INTRODUCTION: Ketamine, initially developed as an anesthetic and now increasingly prescribed for treatment-resistant depression, is also widely misused in recreational contexts. Chronic ketamine use, often leading to dependence, has been associated with severe physical complications, including ulcerative cystitis and gastrointestinal dysfunction, as well as cognitive, affective, and psychotic...
Preclinical and clinical studies reported that 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') can cause adverse effects in the central nervous system (CNS). Recently, preclinical studies have demonstrated that certain psychoactive substances may exacerbate the noxious central effects of MDMA when co-administered, including substances that are contained as adulterants in tablets sold as...
Background: Ketamine, a dissociative anaesthetic and non-competitive NMDA receptor antagonist, has legitimate medical applications. However, rising illicit use across the United Kingdom (UK) has been accompanied by growing reports of toxicity, dependence, and deaths. These have led to renewed policy discussions. Rationale and Aim: Previous national studies have reported ketamine-related deaths...
Novel psychoactive substances (NPS) are increasingly used by young individuals for their psychoactive effects and have been frequently associated with the emergence of psychotic symptoms and schizophrenia spectrum disorders. However, it remains unclear whether NPS use directly increases the risk of psychosis onset or whether individuals with a predisposition to psychosis are more likely to...
Background: Synthetic cannabinoid receptor agonists (SCRAs, commercially known as "Spice") have become a leading cause of substance-induced psychosis worldwide. These compounds show strong associations not only with acute psychotic episodes but also, in a subset of patients, with persistent or relapsing psychotic disorders, patterns that raise concern about progression to schizophrenia. Yet...
Numerous individuals suffer from mental health issues including depression and anxiety, resulting in substantial societal burden. Data suggests individuals are choosing to self-medicate with Novel Psychoactive Substances (NPS); however, this phenomenon is poorly understood. We aimed to investigate which NPS are being used to self-medicate, evaluate their perceived effectiveness and examine...
Diarylethylamine drugs possess dissociative properties. These emerged as drugs of misuse, with reports of strong addictive potential, high tolerance and compulsive intake. Since one of these drugs, diphenidine, was added to the 1971 Convention on Psychotropic Substances, the United Kingdom (UK) had to consider its control. The Advisory Council on the Misuse of Drugs 2023 advice included...
Background: "Chemsex" involves the intake of a range of drugs (e.g., synthetic cathinones, gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL), ketamine, methamphetamine, "poppers", type V phosphodiesterase (PDE) inhibitors, MDMA/ecstasy, cocaine, cannabis, and occasionally a few other molecules as well, to enhance and prolong sexual experiences. This paper aims to provide an overview of...
Abstract Xylazine, traditionally used as a veterinary sedative, has recently emerged as a new psychoactive substance, being typically ingested in combination with fentanyl derivatives and hence raising significant public health concerns. Despite its increasing prevalence, little is known about its molecular interactions with human neuroreceptors, specifically the serotonin 7 (5‐HT 7 R) and...
BACKGROUND: 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...
Intranasal esketamine, approved with oral antidepressants for adults with treatment-resistant depression (TRD), is the S-enantiomer of ketamine and has higher potency and affinity for N-Methyl-d-Aspartate receptors. Administered intranasally, it offers rapid absorption and onset, essential for severe depressive symptoms or suicidal impulses. Comparative studies on esketamine and ketamine's...
Background: Piperazines, synthetic compounds known for their stimulant and hallucinogenic effects, have gained prominence among novel psychoactive substances (NPS) and are frequently associated with adverse psychiatric outcomes, including psychosis. Methods: A systematic review of the literature available up to 23 May 2024 was conducted, using the PubMed, Scopus, and Web of Science databases,...
Abstract Currently, novel psychoactive substance (NPS) use presents a challenging issue for authorities. To effectively tackle the use of NPS, a deeper understanding of the motivations of those who use NPS is required. Evidence suggests that a subset of NPS users declare their use as ‘self-medicating’; however, there is a paucity of research in this area. The aim of this review is to provide an...
Clinicians should be regularly informed about the range of NPS and their medical, psychobiological and psychopathological risks both in the acute and long term. Future research should focus on an integrative model in which pro-drug websites' analyses are combined with advanced research approaches, including computational chemistry studies so that in vitro and in vivo preclinical studies of...
The proliferation of Novel Psychoactive Substances (NPS) presents a challenge for global drug policy. The ease of online drug purchase and the emergence of the dark web have created new avenues for the growth of NPS. Despite the global nature of this issue, limited research has examined motivations of use. These include perceived safety or convenience, an interest in novel pharmacology and...
Psilocybin has been suggested as a promising transdiagnostic treatment strategy for a wide range of psychiatric disorders. Recent findings showed that psychedelic-assisted/”psycholitic” psychotherapy should provide significant and sustained alleviation of depressive symptoms. However, to date, there have been several study limitations (e.g., small sample sizes, blinding, limited follow-up,...
The use of several new psychoactive substances (NPS) has become very popular and is posing global health risks. Chemically and pharmacologically diverse molecules are constantly emerging and are presenting with a wide range of clinical implications. Serotonin toxicity, and specifically Serotonin Syndrome (SS), might develop as a result of an over-activation of the serotoninergic system caused...
Psychedelics alter the perception of reality through agonist or partial agonist interaction with the 2A serotoninergic receptor. They are classified as phenethylamines, tryptamines and lysergamides. These classes, according to the United Nations Office on Drugs and Crime (UNODC) and European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), account for an important percentage of the new...
COVID-19-related disruptions of people and goods' circulation can affect drug markets, especially for new psychoactive substances (NPSs). Drug shortages could cause a change in available NPS, with the introduction of new, unknown, substances. The aims of the current research were to use a web crawler, NPSfinder®, to identify and categorize emerging NPS discussed on a range of drug...
BACKGROUND: Both prescription and over-the-counter (OTC) drugs recently emerged among novel psychoactive substances (NPS) being reported as ingested for recreational purposes. Among them, benzydamine (BZY), normally prescribed as an OTC anti-inflammatory drug, is reportedly being diverted and recreationally used. OBJECTIVE: The aim of this study was to investigate how the misuse of BZY has been...
In this study, we described the acute psychiatric presentations related to recreational drug use in subjects on holiday in Ibiza. The use of psychoactive substances was characterized by poly-use of both traditional and novel substances, with several psychopathological consequences. Future research should focus on a better understanding of the psychopathological effects of specific substances,...
There is growing recognition that substance use is associated with the emergence of psychosis.Elements of post-modernity dominate contemporary social contexts and operate as existential background factors that contribute to the emergence of substance-related psychotic phenomena, particularly use of potent and highly rewarding novel psychoactive substances (NPS). About 25% of first-episode...
Background: A wide range of novel psychoactive substances (NPS) is regularly searched and discussed online by web-based drug enthusiasts (i.e. the e-psychonauts). Among NPS, the range of synthetic cannabinoids (SC; 'Spice') currently represents a challenge for governments and clinicians. Methods: Using a web crawler (i.e. the NPS.Finder®), the present study aimed at assessing psychonauts'...
The critical spread and dissemination of novel psychoactive substances (NPS), particularly among the most vulnerable youngsters, may pose a further concern about the psychotic trajectories related to the intake of new synthetic drugs. The psychopathological pattern of the "new psychoses" appears to be extremely different from the classical presentation. Therefore, clinicians need more data on...