mdma, amphetamine, mephedrone +1 moremdma, amphetamine, mephedrone, methamphetamine show less
Methylone
3,4-methylenedioxy-N-methylcathinone
Methylone (3,4-methylenedioxy-N-methylcathinone) — bk-MDMA — is a synthetic empathogen-stimulant of the substituted cathinone class. It is the β-keto structural analog of MDMA — structurally nearly identical, but shorter-acting and less intense. It triggers the simultaneous release of serotonin, dopamine, and norepinephrine from nerve terminals,[1][2] producing both empathogenic warmth and stimulant energy.
Methylone (3,4-methylenedioxy-N-methylcathinone) — bk-MDMA — is a synthetic empathogen-stimulant of the substituted cathinone class. It is the β-keto structural analog of MDMA, shorter-acting and less intense. Methylone is a non-selective monoamine releasing agent, producing its effects by triggering serotonin, dopamine, and norepinephrine release from nerve terminals.[1][2]
mdma, amphetamine, mephedrone +1 moremdma, amphetamine, mephedrone, methamphetamine show less
Synthesized by Peyton Jacob III and Alexander Shulgin in the mid-1990s, methylone was patented in 1996 as a potential antidepressant, though no clinical development followed.[3] It spread through "bath salts" products in the early 2010s, triggering emergency department crises and rapid international scheduling.[4] It is now Schedule I in the United States,[5] while simultaneously advancing through FDA clinical trials for PTSD.[6]
Subjective effects include empathogenic warmth, euphoria, enhanced sociability, and stimulant energy. The experience resembles a compressed version of MDMA — the same emotional openness and drive to connect, but shorter and with a more physically driven quality.[7] Jaw tension, elevated heart rate, and anxiety are common unsought effects; the short duration makes repeated dosing tempting.
Methylone produces moderate reinforcement and serious cardiovascular toxicity — sudden cardiac death has occurred in both healthy and predisposed individuals.[8][9] Risk sharpens in hot, crowded environments, and combining it with MAOIs or other serotonin-raising drugs can trigger a life-threatening overheating crisis.[10][11] No lethal dose has been established, blood concentration does not predict fatality, and most of what is known comes from forensic cases rather than clinical research.[12]
History[edit]
Discovery
Methylone was synthesized by Peyton Jacob III and Alexander Shulgin in the mid-1990s and patented in 1996 as a potential antidepressant and antiparkinsonian agent, though no clinical development followed.[3] The compound postdated Shulgin's PiHKAL and later appeared in The Shulgin Index (2011).[3]
Recreational emergence and prohibition
Methylone became the first synthetic cathinone reported to European drug monitoring in 2005[3] and was briefly sold legally in Dutch smartshops and New Zealand.[7][4] By 2008–2010 it had spread into "bath salts" products across the US and Europe, triggering emergency crises and rapid international scheduling.[4][7] The DEA permanently placed it on Schedule I in April 2013.[5]
Therapeutic rediscovery
Transcend Therapeutics began clinical trials of methylone (designated TSND-201) for PTSD around 2022–2023. A Phase 2 trial showed significant symptom improvement,[6] earning FDA Breakthrough Therapy Designation in 2025[13] and a Priority Review Voucher in 2026.[14]
The name "methylone" comes from its N-methyl group and ketone structure, following standard cathinone nomenclature. The alternate name "bk-MDMA" reflects its structural relationship to MDMA but fell out of common use. During its legal period in the Netherlands, it was sold under the brand name "Bliss".[7]
Chemistry[edit]
Structural class
Methylone belongs to the substituted cathinone class — synthetic analogs of cathinone, the active compound in the khat plant (Catha edulis).
It shares the methylenedioxy ring system with MDMA and MDA, and its β-keto group (a carbonyl on the phenethylamine backbone) makes it the direct β-keto analog of MDMA. Its molecular formula is C₁₁H₁₃NO₃ (molecular weight 207.23 g/mol).
Pharmacology[edit]
Mechanism of action
Methylone enters nerve terminals and triggers the simultaneous release of serotonin, dopamine, and norepinephrine into the synapse, while also blocking their reabsorption.[1][2][15] This dual action distinguishes it from cocaine, which only blocks reuptake. Serotonin release is the dominant effect,[2] giving methylone its empathogenic character alongside stimulant drive.
Neuroplastogenic activity
Recent research has found that methylone stimulates the growth of new neuronal branches in cultured cortical neurons,[16] placing it alongside ketamine as a rapid-acting compound that promotes structural brain change. In animal models, it produces lasting improvements in fear extinction — the process by which traumatic associations lose their grip.[16] This is the likely basis for its clinical trial results in PTSD.[6]
Pharmacokinetics
No controlled human pharmacokinetic study has been published.[6] In rats, the brain accumulates nearly eight times the concentration found in blood, with peak levels within 30 minutes.[10] The main breakdown pathway produces nor-methylone, an active metabolite with potency comparable to the parent compound.[17][10]
Neuroscience[edit]
Where it acts
Methylone engages two major brain systems. Dopamine release in the mesolimbic pathway produces stimulation and euphoria.[18][2] Serotonin release drives circuits of empathy and emotional connection,[2] and is expected to dampen fear responses in the amygdala — the mechanism central to its proposed therapeutic use in PTSD.
Methylone also disrupts temperature regulation in a dose-dependent way, with the effect amplified significantly in crowded or physically active environments.[10]
Why it matters
Methylone is being recharacterized as a neuroplastogen — a compound that rapidly promotes structural brain change,[6] placing it alongside ketamine as an alternative to psychedelic-assisted therapies. It achieves this without activating the receptors responsible for psychedelic experiences.[6] The fear extinction benefit is driven by norepinephrine release, not serotonin.[16]
Human pharmacokinetic data — half-life, bioavailability, peak time — remain unpublished despite a completed Phase 1 study. Which liver enzymes metabolize methylone is unknown, creating a gap in predicting drug interactions. Whether neuroplastogenic effects seen in cell cultures translate to clinical doses in humans has not been confirmed. The differential toxicity and absorption of the two enantiomers[19][20] raises the question of whether a single-enantiomer formulation could improve safety.
Subjective Effects[edit]
Methylone lands between pure stimulant and full empathogen — warm, socially energizing, and emotionally open. The empathogenic quality is the defining feature: a genuine drive toward connection that feels real rather than chemical. The stimulant component is more forward than in classic entactogens, giving the experience a driven, slightly restless undercurrent.[10]
Relative to MDMA, methylone runs shorter and less intense — a compressed empathogenic window with more prominent motor drive.[4] Compared to purely stimulant cathinones, the serotonin component produces a warmer, more prosocial experience with less compulsive edge.[18]
Synthesized by Peyton Jacob III and Alexander Shulgin in the mid-1990s and patented as a potential antidepressant,[3] methylone was the first synthetic cathinone reported to European drug monitoring.[4] It circulated widely in "bath salts" products through the early 2010s before permanent DEA Schedule I classification in 2013. A Phase 2 trial for PTSD led to FDA Breakthrough Therapy Designation in 2025[5] and a Priority Review Voucher in 2026.[6]
Subjective effects include empathogenic warmth, euphoria, psychomotor stimulation, and enhanced sociability. The experience resembles a compressed version of MDMA — similar emotional openness and prosocial drive, but shorter and with more prominent stimulant energy.[7] Jaw tension, anxiety, and elevated heart rate are common unsought effects.
Methylone demonstrates moderate reinforcement without the dose escalation seen with cocaine or methamphetamine,[8] but cardiovascular toxicity is serious — sudden cardiac death has occurred in both predisposed and previously healthy individuals.[9][10] Blood concentration does not reliably predict lethality,[11] and hyperthermia risk escalates sharply in hot, crowded environments.[12] No controlled human pharmacokinetic study has been published, no lethal dose is established, and clinical trial data remain limited to a single Phase 2 study.[13]
History[edit]
Discovery
Methylone was synthesized by Peyton Jacob III and Alexander Shulgin in the mid-1990s and patented in 1996 as a potential antidepressant and antiparkinsonian agent, though no clinical development followed.[3] The compound postdated Shulgin's PiHKAL (1991) and later appeared in The Shulgin Index (2011).[3]
Recreational emergence and prohibition
Methylone became the first synthetic cathinone reported to the EMCDDA in 2005[3] and was sold legally in Netherlands smartshops and New Zealand through the late 2000s.[7][4] By 2008–2010, it appeared in "bath salts" products in the United States and Europe,[4][7] triggering a wave of emergency department presentations and rapid international scheduling — culminating in permanent DEA Schedule I placement in April 2013.[14]
Therapeutic rediscovery
Transcend Therapeutics initiated clinical investigation of methylone (designated TSND-201) for post-traumatic stress disorder around 2022–2023, positioning it as a mechanistically distinct alternative to psychedelic-assisted therapies. A Phase 2 trial (IMPACT-1) demonstrated significant PTSD symptom improvement,[13] leading to FDA Breakthrough Therapy Designation in July 2025[5] and a Priority Review Voucher in April 2026.[6]
The name "methylone" derives from the N-methyl group and the ketone moiety, following standard cathinone nomenclature. The alternate designation "bk-MDMA" (beta-keto MDMA) reflects its structural relationship to MDMA but fell out of common usage. During its legal period in the Netherlands, it was marketed under the brand name "Bliss".[7]
Chemistry[edit]
Structural class
Methylone belongs to the substituted cathinone family — synthetic analogs of cathinone, the principal psychoactive alkaloid of the khat plant (Catha edulis). It is specifically a 3,4-methylenedioxy-substituted cathinone, sharing the methylenedioxy ring system with MDMA and MDA. The defining structural feature is the β-keto group — a carbonyl at the β-carbon of the phenethylamine backbone — making methylone the β-keto analog of MDMA.
Molecular properties
| Molecular formula | C₁₁H₁₃NO₃ |
| Molecular weight | 207.23 g/mol |
The molecule consists of a benzodioxole ring system attached to a propan-1-one chain bearing an N-methylamino group. The ketone at the β-position reduces lipophilicity compared to MDMA. Its high water solubility (357 mg/mL) facilitates both oral and intranasal administration.citation needed
Stereochemistry
Methylone possesses one chirality center at the α-carbon, yielding R and S enantiomers. The compound is typically encountered as a racemate. The enantiomers differ in pharmacologically relevant ways: S-(−)-methylone shows greater intestinal absorption,[15] while R-(+)-methylone is the more toxic enantiomer in neuronal cell models.[16]
Pharmacology[edit]
Mechanism of action
Methylone is a non-selective monoamine transporter substrate (releaser) that simultaneously blocks monoamine reuptake.[1][2][17] It acts at all three monoamine transporters — dopamine (DAT), norepinephrine (NET), and serotonin (SERT) — triggering the release of stored neurotransmitters into the synapse while preventing their removal. This dual mechanism distinguishes it from pure reuptake blockers like cocaine.
In brain tissue, serotonin release exceeds dopamine release,[2] consistent with methylone's entactogenic character rather than a purely stimulant profile. The norepinephrine transporter shows the highest releasing potency among the three targets.[18] Methylone's release and selectivity profile closely parallels MDMA.[2][1]
One critical distinction from MDMA: the β-keto group eliminates activity at TAAR1 (trace amine-associated receptor 1).[1] This receptor contributes to some of MDMA's serotonergic signaling, and its absence may account for experiential differences between the two compounds.
Neuroplastogenic activity
Recent research has recharacterized methylone as a rapid-acting neuroplastogen.[13] In cultured cortical neurons, it stimulates the growth of new neuronal branches and extensions through two distinct signaling pathways — one dependent on monoamine transporter activity, the other mediated by trkB receptor and mTOR signaling.[19]
Behaviorally, methylone produces rapid and lasting improvements in fear extinction recall in rodent models — an effect that requires norepinephrine transporter activity specifically.[19] Notably, methylone does not directly activate 5-HT₂A receptors, distinguishing its mechanism entirely from classical psychedelics.[13]
Pharmacokinetics
No controlled human pharmacokinetic study has been published. A Phase 1 dose study has been completed but results remain unpublished.[13]
In rats, peak brain concentrations occur at 30 minutes after administration, with the brain accumulating nearly eight times the concentration found in blood.[12] Two primary metabolic pathways have been identified: N-demethylation produces nor-methylone, a pharmacologically active metabolite with potency comparable to the parent compound, and O-demethylenation (ring opening) produces a catechol metabolite subject to further modification.[20][12]
The specific liver enzymes responsible for methylone metabolism in humans have not been mapped. CYP2D6 and CYP3A4 involvement is inferred from structural similarity to MDMA, but this remains unconfirmed.inferred
Neuroscience[edit]
Where it acts
Methylone's dual stimulant-entactogen profile engages two major neural systems. Dopamine release in the nucleus accumbens activates the mesolimbic mesolimbic pathway, producing stimulation and euphoria.[8][2] The predominant serotonin release drives circuits involved in empathy, social bonding, and emotional processing[2] — and is expected to dampen fear responses in the amygdala, a mechanism central to its proposed therapeutic use in PTSD.
Methylone also disrupts temperature regulation in a dose-dependent manner, with the effect significantly amplified in socially active or crowded conditions.[12]
Why it matters
Methylone's characterization as a neuroplastogen[13] places it alongside ketamine as a rapid-acting compound that promotes structural neural change without requiring a psychedelic experience. Its stimulation of neurite outgrowth through trkB/mTOR signaling[19] — without direct 5-HT₂A activation — suggests that the subjective psychedelic state may not be necessary for neuroplasticity-driven therapeutic effects.
The finding that NET activity (not SERT activity) mediates methylone's enhancement of fear extinction[19] points to noradrenergic modulation of amygdala-prefrontal circuits as the likely mechanism behind its therapeutic potential in trauma processing.
Human pharmacokinetic parameters — half-life, bioavailability, peak time — remain unpublished despite a completed Phase 1 study. Which liver enzymes metabolize methylone is unknown, creating a blind spot for drug interaction prediction, particularly for individuals with genetic CYP2D6 variations.
Subjective Effects[edit]
Methylone occupies a middle ground between pure stimulants and full entactogens — a warm, socially energizing experience with an empathogenic core that falls short of MDMA's emotional depth. The stimulant component is more forward than in MDMA, lending a driven, physically active quality. Set and setting strongly modulate the experience: crowded social environments amplify empathogenic warmth, while solitary use tends to foreground stimulant restlessness.[12]
Relative to MDMA, users consistently describe methylone as qualitatively similar but shorter and less intense — a compressed empathogenic window with more prominent motor drive.[4] Compared to purely stimulant cathinones such as MDPV, methylone's serotonergic predominance produces a warmer, more prosocial character with less compulsive redosing tendency.[8]
Effect Grid
At common doses (150–225 mg oral), the full entactogenic-stimulant experience emerges. Pronounced empathogenic warmth, euphoria, and enhanced emotional openness characterize the peak. Social interactions feel deeply engaging, and sensory appreciation — particularly of music and tactile stimulation — intensifies. Thought acceleration is marked, and introspective or emotionally significant thoughts may arise.
Physically, tachycardia, jaw tension (bruxism), sweating, and elevated body temperature become more prominent. Appetite suppression is typical. Mild to moderate peripheral vasoconstriction may produce cold extremities.
Sleep is unlikely for 3–5 hours post-ingestion. The total experience commitment is approximately 3–5 hours including residual stimulation.
Modeled from the effect's dose-dependence curve — not per-substance measurements.
Color enhancement
Body high · Appetite suppression · Tactile euphoria · Spontaneous body sensations · Dehydration sensation · Bruxism · Dry mouth · Heart rate perception changes · Insomnia · Restlessness · Vasoconstriction · Excessive sweating · Sexual arousal enhancement · Headache · Muscle tension · Nausea · Nystagmus (eye wobbles) · Physical fatigue · Tingling / electric sensations · Increased urination · Dizziness · Laughter fits · Vibrations / buzzing · Trembling · Vomiting
Spontaneous body sensations · Dehydration sensation · Bruxism · Dry mouth · Heart rate perception changes · Insomnia · Restlessness · Excessive sweating · Sexual arousal enhancement · Headache · Muscle tension · Nausea · Nystagmus (eye wobbles) · Physical fatigue · Tingling / electric sensations · Increased urination · Dizziness · Laughter fits · Vibrations / buzzing · Trembling · Vomiting
Cognitive fatigue · Immersion enhancement · Motivation enhancement · Motivation suppression · Aesthetic enhancement · Cognitive flexibility · Introspection enhancement · Creativity enhancement · Focus enhancement · Humor enhancement · Language enhancement · Cognitive impairment · Novelty enhancement · Thought connectivity · Information processing enhancement · Thought deceleration · Delusions
Motivation suppression · Aesthetic enhancement · Cognitive flexibility · Introspection enhancement · Creativity enhancement · Focus enhancement · Humor enhancement · Language enhancement · Cognitive impairment · Novelty enhancement · Thought connectivity · Information processing enhancement · Thought deceleration
Anxiety suppression · Irritability · Anxiety · Dysphoria · Catharsis · Emotional lability · Simultaneous emotions
Catharsis · Emotional lability · Simultaneous emotions
Trust enhancement · Craving · Emotional susceptibility · Flow state · Boundary dissolution
Boundary dissolution
Timeline
First alerts appear as subtle mood shift and mild physical awareness — slight warmth, faint increase in heart rate. Effects may be mistaken for anticipatory excitement.
Stimulation and empathogenic warmth build steadily. Sociability increases, music sounds richer, and mild jaw tension may appear. Some users experience transient nausea during this phase.
Full entactogenic-stimulant effects: pronounced euphoria, emotional openness, enhanced sociability, and sensory appreciation. Tachycardia, bruxism, sweating, and elevated body temperature are typical. The dominant experiential quality is empathogenic warmth with energetic drive.
Effects begin a gradual decline from peak intensity. Empathogenic warmth persists but stimulation becomes more prominent as serotonergic effects wane. Sociability and mood elevation remain above baseline.
Empathogenic effects fade; residual stimulation and mild restlessness predominate. Appetite begins to return. Jaw tension and tachycardia subside.
Residual low-level stimulation, mild fatigue, and variable mood characterize the hours following the acute experience. Some users report a gentle positive mood; others experience mild low mood or cognitive sluggishness.
⚠ Do not drive or operate heavy machinery for at least 6 hours after the last dose, as residual stimulation and fatigue may impair reaction time and judgment.
Safety[edit]
- Acute toxicity
- High
- Chronic toxicity
- Moderate
- Withdrawal
- None
- Tolerance buildup
- moderate
- Tolerance reset
- 31 days
- Physical
- Low
- Psychological
- Moderate
- Compulsive redosing
- Moderate
- Dose escalation
- Low
- Cross-tol.
- mdma · amphetamine · mephedrone
Toxicity
Acute toxicity
No lethal dose has been established for methylone in humans. Blood concentration does not reliably predict whether a dose will be fatal[21][12] — people have survived concentrations exceeding those found in fatal cases.[12]
Deaths attributed to methylone include sudden cardiac arrest in a previously healthy 19-year-old[8] and a 16-year-old with pre-existing heart and respiratory conditions.[9] A systematic review confirmed multiple methylone-attributed deaths via cardiac arrest, dangerously elevated body temperature, multi-organ failure, and serotonin syndrome.[22] In rats, doses only moderately above active levels proved lethal in some animals.[10]
Heart and circulation
Catecholamine release from stimulant effects causes rapid heart rate, high blood pressure, irregular heart rhythms, and heart attack.[23] Sudden cardiac death is the primary acute fatality mechanism. Pre-existing heart conditions substantially increase risk.[8][9]
Hyperthermia
Body temperature elevation is dose-dependent and worsens significantly in crowded or physically active environments.[10] Dangerous temperature elevation is a precursor to organ failure and a leading cause of methylone deaths.
Serotonin syndrome
Combining methylone with other serotonin-raising drugs can cause muscle rigidity, rapid heart rate, rising body temperature, agitation, and altered consciousness — a condition that becomes life-threatening without treatment.[11][24] Risk escalates sharply with high doses or MAOI combinations.
Other acute risks
Muscle breakdown leading to kidney failure has been documented with synthetic cathinones.[23] Extreme agitation combined with dangerously elevated body temperature and altered consciousness is the most severe acute presentation and carries significant mortality risk.[25]
Neurotoxicity
Unlike MDMA, repeated methylone dosing in rats does not produce lasting serotonin depletion, suggesting lower risk of long-term serotonergic damage.[2][26] However, prolonged high-concentration exposure partially inhibits neuronal activity in a non-reversible manner in laboratory models.[27] The more toxic enantiomer causes cell damage through oxidative stress.[20]
Psychological risks
No controlled study has characterized methylone's psychological risk profile. Reported acute adverse effects include anxiety, paranoia, agitation, psychosis, and extreme agitation with altered consciousness.[25][23]
Long-term psychological effects have not been studied. No published data exist on persistent perceptual changes, lasting psychosis, or post-use depressive episodes specific to methylone. In the Phase 2 PTSD trial, adverse events were mostly transient and resolved on the day of dosing[6] — but this controlled setting does not generalize to unsupervised use.
Tolerance & dependence
In animal models, methylone functions as a reinforcer with self-administration rates exceeding MDMA.[18] Extended access does not produce the escalating intake pattern seen with cocaine and methamphetamine, suggesting lower compulsive use potential.[18] Dopamine transporter activity is associated with addiction risk across the cathinone class.[1]
No methylone-specific tolerance study or characterization of physical dependence or withdrawal has been published.safety citation needed
Drug Interactions
The primary risk is serotonin syndrome. Methylone raises serotonin — combining it with any drug that also raises serotonin creates additive toxicity.[11]
MAOIs are the highest-risk combination and an absolute contraindication. By preventing breakdown of released serotonin, MAOIs can turn manageable release into a life-threatening syndrome. This applies to irreversible MAOIs (phenelzine, tranylcypromine), reversible ones (moclobemide), and dietary sources.[11]
SSRIs and SNRIs create dual risk: they add more serotonin while competing at the transporter, potentially altering methylone's effects while still elevating total synaptic serotonin.
Other entactogens — including MDMA, MDA, and other cathinones — produce additive serotonin and catecholamine release, increasing both serotonin syndrome and hyperthermia risk.[11][24]
Tramadol poses serotonergic risk and lowers seizure threshold.safety citation needed
Stimulants — including cocaine, amphetamine, and methamphetamine — add cardiovascular stress and hyperthermia.
Alcohol interaction data specific to methylone have not been published. As with other stimulants, co-use may mask sedation and promote excessive alcohol intake.
Methylone is not detected by standard MDMA urine drug screens.[4][24] Confirmatory identification requires mass spectrometry.[28][21]
Contraindications
11 knownPre-existing heart conditions are the strongest absolute contraindication. Fatal cases show that congenital heart malformation, irregular rhythms, and structural heart disease substantially increase sudden death risk, even at low methylone concentrations.[9][8]
Respiratory conditions: Asthma was identified as a predisposing factor in a fatal case.[9]
Serotonergic medications — MAOIs, SSRIs, SNRIs, and tramadol — constitute a relative to absolute contraindication. MAOI co-administration is an absolute contraindication due to fatal serotonin syndrome risk.[11]
High blood pressure increases cardiovascular risk given methylone's stimulant catecholamine release.
Liver or kidney impairment may impair clearance of methylone and its active metabolite, though substance-specific data are unavailable.inferred
Pregnancy and lactation: No reproductive toxicity data exist. Given methylone's high brain penetration, fetal exposure risk is assumed to be substantial.
Harm Reduction[edit]
Forms & Identification
Methylone is not detected by standard MDMA urine immunoassays.[4][24] Material sold as "molly" or "ecstasy" could contain methylone without triggering a positive MDMA test. Reagent testing distinguishes methylone from MDMA and from more dangerous cathinones. Confirmatory identification requires mass spectrometry,[28] but field-level reagent kits are a practical first line.
Because blood concentration does not predict lethality,[12] precise dosing matters. Weigh material with a milligram-precision scale rather than estimating visually.
Guidelines
- Test all material with reagent kits before use.
- Weigh doses with a milligram-precision scale — never estimate by eye.
- Start with a low dose and wait at least 90 minutes before considering redosing; the shorter duration encourages compulsive redosing.
- Stay in well-ventilated, temperature-controlled environments. Avoid prolonged dancing in hot, crowded spaces without breaks.
- Drink water at a steady pace — approximately 250 mL per hour when active — but avoid overhydration.
- Monitor heart rate. If resting heart rate exceeds 120 bpm or chest discomfort develops, stop activity and seek a cool, quiet space.
- Do not use alone. A sober companion can recognize emergencies that the user cannot.
Set & Setting
Methylone's effects are notably context-dependent. Crowded, warm environments amplify both the empathogenic warmth and the physiological risks — particularly dangerously elevated body temperature.[10] Adequate ventilation, access to cool spaces, and regular hydration reduce hyperthermia risk significantly.
Social settings enhance the entactogenic character; solitary use tends to foreground stimulant restlessness. A sober, trusted companion provides both safety monitoring and emotional grounding.
Aftercare & integration. The comedown may bring low mood, fatigue, irritability, and difficulty concentrating — effects consistent with temporary monoamine depletion. Prioritize sleep, nutrition, and light physical activity in the 24–48 hours following use.
Avoid redosing to counter comedown symptoms. The short duration makes repeated dosing tempting, but each additional dose increases cardiovascular and hyperthermic risk without proportional return of desired effects. If low mood persists beyond 3–5 days, or if anxiety or paranoia intensifies rather than resolving, consult a mental health professional.
Recovery & Support
While methylone shows lower compulsive use potential than cocaine or methamphetamine in animal models,[18] regular use can become habitual. Patterns to watch for include escalating frequency, using to manage mood, and difficulty engaging socially without the substance.
Support resources include SAMHSA's National Helpline (1-800-662-4357), local harm reduction organizations, and therapists experienced with substance use. Peer support communities — both online and in-person — can provide non-judgmental spaces for examining one's relationship with stimulant or entactogen use.
Recovery resources, crisis lines, and support pathways → View all
Emergency Response
Recognizing an emergency:
The following signs require immediate medical attention:
- Chest pain, pressure, or irregular heartbeat
- Body temperature hot to the touch through clothing
- Seizures or loss of consciousness
- Extreme agitation, confusion, or delirium
- Rigid muscles with high fever (possible serotonin syndrome)
Immediate steps:
- 1. Call emergency services immediately if any of the above signs are present.
- 2. Move the person to a cool, quiet area. Remove excess clothing.
- 3. If unconscious but breathing, place in the recovery position (on their side, airway clear).
- 4. Apply cool (not ice-cold) water to skin and fan the body. Cooling is the single most important intervention for hyperthermia.
- 5. Do not restrain a person in excited delirium unless there is immediate danger to self or others.
- 6. Do not induce vomiting.
What to tell the dispatcher:
State the substance taken (methylone or synthetic cathinone), estimated amount, time of ingestion, and current symptoms. Good Samaritan laws in many jurisdictions protect callers from drug-related prosecution — calling for help can save a life.
Legal Status[edit]
Methylone is a controlled substance in most major jurisdictions, while simultaneously advancing through FDA clinical trials as TSND-201 for PTSD — a pattern shared with MDMA and psilocybin.
| Jurisdiction | Classification | Key provisions |
|---|---|---|
| United States | Schedule I (CSA) | Permanently scheduled April 12, 2013; preceded by temporary scheduling October 2012[5][29] |
| United Kingdom | Class B (Misuse of Drugs Act 1971) | Controlled since April 16, 2010[30] |
| Germany | Anlage II (BtMG) | Scheduled January 2012[30] |
| Australia | Schedule 9 (Prohibited substance) | TGA Poisons Standard, April 2018[31] |
| Netherlands | Prohibited | Public Health Decree, reported April 2005[30] |
| Denmark | Controlled (hard drug) | Classified February 8, 2008[30] |
| Brazil | Controlled | ANVISA, February 18, 2014[30] |
| Canada | Status unclear | Not explicitly listed on controlled drug schedules as of 2013; may be covered under analogue provisionscitation needed |
Within the European Union, individual member states control methylone under national law; the EMCDDA has monitored the compound since 2005, when it became the first synthetic cathinone reported to that system. Despite Schedule I status in the United States, the FDA has issued a Priority Review Voucher for methylone as TSND-201,[14] and a Phase 3 trial is currently recruiting.
Legal classifications change frequently. The information above reflects known status as of 2025–2026 and is not legal advice.
Safety[edit]
- Acute toxicity
- High
- Chronic toxicity
- Moderate
- Withdrawal
- None
- Tolerance buildup
- moderate
- Tolerance reset
- 31 days
- Physical
- Low
- Psychological
- Moderate
- Compulsive redosing
- Moderate
- Dose escalation
- Low
- Cross-tol.
- mdma · amphetamine · mephedrone
Toxicity
Acute toxicity
No lethal dose or therapeutic index has been established for methylone in humans. Blood concentration does not reliably predict whether a dose will be fatal[21][11] — forensic reviews have documented survival at concentrations far exceeding those found in fatal cases.[11]
Published deaths include sudden cardiac arrest in a previously healthy 19-year-old[9] and fatal cardiac arrest in a 16-year-old with pre-existing heart and respiratory conditions.[10] A systematic review confirms multiple methylone-attributed deaths via cardiac arrest, dangerously elevated body temperature, multi-organ failure, and serotonin syndrome.[22]
In rats, doses only moderately above active levels proved lethal in some animals, indicating a narrow margin at the high end of the dose range.[12]
Heart and circulation
Rapid heart rate, high blood pressure, irregular heart rhythms, and heart attack result from the direct stimulant effects of catecholamine release.[23] Sudden cardiac death is the primary acute fatality mechanism. Pre-existing heart conditions substantially increase risk.[9][10]
Hyperthermia
Body temperature elevation is dose-dependent and significantly worsened in crowded or physically active environments.[12] Dangerously elevated body temperature is a precursor to organ failure and a leading contributor to methylone fatalities.
Serotonin syndrome
Risk increases with high doses or combination with other serotonergic substances.[24][25] Symptoms include muscle rigidity, rapid heart rate, elevated temperature, agitation, and altered consciousness.
Other acute risks
Muscle breakdown leading to kidney failure has been documented with synthetic cathinones.[23] Excited delirium — extreme agitation with dangerously elevated body temperature and altered consciousness — represents the most severe acute presentation and carries significant mortality risk.[26]
Neurotoxicity
Unlike MDMA, repeated methylone dosing in rats does not produce long-term serotonin depletion, suggesting reduced risk of lasting serotonergic damage.[2][27] However, prolonged high-concentration exposure partially inhibits neuronal activity in a non-reversible manner in laboratory models.[28]
The R-(+) enantiomer is the more toxic form, with oxidative stress identified as the primary mechanism of cell damage.[16]
Psychological risks
No controlled study has characterized methylone's psychological risk profile. Reported acute adverse effects include anxiety, paranoia, agitation, psychosis, and excited delirium.[26][23]
Long-term psychological effects have not been systematically studied. No published data exist on persistent perceptual changes, lasting psychosis, or post-use depressive episodes specific to methylone.
In the Phase 2 PTSD trial, adverse events were predominantly transient and resolved on the day of dosing.[13] This controlled clinical context does not generalize to unsupervised use.
Tolerance & dependence
Methylone functions as a reinforcer in animal self-administration models, with response rates exceeding those seen with MDMA.[8] However, extended-access sessions do not produce the escalating intake pattern characteristic of cocaine and methamphetamine, suggesting lower compulsive use potential.[8]
The pharmacological action at the DAT is associated with addiction risk across the cathinone class.[1] Physical dependence has not been characterized. Tolerance development is expected based on general stimulant pharmacology, but no methylone-specific tolerance study exists.safety citation needed
Cross-tolerance with other dopaminergic stimulants is mechanistically plausible but has not been formally demonstrated. No published study characterizes methylone withdrawal.
Drug Interactions
The primary interaction risk is serotonin syndrome: as a serotonin-releasing agent, methylone combined with any drug that increases serotonin creates additive or synergistic toxicity risk.[24]
MAOIs are the highest-risk combination. By preventing breakdown of released serotonin, MAOIs can convert manageable serotonin release into a life-threatening syndrome. This applies to all MAOIs — irreversible (phenelzine, tranylcypromine), reversible (moclobemide), and dietary sources.[24]
SSRIs and SNRIs create dual risk: serotonergic additivity increasing serotonin syndrome probability, and competition at the SERT that may paradoxically alter methylone's releasing activity while still elevating total synaptic serotonin.
Other entactogens — including MDMA, MDA, and other cathinones — produce additive serotonin and catecholamine release with additive serotonin toxicity and hyperthermia risk.[24][25]
Tramadol poses both serotonergic risk and seizure threshold lowering.safety citation needed
Stimulants — including cocaine, amphetamine, and methamphetamine — produce additive cardiovascular stress and hyperthermia.
Alcohol interaction data specific to methylone have not been published. As with other stimulants, co-administration may mask sedation and promote excessive alcohol consumption.
Methylone is generally not detected by standard urine drug screens, including MDMA panels.[4][25] Confirmatory identification requires mass spectrometry.[29][21]
Contraindications
11 knownPre-existing heart conditions are the strongest absolute contraindication. Fatal cases demonstrate that congenital heart malformation, irregular heart rhythms, and structural heart disease substantially increase the risk of sudden death, even at low methylone concentrations.[10][9]
Respiratory conditions: Asthma was identified as a predisposing factor in a fatal case.[10]
Concurrent serotonergic medication — including MAOIs, SSRIs, SNRIs, and tramadol — constitutes a relative to absolute contraindication. MAOI co-administration is an absolute contraindication due to fatal serotonin syndrome risk.[24]
High blood pressure increases cardiovascular risk given methylone's stimulant catecholamine release.
Liver or kidney impairment may impair clearance of methylone and its active metabolite, though substance-specific data are unavailable.inferred
Pregnancy and lactation: No reproductive toxicity data exist. Given methylone's high brain penetration, fetal exposure risk is assumed to be substantial.
Harm Reduction[edit]
Forms & Identification
Methylone is not detected by standard MDMA urine immunoassays,[4][25] meaning material sold as "molly" or "ecstasy" could contain methylone without triggering a positive MDMA test. Reagent testing distinguishes methylone from MDMA and from more dangerous cathinones. Confirmatory identification requires mass spectrometry,[29] but field-level reagent kits provide a practical first line of defense.
Because blood concentration does not predict lethality,[11] precise dosing matters — weigh material with a milligram-precision scale rather than estimating visually.
Guidelines
- Test all material with reagent kits before use.
- Weigh doses with a milligram-precision scale — never estimate by eye.
- Start with a low dose and wait at least 90 minutes before considering redosing; the shorter duration encourages compulsive redosing.
- Stay in well-ventilated, temperature-controlled environments. Avoid prolonged dancing in hot, crowded spaces without breaks.
- Drink water at a steady pace — approximately 250 mL per hour when active — but avoid overhydration.
- Monitor heart rate. If resting heart rate exceeds 120 bpm or chest discomfort develops, stop activity and seek a cool, quiet space.
- Do not use alone. A sober companion can recognize emergencies that the user cannot.
Set & Setting
Methylone's effects are notably context-dependent. Crowded, warm environments amplify both the empathogenic warmth and the physiological risks — particularly dangerously elevated body temperature.[12] Adequate ventilation, access to cool spaces, and regular hydration reduce hyperthermia risk significantly.
Social settings enhance the entactogenic character; solitary use tends to foreground stimulant restlessness. A sober, trusted companion provides both safety monitoring and emotional grounding.
Aftercare & integration. The comedown period may include low mood, fatigue, irritability, and difficulty concentrating — effects consistent with temporary monoamine depletion. Prioritize sleep, nutrition, and light physical activity in the 24–48 hours following use.
Avoid redosing to counter comedown symptoms. The short duration of methylone makes repeated dosing tempting, but each additional dose increases cardiovascular and hyperthermic risk without proportional return of desired effects. If low mood persists beyond 3–5 days, or if anxiety or paranoia intensifies rather than resolving, consult a mental health professional.
Recovery & Support
While methylone shows lower compulsive use potential than cocaine or methamphetamine in animal models,[8] regular use can become habitual. Patterns to watch for include escalating frequency, using to manage mood, and difficulty engaging socially without the substance.
Support resources include SAMHSA's National Helpline (1-800-662-4357), local harm reduction organizations, and therapists experienced with substance use. Peer support communities — both online and in-person — can provide non-judgmental spaces for individuals examining their relationship with stimulant or entactogen use.
Recovery resources, crisis lines, and support pathways → View all
Emergency Response
Recognizing an emergency:
The following signs require immediate medical attention:
- Chest pain, pressure, or irregular heartbeat
- Body temperature hot to the touch through clothing
- Seizures or loss of consciousness
- Extreme agitation, confusion, or delirium
- Rigid muscles with high fever (possible serotonin syndrome)
Immediate steps:
- 1. Call emergency services immediately if any of the above signs are present.
- 2. Move the person to a cool, quiet area. Remove excess clothing.
- 3. If unconscious but breathing, place in the recovery position (on their side, airway clear).
- 4. Apply cool (not ice-cold) water to skin and fan the body. Cooling is the single most important intervention for hyperthermia.
- 5. Do not restrain a person in excited delirium unless there is immediate danger to self or others.
- 6. Do not induce vomiting.
What to tell the dispatcher:
State the substance taken (methylone or synthetic cathinone), estimated amount, time of ingestion, and current symptoms. Good Samaritan laws in many jurisdictions protect callers from drug-related prosecution — calling for help can save a life.
Legal Status[edit]
Methylone occupies a dual regulatory position: it is a controlled substance in most major jurisdictions based on its recreational use profile, while simultaneously advancing through FDA clinical trials for therapeutic use as TSND-201. This reflects the broader regulatory challenge of Schedule I compounds entering therapeutic development — a pattern shared with MDMA and psilocybin.
| Jurisdiction | Classification | Key provisions |
|---|---|---|
| United States | Schedule I (CSA) | Permanently scheduled April 12, 2013; preceded by temporary scheduling October 2012[14][30] |
| United Kingdom | Class B (Misuse of Drugs Act 1971) | Controlled since April 16, 2010[31] |
| Germany | Anlage II (BtMG) | Scheduled January 2012[31] |
| Australia | Schedule 9 (Prohibited substance) | TGA Poisons Standard, April 2018[32] |
| Netherlands | Prohibited | Public Health Decree, reported April 2005[31] |
| Denmark | Controlled (hard drug) | Classified February 8, 2008[31] |
| Brazil | Controlled | ANVISA, February 18, 2014[31] |
| Canada | Status unclear | Not explicitly listed on controlled drug schedules as of 2013; may be covered under analogue provisionscitation needed |
Within the European Union, no single EU-wide schedule governs methylone. The EMCDDA has monitored the compound since 2005, when it became the first synthetic cathinone reported to that monitoring system. Individual member states have implemented national controls at different times and under varying classifications.
Despite its Schedule I status in the United States, the FDA has issued a Priority Review Voucher for methylone (as TSND-201) for PTSD treatment,[6] and a Phase 3 trial (EMPOWER-1) is currently recruiting. This creates an active regulatory pathway toward potential therapeutic rescheduling — contingent on Phase 3 outcomes and FDA approval.
Frequently asked questions
What is Methylone?
Methylone is a synthetic substituted cathinone with stimulant and entactogen properties, acting as a non-selective monoamine releasing agent. First synthesized by Jacob and Shulgin in the 1990s, it received FDA Breakthrough Therapy Designation for PTSD in 2025.
How long does Methylone last?
Total duration by route of administration — Oral: 2.5 – 4 hours. Ranges vary with dose and individual factors; see the duration table for onset, peak, and after-effect phases.
Where can I find dosage information for Methylone?
Psychedex publishes a dosage table for Methylone on this page covering these routes of administration: oral. Dose values are presented only in that table, always alongside their route of administration.
What are dangerous combinations with Methylone?
The highest-severity documented interactions for Methylone: MAOIs (Lethal), 5-HTP, Tryptophan (Dangerous), Alpha-2 adrenergic receptor antagonist (Dangerous), Anticholinergics (Dangerous), Antihistamines (Dangerous). See the interactions section for the full list with mechanisms and severity levels.
Is Methylone addictive?
Psychedex records tolerance and dependence data rather than a yes/no rating. Recorded tolerance indicators for Methylone: tolerance builds moderate; full reset takes 31 days; cross-tolerance develops with mdma, amphetamine, mephedrone, methamphetamine. See the article's dependence and safety sections for recorded dependence data.
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First-person accounts of subjective effects, timing, and outcomes — submitted for harm reduction.
references
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