Neurotoxicity of methamphetamine and 3,4-methylenedioxymethamphetamine

Abstract

Amphetamines are a class of psychostimulant drugs that are widely abused for their stimulant, euphoric, empathogenic and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, methamphetamine and 3,4 methylenedioxymethamphetamine (MDMA) produce persistent damage to dopamine and serotonin nerve terminals. This review summarizes the numerous interdependent mechanisms including excitotoxicity, mitochondrial damage and oxidative stress that have been demonstrated to contribute to this damage. Emerging non-neuronal mechanisms by which the drugs may contribute to monoaminergic terminal damage, as well as the neuropsychiatric consequences of this terminal damage are also presented. Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) have similar chemical structures and pharmacologic properties compared to other abused substances including cathinone (khat), as well as a relatively new class of novel synthetic amphetamines known as ‘bath salts’ that have gained popularity amongst drug abusers.

Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin

“…Our results are also directly relevant to the situation in the human brain, where a loss-of-function mutation in the Tph2 gene has been described resulting in an approximately 80% decrease in serotonin production [30]. We speculate that similar changes may also accompany the severe serotonergic damage that has been described with 3,4-methylenedioxymethamphetamine (MDMA) use [31].…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…A summary of the primary mechanisms is provided here, whereas more in-depth information can be found in relevant reviews Carvalho et al, 2012;Goncalves et al, 2014;Halpin et al, 2014) a. Oxidative stress: DA oxidation and drug metabolites as sources of reactive species. Support for the involvement of oxidative stress as a causal mechanism in amphetamine toxicity comes from a number of studies demonstrating attenuation of METH-and MDMA-induced monoamine loss after coadministration of spin-trapping agents or antioxidants such as N-acetylcysteine, ascorbic acid, vitamin E, and selenium (Wagner et al, 1985;De Vito and Wagner, 1989;Colado and Green, 1995;Fukami et al, 2004;Barayuga et al, 2013).…”

Buprenorphine Added on Brief Cognitive Behavioral Therapy for Treatment of Methamphetamine Use Disorder

“…Methamphetamine use is accompanied by both structural and functional changes in the brain that lead to impairment in executive function (6). Cognitive squeal following MA use may also reduce the efficacy of psychological interventions, such as the Matrix model (7).…”