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Methamphetamine

Group: Stimulants
Tags: Amphetamines
Nicknames: meth, Tina’ ‘ice, glass’ ‘crystal, crank, yaabaa’ (Thai for ‘crazy pills’) and ‘shabbu
Last reviewed: October 2026

Pharmacology

Methamphetamine works mainly by causing a large release of dopamine and noradrenaline in the brain, and to a lesser extent serotonin, while also blocking their reuptake (similar to MDMA). This combination along with its lipophilicity (that allows it to cross the blood brain barrier more easily) is what makes it considerably more potent than amphetamine or cocaine, both in terms of subjective effects and neurotoxic potential.

Taken orally, methamphetamine reaches peak plasma concentration in ≈ 2.5–3.5 hours, with an average elimination half-life of roughly 10 hours (smoked or injected use produces a faster onset but a similar overall half-life). This long half-life is part of why methamphetamine's effects and comedown are typically much longer-lasting than other stimulants.

It's broken down in the liver, mainly by the enzyme CYP2D6, into amphetamine (itself active) and several inactive metabolites. Because a meaningful proportion of the population are "poor metabolisers" of CYP2D6, individual response and comedown length can vary considerably between users. Drugs that inhibit CYP2D6 including some SSRIs (e.g. fluoxetine, paroxetine) can raise methamphetamine levels in the blood and increase the risk of toxicity. Combining methamphetamine with MAOI antidepressants is particularly dangerous, as MAOIs can drastically increase and prolong its effects on noradrenaline release, raising the risk of dangerously high blood pressure.

With repeated heavy use, the brain's dopamine system becomes depleted and desensitised, which is thought to underlie both the severity of the comedown and the psychological dependence that can develop as well as the mood and cognitive difficulties reported by people trying to stop after sustained heavy use.

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