Methamphetamine

N-methyl-1-phenylpropan-2-amine

Overview

Methamphetamine belongs to Stimulants.

Key safety note: Methamphetamine is a powerfully reinforcing stimulant with high addiction and dependence liability.[5][4]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • Intense euphoria and wellbeing with large increases in energy, alertness, confidence, sociability, motivation and libido, plus appetite suppression and wakefulness: most intense and rush-like when smoked or injected.
  • Strong sympathetic effects: raised heart rate and blood pressure, dilated pupils, jaw clenching and teeth grinding, sweating, hyperthermia and tremor.
  • At higher doses, on binges or during the comedown: anxiety, restlessness, insomnia, paranoia, aggression, hallucinations and stimulant psychosis, followed by exhaustion, depression, heavy sleep and craving (the 'crash').
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral, insufflated, smoked (vaporised) or injected. Values below are approximate ORAL figures. Smoking or injecting give a far more intense rush and higher dependence risk.. Methamphetamine is long-acting (8–12 h) and strongly reinforcing, so redosing easily turns into multi-day binges with sleep deprivation, hyperthermia and psychosis: the main sources of harm. Insufflated doses are similar to oral. Smoking or injecting produce a rush and much higher dependence and overdose risk. Use a milligram scale, keep doses low, avoid redosing, stay hydrated and cool, and never combine with other stimulants or MAOIs. Illicit product varies in strength and is often adulterated: test it.

Dose ranges

Threshold

< 5 mg

Light

5–10 mg

Common

10–25 mg

Strong

25–50 mg

Heavy

50 mg +

Duration

onset

15–45 min (oral), 3–5 min insufflated/smoked

total

8–12 h

after effects

12–24 h (crash: fatigue, low mood, craving)

Chemical & Physical Properties
FormulaC10H15N
Molar mass149.24 g/mol
StateSolid (usually the hydrochloride salt, crystalline: 'crystal meth', free base is a volatile oil)
Melting point170–175 °C (hydrochloride salt)
Boiling point212 °C (free base)
DensityNot reported
Vapor pressureNot reported
pKa9.9
LogP2.07 (free base)
SolubilityHydrochloride salt: freely soluble in water and ethanol. Free base soluble in organic solvents (ether, chloroform)
Refractive indexNot reported
Identifiers & Synonyms
CAS537-46-2
CAS (enantiomer)
PubChem CID10836
InChIKeyMYWUZJCMWCOHBA-VIFPVBQESA-N
InChIInChI=1S/C10H15N/c1-9(11-2)8-10-6-4-3-5-7-10/h3-7,9,11H,8H2,1-2H3/t9-/m0/s1
SMILESC[C@@H](CC1=CC=CC=C1)NC

Synonyms

  • N-methylamphetamine
  • Desoxyephedrine
  • Desoxyn
  • Crystal meth
  • (S)-(+)-methamphetamine
  • Meth
  • Ice
  • Tina
  • Crank
  • Shard
Pharmacodynamics & Biochemistry

Methamphetamine (N-methylamphetamine) is a potent synthetic stimulant of the amphetamine class. Like amphetamine it is a substrate-type releaser rather than a simple reuptake blocker: it is carried into the nerve terminal by the dopamine (DAT) and noradrenaline (NET) transporters (and, more weakly, SERT), enters synaptic vesicles via VMAT2 and displaces stored dopamine, noradrenaline and serotonin into the cytosol, and the transporters then run in reverse ('reverse transport'), flooding the synapse with monoamines. It is additionally an agonist at the trace-amine-associated receptor TAAR1, which modulates transporter trafficking and dopamine-neuron firing. Its extra N-methyl group makes it more lipophilic and CNS-penetrant than amphetamine (to which it is N-demethylated as an active metabolite), giving a faster, more intense and more reinforcing effect. Methamphetamine is chiral, and the two enantiomers differ markedly. (S)-(+)-methamphetamine (dextromethamphetamine) is the potent central stimulant: the form sold illicitly as 'crystal meth' and the active ingredient of the prescription drug Desoxyn. (R)-(−)-methamphetamine (levomethamphetamine) is a much weaker central stimulant with mainly peripheral vasoconstrictor action, sold over the counter as an inhaled nasal decongestant, and is seldom misused. Illicit 'meth' is usually the (S)-isomer or an (S)-rich mixture. In rat brain synaptosomes, (S)-(+)-methamphetamine releases noradrenaline most potently (EC50 ≈ 12 nM), then dopamine (≈ 24 nM), and serotonin only weakly (≈ 736 nM): a strongly catecholamine-biased profile that underlies its powerful psychostimulant and sympathomimetic effects and its high addiction liability.

Biological targets

  • DAT
  • NET
  • SERT
  • VMAT2
  • TAAR1

Binding & functional measurements

TargetMeasurementSpecies
Noradrenaline transporterEC50 13 nMRat
Dopamine transporterEC50 11 nMRat
Serotonin transporterEC50 695 nMRat
5-HT1A receptorKi 8,070 ± 750 nMHuman
Dopamine transporterEC50 435 ± 74 nM
Emax 101.3 ± 2.9%		Human
Dopamine transporterKi 4,580 ± 760 nMHuman
Dopamine transporterKi 470 ± 80 nMMouse
Noradrenaline transporterEC50 125 ± 24 nM
Emax 102.6 ± 3%		Human
Noradrenaline transporterKi 1,820 ± 230 nMHuman
Noradrenaline transporterKi 190 ± 50 nMMouse
Serotonin transporterKi 9,280 ± 860 nMMouse
TAAR1Ki 550 ± 200 nMMouse
TAAR1Ki 350 ± 120 nMRat
α2-adrenoceptorKi 6,100 ± 1,600 nMHuman
Pharmacokinetics
BioavailabilityOral ≈67%, smoked/IV ≈90–100%
TmaxOral ≈3 h
Half-life≈9–12 h (urine pH dependent, acidic urine shortens)
Vd≈3–4 L/kg
Protein bindingLow (≈10–20%)
MetabolismHepatic CYP2D6 N-demethylation to active amphetamine. 4-hydroxylation
ExcretionRenal. ≈30–50% unchanged, increased by acidic urine
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

54 mg/kg (mouse, i.p.)

Methamphetamine is a powerfully reinforcing stimulant with high addiction and dependence liability. Compulsive redosing drives multi-day binges ('runs') with severe sleep deprivation, not eating and escalating doses. Acute risks are dominated by sympathetic overdrive and hyperthermia: dangerously high heart rate and blood pressure, chest pain, arrhythmias, stroke, seizures and heat stroke: worse with exertion, hot environments or other stimulants. It commonly causes intense anxiety, agitation, paranoia and a stimulant psychosis with hallucinations and delusions that can persist after use. Long-term use is linked to dopaminergic neurotoxicity, cognitive impairment, mood and psychotic disorders, marked weight loss, skin sores from compulsive picking, and severe dental decay ('meth mouth'). Smoking or injecting give the most intense rush and the highest dependence risk. Injecting adds infection, overdose and blood-borne-virus risk. There is no opioid-style antidote: overdose care is supportive (cooling, benzodiazepine sedation, blood-pressure control). Tolerance builds quickly, cardiac events and psychosis can occur even at ordinary doses in susceptible people, and it must never be combined with MAOIs (hypertensive crisis) or other stimulants.[5][4]

Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
Interactions & Contraindications

Drug interactions

MAOIs Hypertensive crisis, contraindicated within 14 days.[5][4]
SSRIs, SNRIs, Other serotonergic drugs Serotonin-syndrome risk (SSRIs/SNRIs, MDMA).[5]
Stimulants (amphetamines, cocaine) Additive cardiovascular stimulation and hyperthermia with other sympathomimetics.[5]
Urinary acidifiers or alkalinisers Acidifiers reduce and alkalinisers increase plasma levels (pH-dependent renal excretion).[4][5]

Contraindications

Cardiovascular disease, hypertension or arrhythmia symptomatic disease, moderate to severe hypertension or arrhythmias.[5]
Hyperthyroidism[5]
Closed-angle glaucoma[5]
Personal or family history of psychosis, schizophrenia or bipolar disorder or marked agitation.[5]
History of stimulant or substance use disorder
Concurrent MAOI, SSRI/SNRI or other serotonergic medication concurrent or recent MAOI use.
Usage & Context
  • A widely misused illicit stimulant ('crystal meth', 'ice', 'tina', 'crank'), taken for intense euphoria, energy, wakefulness, confidence, heightened libido and appetite suppression: smoked, insufflated, swallowed or injected.
  • A prescription medicine in a few countries: dextromethamphetamine (Desoxyn) is approved in the US for ADHD and short-term obesity treatment, though rarely used.
  • The (R)-(−) enantiomer is an over-the-counter nasal decongestant in some inhalers. Methamphetamine also has a long history of medical, military and industrial 'stay-awake' use (e.g. Pervitin).
Sources & Evidence
  1. PubChem: Methamphetamine (CID 10836) — identifiers & experimental properties
  2. FDA / DailyMed: Methamphetamine prescribing information — pharmacokinetics & metabolism
  3. Rothman RB, Baumann MH, Dersch CM, et al. (2001). Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39:32-41.

    PMID 11071707 · doi:10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3

  4. Cruickshank CC, Dyer KR (2009). A review of the clinical pharmacology of methamphetamine. Addiction 104:1085-99.

    PMID 19426289 · doi:10.1111/j.1360-0443.2009.02564.x

  5. Wikipedia: Methamphetamine — pharmacology (enantiomers, releaser mechanism, TAAR1), effects, harms & legal status CC BY-SA 4.0
  6. PsychonautWiki: Methamphetamine — dosage, duration & subjective effects CC BY-SA 4.0
  7. DEA Diversion Control Division: Controlled Substance Schedules (methamphetamine is Schedule II)
  8. GOV.UK: Controlled drugs list — methamphetamine is Class A (Misuse of Drugs Act 1971) OGL v3.0
  9. Anlage II BtMG — Betäubungsmittelgesetz (Gesetze im Internet): Metamfetamin/Methamphetamin, verkehrsfähig aber nicht verschreibungsfähig
  10. Fitzgerald LR, Gannon BM, Walther D, et al. (2024). Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones. Neuropharmacology 245:109827.

    PMID 38154512 · doi:10.1016/j.neuropharm.2023.109827

  11. Simmler LD, Buser TA, Donzelli M, et al. (2013). Pharmacological characterization of designer cathinones in vitro. Br J Pharmacol 168:458-70.

    PMID 22897747 · doi:10.1111/j.1476-5381.2012.02145.x

  12. Eshleman AJ, Wolfrum KM, Reed JF, et al. (2017). Structure-Activity Relationships of Substituted Cathinones, with Transporter Binding, Uptake, and Release. J Pharmacol Exp Ther 360:33-47.

    PMID 27799294 · doi:10.1124/jpet.116.236349

  13. Han DD, Gu HH (2006). Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs. BMC Pharmacol 6:6.

    PMID 16515684 · doi:10.1186/1471-2210-6-6

Further Information