Abstract
The use of new psychoactive substances (NPS) is increasing and currently >600 NPS have been reported. However, limited information on neuropharmacological and toxicological effects of NPS is available, hampering risk characterization. We reviewed the literature on the in vitro neuronal modes of action to obtain effect fingerprints of different classes of illicit drugs and NPS. The most frequently reported NPS were selected for review: cathinones (MDPV, α-PVP, mephedrone, 4-MEC, pentedrone, methylone), cannabinoids (JWH-018), (hallucinogenic) phenethylamines (4-fluoroamphetamine, benzofurans (5-APB, 6-APB), 2C-B, NBOMes (25B-NBOMe, 25C-NBOMe, 25I-NBOMe)), arylcyclohexylamines (methoxetamine) and piperazine derivatives (mCPP, TFMPP, BZP). Our effect fingerprints highlight the main modes of action for the different NPS studied, including inhibition and/or reversal of monoamine reuptake transporters (cathinones and non-hallucinogenic phenethylamines), activation of 5-HT2receptors (hallucinogenic phenethylamines and piperazines), activation of cannabinoid receptors (cannabinoids) and inhibition of NDMA receptors (arylcyclohexylamines). Importantly, we identified additional targets by relating reported effect concentrations to the estimated human brain concentrations during recreational use. These additional targets include dopamine receptors, α- and β-adrenergic receptors, GABAAreceptors and acetylcholine receptors, which may all contribute to the observed clinical symptoms following exposure. Additional data is needed as the number of NPS continues to increase. Also, the effect fingerprints we have obtained are still incomplete and suffer from a large variation in the reported effects and effect sizes. Dedicated in vitro screening batteries will aid in complementing specific effect fingerprints of NPS. These fingerprints can be implemented in the risk assessments of NPS that are necessary for eventual control measures to reduce Public Health risks.
Highlights
The use of illicit drugs is high; around 5% of the adult population worldwide used an illicit drug in the last year (World Drug Report, 2016)
For other common illicit drugs (THC, amphetamine and MDMA) that were considered relevant for comparison with new psychoactive substances (NPS), data was gathered using selected articles and reviews, in addition to relevant articles derived from the search strategy, rather than using a full search strategy
Ephedrone was prohibited in the 1990s, but numerous new synthetic derivatives of cathinone have emerged on the recreational drug scene in the last decade
Summary
The use of illicit drugs is high; around 5% of the adult population worldwide used an illicit drug in the last year (World Drug Report, 2016). The most commonly used definition of NPS is 'a new narcotic or psychotropic drug, in pure form or in preparation, that is not controlled by the United Nations drug conventions, but which may pose a public health threat comparable to that posed by substances listed in these conventions' (EMCDDA, 2016a) These conventions date back to 1961 and 1971 and the term ‘new’ does not necessarily refer to newly developed drugs, since several NPS were first synthesized as pharmaceutical candidates already 40 years ago. Phenethylamines are a class of substances that were on the drug market long before active monitoring was put into place This class includes older drugs like amphetamine and MDMA, all of which are controlled under the 1971 Convention (EMCDDA, 2012). Compared to other classes of NPS, the number of new piperazines reported annually
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