Special Issue "Recent Changes in Drug Abuse Scenario: The Novel Psychoactive Substances (NPS) Phenomenon"

A special issue of Brain Sciences (ISSN 2076-3425).

Deadline for manuscript submissions: closed (5 March 2018).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Dr. Fabrizio Schifano
E-Mail Website
Guest Editor
University of Hertfordshire, Hatfield, Hertfordshire, United Kingdom
Interests: drug abuse; drug misuse; novel psychoactive substances; NPS; dual diagnosis; psychopharmacology; prescribing drugs’ misuse

Special Issue Information

Dear Colleagues,

In parallel with a decrease/stabilization in the use of internationally controlled drugs, the market of novel psychoactive substances (NPS) continues increasing, year after year, with the Internet playing a pivotal role in contributing to this complex scenario. At times, although misleading, the terms ‘legal highs’ or ’research chemicals’ have been used to describe these molecules. Overall, about 5% of 19–24-year-old European people have already experimented with them, because both NPS’ intense psychoactive effects and their virtual non-detectability in routine drug screenings. Although ‘novel’ typically refers to molecules that have recently become a reason of current/potential public health concern, at times, the NPS scenario may indeed focus on pharmaceutical molecules. These may have either not entered the market, or are currently prescribed, with their potential for misuse resulting from the relating high dosages/idiosyncratic ways of self-administration. A concurrent use of a range of different NPS, and/or medications, is frequently being reported and this may be a reason of further clinical complications. Given their complex pharmacodynamics, there are increasing levels of concern about the onset of acute/chronic psychopathological associated with NPS intake. This Special Issue aims at providing an overview of a range of NPS-related issues, e.g., preclinical, epidemiological, and clinical pharmacological; the medical and psychopathological consequences associated with their intake; and, finally, the analytical chemistry and forensic analysis challenges associated with the NPS phenomenon.

Prof. Dr. Fabrizio Schifano
Guest Editor

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Keywords

  • drug abuse
  • drug misuse
  • novel psychoactive substances
  • NPS
  • prescribing drugs’ misuse

Published Papers (14 papers)

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Editorial

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Open AccessEditorial
Recent Changes in Drug Abuse Scenarios: The New/Novel Psychoactive Substances (NPS) Phenomenon
Brain Sci. 2018, 8(12), 221; https://doi.org/10.3390/brainsci8120221 - 13 Dec 2018
Cited by 9 | Viewed by 1603
Abstract
Over the last decade, the emergence of a vast range of new/novel/emerging psychoactive substances (NPS) has progressively changed drug market scenarios, which have shifted from the ‘street’ to a ‘virtual’/online environment. [...] Full article

Research

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Open AccessArticle
Synthetic Cannabinoid use in a Case Series of Patients with Psychosis Presenting to Acute Psychiatric Settings: Clinical Presentation and Management Issues
Brain Sci. 2018, 8(7), 133; https://doi.org/10.3390/brainsci8070133 - 14 Jul 2018
Cited by 8 | Viewed by 2296
Abstract
Background: Novel Psychoactive Substances (NPS) are a heterogeneous class of synthetic molecules including synthetic cannabinoid receptor agonists (SCRAs). Psychosis is associated with SCRAs use. There is limited knowledge regarding the structured assessment and psychometric evaluation of clinical presentations, analytical toxicology and clinical management [...] Read more.
Background: Novel Psychoactive Substances (NPS) are a heterogeneous class of synthetic molecules including synthetic cannabinoid receptor agonists (SCRAs). Psychosis is associated with SCRAs use. There is limited knowledge regarding the structured assessment and psychometric evaluation of clinical presentations, analytical toxicology and clinical management plans of patients presenting with psychosis and SCRAs misuse. Methods: We gathered information regarding the clinical presentations, toxicology and care plans of patients with psychosis and SCRAs misuse admitted to inpatients services. Clinical presentations were assessed using the PANSS scale. Vital signs data were collected using the National Early Warning Signs tool. Analytic chemistry data were collected using urine drug screening tests for traditional psychoactive substances and NPS. Results: We described the clinical presentation and management plan of four patients with psychosis and misuse of SCRAs. Conclusion: The formulation of an informed clinical management plan requires a structured assessment, identification of the index NPS, pharmacological interventions, increases in nursing observations, changes to leave status and monitoring of the vital signs. The objective from using these interventions is to maintain stable physical health whilst rapidly improving the altered mental state. Full article
Open AccessFeature PaperArticle
A Study on Photostability of Amphetamines and Ketamine in Hair Irradiated under Artificial Sunlight
Brain Sci. 2018, 8(6), 96; https://doi.org/10.3390/brainsci8060096 - 28 May 2018
Cited by 5 | Viewed by 2760
Abstract
Drugs incorporated into hair are exposed to the environment, and cosmetic and chemical treatments, with possible decreases in their content. Knowledge concerning the effect of sunlight on drug content in hair can be helpful to forensic toxicologists, in particular, when investigating drug concentrations [...] Read more.
Drugs incorporated into hair are exposed to the environment, and cosmetic and chemical treatments, with possible decreases in their content. Knowledge concerning the effect of sunlight on drug content in hair can be helpful to forensic toxicologists, in particular, when investigating drug concentrations above or below pre-determined cut-offs. Twenty authentic positive hair samples were selected which had previously tested positive for amphetamines and/or ketamine. Washed hair were divided into two identical strands, with the former exposed at 765 W/m2 (300–800 nm spectrum of irradiance) for 48 h in a solar simulator, and the latter kept in the dark. Hair samples were extracted and analyzed by liquid chromatography high-resolution mass spectrometry detection. The percentage of photodegradation was calculated for each analyte (i.e., amphetamine, methamphetamine, methylendioxyamphetamine, ketamine, and norketamine). In parallel, photodegradation processes of standard molecules dissolved in aqueous and organic solutions were studied. In 20 hair samples positive for the targeted analytes, exposure to artificial sunlight induced an appreciable decrease in drug concentrations. The concentration ranges in the non-irradiated hair samples were 0.01–24 ng/mg, and 65% of samples exhibited a decrease in post-irradiation samples, with reduction from 3% to 100%. When more drugs were present in the same hair sample (i.e., MDMA and ketamine) the degradation yields were compound dependent. A degradation product induced by irradiation of ketamine in aqueous and methanol solutions was identified; it was also found to be present in a true positive hair sample after irradiation. Ketamine, amphetamines, and their metabolites incorporated in the hair of drug users undergo degradation when irradiated by artificial sunlight. Only for ketamine was a photoproduct identified in irradiated standard solutions and in true positive irradiated hair. When decisional cut-offs are applied to hair analysis, photodegradation must be taken into account since sunlight may produce false negative results. Moreover, new markers could be investigated as evidence of illicit drug use. Full article
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Open AccessArticle
Mechanistic Insights into the Stimulant Properties of Novel Psychoactive Substances (NPS) and Their Discrimination by the Dopamine Transporter—In Silico and In Vitro Exploration of Dissociative Diarylethylamines
Brain Sci. 2018, 8(4), 63; https://doi.org/10.3390/brainsci8040063 - 07 Apr 2018
Cited by 7 | Viewed by 4169
Abstract
Novel psychoactive substances (NPS) may have unsuspected addiction potential through possessing stimulant properties. Stimulants normally act at the dopamine transporter (DAT) and thus increase dopamine (DA) availability in the brain, including nucleus accumbens, within the reward and addiction pathway. This paper aims to [...] Read more.
Novel psychoactive substances (NPS) may have unsuspected addiction potential through possessing stimulant properties. Stimulants normally act at the dopamine transporter (DAT) and thus increase dopamine (DA) availability in the brain, including nucleus accumbens, within the reward and addiction pathway. This paper aims to assess DAT responses to dissociative diarylethylamine NPS by means of in vitro and in silico approaches. We compared diphenidine (DPH) and 2-methoxydiphenidine (methoxphenidine, 2-MXP/MXP) for their binding to rat DAT, using autoradiography assessment of [125I]RTI-121 displacement in rat striatal sections. The drugs’ effects on electrically-evoked DA efflux were measured by means of fast cyclic voltammetry in rat accumbens slices. Computational modeling, molecular dynamics and alchemical free energy simulations were used to analyse the atomistic changes within DAT in response to each of the five dissociatives: DPH, 2-MXP, 3-MXP, 4-MXP and 2-Cl-DPH, and to calculate their relative binding free energy. DPH increased DA efflux as a result of its binding to DAT, whereas MXP had no significant effect on either DAT binding or evoked DA efflux. Our computational findings corroborate the above and explain the conformational responses and atomistic processes within DAT during its interactions with the dissociative NPS. We suggest DPH can have addictive liability, unlike MXP, despite the chemical similarities of these two NPS. Full article
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Open AccessArticle
Exploration of the Use of New Psychoactive Substances by Individuals in Treatment for Substance Misuse in the UK
Brain Sci. 2018, 8(4), 58; https://doi.org/10.3390/brainsci8040058 - 30 Mar 2018
Cited by 10 | Viewed by 4265
Abstract
Substance misuse services need to meet the growing demand and needs of individuals using new psychoactive substances (NPS). A review of the literature identified a paucity of research regarding NPS use by these individuals and UK guidelines outline the need for locally tailored [...] Read more.
Substance misuse services need to meet the growing demand and needs of individuals using new psychoactive substances (NPS). A review of the literature identified a paucity of research regarding NPS use by these individuals and UK guidelines outline the need for locally tailored strategies. The purpose of this qualitative study was to identify and explore key themes in relation to the use of NPS by individuals receiving community treatment for their substance use. Electronic records identified demographics and semi-structured interviews were undertaken. A thematic analysis of transcripts identified a variety of substance use histories; 50% were prescribed opiate substitutes and 25% used NPS as a primary substance. All were males, age range 26–59 years (SD = 9), who predominantly smoked cannabinoids and snorted/injected stimulant NPS. The type of NPS used was determined by affordability, availability, side-effect profile and desired effects (physical and psychological: 25% reported weight loss as motivation for their use). Poly-pharmacy, supplementation and displacement of other drugs were prevalent. In conclusion, NPS use and associated experiences vary widely among people receiving substance use treatment. Development of effective recovery pathways should be tailored to individuals, and include harm reduction strategies, psychosocial interventions, and effective signposting. Services should be vigilant for NPS use, “on top” use and diversion of prescriptions. Full article
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Open AccessCommunication
The Dynamic Environment of Crypto Markets: The Lifespan of New Psychoactive Substances (NPS) and Vendors Selling NPS
Brain Sci. 2018, 8(3), 46; https://doi.org/10.3390/brainsci8030046 - 16 Mar 2018
Cited by 16 | Viewed by 3256
Abstract
The Internet has played a major role in the distribution of New Psychoactive Substances (NPS), and crypto markets are increasingly used for the anonymous sale of drugs, including NPS. This study explores the availability of individual NPS and vendors on the crypto markets [...] Read more.
The Internet has played a major role in the distribution of New Psychoactive Substances (NPS), and crypto markets are increasingly used for the anonymous sale of drugs, including NPS. This study explores the availability of individual NPS and vendors on the crypto markets and considers whether crypto markets are a reliable platform for the sale of NPS. Data was collected from 22 crypto markets that were accessed through the hidden web using the Onion Router (Tor). Data collection took place bimonthly from October 2015 to October 2016 as part of the CASSANDRA (Computer Assisted Solutions for Studying the Availability aNd DistRibution of novel psychoActive substances) project. In seven snapshots over 12 months, 808 unique vendors were found selling 256 unique NPS. The total number of individual NPS and vendors increased across the data collection period (increase of 93.6% and 71.6%, respectively). Only 24% (n = 61) of the total number of NPS and 4% (n = 31) of vendors appeared in every snapshot over the 12 months, whereas 21% (n = 54) of NPS and 45% (n = 365) of vendors only appeared once throughout the data collection. The individual NPS and vendors did not remain the same over the 12 months. However, the availability of NPS and vendors selling NPS grew. NPS consistently available on crypto markets could indicate popular substances. Full article
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Open AccessArticle
Octodrine: New Questions and Challenges in Sport Supplements
Brain Sci. 2018, 8(2), 34; https://doi.org/10.3390/brainsci8020034 - 20 Feb 2018
Cited by 13 | Viewed by 4456
Abstract
Background: Octodrine is the trade name for Dimethylhexylamine (DMHA), a central nervous stimulant that increases the uptake of dopamine and noradrenaline. Originally developed as a nasal decongestant in the 1950’s, it has recently been re-introduced on the market as a pre-workout and [...] Read more.
Background: Octodrine is the trade name for Dimethylhexylamine (DMHA), a central nervous stimulant that increases the uptake of dopamine and noradrenaline. Originally developed as a nasal decongestant in the 1950’s, it has recently been re-introduced on the market as a pre-workout and ‘fat-burner’ product but its use remains unregulated. Our work provides the first observational cross-sectional analytic study on Octodrine as a new drug trend and its associated harms after a gap spanning seven decades. Methods: A comprehensive multilingual assessment of literature, websites, drug fora and other online resources was carried out with no time restriction in English, German, Russian and Arabic. Keywords included Octodrine’s synonyms and chemical isomers. Results: Only five relevant publications emerged from the literature search, with most of the available data on body building websites and fora. Since 2015, Octodrine has been advertised online as “the next big thing” and “the god of stimulants,” with captivating marketing strategies directed at athletes and a wider cohort of users. Reported side-effects include hypertension, dyspnoea and hyperthermia. Conclusions: The uncontrolled use of Octodrine, its physiological and psychoactive effects raise serious health implications with possible impact on athletes and doping practices. This new phenomenon needs to be thoroughly studied and monitored. Full article
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Review

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Open AccessReview
Novel Synthetic Opioids: The Pathologist’s Point of View
Brain Sci. 2018, 8(9), 170; https://doi.org/10.3390/brainsci8090170 - 02 Sep 2018
Cited by 23 | Viewed by 2387
Abstract
Background: New Psychoactive Substances (NPS) constitute a broad range of hundreds of natural and synthetic drugs, including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and other NPS classes, which were not controlled from 1961 to 1971 by the United Nations drug control conventions. Among [...] Read more.
Background: New Psychoactive Substances (NPS) constitute a broad range of hundreds of natural and synthetic drugs, including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and other NPS classes, which were not controlled from 1961 to 1971 by the United Nations drug control conventions. Among these, synthetic opioids represent a major threat to public health. Methods: A literature search was carried out using public databases (such as PubMed, Google Scholar, and Scopus) to survey fentanyl-, fentanyl analogs-, and other synthetic opioid-related deaths. Keywords including “fentanyl”, “fentanyl analogs”, “death”, “overdose”, “intoxication”, “synthetic opioids”, “Novel Psychoactive Substances”, “MT-45”, “AH-7921”, and “U-47700” were used for the inquiry. Results: From our literature examination, we inferred the frequent implication of fentanyls and synthetic opioids in side effects, which primarily affected the central nervous system and the cardiovascular and pulmonary systems. The data showed a great variety of substances and lethal concentrations. Multidrug-related deaths appeared very common, in most reported cases. Conclusions: The investigation of the contribution of novel synthetic opioid intoxication to death should be based on a multidisciplinary approach aimed at framing each case and directing the investigation towards targeted toxicological analyses. Full article
Open AccessEditor’s ChoiceReview
Sales and Advertising Channels of New Psychoactive Substances (NPS): Internet, Social Networks, and Smartphone Apps
Brain Sci. 2018, 8(7), 123; https://doi.org/10.3390/brainsci8070123 - 29 Jun 2018
Cited by 24 | Viewed by 3854
Abstract
In the last decade, the trend of drug consumption has completely changed, and several new psychoactive substances (NPS) have appeared on the drug market as legal alternatives to common drugs of abuse. Designed to reproduce the effects of illegal substances like cannabis, ecstasy, [...] Read more.
In the last decade, the trend of drug consumption has completely changed, and several new psychoactive substances (NPS) have appeared on the drug market as legal alternatives to common drugs of abuse. Designed to reproduce the effects of illegal substances like cannabis, ecstasy, cocaine, or ketamine, NPS are only in part controlled by UN conventions and represent an emerging threat to global public health. The effects of NPS greatly differ from drug to drug and relatively scarce information is available at present about their pharmacology and potential toxic effects. Yet, compared to more traditional drugs, more dangerous short- and long-term effects have been associated with their use, and hospitalizations and fatal intoxications have also been reported after NPS use. In the era of cyberculture, the Internet acts as an ideal platform to promote and market these compounds, leading to a global phenomenon. Hidden by several aliases, these substances are sold across the web, and information about consumption is shared by online communities through drug fora, YouTube channels, social networks, and smartphone applications (apps). This review intends to provide an overview and analysis of social media that contribute to the popularity of NPS especially among young people. The possibility of using the same channels responsible for their growing diffusion to make users aware of the risks associated with NPS use is proposed. Full article
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Open AccessEditor’s ChoiceReview
Abuse of Prescription Drugs in the Context of Novel Psychoactive Substances (NPS): A Systematic Review
Brain Sci. 2018, 8(4), 73; https://doi.org/10.3390/brainsci8040073 - 22 Apr 2018
Cited by 28 | Viewed by 5284
Abstract
Recently, a range of prescription and over-the-counter drugs have been reportedly used as Novel Psychoactive Substances (NPS), due to their potential for abuse resulting from their high dosage/idiosyncratic methods of self-administration. This paper provides a systematic review of the topic, focusing on a [...] Read more.
Recently, a range of prescription and over-the-counter drugs have been reportedly used as Novel Psychoactive Substances (NPS), due to their potential for abuse resulting from their high dosage/idiosyncratic methods of self-administration. This paper provides a systematic review of the topic, focusing on a range of medications which have emerged as being used recreationally, either on their own or in combination with NPS. Among gabapentinoids, pregabalin may present with higher addictive liability levels than gabapentin, with pregabalin being mostly identified in the context of opioid, polydrug intake. For antidepressants, their dopaminergic, stimulant-like, bupropion activities may explain their recreational value and diversion from the therapeutic intended use. In some vulnerable clients, a high dosage of venlafaxine (‘baby ecstasy’) is ingested for recreational purposes, whilst the occurrence of a clinically-relevant withdrawal syndrome may be a significant issue for all venlafaxine-treated patients. Considering second generation antipsychotics, olanzapine appears to be ingested at very large dosages as an ‘ideal trip terminator’, whilst the immediate-release quetiapine formulation may possess proper abuse liability levels. Within the image- and performance- enhancing drugs (IPEDs) group, the beta-2 agonist clenbuterol (‘size zero pill’) is reported to be self-administered for aggressive slimming purposes. Finally, high/very high dosage ingestion of the antidiarrhoeal loperamide has shown recent increasing levels of popularity due to its central recreational, anti-withdrawal, opiatergic effects. The emerging abuse of prescription drugs within the context of a rapidly modifying drug scenario represents a challenge for psychiatry, public health and drug-control policies. Full article
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Open AccessReview
Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives
Brain Sci. 2018, 8(3), 47; https://doi.org/10.3390/brainsci8030047 - 16 Mar 2018
Cited by 22 | Viewed by 7169
Abstract
Hallucinogen Persisting Perception Disorder (HPPD) is a rare, and therefore, poorly understood condition linked to hallucinogenic drugs consumption. The prevalence of this disorder is low; the condition is more often diagnosed in individuals with a history of previous psychological issues or substance misuse, [...] Read more.
Hallucinogen Persisting Perception Disorder (HPPD) is a rare, and therefore, poorly understood condition linked to hallucinogenic drugs consumption. The prevalence of this disorder is low; the condition is more often diagnosed in individuals with a history of previous psychological issues or substance misuse, but it can arise in anyone, even after a single exposure to triggering drugs. The aims of the present study are to review all the original studies about HPPD in order to evaluate the following: (1) the possible suggested etiologies; (2) the possible hallucinogens involved in HPPD induction; (3) the clinical features of both HPPD I and II; (4) the possible psychiatric comorbidities; and (5) the available and potential therapeutic strategies. We searched PubMed to identify original studies about psychedelics and Hallucinogen Persisting Perception Disorder (HPPD). Our research yielded a total of 45 papers, which have been analyzed and tabled to provide readers with the most updated and comprehensive literature review about the clinical features and treatment options for HPPD. Full article
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Open AccessReview
Mood Fluctuation and Psychobiological Instability: The Same Core Functions Are Disrupted by Novel Psychoactive Substances and Established Recreational Drugs
Brain Sci. 2018, 8(3), 43; https://doi.org/10.3390/brainsci8030043 - 13 Mar 2018
Cited by 6 | Viewed by 2912
Abstract
Many novel psychoactive substances (NPS) have entered the recreational drug scene in recent years, yet the problems they cause are similar to those found with established drugs. This article will debate the psychobiological effects of these newer and more traditional substances. It will [...] Read more.
Many novel psychoactive substances (NPS) have entered the recreational drug scene in recent years, yet the problems they cause are similar to those found with established drugs. This article will debate the psychobiological effects of these newer and more traditional substances. It will show how they disrupt the same core psychobiological functions, so damaging well-being in similar ways. Every psychoactive drug causes mood states to fluctuate. Users feel better on-drug, then feel worse off-drug. The strength of these mood fluctuations is closely related to their addiction potential. Cyclical changes can occur with many other core psychobiological functions, such as information processing and psychomotor speed. Hence the list of drug-related impairments can include: homeostatic imbalance, HPA axis disruption, increased stress, altered sleep patterns, neurohormonal changes, modified brain rhythms, neurocognitive impairments, and greater psychiatric vulnerability. Similar patterns of deficit are found with older drugs such as cocaine, nicotine and cannabis, and newer substances such as 3,4-methylenedioxymethamphetamine (MDMA), mephedrone and spice. All psychoactive drugs damage human well-being through similar basic neuropsychobiological mechanisms. Full article
Open AccessEditor’s ChoiceReview
The Effects of Cannabinoids on Executive Functions: Evidence from Cannabis and Synthetic Cannabinoids—A Systematic Review
Brain Sci. 2018, 8(3), 40; https://doi.org/10.3390/brainsci8030040 - 27 Feb 2018
Cited by 35 | Viewed by 5907
Abstract
Background—Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short and long-term range of adverse effects. Recently, new types of designer-drugs containing synthetic cannabinoids have been widespread. These synthetic cannabinoid drugs are associated with [...] Read more.
Background—Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short and long-term range of adverse effects. Recently, new types of designer-drugs containing synthetic cannabinoids have been widespread. These synthetic cannabinoid drugs are associated with undesired adverse effects similar to those seen with cannabis use, yet, in more severe and long-lasting forms. Method—A literature search was conducted using electronic bibliographic databases up to 31 December 2017. Specific search strategies were employed using multiple keywords (e.g., “synthetic cannabinoids AND cognition,” “cannabis AND cognition” and “cannabinoids AND cognition”). Results—The search has yielded 160 eligible studies including 37 preclinical studies (5 attention, 25 short-term memory, 7 cognitive flexibility) and 44 human studies (16 attention, 15 working memory, 13 cognitive flexibility). Both pre-clinical and clinical studies demonstrated an association between synthetic cannabinoids and executive-function impairment either after acute or repeated consumptions. These deficits differ in severity depending on several factors including the type of drug, dose of use, quantity, age of onset and duration of use. Conclusions—Understanding the nature of the impaired executive function following consumption of synthetic cannabinoids is crucial in view of the increasing use of these drugs. Full article

Other

Open AccessCase Report
Transitioning Bodies. The Case of Self-Prescribing Sexual Hormones in Gender Affirmation in Individuals Attending Psychiatric Services
Brain Sci. 2018, 8(5), 88; https://doi.org/10.3390/brainsci8050088 - 14 May 2018
Cited by 7 | Viewed by 2634
Abstract
Self-prescribing of sexual hormones for gender affirmation is a potentially widespread and poorly studied phenomenon that many clinicians are unaware of. The uncontrolled use of hormones poses significant health hazards, which have not been previously reported in the literature. We have collected seven [...] Read more.
Self-prescribing of sexual hormones for gender affirmation is a potentially widespread and poorly studied phenomenon that many clinicians are unaware of. The uncontrolled use of hormones poses significant health hazards, which have not been previously reported in the literature. We have collected seven clinical cases in general adult psychiatry settings (both inpatient and outpatients), describing transgender and gender non-conforming individuals’ (TGNC) self-prescribing and self-administering hormones bought from the Internet without any medical consultation. Among these cases, two were taking androgens, and the rest were taking oestrogens. The main reason for self-administration of hormones seems to be the lack of access to specialised care due to discrimination and long waiting lists. We advocate for clinicians to be aware of the phenomenon and proactively help TGNC individuals by enquiring about self-prescribing of hormones, providing information and referring to the most appropriate treatment centre as well as encourage a public debate on the discrimination and the stigma that TGNC population suffer from. Overall, there is an urgent need for the implementation of different and innovative health care services for TGNC individuals as well as more targeted prevention strategies on such underreported and highly risky behaviours. Furthermore, it is necessary for every clinician involved in the care for TGNC people to be aware of their special needs and be able to be an allied and an advocate to help in reducing stigma and discrimination that affect the access to care for this often underserved population. Full article
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