4-FA is popular in the Netherlands where it is predominantly used for its specific effects (77% of users) rather than its legal status (18%).[4] 4-FA has become illegal since May 2017.[5]
The subjective effects of 4-fluoroamphetamine includeeuphoria which some find similar to the effects ofMDMA and amphetamine,[4] increased energy (stimulation), mood elevation, feelings of warmth and empathy, excessive talking,bruxism, and suppressed appetite (anorexic). The general course of effects involves primarily empathogenic effects for the first few hours, which fades out as increased stimulation develops over the next several hours.[medical citation needed]
4-Fluoroamphetamine has been found to be a weakmonoamine oxidase A (MAO-A)inhibitor, with anIC50Tooltip half-maximal inhibitory concentration of 16,000nM.[12] For comparison, theIC50Tooltip half-maximal inhibitory concentration ofamphetamine for MAO-A inhibition was 11,000nM.[12]
Regarding the metabolic fate of 4-FA, the C-F bond at the 4-position on the phenyl ring likely resists deactivation in the liver bycytochrome P450 oxidase.[13][14]
4-FA does not cause long-lasting depletion of brain serotonin, unlike itsanalogs4-CA and4-BA.[15] This is thought to "reflect the inability of the fluoro-compound to be metabolized in the same way as the other haloamphetamines."[16]
Neurotoxicity does not increase down the series ofpara-halogenated amphetamine derivatives, even though serotonin releasing potency does follow this trend. For example, 4-iodoamphetamine is less toxic than is 4-chloroamphetamine.[6][17] Hence, this property is not related to serotonin releasing potency as such, sincePAL-287 was reported to be not at all neurotoxic even though it is a powerful 5-HT releasing agent.[18] It is unclear where4-methylamphetamine fits in on the neurotoxicity scale. The extensive serotonergic neurotoxicity of 4-chloroamphetamine (and its brominated derivative), and the increased serotonergic toxicity of 4-methylamphetamine[19] suggest that para-substitution seems to increase overall serotonergic (neuro)toxicity, compared to amphetamine. Exceptions include4-MTA, apara-substituted, non-neurotoxic amphetamine.[20][21][22]
As of October 2015, 4-FA is a controlled substance in China.[25] 4-FA is banned in the Czech Republic.[26] As of 25 May 2017 4-FA is a controlled substance in the Netherlands.[27] 4-FA is also controlled in Australia, Belgium, UK, Germany, Israel, Slovakia, Bulgaria, Chile, Brazil, Canada, Croatia, Sweden, New Zealand and France.[citation needed]
4-FA is a controlled substance as of 27 August 2014 in South Korea.[28]
In the United States, on June 3, 2025 the DEA announced by federal register its intent to place 4-Fluoroamphetamine into Schedule I status with public comments closing on July 3, 2025.[29]
^Rösner P, Quednow B, Girreser U, Junge T (March 2005). "Isomeric fluoro-methoxy-phenylalkylamines: a new series of controlled-substance analogues (designer drugs)".Forensic Science International.148 (2–3):143–156.CiteSeerX10.1.1.670.7372.doi:10.1016/j.forsciint.2004.05.003.PMID15639609.
^abNagai F, Nonaka R, Satoh Hisashi Kamimura K (March 2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain".European Journal of Pharmacology.559 (2–3):132–137.doi:10.1016/j.ejphar.2006.11.075.PMID17223101.
^abLinsen F, Koning RP, van Laar M, Niesink RJ, Koeter MW, Brunt TM (July 2015). "4-Fluoroamphetamine in the Netherlands: more than a one-night stand".Addiction.110 (7):1138–1143.doi:10.1111/add.12932.PMID25808511.
^abMarona-Lewicka D, Rhee GS, Sprague JE, Nichols DE (December 1995). "Psychostimulant-like effects of p-fluoroamphetamine in the rat".European Journal of Pharmacology.287 (2):105–113.doi:10.1016/0014-2999(95)00478-5.PMID8749023.
^abcKuypers KP, De Sousa Fernandes Perna EB, Theunissen EL, Toennes SW, Mason NL, Hutten NR, Ramaekers JG (2019). "A First-in-Man Study with 4-Fluoroamphetamine Demonstrates it Produces a Mild Psychedelic State".J Psychoactive Drugs.51 (3):225–235.doi:10.1080/02791072.2019.1569286.PMID30676284.
^Toennes SW, Schneider D, Pogoda W, Paulke A, Wunder C, Theunissen EL, et al. (July 2019). "Pharmacokinetic properties of 4-fluoroamphetamine in serum and oral fluid after oral ingestion".Drug Testing and Analysis.11 (7):1028–1034.doi:10.1002/dta.2595.PMID30912312.S2CID85518011.
^abRickli A, Hoener MC, Liechti ME (March 2015). "Monoamine transporter and receptor interaction profiles of novel psychoactive substances: para-halogenated amphetamines and pyrovalerone cathinones".Eur Neuropsychopharmacol.25 (3):365–376.doi:10.1016/j.euroneuro.2014.12.012.PMID25624004.
^Fisher MB, Henne KR, Boer J (January 2006). "The complexities inherent in attempts to decrease drug clearance by blocking sites of CYP-mediated metabolism".Current Opinion in Drug Discovery & Development.9 (1):101–109.PMID16445122.
^Toennes SW, Schneider D, Pogoda W, Paulke A, Wunder C, Theunissen EL, et al. (July 2019). "Pharmacokinetic properties of 4-fluoroamphetamine in serum and oral fluid after oral ingestion".Drug Testing and Analysis.11 (7):1028–1034.doi:10.1002/dta.2595.PMID30912312.S2CID85518011.
^Fuller RW, Baker JC, Perry KW, Molloy BB (October 1975). "Comparison of 4-chloro-, 4-bromo- and 4-fluoroamphetamine in rats: drug levels in brain and effects on brain serotonin metabolism".Neuropharmacology.14 (10):739–746.doi:10.1016/0028-3908(75)90099-4.PMID1196472.S2CID9620299.
^Rothman RB, Blough BE, Woolverton WL, Anderson KG, Negus SS, Mello NK, et al. (June 2005). "Development of a rationally designed, low abuse potential, biogenic amine releaser that suppresses cocaine self-administration".The Journal of Pharmacology and Experimental Therapeutics.313 (3):1361–1369.doi:10.1124/jpet.104.082503.PMID15761112.S2CID19802702.
^Blanckaert P, van Amsterdam J, Brunt T, van den Berg J, Van Durme F, Maudens K, van Bussel J (September 2013). "4-Methyl-amphetamine: a health threat for recreational amphetamine users".Journal of Psychopharmacology.27 (9):817–822.doi:10.1177/0269881113487950.PMID23784740.S2CID35436194.
^Huang X, Marona-Lewicka D, Nichols DE (December 1992). "p-methylthioamphetamine is a potent new non-neurotoxic serotonin-releasing agent".European Journal of Pharmacology.229 (1):31–38.doi:10.1016/0014-2999(92)90282-9.PMID1473561.
^Li Q, Murakami I, Stall S, Levy AD, Brownfield MS, Nichols DE, Van de Kar LD (December 1996). "Neuroendocrine pharmacology of three serotonin releasers: 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (MBDB), 5-methoxy-6-methyl-2-aminoindan (MMAi) and p-methylthioamphetamine (MTA)".The Journal of Pharmacology and Experimental Therapeutics.279 (3):1261–1267.doi:10.1016/S0022-3565(25)21285-X.PMID8968349.
^Murphy J, Flynn JJ, Cannon DM, Guiry PJ, McCormack P, Baird AW, et al. (May 2002). "In vitro neuronal and vascular responses to 5-hydroxytryptamine: modulation by 4-methylthioamphetamine, 4-methylthiomethamphetamine and 3,4-methylenedioxymethamphetamine".European Journal of Pharmacology.444 (1–2):61–67.doi:10.1016/S0014-2999(02)01586-8.PMID12191583.
^Costa E, Garattini S (1970).Amphetamines and Related Compounds. New York: Raven Press. p. 28.
^"关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Archived fromthe original on 1 October 2015. Retrieved1 October 2015.
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