Abstract

BackgroundNew psychoactive substances (NPS) are chemical analogues designed to mimic the effects of various classic recreational drugs of abuse including MDMA, LSD, and cannabis. NPS use is associated with concern about the acute and longer-term effects particular substances might have, with abuse and addiction as potential consequences. Impulsivity and sensitivity to the rewarding effects of drugs have been considered as risk factors for drug abuse. In light of the popularity of 4-fluoroamphetamine (4-FA), it is important to assess whether 4-FA can lead to subjective drug liking and wanting, and impulsive behavior, all factors contributing to the abuse likelihood of a substance.MethodsA placebo-controlled 2-way crossover study in 12 healthy poly-drug using participants was conducted to test subjective and behavioral effects of 4-FA (100 mg). 4-FA concentrations were determined in serum up to 12 h after administration and two impulsivity tasks and two drug experience questionnaires assessing drug liking and wanting, and good and bad drug effect, were administered between 1 and 11 h post-administration.ResultsFindings showed that 4-FA did not affect impulsive behavior. Self-ratings of drug liking and wanting and good drug effect were increased 1 h after administration; this effect was absent 11 h after drug intake.Discussion and conclusionTo conclude, 4-FA (single dose) increased self-rated liking and wanting, which is known to contribute to the abuse likelihood of a substance; however, it left another factor impulsive behavior unaffected. It has to be noted that the current picture is limited and might change with increased sample size, and/or different 4-FA doses.Clinical trial registrationTrial acronym: 4-FA. URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6164. Registration number: NTR6164 (Dutch clinical trial registry number).

Highlights

  • New psychoactive substances (NPS) are chemical analogues designed to mimic the effects of various classic recreational drugs of abuse including MDMA, LSD, and cannabis (EMCDDA 2015)

  • The quadratic interaction (F1,10 = 12.57; p = 0.005; ƞp2 = 0.56) between treatment and time demonstrated that while the ratings in the placebo condition were low and decreased slightly over time, the ratings in the 4-FA condition were very pronounced at T1 and steeply decreased from T1 to T3 while remaining at the same low level at T5 compared to T3 (Fig. 1c)

  • Post-hoc analyses showed that this was a quadratic effect (F1,10 = 2.19; p = 0.02; ƞp2 = 0.43) with the highest rating showing at T3 for 4-FA compared to the other time-points and placebo; this effect was probably driven by the statistically significant increased levels of fatigue and confusion, two of the sub-scales included in this composite scale bad drug effect which were the highest at this time-point

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Summary

Introduction

New psychoactive substances (NPS) are chemical analogues designed to mimic the effects of various classic recreational drugs of abuse including MDMA, LSD, and cannabis (EMCDDA 2015). 4-Fluoroamphetamine (4-FA) is a prototypical example of an NPS, belonging to the chemical class of phenethylamines (Hondebrink et al 2017) It appeared on the Dutch Bdrug market^ between 2007 and 2009 where after reports of acute toxic effects steadily increased to even 16% of all reported cases on large scale events (Wijers et al 2017). It was first used as an adulterant in drugs such as amphetamine and MDMA, it became a drug of choice, liked by users for its effects (Linsen et al 2015).

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