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.
International Journal of Molecular Sciences
September 23, 2018
Domenico de Berardis, Michele Fornaro, Alessandro Valchera et al.
171 citations
Suicide remains difficult to predict despite advances in neuroscience. The World Health Organization reports one million suicide deaths annually, with one every 40 seconds. Recent genomic studies suggest genetics influence suicide risk. Combining genomic and clinical assessments has identified biomarkers for suicidal ideation involved in neural connectivity, mood, and immune response, including the mammalian target of rapamycin (mTOR) signaling pathway. This provides a neurobiological basis for drugs like ketamine, an NMDA antagonist, which has shown rapid antidepressant and anti-suicidal effects. This review examines preclinical and clinical evidence for ketamine's efficacy in treating suicidal ideation in mood disorders, addressing the neurobiological processes of suicide and potential therapeutics.
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.
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.
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.
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.
Current Topics in Medicinal Chemistry
January 31, 2020
Domenico de Berardis, Carmine Tomasetti, Maurizio Pompili et al.
38 citations
Abnormalities in glutamatergic neurotransmission are hypothesized to play a role in mood disorders, prompting investigation of NMDA receptor modulators for Major Depressive Disorder (MDD). Intranasal esketamine, an NMDA receptor antagonist, has been developed for treatment-resistant depression (TRD) and for rapidly reducing depressive symptoms, including suicidal ideation, in MDD patients at imminent suicide risk. A systematic review of literature up to October 2019 found that intravenous esketamine elicits rapid and sustained antidepressant effects in refractory patients. Phase II studies showed intranasal esketamine had rapid onset and persistent efficacy in TRD and MDD patients at suicide risk, though phase III data had discrepancies.
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.
Human psychopharmacology
May 1, 2020
Laura Orsolini, Stefania Chiappini, Duccio Papanti et al.
27 citations
Ayahuasca, a hallucinogenic plant preparation used in sacred ceremonies by indigenous Amazonian groups, may offer therapeutic benefits for mental health. Evidence from preclinical, observational, and experimental studies suggests it acts as a fast-acting and enduring antidepressant, emotional regulator, anxiolytic, and antiaddictive drug. It appears safe and well tolerated, with nausea and vomiting as the most common transient side effects. However, findings indicate it should not be used in bipolar or psychotic patients due to increased risk of manic switch or psychotic onset. Further research with randomized, double-blind, placebo-controlled trials and neuroimaging is needed to better evaluate its therapeutic potential in mental disorders.
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.
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.
European Psychiatry
March 1, 2016
Laura Orsolini, Alessandro Valchera, Duccio Papanti et al.
3 citations
Hallucinogen Persisting Perception Disorder (HPPD) is a syndrome marked by prolonged or recurring perceptual symptoms similar to acute hallucinogen effects, associated with substances like LSD, cannabis, MDMA, psilocybin, and mescaline. Symptoms mainly involve visual disturbances such as geometric pseudo-hallucinations, halos, flashes of light, motion-perception deficits, afterimages, and micropsy, though depressive and thought disorders may co-occur. First described in 1954, HPPD was formally established as a syndrome in the DSM-IV-TR in 2000. The neuronal substrate, risk factors, etiology, and pathogenesis remain unknown and under investigation. This critical review covers psychopathological bases, etiological hypotheses, and psychopharmacological approaches, presenting a case report and offering practical clinical recommendations.