{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:06:02Z","timestamp":1780635962532,"version":"3.54.1"},"reference-count":29,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Methamphetamine presents a significant scientific and legal challenge for sentencing because, although it is a Class A drug in England and Wales, it is not assigned explicit indicative quantity thresholds within the principal Sentencing Council guideline. This review provides a comparative expert synthesis of methamphetamine in relation to amphetamine, cocaine and heroin, with particular emphasis on pharmacodynamics, pharmacokinetics, route-specific harms, fatal toxicity indicators and broader patterns of individual-harm profiles. The analysis draws on human laboratory studies, neuroimaging, pharmacokinetic investigations, toxicological literature, drug-related mortality data and policy sources to assess where methamphetamine most appropriately sits within a harm-based sentencing framework. The evidence indicates that methamphetamine is pharmacologically closest to amphetamine, sharing core monoaminergic mechanisms of transporter-mediated neurotransmitter release and vesicular disruption, but differing across several pharmacokinetic and toxicity-related parameters. Compared with amphetamine, methamphetamine shows greater lipid solubility, more efficient central nervous system penetration, longer persistence, and exposure that may, under common high-intensity routes of use, be associated with higher risk of neuropsychiatric, cardiovascular and cerebrovascular harms. Smoked methamphetamine in particular achieves high systemic bioavailability and rapid onset, creating a pattern of exposure more severe than conventional amphetamine preparations and, in some practical respects, closer to high-intensity stimulant models such as crack cocaine. Contemporary evidence further indicates that methamphetamine is associated with higher fatal toxicity than amphetamine, although the magnitude of difference varies by endpoint and no single universal gram-for-gram conversion is supported or recommended. Overall, the literature does not justify treating methamphetamine as simply equivalent to amphetamine, nor does it support conflating it fully with heroin or crack cocaine. The most defensible interpretation is that amphetamine should remain the primary scientific comparator, but with upward adjustment to reflect methamphetamine\u2019s greater persistence and toxicity-related burden, while cocaine may serve as a secondary comparator for proportionality within the Class A sentencing framework. Taken together, the evidence supports consideration of an upward-adjusted amphetamine-based interpretation rather than an unadjusted amphetamine analogue.<\/jats:p>","DOI":"10.3390\/brainsci16060602","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:17:31Z","timestamp":1780467451000},"page":"602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Psychopharmacology of Methamphetamine in Relation to the United Kingdom Sentencing Guidance: Comparative Analysis with Amphetamine, Cocaine and Heroin"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8255-0660","authenticated-orcid":false,"given":"Amira","family":"Guirguis","sequence":"first","affiliation":[{"name":"Pharmacy, Faculty of Medicine, Health and Life Science, Swansea University, Singleton Campus, The Grove, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0441-9787","authenticated-orcid":false,"given":"Arianna","family":"Giorgetti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40121 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7199-3041","authenticated-orcid":false,"given":"Jegak","family":"Seo","sequence":"additional","affiliation":[{"name":"Royal College of Pharmacy, 66-68 East Smithfield, London E1W 1AW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3849-817X","authenticated-orcid":false,"given":"John Martin","family":"Corkery","sequence":"additional","affiliation":[{"name":"Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, University of Hertfordshire, College Lane Campus, Hatfield AL10 9AB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4178-5401","authenticated-orcid":false,"given":"Fabrizio","family":"Schifano","sequence":"additional","affiliation":[{"name":"Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, University of Hertfordshire, College Lane Campus, Hatfield AL10 9AB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"ref_1","unstructured":"(2026, March 26). 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