Abuse of Amphetamines and Structural Abnormalities in the Brain

Abstract

We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse, and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques that include manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common, and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre-existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain structure.

The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans

“…A major study strength is the within-subjects, placebocontrolled design that allowed for participants to serve as their own controls, addressing issues related to the comparison of medication effects across participants that may have differential structural brain changes due to varying histories of methamphetamine use (Berman et al, 2008). Another strength is the investigation of medication-induced alterations in CBF.…”

Illicit substance use in pregnancy – a review

“…44 There is evidence that prenatal exposure to amphetamines in rodents and humans is associated with abnormal neurological development with lower CNS striatal volumes. 45 As with other vasoconstrictive illicit drugs, an association between amphetamines and gastroschisis has been reported. 15,27 Neonates exposed to amphetamine in utero display increased physiological stress, lethargy and lower arousal in the early postpartum period, 46 and long-term data suggest lower performance at 14 years of age 47 associated with smaller head circumference at birth, although overall follow-up data are limited.…”

Stereological Analysis of the Brain in Methamphetamine Abusers Compared to the Controls

“…In addition, magnetic resonance imaging (MRI) investigations also revealed 3 key changes in the brain structure of MA consumers (4,26); reduction of the gray matter volume in the limbic system and cingulate gyrus, explicit hypertrophy in the white matter of temporal lobe (especially around hippocampus), and reduction of hippocampus volume (27). Some volumetric studies also showed that MA abuse can cause reduction of volume in striatum (28), hippocampus (29), basal ganglia and cerebellum, and increment of cortical gray and white matters of some areas of the brain (30,31).…”

“…Other MA side effects include cardiovascular disorders, hyperthermia, decreased appetite, insomnia, seizure, epistaxis, extreme weight-loss, nausea, vomiting, severe dental problems (meth mouth), losing teeth, gum disease, stroke, muscle cramps, and tremor (14). Important issue about MA chronic use can remain psychological complications such as depression, anxiety, and paramnesia even after years of pulling out of its use (4,16). Therefore, it seems that MA consumers, compared to abusers of other addictive materials, face more and various psychological disorders (17).…”

“…MA is a white and crystalline powder with bitter taste. It is prescribed by physicians to treat attentiondeficit/hyperactivity disorder (ADHD); nowadays due to its high potential for abuse as well as addictive and stimulant effects, medical uses of MA are limited (4).…”