Methamphetamine
Methamphetamine is a potent synthetic stimulant of the substituted amphetamine class. First synthesized in 1893 by Japanese chemist Nagayoshi Nagai, it saw widespread use during World War II to combat fatigue and was later prescribed for obesity and attention deficit disorder under the brand name Desoxyn.1 Because it is more lipid-soluble than amphetamine, it enters the brain faster. Methamphetamine carries a significant risk of addiction and remains widely used as a street drug.2
Contents
Dosage & Duration
Dosage
Duration
Subjective Effects
Effects vary widely by individual, dose, and context.
Physical
The physical effects of Methamphetamine can be broken down into several components which progressively intensify proportional to dosage.
Cognitive
The cognitive effects of methamphetamine can be broken down into several components which progressively intensify proportional to dosage. The general head space of methamphetamine is described by many as one of extreme mental stimulation, increased focus, and powerful euphoria. It contains a large number of typical stimulant cognitive effects. Although negative side effects are usually mild at low to moderate dosages, they become increasingly likely to manifest themselves with higher amounts or extended usage. This particularly holds true during the offset of the experience.
Reagent Testing
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Pharmacology
Pharmacodynamics
Methamphetamine acts primarily as a potent releasing agent of dopamine, norepinephrine, and to a lesser extent serotonin through several converging mechanisms. As a potent full agonist at trace amine-associated receptor 1 (TAAR1), it induces phosphorylation and functional reversal of monoamine transporters on the cell membrane, driving neurotransmitter efflux into the synaptic cleft.2 It also inhibits vesicular monoamine transporter 2 (VMAT2), preventing monoamine storage in synaptic vesicles and promoting their release into the cytosol. Additional contributing mechanisms include increased intracellular calcium driving dopamine transporter phosphorylation, enhanced expression of the dopamine-synthesizing enzyme tyrosine hydroxylase, and reduced surface expression of dopamine transporters. Methamphetamine also acts as an agonist at alpha-2 adrenergic and sigma receptors (with greater affinity for σ1 than σ2) and inhibits both monoamine oxidase A and B.
Pharmacokinetics
Methamphetamine is metabolized primarily by the liver enzyme CYP2D6, with amphetamine and 4-hydroxymethamphetamine as its principal metabolites. Several additional minor metabolites are produced, a number of which retain sympathomimetic activity. Methamphetamine is itself a CYP2D6 inhibitor, and co-administration of other CYP2D6 inhibitors prolongs its elimination half-life. The elimination half-life averages 9 to 12 hours but ranges broadly from 5 to 30 hours. Oral bioavailability is approximately 67%, rising to 79% via the intranasal route and 67 to 90% when smoked, with complete bioavailability when administered intravenously.
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.
Unsafe
AvoidThere is considerable risk of physical harm when taking these combinations, they should be avoided where possible.
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Tolerance
Dopaminergic stimulants
Harm Potential
Addiction & Dependence
Psychological
Extremely HighMethamphetamine is widely considered one of the most addictive substances due to the intense euphoria it produces. It has extremely high abuse liability with strong compulsive redosing patterns, particularly when vaporized or injected. The drug produces powerful cravings and psychological dependence develops readily with repeated use.
Physical
HighPhysical dependence develops with regular use. Withdrawal symptoms occur in up to 87.6% of chronic high-dose users and persist for three to four weeks with a marked crash phase in the first week. Symptoms include anxiety, drug craving, dysphoric mood, fatigue, increased appetite, lack of motivation, and vivid dreams. Depression from methamphetamine withdrawal lasts longer and is more severe than that of cocaine withdrawal.
Toxicity
At moderate to heavy recreational doses, methamphetamine is directly neurotoxic to dopaminergic and serotonergic neurons, causing adverse changes in brain structure and function including reductions in grey matter volume. Chronic abuse is associated with an increased risk of Parkinson's disease.
Methamphetamine produces vasoconstriction, tachycardia, and hypertension, with elevated risk of stroke and heart attack.1 Abnormal heartbeats and irregular heart rhythms may be life-threatening. Chronic consumption is associated with brain hemorrhages and coronary atherosclerosis.
Kidney damage and fatal kidney disorders have been reported with chronic use. Kidney failure may occur in overdose situations.
Liver damage has been associated with chronic methamphetamine use.
Fatal lung disorders and pulmonary fibrosis have been associated with chronic use. Pulmonary hypertension may occur in overdose.
Heavy users may lose their teeth abnormally quickly regardless of route of administration, a condition known as meth mouth. This is caused by poor oral hygiene, dry mouth, teeth grinding, and the habit of consuming sugary beverages to relieve dry mouth symptoms.
Long-term users may develop skin sores from scratching due to itchiness or delusional parasitosis, compounded by poor diet and hygiene.
Rhabdomyolysis may occur during overdose or extended binges.
Psychosis Risk
Chronic high-dose use can induce stimulant psychosis presenting with paranoia, hallucinations, delusions, and delirium. This is similar to paranoid schizophrenia and may include bizarre and violent behavior. About 5-15% of users who develop amphetamine psychosis fail to recover completely. Symptoms are magnified by sleep deprivation which commonly accompanies heavy use. Psychosis very rarely arises from therapeutic use.
Seizure Risk
Seizures are an uncommon effect but can occur in those predisposed to them, especially during physical stress such as dehydration, fatigue, or malnourishment, or with extended misuse. Death from methamphetamine poisoning is typically preceded by convulsions and coma.
History & Culture
Discovery and Early Synthesis
The development of methamphetamine followed shortly after the creation of its parent compound. Romanian chemist Lazăr Edeleanu first synthesized amphetamine in Germany in 1887, naming it phenylisopropylamine. Six years later, Japanese chemist Nagai Nagayoshi achieved the first synthesis of…
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Legality
International
UN Convention on Psychotropic Substances 1971: Schedule II
By Country
References
Source Pages
Citations
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Further Reading
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