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According to the United Nations Office on Drugs and Crimes, N-ethylhexedrone (NEH) and N-ethyl-nor-pentedrone (NEP) were identified among the most frequently seized SCs worldwide. However, still, little is known with regard to their pharmacological effects in humans. Methods: For the first time, we conducted a naturalistic, prospective observational study in 16 participants (7 women and 9 men) with a previous history of psychostimulant recreational use. They intranasally self-administered a single dose of NEP (n = 8, 20\u201340 mg) or NEH (n = 8, 20\u201340 mg). The physiological effects (systolic and diastolic blood pressure, heart rate, and temperature) and subjective effects (visual analogue scales, Addiction Research Center Inventory questionnaire and Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire) were assessed up to 4 h after the self-administration at different time points (0, 20 and 40 min and 1, 1.5, 2, 3 and 4 h). Results: Despite several differences, both NEP and NEH produced significant effects within 20 min, with a return to baseline 3\u20134 h after self-administration. In general, NEP showed a faster onset and a more rapid disappearance of subjective effects than NEH. Moreover, intranasal self-administration of NEH and NEP in experienced recreational drug users, within a non-controlled setting, induces a constellation of psychostimulant-like effects. Conclusion: NEH and NEP showed similar pharmacological properties after insufflation, with typical effects of SCs<\/jats:p>","DOI":"10.3390\/ph18050721","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T10:06:52Z","timestamp":1747217212000},"page":"721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Acute Pharmacological Effects of Two Synthetic Cathinones in Humans: An Observational Study of N-Ethylhexedrone and N-Ethyl-nor-pentedrone"],"prefix":"10.3390","volume":"18","author":[{"given":"Melani","family":"N\u00fa\u00f1ez-Montero","sequence":"first","affiliation":[{"name":"National Center on Addiction and Doping, National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy"},{"name":"Clinical Pharmacology Department, Hospital Universitari Germans Trias I Pujol (HUGTP-IGTP), Carretera de Canyet s\/n, 08916 Badalona, Spain"},{"name":"Department of Pharmacology, Therapeutics and Toxicology, Universitat Aut\u00f3noma de Barcelona, Cerdanyola del Vall\u00e9s, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6343-6918","authenticated-orcid":false,"given":"Clara","family":"P\u00e9rez-Ma\u00f1\u00e1","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitari Germans Trias I Pujol (HUGTP-IGTP), Carretera de Canyet s\/n, 08916 Badalona, Spain"},{"name":"Department of Pharmacology, Therapeutics and Toxicology, Universitat Aut\u00f3noma de Barcelona, Cerdanyola del Vall\u00e9s, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6230-5876","authenticated-orcid":false,"given":"Olga","family":"Hladun","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitari Germans Trias I Pujol (HUGTP-IGTP), Carretera de Canyet s\/n, 08916 Badalona, Spain"},{"name":"Department of Pharmacology, Therapeutics and Toxicology, Universitat Aut\u00f3noma de Barcelona, Cerdanyola del Vall\u00e9s, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4641-8600","authenticated-orcid":false,"given":"Lourdes","family":"Poyatos","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitari Germans Trias I Pujol (HUGTP-IGTP), Carretera de Canyet s\/n, 08916 Badalona, Spain"},{"name":"Department of Pharmacology, Therapeutics and Toxicology, Universitat Aut\u00f3noma de Barcelona, Cerdanyola del Vall\u00e9s, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6523-0265","authenticated-orcid":false,"given":"Dolly Andrea","family":"Caicedo","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitari Germans Trias I Pujol (HUGTP-IGTP), Carretera de Canyet s\/n, 08916 Badalona, Spain"},{"name":"Department of Pharmacology, Therapeutics and Toxicology, Universitat Aut\u00f3noma de Barcelona, Cerdanyola del Vall\u00e9s, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina","family":"De la Rosa","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitari Germans Trias I Pujol (HUGTP-IGTP), Carretera de Canyet s\/n, 08916 Badalona, Spain"},{"name":"Department of Pharmacology, Therapeutics and Toxicology, Universitat Aut\u00f3noma de Barcelona, Cerdanyola del Vall\u00e9s, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2139-6913","authenticated-orcid":false,"given":"Martha Catalina","family":"Argote","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitari Germans Trias I Pujol (HUGTP-IGTP), Carretera de Canyet s\/n, 08916 Badalona, Spain"},{"name":"Department of Pharmacology, Therapeutics and Toxicology, Universitat Aut\u00f3noma de Barcelona, Cerdanyola del Vall\u00e9s, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraya","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitari Germans Trias I Pujol (HUGTP-IGTP), Carretera de Canyet s\/n, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Ventura","sequence":"additional","affiliation":[{"name":"Energy Control, Associaci\u00f3 Benestar i Desenvolupament, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0127-4225","authenticated-orcid":false,"given":"Nunzia La","family":"Maida","sequence":"additional","affiliation":[{"name":"National Center on Addiction and Doping, National Institute of Health, Viale 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