Abstract

Use of illicit stimulants such as methamphetamine, cocaine, and ecstasy is an increasing health problem. Chronic use can cause neurotoxicity in animals and humans but the long-term consequences are not well understood. The aim of the current study was to investigate the long-term effect of stimulant use on the morphology of the human substantia nigra. We hypothesised that history of illicit stimulant use is associated with an abnormally bright and enlarged substantia nigra (termed ‘hyperechogenicity’) when viewed with transcranial sonography. Substantia nigra morphology was assessed in abstinent stimulant users (n = 36; 31±9 yrs) and in two groups of control subjects: non-drug users (n = 29; 24±5 yrs) and cannabis users (n = 12; 25±7 yrs). Substantia nigra morphology was viewed with transcranial sonography and the area of echogenicity at the anatomical site of the substantia nigra was measured at its greatest extent. The area of substantia nigra echogenicity was significantly larger in the stimulant group (0.273±0.078 cm2) than in the control (0.201±0.054 cm2; P<0.001) and cannabis (0.202±0.045 cm2; P<0.007) groups. 53% of stimulant users exhibited echogenicity that exceeded the 90th percentile for the control group. The results of the current study suggest that individuals with a history of illicit stimulant use exhibit abnormal substantia nigra morphology. Substantia nigra hyperechogenicity is a strong risk factor for developing Parkinson's disease later in life and further research is required to determine if the observed abnormality in stimulant users is associated with a functional deficit of the nigro-striatal system.

Highlights

  • Illicit stimulants such as amphetamine, methamphetamine, cocaine, and ecstasy (3,4-methylenedioxymethamphetamine or MDMA) temporarily increase alertness, mood, and euphoria

  • Amphetamine, methamphetamine, and cocaine administration all result in excess accumulation of mainly dopamine [1,2,3] whereas ecstasy administration results in accumulation of mainly serotonin and noradrenaline [4]

  • Animal and in vitro studies show that amphetamine and methamphetamine disrupt synaptic vesicles, inhibit monoamine oxidase [5,6], and block and/ or reverse vesicular monoamine transporters [7,8]

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Summary

Introduction

Illicit stimulants such as amphetamine, methamphetamine, cocaine, and ecstasy (3,4-methylenedioxymethamphetamine or MDMA) temporarily increase alertness, mood, and euphoria These effects arise from their acute mechanism of action on the monoamine neurotransmitters dopamine, noradrenaline, and serotonin. Animal and in vitro studies show that amphetamine and methamphetamine disrupt synaptic vesicles, inhibit monoamine oxidase [5,6], and block and/ or reverse vesicular monoamine transporters [7,8]. Both amphetamines and cocaine affect dopamine reuptake transporters [7,8,9]

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