12 Several clinical and postmortem studies clearly associate the use of methamphetamine with cardiovascular disease, 13 and cardiovascular disease represents the second leading cause of death among methamphetamine abusers following only accidental overdose. While exposure of methamphetamine results in deleterious consequences to the neurological system, it also elicits a range of other adverse effects. α2 AR indicates α2 adrenergic receptor σ1r, sigma-1 receptor DAT, dopamine transporter NET, norepinephrine transporter TAAR1, trace amino acid receptor 1 and VMAT2, vesicular monoamine transporter 2. C, Catecholamine-independent effects of methamphetamine.

B, Effects of methamphetamine on catecholamine signaling. A, Chemical structures of the catecholamines dopamine and norepinephrine, amphetamine, and methamphetamine. 11 Additionally, methamphetamine induces neuronal cell death associated with endoplasmic reticulum stress, mitochondrial dysfunction, and enhanced reactive oxygen species (ROS) production. 10, 11 Although this results in acute increases in dopamine and norepinephrine signaling driving the methamphetamine-associated euphoria, chronic methamphetamine use induces neurotoxicity in dopaminergic axon terminals, associated with reduced dopamine production and reduced expression of the DAT. Interaction between methamphetamine and the DAT (dopamine transporter) and NET (norepinephrine transporter) prevents catecholamine uptake and stimulates catecholamine release through exchange diffusion and modulation of receptor activity ( Figure 1B). 10, 11 Additionally, methamphetamine inhibits the catecholamine catabolizing enzyme monoamine oxidase to stabilize cytosolic catecholamine levels. Methamphetamine binds vesicular monoamine transporter-2 and accumulates in vesicles where it alters the pH resulting in catecholamine release into the cytosol ( Figure 1B). 5 Methamphetamine functions in neuronal tissue by promoting catecholamine (eg, dopamine and norepinephrine) signaling through multiple mechanisms. This moiety makes methamphetamine highly lipophilic, thereby allowing it to increasingly penetrate the blood-brain barrier. Methamphetamine (N-methyl-alpha-methylphenethylamine) is a cationic molecule and chiral compound based around a phenylethylamine core, obviously distinguishable from its amphetamine analogs by an additional methyl group ( Figure 1A). 8, 9 Methamphetamine use is a growing worldwide phenomenon, with the consumption of the drug occurring independently of wealth, geographic location, and culture. Epidemiological studies demonstrate that amphetamine-type stimulants are the most widely used illicit drug in the world after cannabis, with ≤51 million global users between the ages of 15 and 64 years. 7 These effects are largely due to the ability of methamphetamine to enhance monoamine (eg, dopamine and noradrenaline) levels in the synaptic cleft. 5, 6 Widely used for its ability to increase wakefulness and physical activity and decrease appetite, methamphetamine’s widespread misuse results from the intense euphoria the drug produces. 4 Methamphetamine-a highly potent amphetamine derivative-produces significant effects on physical, behavioral, cognitive, and psychiatric output. 1–3 At the same time, however, methamphetamine use has also been increasing across the country, indicating that the use of this drug is developing into its own epidemic. Reports from a variety of sources suggest that the United States is currently experiencing an opioid epidemic initiated by the unanticipated proliferation of opioid prescriptions starting in the late 1990s, with the subsequent accelerated misuse of these drugs for nonmedical purposes. Remodeling of cardiac tissue following methamphetamine exposure promotes dilated cardiomyopathy and may enhance the susceptibility to cardiac arrhythmias. Symptoms of myocardial infarction among methamphetamine users result from both acute coronary vasospasm and enhanced atherosclerotic plaque formation. The use of methamphetamine is associated with pulmonary hypertension, particularly in patients showing specific polymorphisms in the methamphetamine catabolizing enzyme carboxylesterase 1. Methamphetamines may promote cardiovascular disease through catecholamine toxicity or through direct effects on cardiac and vascular tissue. Methamphetamine use is rising globally resulting in significant morbidity and mortality driven by a poorly understood increase in multiple forms of cardiovascular disease.

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Stroke: Vascular and Interventional Neurology.

Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).

Amphetamine vs methamphetamine