Current Neuropharmacology - Volume 23, Issue 8, 2025

The widespread availability and accessibility of over-the-counter (OTC) medicines play a vital role in modern healthcare systems, enabling individuals to manage minor health concerns independently. However, certain OTC medications possess pharmacological properties that render them susceptible to misuse and abuse, including stimulants, laxatives, sedatives, and opiate-containing products. Misuse involves improper dosage, duration, or indication, while abuse entails non-therapeutic use to achieve psychoactive effects or other illicit purposes, potentially leading to dependence and addiction. This review explores the risk of developing psychotic symptoms associated with OTC drug misuse. Synthesizing existing literature, it comprehensively examines the relationship between antihistamines, cough medicines, and decongestants misuse, and the onset of psychotic symptoms.

A systematic literature review was carried out using Pubmed, Scopus and Web of Science databases through the following search strategy: (“diphenhydramine” OR “promethazine” OR “chlorpheniramine” OR “dimenhydrinate” OR “dextromethorphan” OR “pseudoephedrine” OR codeine- based cough medicines) AND (“abuse” OR “misuse” OR “craving” OR “addiction”) NOT review NOT (animal OR rat OR mouse). For data gathering purposes, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed. Research methods were registered on PROSPERO (CRD42024527558).

We analysed 46 relevant studies out of an initial pool of 2,677 articles. Key findings indicate that antihistamines, dextromethorphan, and other OTC drugs can induce psychotic symptoms, such as paranoia, hallucinations, and thought disorders when abused. Dextromethorphan is particularly associated with a chronic tendency towards psychosis, whereas other substances more commonly result in acute substance-induced psychosis.

The study underscores the necessity for increased awareness and specific interventions to address the misuse of OTC drugs and their potential to cause significant psychiatric disorders, emphasizing the broader public health implications of such misuse.

Glucagon-Like Peptide-1 Receptor (GLP1R) agonists have become widespread anti-obesity/diabetes pharmaceuticals in the United States.

This article aimed to provide our current knowledge on the plausible mechanisms linked to the role of Ozempic (Semaglutide), which is generalized as one of the anti-addiction compounds.

The effects of GLP1R agonists in Alcohol Use Disorder (AUD) and substance use disorder (SUD) are mediated, in part, through the downregulation of dopamine signaling. We posit that while GLP1R agonism could offer therapeutic advantages in hyperdopaminergia, it may be detrimental in patients with hypodopaminergia, potentially leading to long-term induction of Suicidal Ideation (SI). The alleged posit of GLP1 agonists to induce dopamine homeostasis is incorrect. This study refined 31 genes based on the targets of Ozempic, GLP1R, and related enzymes for SI and 10 genes of the Genetic Addiction Risk Score (GARS) test. STRING-MODEL refined 29 genes, and further primary analyses indicated associations of GLP1R with DRD3, BDNF, CREB1, CRH, IL6, and DPP4.

In-depth silico enrichment analysis revealed an association between candidate genes and depressive phenotypes linked with dopaminergic signaling. Finally, through primary and in-depth silico analyses, we demonstrated multiple findings supporting that GLP1R agonists can induce depression phenotypes.

Our findings suggest that associated polymorphisms seem to have overlapping effects with addictive behaviors of Reward Deficiency Syndrome (RDS) and dopamine regulation. Consequently, GLP1R agonists may represent a double-edged sword, potentially triggering both anti-addictive effects and SI by exacerbating depressive phenotypes. Thus, we encourage the scientific community to perform further empirical clinical studies to confirm this proposed pathway.

Schizophrenia with substance use disorder is a complex clinical condition that may increase treatment resistance. Cannabis use disorder is frequently associated with psychosis and the causal link has still to be defined. Partial D2/3 agonists may ensure limbic dopamine release normalization while avoiding reduced frontocortical dopamine release, which would contribute to negative symptoms. We aimed to observe the clinical course of patients with schizophrenia comorbid with cannabis use disorder while being treated with oral or long-acting injectable D2/3 partial agonists.

We observed 96 young adults with schizophrenia/schizoaffective disorder comorbid with cannabis use disorder during 18 months of treatment with aripiprazole long-acting injectable or oral aripiprazole or brexpiprazole. The assessment comprised Clinical Global Impressions-Severity, Positive And Negative Syndrome Scale, Brief Psychiatric Rating Scale, Barratt Impulsiveness Scale, and Visual Analog Scale for Craving.

Included were 17 women and 79 men (mean age = 26.89 ± 4.74 years). The sample responded favorably to treatment as assessed by all clinical scales, save for the impulsiveness scale which showed no significant change. The four treatment samples responded well without differences, but employing a general linear model, long-acting injectable aripiprazole and brexpiprazole were better and similar on all clinical and craving scales compared to oral aripiprazole and to other antipsychotics. Long-acting injectable aripiprazole fared better than brexpiprazole on general psychopathology, negative symptoms, and craving, while the reverse was true for global severity. However, the sample size imbalance did not allow for drawing strong conclusions. We found no significant treatment resistance in our 96-patient sample.

Partial D2/3 agonists may treat comorbid schizophrenia/schizoaffective disorder and cannabis use disorder, improving the symptoms of both disorders and substance craving.