Independent elevation of peripheral oxytocin concentrations and reduction in cognitive empathy during 4‐fluoroamphetamine intoxication

Abstract

Objectives 4‐Fluoroamphetamine (4‐FA) is a novel psychoactive substance with a pharmacological profile and reported subjective effects (e.g., empathy) intermediate between 3,4‐methylenedioxymethamphetamine (MDMA) and amphetamine. Studies have shown that MDMA and amphetamine increase emotional empathy without affecting cognitive empathy; MDMA simultaneously leads to elevated levels of oxytocin, unrelated to its behavioral effects. The aim of the present study was to assess the reported enhancement of empathy by 4‐FA, to assess its effects on oxytocin, and to test potential associations between both. Methods Twelve healthy poly‐drug users were included in a double‐blind placebo‐controlled two‐way crossover study. Treatments were 4‐FA (100 mg) and placebo; empathy was assessed by means of the multifaceted empathy test, and blood samples were taken before and after treatment administration to determine oxytocin concentrations. Results 4‐FA reduced cognitive empathy, whereas emotional empathy was left unaffected. One hour after treatment, plasma oxytocin levels were significantly increased compared with placebo. Behavioral and hormonal effects were unrelated. Conclusion Although 4‐FA shares its pharmacological mechanism with MDMA and amphetamine, current findings seem to indicate that it affects empathy differently. The 4‐FA‐induced increase in oxytocin levels was independent of behavioral effects, which confirms previous findings that drug‐induced effects on peripheral oxytocin levels are not associated with empathy.

Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy

“…The conclusion reached by these authors was that the effects of 4-FA lie between those of dextroamphetamine and MDMA, which would indicate that the term psychedelic may be somewhat inaccurate in describing the qualitative effects of 4-FA. On average, 4-FA reduced cognitive empathy and did not affect emotional empathy in the 12 volunteers (Dolder et al, 2018b), which stands in contrast to MDMA, which was shown to leave cognitive empathy unaffected and to increase emotional empathy in a study using 118 volunteers (Kuypers et al, 2017). Overall, the subjective effects of 4-FA seem to be tolerated well by most users, as it was found that drug liking and drug wanting had significantly increased during the acute phase of the trial (1-3 h), but that this effect and drug wanting were absent at the 11-h mark (Kuypers et al, 2018b), indicating that 4-FA also does not exhibit significant abuse potential compared with non-halogenated amphetamines.…”

Pharmacokinetic properties of 4‐fluoroamphetamine in serum and oral fluid after oral ingestion

“…As expected for an oral ingestion, it took at least 1 hour (typically 2 hours, range 1−3 hours) to reach maximum concentrations. This was known from oral amphetamine dosing and respected in the design of the time scheme of the psychomotoric tests . It appeared that maximal concentrations were reached sooner in the higher dosing condition (Figure ) but this might be a consequence of the lower subject number.…”

“…This was known from oral amphetamine dosing 14,15 and respected in the design of the time scheme of the psychomotoric tests. 2,16,17 It appeared that maximal concentrations were reached sooner in the higher dosing condition (Figure 1) but this might be a consequence of the lower subject number.…”

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

“…Stimulants also present complex interactions with neuroendocrine molecules, e.g., they increase oxytocin levels, although the latter, as demonstrated for 4-Fluoroamphetamine, might be unrelated to cognitive and emotional behavior and empathy [ 132 ]. Amphetamine-type psychostimulant include derivatives of aminorex, such as 4-methylaminorex (4-MAR) and 4,4′-dimethylaminorex (4,4′-DMAR) [ 133 , 134 ]. Although both are derivatives of aminorex, the former appears as a more typical stimulant, with a high DAT/SERT ratio, while the latter is thought to lead mainly to empathogenic effects [ 125 ].…”