was identified through manual reference tracking, resulting in a total of 42 studies for inclusion. Six were clinical studies, including pilot studies, secondary analyses, RCTthe rest were preclinical studies mainly in rodents.

Preclinical models and behavioral paradigms

Preclinical studies have used validated behavioral paradigms to assess substance-seeking behaviors, including oral self-administration, intravenous administration, drug- and cue-induced reinstatement, conditioned place preference, and operant conditioning.

Clinical focus and research substances

Clinical research primarily addresses nicotine and alcohol use disorders, including intake, craving, abstinenceand associated neuroendocrine or metabolic parameters. Across studies, the most frequently investigated substance was alcohol, followed by cocaine, nicotine, and opioids.

Evaluation of GLP-1 receptor agonists

GLP-1 R.A. They include liraglutide, dulaglutide, exendin-4, and semaglutide. Exendin-4 was evaluated in cocaine and nicotine models. Liraglutide and semaglutide were primarily studied in the context of opioid and alcohol use disorders. Dulaglutide has been studied only in clinical trials for alcohol-related outcomes and smoking cessation, with alcohol consumption often evaluated as a secondary outcome.

Outcomes assessed across studies

The study evaluated a wide range of outcomes, including neurobiological, clinical, and behavioral domains. Neurobiological outcomes include changes in dopaminergic signaling, neuroinflammatory markers, circulating insulin, and GLP-1 level, and activation of reward-related brain areas.

Behavioral outcomes include substance intake, operant motivation, relapse-like return, and drug-seeking behavior. Clinical endpoints focused on craving intensity, daily drug use, weight change, treatment tolerability, and abstinence duration.

Clinical evidence of alcohol use disorder

Two clinical studies primarily investigated the effects of: GLP-1 R.A. In alcohol use disorder (australian dollar). A study examining semaglutide in patients australian dollar They demonstrated reductions in alcohol intake but reported inconsistent effects on heavy drinking days.

In another trial, no overall reduction in heavy drinking days was observed with exenatide. However, a secondary analysis showed a significant reduction among people with the following symptoms: body mass index (BMI) over 30 kg/m2. Additionally, the dulaglutide smoking cessation trial included a secondary analysis of alcohol outcomes, reporting a reduction in weekly alcohol intake and a weaker effect in heavy drinkers.

Preclinical evidence of alcohol use disorder

Preclinical studies also support the following uses: GLP-1 R.A. in australian dollar process. Exendin-4 has been reported to reduce relapse-like drinking behavior, delay the onset of new drinking, and reduce the frequency of drinking in mice.

Similarly, semaglutide reduced relapse-like drinking behavior and alcohol consumption in rodents. Additionally, liraglutide treatment significantly reduced alcohol consumption in rodents with high baseline alcohol intake.

Evidence of smoking disorder

in one RCT inspect GLP-1 R.A. In smoking disorders, semaglutide treatment reduced daily smoking. Dulaglutide treatment significantly reduced weight gain after smoking cessation.

A pilot study reported that the combination of exenatide and nicotine replacement therapy improved smoking cessation rates, reduced withdrawal symptoms, and reduced weight gain after smoking cessation. In preclinical studies, liraglutide significantly reduced nicotine self-administration and relapse behavior in rats, and attenuated withdrawal-induced hyperphagia and associated weight gain.

Evidence of cocaine use disorder

One clinical study found no differences in self-reported euphoria, craving, or cocaine infusions in cocaine use disorder patients treated with exenatide compared to placebo. However, exenatide reduces circulating insulin and GLP-1 A level that emphasizes metabolic regulation.

Targeted injections of exendin-4 into the posterior dorsal tegmental nucleus suppressed cocaine-seeking behavior in rats without affecting body weight, food intake, or sucrose-seeking behavior. In another rodent study, exenatide significantly reduced cocaine-stimulated reinstatement without affecting sucrose-seeking behavior.

Evidence of Opioid Use Disorder

Several preclinical studies have focused on opioid-related behaviors. Treatment with liraglutide has been reported to suppress heroin self-administration and drug-induced reinstatement in rats with high drug intake.

In contrast, one study showed that exendin-4 did not reduce remifentanil self-administration or opioid withdrawal symptoms in mice.

Overall conclusion and future directions

This study provided a comprehensive overview of the evidence regarding: GLP-1 R.A. Use in the treatment of substance use disorders. We consistently support preclinical research efficacy of GLP-1 R.A. over multiple foam.

Clinical studies suggest potential benefits, particularly in nicotine and alcohol use disorders. However, the clinical evidence base is still preliminary, heterogeneous, and limited in size, and some trials are not primarily aimed at detecting addiction-related outcomes.

Most clinical trials are used GLP-1 R.A. Dosing regimens are consistent with approved metabolic indications, and optimal dosing strategies for addiction-specific outcomes remain uncertain. Large-scale, well-designed randomized controlled trials are warranted to clarify efficacy, confirm the findings of addiction-focused studies with adequate power, identify responsive subgroups, and establish appropriate treatment protocols.

whole, GLP-1 R.A. represents a new treatment strategy that bridges the neuropsychiatric and metabolic fields in addiction medicine.

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