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.
Human Psychopharmacology Clinical and Experimental
July 1, 2013
Duccio Papanti, Fabrizio Schifano, Giulia Botteon et al.
191 citations
Synthetic cannabimimetics (SC), known as 'spice' drugs, are increasingly used by teenagers and young adults. A systematic review of 41 studies found that the average age of SC users was 22.97 years, with a male-to-female ratio of 3.16:1. The most commonly detected SC compounds in biological samples were JWH-018, JWH-073, JWH-122, CP-47,497, and JWH-250. Evidence suggests that psychotic symptoms such as hallucinations and delusions can occur in acute or chronic SC users. Although a clear causal link cannot be established, SC appears to trigger acute psychosis in vulnerable individuals and exacerbate psychotic episodes in those with prior psychiatric history.
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.
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.
CNS Spectrums
June 25, 2020
Giovanni Martinotti, Luisa de Risio, Chiara Vannini et al.
102 citations
About 25% of first-episode psychoses are substance-induced. The DSM-5 definition assumes symptoms are transient and disappear after sustained abstinence, but this does not account for persistent cases. A new diagnostic framework is needed to differentiate comorbid conditions from substance-related psychoses. The authors propose a novel clinical entity called substance-related exogenous psychosis (SREP), covering both transient and persistent psychoses linked to substance use. SREP is distinct from schizophrenia, characterized by altered consciousness, persecutory delusions, visual and cenesthetic hallucinations, impulsivity, psychomotor agitation, affective and negative symptoms, a pervasive feeling of unreality, and intact insight. Delusions are secondary to abnormal perception from a 'sensorialization' of the world. Longitudinal studies are needed to validate this category.
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.
Current Clinical Pharmacology
May 1, 2011
Ornella Corazza, Fabrizio Schifano, Magı́ Farré et al.
98 citations
Bromo-Dragonfly (B-fly) is a potent, long-lasting hallucinogenic drug similar to LSD, associated with acute intoxications and fatalities in several countries. This paper reviews its pharmacology, chemistry, toxicology, and behavioral effects using both scientific literature and web sources. The authors critically discuss the potential for misuse and the methodological limitations of analyzing non-peer-reviewed online material. They conclude that online information about novel psychoactive drugs like B-fly poses a public health challenge and call for better international collaboration to address this growing phenomenon.
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.
International Journal of Culture and Mental Health
December 1, 2009
Fabrizio Schifano, Ornella Corazza, Paolo Deluca et al.
79 citations
An 8-language qualitative assessment of about 200 web pages found that Spice, an herbal smoking blend sold as a legal cannabis substitute, is popular online because of its legal status, undetectability in drug tests, easy online access, and cannabis-like effects. Users discussed unusual drug combinations not found in medical literature. Product descriptions rarely mentioned the synthetic THC receptor agonists responsible for the psychoactive effects. The web serves as a resource for both information on and purchase of Spice products, which health professionals should be aware of.
Journal of psychopharmacology (Oxford, England)
November 1, 2005
Fabrizio Schifano, Paolo Deluca, Lisa Agosti et al.
70 citations
The compound 2C-T-7 ('Blue Mystic'), which resembles MDMA and other designer drugs, has rarely been identified in the EU, yet online discussion among experimenters has recently grown. A review of cyber and street market information found that 2C-T-7 was first synthesized in 1986 and produces desired effects of empathy and well-being, with anecdotal reports of hallucinations, nausea, anxiety, panic attacks, and paranoid ideation. Street-level availability in Europe appears very low, though one US death from mono-intoxication is documented. From an initial 360 websites, 118 were analyzed: 14 (11.9%) described synthesis, and 5 (4.2%) offered the drug for sale.
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.
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.
Human Psychopharmacology Clinical and Experimental
July 1, 2015
Stefania Chiappini, Hugh Claridge, John M. Corkery et al.
45 citations
Methoxetamine (MXE), a novel psychoactive substance, was found in eight fatalities in the UK between 2011 and 2013. The median age at death was 27 years; most decedents were White and male. MXE was directly implicated in four deaths and likely contributed to two others, and in seven of eight cases it was used alongside other substances. The report calls for more research into MXE's health effects and toxicity, and for healthcare professionals to be aware of its harms to develop early interventions and reduce poisonings and deaths.
Substance Use & Misuse
March 1, 2010
Ornella Corazza, Fabrizio Schifano
43 citations
Recreational ketamine use may trigger experiences resembling near-death experiences (NDEs). In a sample of 50 ketamine misusers who scored at least 7 on the Greyson NDE Scale, 90% reported altered time perception, 88% felt detached from their own body, and 76% experienced peace or joy. Most NDEs occurred during the first few uses, and participants reported an average lifetime intake of 140 occasions. The sample was self-selected, nonrandomized, and small, but the findings suggest a link between recreational ketamine and NDE-like states.
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.
Human Psychopharmacology Clinical and Experimental
July 1, 2015
Giuseppe Valeriani, Ornella Corazza, Francesco Saverio Bersani et al.
41 citations
People who use novel psychoactive substances (NPS) often self-administer olanzapine to manage psychotic crises or 'bad trips,' a practice facilitated by online sharing of experiences and easy access to medications. Exploratory searches of 163 discussion forums and websites in four languages from November 2012 to 2013 found that olanzapine is the most frequently self-prescribed drug for this purpose, typically taken for a few days at 5–50 mg/day. Only a few formal studies have assessed olanzapine's effectiveness for NPS-induced psychosis, yet pro-drug websites describe it as the 'ideal' molecule to terminate bad trips. Health professionals should be informed about risks of olanzapine misuse.