Pharmacotherapy of Patients Taking New Psychoactive Substances: A Systematic Review and Analysis of Case Reports

Background: In recent years, an increase in the frequency of hospitalizations of patients taking newer and newer psychoactive substances has been observed around the world. Each year, authors publish case reports of patients who consumed previously unknown NPS. Most publications of this type concern the period between 2014 and 2016. However, no publication systematically reviews the pharmacotherapy used in these cases. This study aims to review the case reports of patients taking NPS published between 2010 and 2019, as well as analyzing the pharmacotherapy used.Methods: We searched the Thomson (Web of Knowledge), PubMed/Medline, Science Direct, Scopus and Google Scholar databases. The search was performed using all possible combinations of the term “case report” describing the use of NPS, also referred to as designer medications, internet medications, research chemicals and herbal highs.Results: We analyzed 51 case reports on the intake of various types of NPS. Most of them (p < 0.001) concerned the use of synthetic cannabinoids (41.2%) and cathinones (31.4%). The pharmacotherapy applied primarily (p < 0.001) consisted of administering benzodiazepines to patients (62.7%), most of whom took only this group of medications (25.5%), followed by groups receiving benzodiazepines combined with neuroleptics (15.7%) and muscle relaxants (11.8%). Opioids were administered primarily to patients taking synthetic opioids (p < 0.001). Of the 5 cases of deaths from NPS reported in the literature, three relate specifically to the synthetic opioid MT-45. The later the time period, the more medications patients were administered (p = 0.02).Conclusion: In the pharmacotherapy for NPS poisoning, one should focus primarily on combating psychomotor agitation.

‘New/Designer Benzodiazepines’: An Analysis of the Literature and Psychonauts’ Trip Reports

Background: NPS belonging to the benzodiazepine (BZD) class, e.g., ‘legal/designer BZDs’/‘research chemicals’, have recently emerged in the drug (mainly online/virtual) market. Objective: While certain NPS belonging to the BZD class possess pharmacological profiles similar to controlled pharmaceutical BZDs, clinical and pharmacological profiles of current emerging BZDs are still not well-described. Therefore, there is a need to increase clinicians’/public health knowledge/awareness, to incentive harm reduction strategies. Methods: A comprehensive overview was carried out by using the EMCDDA/EDND database regularly monitored by our research team, by specifically looking at the ‘new BZDs’ so far notified. Furthermore, given the limitation of peer-reviewed data published so far, a nonparticipant multilingual qualitative netnographic study was conducted to obtain further clinical/pharmacological/ toxicological data, including psychonauts’ online trip reports. Results: First designer BZDs appeared as NPS around 2007. So far, 29 designer BZDs have been notified to the EMCDDA, being some of them extremely powerful, also at lower dosages. They are sold as tablets/powder/pellets/capsules/blotters/liquids, at very affordable prices, and variably administered. Some are also sold on the illicit drugmarket as counterfeit forms of traditional BZDs or as either adulterants or diluents in heroin or other synthetic opioids/cannabinoids. Nowadays, there is no guarantee of the quality of designer BZDs composition/purification and, hence, most NPS consumers may be inadvertently exposed to unsafe and harmful compounds. Conclusions: Given the limited information on their pharmacology/toxicity, variations in dosage, onset of effects, combination of substances, potency, and general patient or individual variability, the concomitant use of these substances with other drugs entails several and unpredictable risks.

Adverse Effects of Amphetamines on the Cardiovascular System: Review and Retrospective Analyses of Trends

BACKGROUND: Amphetamine and amphetamine-type stimulants are powerful physical and psychostimulants; they are phenethylamine derivatives. The use of amphetamines can be either medicinal or illicit. Several amphetamines have been redesigned into illegal drugs of potent properties, also known as research chemicals and designer drugs. Hence, they are named novel (new) psychoactive substances (NPS).MATERIALS & METHODS: This study is a hybrid study of; data crunching and retrospective analysis of a trends database (1), and a systematic review of literature in relation to the amphetamines-induced adverse effects on the cardiovascular system (2). Google Trends database has been analysed in retrospect (2012-2017) to evaluate the attentiveness of surface web users towards amphetamine and a potent renowned amphetamine derivative known as captagon (fenethylline).RESULTS: Amphetamines appear to be highly popular worldwide, particularly in the developed world including North America and European countries, and to a less extent in the developing countries including the Middle East. However, the trends are oscillating with time with significant year-to-year changes although there was some steadiness in the temporal patterns (trends), for example in 2013-2014 (p-value=0.258). Variations in the trends were found to be correlated with global events including international terrorism. The adverse effects of amphetamines were found to be highly related to the cardiovascular system with a high incidence of intoxications and deaths among substance (ab)users.CONCLUSION: Several amphetamines are potent and used illicitly beyond their original therapeutic potential, as in the case of captagon, culminating in monumental public and economic threats. Legalising bodies should exercise tremendous and systematic efforts to counteract these threats. Database analyses can provide an accurate insight into this phenomenon that has been growing exponentially in the past decade.

Development of legal highs

New psychoactive substances (NPS) or ‘legal highs’ are defined as unregulated psychoactive substances including synthetic and/or plant derived substances (marketed as research chemicals, party pills and herbal highs) that are intended to mimic the effects of controlled drugs. Psychiatric services around the country are seeing a rise in the use of NPS complicating mental health presentations. The challenge surrounding these substances is the fact that they are not under the international drug control system and are proving to have a detrimental health effect on users. This article reviews the current literature on this subject and discusses some of the most common examples of NPS and their potential effects on mental health.