Frontiers in Psychiatry
February 9, 2021
Valeria Catalani, Davide Arillotta, John Corkery et al.
38 citations
During the first eight months of the COVID-19 pandemic, a web crawler called NPSfinder® identified 229 new psychoactive substances (NPSs) being discussed on drug enthusiast forums and social media. Of these, 18 NPSs were detected for the first time, including six cathinones, six opioids, two synthetic cannabinoid receptor agonists, two PCP-like molecules, and two psychedelics. Ten of these 18 substances had not been previously reported to either the UNODC or EMCDDA databases. Opioids and cathinones generated the most discussion on social media and Reddit. Automated web crawlers combined with social listening may help identify emerging NPSs, and pandemic-related restrictions may influence demand for specific NPS classes.
Expert Review of Clinical Pharmacology
November 2, 2023
Fabrizio Schifano, Alessandro Vento, Norbert Scherbaum et al.
30 citations
Clinicians need regular updates on novel psychoactive substances (NPS) and their acute and long-term medical, psychobiological, and psychopathological risks. Future research should combine pro-drug website analysis with computational chemistry to organize preclinical studies of new psychoactives. Psychedelic research should develop robust study designs to assess potential therapeutic benefits, as these molecules likely have limited dependence liability.
Drugs and Alcohol Today
August 30, 2010
Zoe Davey, Ornella Corazza, Fabrizio Schifano et al.
30 citations
The internet has accelerated the growth of the licit recreational drug market, notably for mephedrone and related cathinones. Keeping up with these new drugs is difficult due to a lack of balanced information and the risk of widespread misinformation. This article examines how inaccurate information about mephedrone and substituted cathinones spreads, drawing on the European Commission-funded Psychonaut Web Mapping project, which used online resources to detect emerging trends, monitor their diffusion, and develop a reasonably accurate profile of these new psychoactive compounds. The implications for harm reduction and future research are discussed.
Current Neuropharmacology
December 2, 2016
Laura Orsolini, Paul St John‐smith, Daniel Mcqueen et al.
28 citations
Multiple evolutionary mechanisms—optimal foraging, costly signaling, and reproduction at the expense of health—may jointly explain the recent spread and diffusion of the novel psychoactive substances (NPS) market, representing a reason for concern.
Frontiers in Psychiatry
May 22, 2018
Laura Orsolini, Michela Ciccarese, Duccio Papanti et al.
25 citations
A new 'psychedelic trend' has emerged, driven by psychonauts who consume a variety of novel psychoactive substances (NPS) from animals. This review identifies several species—including ants, amphibians, and fish—that possess psychoactive properties and are abused recreationally. Routes of administration vary by animal, substance, metabolism, toxicity, and cultural context. Online access to these animals is facilitated through tourism-related search terms such as 'frog trip' and 'religious trip.' The review combines online psychonaut reports with literature searches from PubMed/Medline and Google Scholar to provide an overview of commonly abused 'psychedelic animals.'
Advances in Dual Diagnosis
August 12, 2014
Duccio Papanti, Laura Orsolini, Giulia Francesconi et al.
24 citations
Synthetic cannabinoids, sold as 'Spice' products, are designer drugs that act as full agonists on cannabinoid receptors, unlike the partial agonist THC in cannabis. This stronger activation can produce severe physiological and psychological disturbances. Evidence suggests a relationship between synthetic cannabinoid use and psychosis, termed 'Spiceophrenia'. Acute intoxication typically involves tachycardia, hypertension, hallucinations, mydriasis, agitation, anxiety, tachypnoea, nausea, vomiting, and seizures. The lack of clinical trials and longitudinal studies, along with the heterogeneity of compounds, hinders precise health risk assessment, especially for long-term effects. Large-scale, non-judgmental prevention campaigns highlighting differences from cannabis are needed.
Frontiers in Psychiatry
August 31, 2020
Giovanni Martinotti, Attilio Negri, Stefania Schiavone et al.
22 citations
Recreational drug use among holidaymakers in Ibiza often involves multiple substances, both traditional and novel, leading to acute psychiatric emergencies. The pattern of poly-substance use is linked to a range of psychopathological consequences. Better understanding of the specific effects of individual drugs, clearer diagnostic signs and symptoms, and long-term follow-up studies are needed.
Human Psychopharmacology Clinical and Experimental
July 1, 2015
Giulia Francesconi, Laura Orsolini, Duccio Papanti et al.
22 citations
Venlafaxine, a widely prescribed antidepressant, carries a risk of misuse, with users ingesting or snorting doses 10-15 times higher than clinically advised to obtain MDMA/amphetamine-like stimulant and psychedelic effects. Polydrug misuse is common, and the drug is readily available online. Physicians should assess patients for drug dependence history and monitor for signs of misuse.
Current Neuropharmacology
January 14, 2021
Stefania Chiappini, Andrea Miuli, Alessio Mosca et al.
19 citations
Benzydamine, an over-the-counter anti-inflammatory drug, is being diverted and used recreationally at high dosages (500–1500 mg) for its hallucinogenic properties. A systematic review of eleven articles from 1997–2019, including case reports, surveys, and case series, along with analysis of European adverse drug reaction reports from 2005–2020, found three reported abuse cases. The findings suggest healthcare professionals should be aware of potential misuse and that emergency physicians should consider benzydamine abuse when patients present with psychotic symptoms.
Psychotherapy and Psychosomatics
January 1, 2020
Fabrizio Schifano
19 citations
Coming off prescribed psychotropic medications can be difficult, and insights from how these drugs are used recreationally may help understand withdrawal and dependence. The article draws on evidence from recreational use to explore the pharmacological and psychological factors that make discontinuing medications like antidepressants and benzodiazepines challenging. It suggests that the reinforcing properties and withdrawal symptoms seen in recreational contexts parallel those experienced by patients, and that understanding these mechanisms could improve clinical strategies for tapering and discontinuation. The author argues that recognizing the potential for dependence and tailoring withdrawal protocols accordingly may reduce relapse and improve outcomes for patients.
European Neuropsychopharmacology
April 13, 2021
Valeria Catalani, John Corkery, Amira Guirguis et al.
18 citations
A software tool called NPSfinder crawled websites frequented by psychonauts and online NPS resources from November 2017 to February 2020, detecting 1,344 psychedelic new psychoactive substances (NPS)—nearly ten times more than the combined total reported by the United Nations and European monitoring agencies. Of these, 994 were previously unknown molecules identified as potential novel psychedelics, indicating a large gap between online availability and officially reported NPS. The findings suggest strong interest in psychedelics among psychonauts and possibly recreational drug users, and that monitoring online spaces may help assess real-world availability, understand drug trends, and predict future scenarios.
Human Psychopharmacology Clinical and Experimental
May 1, 2017
Barbara Loi, Mire Zloh, Maria Antonietta de Luca et al.
17 citations
4,4'-DMAR ("Serotoni") is a potent stimulant recently linked to multiple fatalities in Europe. Online drug-forum discussions provide technical knowledge about its use, including routes of administration, doses, desired and adverse effects, comparisons with other drugs, combinations, medications used to reverse its action, and harm-reduction advice. A critical review of evidence-based literature together with qualitative data from six website fora reveals that while netnography (social-network web monitoring) has methodological limitations, it can help clarify clinical and psychopharmacological issues for novel psychoactive substances like 4,4'-DMAR, for which scientific knowledge is extremely scarce.
The International journal on drug policy
August 1, 2023
Tayler Holborn, Fabrizio Schifano, Paolo Deluca
15 citations
People are using novel psychoactive substances (NPS) to self-treat conditions such as ADHD, anxiety, and depression, according to discussions on a Reddit community. Motivations include easier access, lower cost, legality, and dissatisfaction with conventional healthcare. Substances frequently mentioned include etizolam, clonazolam, diclazepam, flualprazolam, 2-FMA, 4F-MPH, 3-FPM, and 3-MeO-PCP. Users often chose NPS based on perceived "functionality," though outcomes varied, and clonazolam use was highlighted as particularly problematic. The findings suggest that improving healthcare providers' knowledge of NPS use, removing barriers to adult ADHD diagnosis, and rebuilding trust in addiction services could help address this challenge.
Pharmaceuticals
December 31, 2022
Antonio Munafò, Davide Arillotta, Guido Mannaioni et al.
15 citations
Psilocybin shows promise as a transdiagnostic treatment for psychiatric disorders, with recent evidence indicating that psychedelic-assisted psychotherapy can provide significant and lasting relief from depressive symptoms. However, existing studies have limitations including small sample sizes, inadequate blinding, short follow-up periods, and highly selected treatment populations. Additional concerns involve practitioner experience, lack of standardized protocols, the legal status of psychedelics, ethical issues, and potential adverse psychological or medical effects. The authors suggest that newer evidence, more precise protocols, and policy changes may clarify psilocybin's therapeutic potential.
Brain sciences
April 22, 2025
Fabrizio Schifano, Stefania Bonaccorso, Davide Arillotta et al.
14 citations
Chemsex involves using drugs like synthetic cathinones, GHB/GBL, ketamine, methamphetamine, and others to enhance and prolong sexual experiences. Stimulants increase sexual arousal, performance, and social interactions; MDMA-like drugs foster emotional closeness; GHB/GBL promotes disinhibition, leading to condomless sex with multiple partners; ketamine facilitates receptive anal intercourse or fisting. Polydrug use can cause serotonergic syndrome, seizures, drug interactions, and sympathomimetic overstimulation, along with psychopathological conditions that may lead to misuse of opioids, gabapentinoids, or antipsychotics. Reducing stigma and providing multidisciplinary medical, psychological, and social support are key to managing these challenges.
Archiv der Pharmazie
March 1, 2025
Giuseppe Floresta, Alberto Granzotto, Vincenzo Patamia et al.
12 citations
Xylazine, a veterinary sedative now used recreationally with fentanyl, interacts with human serotonin 7 (5-HT7R) and kappa-opioid (KOR) receptors. Computational docking and molecular dynamics simulations identified binding motifs and showed that small structural changes can improve xylazine's affinity for these receptors. These findings may help explain xylazine's psychoactive effects and guide treatments for overdoses.
Drugs and Alcohol Today
February 24, 2015
Fabrizio Schifano
12 citations
Novel psychoactive substances (NPS) encompass a diverse and rapidly evolving array of molecules, including psychedelic phenethylamines, synthetic cannabinoids, cathinone derivatives, novel stimulants, synthetic opioids, tryptamines, dissociatives, piperazines, GABA receptor agonists, prescription medications, psychoactive plants, and performance-enhancing drugs. Users seek these substances for their psychoactive effects. Health professionals must understand the effects and toxicity of NPS to address the wide range of medical and psychopathological issues. The EU-MADNESS project aims to improve understanding of NPS pharmacology and disseminate current information to clinicians. Further research is needed to develop evidence-based clinical management strategies.
Journal of Psychoactive Drugs
February 9, 2019
Lorenzo Moccia, A. Tofani, Marianna Mazza et al.
10 citations
A 23-year-old man developed a substance-induced psychotic disorder after intravenously injecting an unspecified amount of methoxetamine (MXE), a ketamine derivative hallucinogen. Clinically, he showed blunted affect, diminished social drive, loss of sense of purpose, and detachment from the environment. Psychometric tests revealed severe dissociation, lack of motivation, and mild impairments in verbal fluency, working memory, and attention. Brain scans using 18F-FDG PET/CT showed significantly reduced tracer uptake in the dorsolateral prefrontal cortex (DLPFC), a region critical for goal-oriented cognition, working memory, and attention. This case indicates that a single acute MXE intoxication can cause severe brain impairment.
Neuroscience & Biobehavioral Reviews
October 19, 2025
Alessio Mosca, Gianluca Mancusi, Stefania Chiappini et al.
6 citations
Synthetic cannabinoids are the novel psychoactive substances most strongly associated with acute psychosis and, in some cases, persistent or relapsing psychotic disorders. Some cases show symptoms overlapping with schizophrenia, suggesting a possible risk of transition to chronic illness. Synthetic cathinones and phenethylamines are also linked to psychotic manifestations including thought disturbances and perceptual abnormalities. While many psychotic episodes are transient, a notable proportion evolve into persistent states, indicating that these substances may unmask latent vulnerabilities or directly contribute to chronic psychotic disorders. Clinicians should systematically assess NPS use in first-episode psychosis patients.
Psychiatry International
September 20, 2024
Alessio Mosca, Stefania Chiappini, Andrea Miuli et al.
5 citations
Piperazines, synthetic compounds with stimulant and hallucinogenic effects, are linked to acute psychotic episodes. A systematic review of 4 studies found that piperazine abuse frequently triggers symptoms such as paranoia, auditory, and visual hallucinations. The compounds' complex polyreceptor action may explain these effects, similar to other novel psychoactive substances. Recovery is common after cessation and treatment, but data on long-term outcomes are limited. Further research into piperazine abuse and specific treatment protocols for substance-induced psychosis is needed.
International Journal of Mental Health and Addiction
November 28, 2023
Tayler Holborn, Robert L. Page, Fabrizio Schifano et al.
5 citations
A review of 24 studies found that people use novel psychoactive substances (NPS) to self-medicate, primarily for anxiety, depression, and ADHD. Specific links emerged between cluster headaches and psychedelic NPS, and between anxiety and novel benzodiazepines. Novel benzodiazepine use among young individuals is a particular concern. The authors call for greater healthcare professional awareness and more qualitative research into motivations.
Current Neuropharmacology
February 20, 2025
Alessio Mosca, Stefania Chiappini, Gianluca Mancusi et al.
3 citations
Abusing certain over-the-counter medications can trigger psychotic symptoms such as paranoia, hallucinations, and thought disorders. Antihistamines, dextromethorphan, and other OTC drugs are implicated. Dextromethorphan misuse is especially linked to chronic psychosis, while other substances more often cause acute substance-induced psychosis. The review analyzed 46 relevant studies from an initial pool of 2,677 articles, highlighting the need for greater awareness and interventions to address OTC drug misuse and its psychiatric consequences.
Journal of psychopharmacology (Oxford, England)
July 1, 2025
John Martin Corkery, Caroline Copeland, Fabrizio Schifano
2 citations
Diarylethylamine drugs, including diphenidine and methoxyphenidine (MXP), are dissociative substances with strong addictive potential. A systematic review of global mortality data found 48 deaths involving these drugs, with 37 occurring in the UK between 2014 and 2019. Most decedents were male (91%), White (95%), with a mean age of 37.2 years. Deaths were primarily accidental (89%) from acute drug toxicity (92%), often involving polysubstance poisoning with opioids, benzodiazepines, or stimulants. One-third of deaths involved MXP or diphenidine alone, suggesting these molecules are relatively toxic. Although diarylethylamine deaths are rare, these substances remain available, indicating ongoing risk.
Current neuropharmacology
January 9, 2026
Maria Antonietta De Luca, Cristina Miliano, Amanda Roxburgh et al.
1 citation
Tablets sold as MDMA frequently contain psychoactive adulterants that vary by region and year, potentially increasing central nervous system harm. A review of studies from 2020 to 2025 covering Continental Europe, the UK, the USA, and Australia found that co-administration of MDMA with common adulterants can exacerbate noxious neurological and psychiatric effects. The composition of tablets differs across these regions, and interactions between MDMA and adulterants may explain some adverse effects seen in users. Expanding drug checking and public health efforts is essential to inform users, first responders, and healthcare professionals about these risks.
Brain Sci
September 17, 2025
Alessio Mosca, Stefania Chiappini, Andrea Miuli et al.
1 citation
Synthetic cannabinoids can cause psychosis that is often severe and difficult to treat. This systematic review examined published case reports and case series to identify effective treatment strategies. The review found that benzodiazepines and antipsychotics are commonly used, but many patients require intensive care and prolonged hospitalization. No single treatment protocol emerged as clearly superior, and outcomes varied widely, with some patients recovering fully while others experienced persistent psychotic symptoms. The authors suggest that early recognition and aggressive management may improve outcomes, but more research is needed to establish standardized treatment guidelines.