Methylone
Methylone is a synthetic stimulant and entactogen of the cathinone class. First synthesized by Peyton Jacob III and Alexander Shulgin in 1996 as a potential antidepressant,12 it later gained popularity as a recreational substance.2 Methylone is frequently used as a substitute for MDMA due to overlapping effects,3 though Shulgin himself described it as lacking MDMA's "unique magic," noting it is more stimulating and less empathogenic. It has been commonly mis-sold as MDMA.
Contents
Dosage & Duration
Dosage
Redosing may not reliably intensify or prolong effects. Maintain adequate hydration throughout the experience.
Duration
Subjective Effects
Effects vary widely by individual, dose, and context.
Physical
Cognitive
The general head space of methylone is described by many as one of extreme mental stimulation, feelings of love or empathy and powerful euphoria. It contains a large number of typical psychedelic, entactogenic and stimulant cognitive effects.
Visual
Reagent Testing
Loading reagent data
Pharmacology
Pharmacodynamics
Methylone acts as a mixed releasing agent and reuptake inhibitor of serotonin, norepinephrine, and dopamine.4 Its serotonin transporter affinity (Ki of 242.1 nM) is roughly 3-fold lower than that of MDMA, while its norepinephrine and dopamine transporter affinities are comparable; its VMAT2 affinity is approximately 13-fold lower, contributing to a profile that balances reuptake inhibition with monoamine release rather than acting as a predominant releaser.45 Methylone is also a variable-potency partial agonist at 5-HT1A, 5-HT1B, and 5-HT1D receptors and shows no significant activity at 5-HT2A or 5-HT2B receptors.67 Its activity at 5-HT2C is uncertain, with one study reporting no significant affinity and another finding potent near-full agonism via the Gαq signaling pathway.7
Pharmacokinetics
In humans, the mean elimination half-life of methylone following oral doses of 50 to 200 mg ranges from 5.8 to 6.9 hours.8 The two major metabolic pathways are N-demethylation to methylenedioxycathinone (MDC) and demethylation followed by O-methylation, producing 4-hydroxy-3-methoxymethcathinone (HMMC) and 3-hydroxy-4-methoxymethcathinone (3-OH-4-MeO-MC).9 An additional metabolite, 3,4-dihydroxymethcathinone (HHMC), has also been identified.9 In rats administered 5 mg/kg, approximately 26% was excreted as HMMC within 48 hours, with less than 3% excreted unchanged.9
Dangerous
Highest riskThese combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.
Tolerance
Dopaminergic stimulants
Harm Potential
Addiction & Dependence
Psychological
ModerateChronic use of methylone can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users.10 Compulsive redosing is commonly reported, likely promoted by the substance's time compression effects which speed up the subjective experience.
Physical
LowWhen addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage. The nature and severity of withdrawal symptoms have not been well characterized.
Toxicity
Higher doses and repeated use have been associated with chest pains, heart palpitations, and elevated blood pressure and heart rate; worrying cardiovascular increases have been reported at doses exceeding 180-200 mg.2
Temperature regulation suppression and increased body temperature occur during use, with hyperthermia risk elevated during physical activity in hot environments such as dance venues.4
Psychosis Risk
Abuse at high dosages for prolonged periods can potentially result in stimulant psychosis presenting with paranoia, hallucinations, or delusions. Based on research into similar stimulants, approximately 5-15% of those who develop stimulant psychosis may not recover completely,13 though antipsychotic medications effectively resolve symptoms of acute psychosis. Psychosis very rarely arises from occasional or moderate use.
Seizure Risk
Limited data on seizure risk from methylone use alone.
History & Culture
Discovery and Development
Methylone was first synthesized by chemists Peyton Jacob III and Alexander Shulgin in the mid-1990s, with the compound first described in scientific literature by 1996.1 The synthesis occurred after the publication of Shulgin's PiHKAL in 1991, and consequently methylone was…
Legality
International
Methylone is listed in Schedule II of the Convention on Psychotropic Substances of 1971. It is not listed under the 1961 Single Convention on Narcotic Drugs or the 1988 Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.
By Country
References
Source Pages
Bluelight: The Big & Dandy bk-MDMA (Methylone) Thread
Disregard Everything I Say
Drug Users Bible by Dominic Milton Trott
Erowid
Erowid Methylone Vault: Dosage
Erowid Methylone Vault: Effects
Isomer Design (TiHKAL/PiHKAL)
PsychonautWiki
TripSit Factsheet: Methylone
TripSit Factsheets
TripSit Wiki: Drug Combinations
Wikipedia
Citations
- Jacob III P, & Shulgin AT. (1996). Novel N-Substituted-2-Amino-3',4'-Methylene-dioxypropiophenones. https://patents.google.com/patent/WO1996039133A1/en1234
- Poyatos L, Pérez-Mañá C, Hladun O, & et al.. (2023). Pharmacological effects of methylone and MDMA in humans. 14. https://doi.org/10.3389/fphar.2023.1122861123
- Poyatos L, Papaseit E, Olesti E, & et al.. (2021). A Comparison of Acute Pharmacological Effects of Methylone and MDMA Administration in Humans and Oral Fluid Concentrations as Biomarkers of Exposure. 10(8), 788. https://doi.org/10.3390/biology100807881
- (2012). The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology, 37(5), 1192–1203. https://doi.org/10.1038/npp.2011.304123
- (n.d.). The [[onset of action]] and [[duration of action]] of methylone in humans are 0.5{{nbsp}}hours and 2.5 to 3.0{{nbsp}}hours, respectively.<ref name="PoyatosLoFaroBerardinelli2022" /. https://doi.org/10.1016/s0014-2999(99)00538-51
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- (2024-02-07). Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA. Frontiers in Neuroscience, 18. https://doi.org/10.3389/fnins.2024.135313112
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