{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T14:57:56Z","timestamp":1768402676453,"version":"3.49.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Alpha-pyrrolidinoisohexanophenone (\u03b1-PHiP) is a synthetic cathinone structurally related to alpha-pyrrolidinopentiophenone (\u03b1-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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u201325\u00a0mg \u03b1-PHiP or 75\u201390\u00a0mg 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\u00a0h post-administration. Biological samples (oral fluid, urine, sweat), were collected to evaluate concentration-time profiles, including a time point of dried blood spot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\u03b1-PHiP was rapidly absorbed, reaching maximum concentrations in oral fluid at 20\u00a0min and showed a short half-life (1.1\u00a0h). 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 \u03b1-PHiP and cocaine increased heart rate while the increase in blood pressure was more sustained for \u03b1-PHiP. Subjective effects of \u03b1-PHiP peaked within the first hour and were very similar to those of cocaine, being the feelings of high and intensity reported lower.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides novel insights into the effects and distribution of \u03b1-PHiP across various biological matrices. \u03b1-PHiP elicited prototypical subjective effects characteristic of psychostimulants, confirming its potential for abuse. Compared to cocaine, \u03b1-PHiP produced similar subjective effects. Future research should further investigate the detection of its metabolites to improve monitoring and understanding of its pharmacokinetics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1728824","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T09:10:30Z","timestamp":1768381830000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Disposition and effects of alpha-pyrrolidinoisohexanophenone (\u03b1-PHiP) in comparison with cocaine: an observational study"],"prefix":"10.3389","volume":"16","author":[{"given":"Georgina","family":"De la Rosa","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitari Germans Trias i Pujol and Institut de Recerca Germans Trias i Pujol (HUGTP-IGTP)","place":["Badalona, Spain"]},{"name":"Department of Pharmacology, Therapeutics and Toxicology, Universitat Aut\u00f2noma de Barcelona","place":["Barcelona, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Iacobone","sequence":"additional","affiliation":[{"name":"National Center on Addiction and Doping, National Institute of Health","place":["Rome, Italy"]},{"name":"Department of Chemistry, Faculty of Mathematical, Physical and Natural Science, \u2018Sapienza\u2019 University of Rome","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Papaseit","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitari Germans Trias i Pujol and Institut de Recerca Germans Trias i Pujol (HUGTP-IGTP)","place":["Badalona, Spain"]},{"name":"Department of Medicine and Life Sciences, Universitat Pompeu Fabra","place":["Barcelona, Spain"]},{"name":"Drug Addiction Unit. 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