The need for speed: an update on methamphetamine addiction

Abstract

The psychostimulant methamphetamine (MA) is a highly addictive drug that has surged in popularity over the last decade in North America. A burgeoning number of clandestine drug laboratories has led to dramatic increases in MA production, which have resulted in significant public health, legal and environmental problems. Current evidence indicates that exposure to MA is neurotoxic, and neuroimaging studies confirm that long-term use in humans may lead to extensive neural damage. These physiological changes are commonly associated with persistent forms of cognitive impairment, including deficits in attention, memory and executive function. In the present review, we provide a comprehensive description of the factors relating to MA use and the major health-related consequences, with an emphasis on MA-induced psychosis. It is hoped that increased knowledge of MA abuse will provide the basis for future treatment strategies.

Fig. 1: Chemical structure of methamphetamine (1), as well as the closely related psychostimulants d-amphetamine (2) and 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) (3). AMPH = amphetamine; METH = methamphetamine

Fig. 2: Physiological mechanisms by which methamphetamine increases synaptic levels of monoamines, principally dopamine (DOPA). Mechanisms include the redistribution of catecholamines from synaptic vesicles to the cytosol (1) and the reverse transport of neurotransmitter through plasma membrane transporters. In addition, amphetamines have been shown to block the activity of monoamine transporters (2), similar to cocaine, and decrease expression of dopamine transporters at the cell surface (3). Amphetamines can increase cytosolic levels of monoamines by inhibiting the activity of monoamine oxidase (MAO) (4) and increase activity and expression of the tyrosine hydroxylase (5). DAT = dopamine transporter; vMAT = vesicular monoamine transporter.

Fig. 3: (A) The central hypothesis of the opponent-process theory of motivation, as envisioned by Solomon and Corbit (14), is that emotions may be considered as pairs of opposites. Thus, when one emotion or affective state is experienced (Emotion a), an opposing emotion or affective state is triggered after a period of time (Emotion b). (B) With repeated stimulations, the opposing emotion or affective state increases in strength, decreasing the experience of the primary emotion or affective state and producing an enduring aftereffect.