Human Psychopharmacology Clinical and Experimental
March 1, 2012
Ornella Corazza, Fabrizio Schifano, Pierluigi Simonato et al.
157 citations
Methoxetamine, a dissociative drug related to ketamine, has a much longer duration of action and intensity of effects, and its availability on the web represents a new recreational trend. The analysis of online, non-peer-reviewed material carries methodological limitations. The online availability of information on novel psychoactive drugs like methoxetamine constitutes a pressing public health challenge, requiring better international collaboration and novel forms of intervention to address this fast-growing phenomenon.
Psychological Medicine
July 22, 2019
Fabrizio Schifano, Flavia Napoletano, Stefania Chiappini et al.
118 citations
A novel web-crawling tool called NPS.Finder® identified several thousand new psychoactive substances (NPS)—roughly four times more than European and international drug agencies report. Synthetic cannabinoids, new synthetic opioids, ketamine-like dissociatives, novel stimulants, novel psychedelics, and certain prescription and over-the-counter medicines were most commonly linked to psychopathological consequences. The rapid proliferation of recreational psychotropics poses a challenge for psychiatry because the pharmacodynamics and pharmacokinetics of many NPS remain poorly understood. Health and mental health professionals need up-to-date information on the range of NPS, their intake methods, sought-after effects, drug combinations, and associated medical and psychopathological risks.
Journal of Clinical Psychopharmacology
August 25, 2012
Fabrizio Schifano, John Corkery, A. Hamid Ghodse
113 citations
Mephedrone, a popular recreational stimulant, has been linked to fatalities in the United Kingdom. Analysis of 62 concluded inquest cases from the UK National Programme on Substance Abuse Deaths database shows that typical victims were young (average age 28.8 years), male, and had a history of drug misuse. A notable 29% of deaths involved self-harm, with 11 of those 18 cases resulting from hanging. Mephedrone alone was identified at postmortem in 13% of cases. The findings suggest caution when using mephedrone, though the exact risks remain unclear.
Frontiers in Psychiatry
November 20, 2017
Laura Orsolini, Gabriele Duccio Papanti, Domenico de Berardis et al.
99 citations
Hallucinogen-persisting perception disorder (HPPD) is a syndrome of prolonged or recurring perceptual symptoms resembling acute hallucinogen effects. It has been linked to LSD, cannabis, MDMA, psilocybin, mescaline, and psychostimulants, and more recently to novel psychoactive substances. Symptoms are mainly visual, including geometric pseudo-hallucinations, haloes, flashes of light, motion-perception deficits, afterimages, and micropsia, though depressive and thought disorders may co-occur. First described in 1954, HPPD was formally recognized as a syndrome in the DSM-IV-TR in 2000. Its neural substrates, risk factors, and causes remain largely unknown. This mini review surveys psychopathological bases, etiological hypotheses, and psychopharmacological approaches, including associations with novel substances, based on a literature search of PubMed/Medline, Google Scholar, and Scopus without time restrictions.
Journal of Psychopharmacology
March 30, 2006
Fabrizio Schifano, John Corkery, Paolo Deluca et al.
96 citations
Over the last decade, the UK saw a yearly increase in ecstasy-related deaths, with 394 mentions identified from 1994 to 2003. In 42% of cases, ecstasy was the sole drug mentioned. The number of fatalities correlated positively with past-year use, number of drug offenders, and number of seizures, but negatively with ecstasy price. Price negatively correlated with use and seizures, and positively with average MDMA dosage per tablet. Other related drugs (MDA, MDEA, MBDB) appeared significantly only up to 1997. Increasing production and falling prices may have boosted consumption and deaths. Only medical death certificates were analyzed, not coroners' reports.
Human Psychopharmacology Clinical and Experimental
September 19, 2003
Fabrizio Schifano, Adenekan Oyefeso, John Corkery et al.
93 citations
Between August 1996 and April 2002, 202 deaths related to ecstasy use occurred in England and Wales, with a steady annual increase. Most victims were young men: the male-to-female ratio was 4:1, and three-quarters were under age 29. In 17% of cases ecstasy was the only drug involved; the rest involved other substances, most often alcohol, cocaine, amphetamines, and opiates. MDMA was detected in 86% of cases and MDA in 13%; MDEA and PMA caused single deaths. This is the largest sample of ecstasy-related deaths reported at the time. The authors propose possible explanations for the rising trend and a rationale for the observed polypharmacy combinations.
Expert Review of Clinical Pharmacology
March 17, 2016
Fabrizio Schifano, Gabriele Duccio Papanti, Laura Orsolini et al.
66 citations
Novel psychoactive substances (NPS), including stimulants and hallucinogens, disrupt multiple neurotransmitter pathways, particularly dopamine, cannabinoid CB1, and 5-HT2A receptors. Their intake is almost never detected by standard drug screening tests. Acute management of NPS misusers should prioritize reducing self-directed and outward-directed aggression and agitation. Benzodiazepines are recommended as first-line treatment, with propofol or antipsychotics as alternatives. Treatment must also address possible rhabdomyolysis and hyperthermia. Future research is needed to develop better-tailored management strategies.
Human Psychopharmacology Clinical and Experimental
July 1, 2013
John Corkery, Simon Elliott, Fabrizio Schifano et al.
52 citations
MDAI (5,6-methylenedioxy-2-aminoindane), a psychoactive substance sold as a 'legal high', is structurally similar to MDMA and shares its behavioral properties. Recreational use began around 2007 in Europe, increasing after 2009 in the UK. Calls to poisons services started in 2010, with few emergency department presentations. A review of recent literature, including grey literature, presents information on MDAI's toxicity, including the first three UK deaths involving MDAI use in 2011 and 2012. 'Serotonin syndrome' appears to be a possible factor in these fatalities. Documentation of further cases, including non-fatal overdoses, is vital to establish a scientific evidence base.
Frontiers in Psychiatry
November 20, 2019
Laura Orsolini, Stefania Chiappini, Duccio Papanti et al.
41 citations
The spread of novel psychoactive substances (NPS), especially among young people, raises concerns about psychosis linked to synthetic drugs. These 'new psychoses' differ clinically from classical psychosis. This mini-review synthesizes clinical and psychopathological features of NPS-induced psychoses and their treatment, based on a PubMed/Medline search for synthetic cannabinoids and cathinones. It contrasts classical psychoses with NPS-induced ones and offers therapeutic guidelines for clinicians in addiction psychiatry.
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.
Current Neuropharmacology
October 20, 2022
Alessio Mosca, Stefania Chiappini, Andrea Miuli et al.
30 citations
Ibogaine and noribogaine, psychedelic substances from plants of the Apocynaceae family, show some efficacy in treating substance use disorders, particularly opiate detoxification. However, their use carries concerning risks of cardiotoxicity and mortality. A meta-analysis of side effects found a significant risk of developing headaches after treatment. The evidence, drawn from case reports, randomized controlled trials, open-label studies, surveys, and observational studies, remains unclear on overall efficacy and toxicity. Further research is needed to evaluate therapeutic benefits and safety.
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.'
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.
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.
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.
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.
Journal of Psychopharmacology
September 29, 2025
Jade Pullen, John Corkery, Rebecca Mcknight et al.
3 citations
Deaths following illicit ketamine use have accelerated in recent years, increasingly involving complex polydrug use and socio-economic vulnerability. Policy responses should extend beyond single-substance legislative controls to include harm reduction, treatment integration, and social support strategies.