World Psychiatry
February 1, 2016
Fabrizio Schifano, Laura Orsolini, G. Duccio Papanti et al.
319 citations
Novel psychoactive substances encompass a wide variety of drugs, including synthetic cannabinoids, cathinone derivatives, psychedelic phenethylamines, novel stimulants, synthetic opioids, tryptamine derivatives, dissociatives, piperazines, GABA receptor agonists, prescribed medications, psychoactive plants, and performance-enhancing drugs. Users are often drawn to them for intense psychoactive effects and their likely undetectability in routine drug tests. These substances act on neurotransmitter pathways such as dopamine, cannabinoid CB1, GABA-A/B, 5-HT2A, glutamate, and kappa opioid receptors—systems whose imbalance is linked to mental health conditions. The paper provides psychiatrists with updated knowledge on the clinical pharmacology and psychopathological consequences of these drugs, along with a brief overview of clinical management.
Forensic science international
March 20, 2011
Martin M Schmidt, Akhilesh Sharma, Fabrizio Schifano et al.
198 citations
A survey of UK-based internet retailers found 1,308 products marketed as "legal highs," averaging £9.69. Most were pills (46.6%), smoking material (29.7%), or plant extracts (18.1%), and claimed to be stimulants (41.7%), sedatives (32.3%), or hallucinogens (12.9%). Safety information was severely lacking: 40.1% failed to list ingredients, 91.9% omitted side effects, 81.9% gave no contraindications, and 86.3% no drug interactions. The most common products included Salvia divinorum, Kratom, Hawaiian Baby Woodrose Seeds, Fly Agaric, and Genie. The authors conclude that uninformed users risk serious adverse effects.
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.
Progress in neuro-psychopharmacology & biological psychiatry
December 3, 2012
John M Corkery, Emma Durkin, Simon Elliott et al.
105 citations
5-MeO-DALT is a psychoactive tryptamine sold online as a 'research chemical' with little scientific study. A review of available knowledge and a first reported death involving the substance is described: a man in his mid-20s died in mid-2010 after being hit by a lorry while under the influence of 5-MeO-DALT, as concluded by the coroner. The authors call for documentation of other cases to build an evidence base.
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.
BioMed Research International
January 1, 2014
Francesco Saverio Bersani, Ornella Corazza, Gabriella Albano et al.
98 citations
25C-NBOMe, sold online as legal LSD or under names like 'N-bomb' and 'Pandora', is a partial agonist of 5-HT2A receptors that carries a high risk of overdose, with acute toxicity and fatalities reported. It is taken orally, sublingually, nasally, by injection, vaginally, rectally, or smoked, producing effects such as sublingual numbing, stimulation, hallucinations, dissociation, and anxiety. Its use is an emerging phenomenon increased by low-cost online availability, and health professionals should be informed about this trend.
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.
Cyberpsychology, behavior and social networking
May 1, 2015
Laura Orsolini, Gabriele Duccio Papanti, Giulia Francesconi et al.
90 citations
Within online drug forums, some highly knowledgeable users—termed 'e-psychonauts'—provide reliable information on psychoactive substances. A netnographic study observed cyber drug communities in early 2014, analyzing posts with phenomenological methods. E-psychonauts typically described themselves as 'psychedelic researchers,' 'new Shamans,' 'philosophers,' or 'alchemists.' They were mainly young, male, unmarried, Caucasian, and in good or excellent employment. They possessed strong IT skills, verbal fluency, and deep chemical/pharmacological knowledge, often testing or synthesizing drugs to explore altered consciousness. The findings suggest a need to improve professional awareness of this group and develop targeted prevention approaches.
Neuropsychobiology
January 1, 2000
Fabrizio Schifano
83 citations
An overview of ecstasy (MDMA) abuse in Italy and other European countries describes clinical cases and a larger report from a public addiction treatment unit. Polydrug users who also consume MDMA are at high risk for psychopathological consequences including depression, psychotic disorders, cognitive disturbances, bulimic episodes, impulse control disorders, panic disorders, and social phobia, especially with longer-term or larger-dose use. Occasional experimenters show a novelty-seeking personality dimension, while heavier users exhibit low harm avoidance scores. Methodological challenges arise because MDMA is rarely the only drug of abuse.
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.
Experimental neurology
May 1, 2021
Fabrizio Schifano, Stefania Chiappini, Andrea Miuli et al.
49 citations
Several new psychoactive substances (NPS) can trigger serotonin syndrome, a dangerous condition of excessive serotonin activity marked by altered mental status, neuromuscular effects, and autonomic hyperactivity. A systematic review of three retrospective studies, two case series, and five case reports identified implicated substances including psychedelic phenethylamines (2C-I, 25I-NBOMe, 5-IT) and synthetic cathinones (mephedrone, MDPV, methylone, butylone, NRG3, AMT, MXP), as well as the antidepressant bupropion when misused at high doses or combined with other serotonergic drugs. Most substances were taken orally, though nasal insufflation and sublingual administration occurred. Psychiatric history was negative for most subjects. Clinicians should recognize NPS risks and diagnostic challenges due to undetectability in routine drug screenings.
Pharmacopsychiatry
April 25, 2017
Norbert Scherbaum, Fabrizio Schifano, Udo Bonnet
46 citations
Hundreds of new psychoactive substances (NPS) have been identified in Europe, mainly synthetic cannabinoids and new synthetic stimulants like cathinones. These are often developed by modifying basic chemical structures such as phenethylamine or tryptamine. Although their pharmacology and toxicology are hardly known, they are sold online as "bath salts" or "incense mixtures" and advertised as "legal highs." Little is known about the prevalence of NPS use, but some molecules may cause severe adverse reactions. Unlike cannabis, synthetic cannabinoid users may experience epileptic seizures, loss of consciousness, and persisting psychopathological disorders. Future studies should inform better-tailored management strategies.
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.
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.
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.'
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.
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.
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.
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.