ArticleFrontiers in pharmacology2025
Disposition and effects of alpha-pyrrolidinoisohexanophenone (α-PHiP) in comparison with cocaine: an observational study.
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Alpha-pyrrolidinoisohexanophenone (α-PHiP) is a synthetic cathinone structurally related to alpha-pyrrolidinopentiophenone (α-PVP) and other pyrrolidinophenones, acting as a potent monoamine transporter inhibitor. Despite its raising prevalence on the recreational drug market, limited data exist about its human pharmacology. This study aimed to assess its concentrations in different matrices and characterize its acute effects in humans in comparison with cocaine when administered by intranasal route. Methods: A non-controlled observational study was conducted under naturalistic conditions in seventeen healthy adults (nine men, eight women) with prior experience using psychostimulants. Participants self-administered intranasal doses of 15-25 mg α-PHiP or 75-90 mg cocaine in two separate sessions. Physiological parameters and subjective effects (VAS, ARCI, and VESSPA-SSE questionnaires) were assessed repeatedly at baseline and up to 5 h post-administration. Biological samples (oral fluid, urine, sweat), were collected to evaluate concentration-time profiles, including a time point of dried blood spot. Results: α-PHiP was rapidly absorbed, reaching maximum concentrations in oral fluid at 20 min and showed a short half-life (1.1 h). The amount excreted unchanged in urine or present in sweat was less than 1%. Dried blood spot levels showed high interindividual variability in the range of intoxication cases. Both α-PHiP and cocaine increased heart rate while the increase in blood pressure was more sustained for α-PHiP. Subjective effects of α-PHiP peaked within the first hour and were very similar to those of cocaine, being the feelings of high and intensity reported lower. Conclusion: This study provides novel insights into the effects and distribution of α-PHiP across various biological matrices. α-PHiP elicited prototypical subjective effects characteristic of psychostimulants, confirming its potential for abuse. Compared to cocaine, α-PHiP produced similar subjective effects. Future research should further investigate the detection of its metabolites to improve monitoring and understanding of its pharmacokinetics.
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