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

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.