Why is parkinsonism not a feature of human methamphetamine users?
For more than 50 years, methamphetamine has been a widely used stimulant drug taken to maintain wakefulness and performance and, in high doses, to cause intense euphoria. Animal studies show that methamphetamine can cause short-term and even persistent depletion of brain levels of the neurotransmitter dopamine. However, the clinical features of Parkinson's disease, a dopamine deficiency disorder of the brain, do not appear to be characteristic of human methamphetamine users. We compared dopamine levels in autopsied brain tissue of chronic methamphetamine users with those in patients with Parkinson's disease and in a control group. Mean dopamine levels in the methamphetamine users were reduced more in the caudate (-61%) than in the putamen (-50%), a pattern opposite to that of Parkinson's disease. Some methamphetamine users had severely decreased dopamine levels, within the parkinsonian range, in the caudate (up to 97% dopamine loss) but not in the putamen. As the putamen and caudate subserve aspects of motor and cognitive function, respectively, our data suggest that methamphetamine users are not parkinsonian because dopamine levels are not sufficiently decreased in the motor component of the striatum. However, the near-total reduction in the caudate could explain reports of cognitive disturbances, sometimes disabling, in some drug users, and suggests that treatment with dopamine substitution medication (e.g. levodopa) during drug rehabilitation might be helpful.
Moszczynska
Anna
A
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada.
Fitzmaurice
Paul
P
Ang
Lee
L
Kalasinsky
Kathryn S
KS
Schmunk
Gregory A
GA
Peretti
Frank J
FJ
Aiken
Sally S
SS
Wickham
Dennis J
DJ
Kish
Stephen J
SJ
D000293:Adolescent; D000328:Adult; D019969:Amphetamine-Related Disorders / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000473:pathology; D002423:Cause of Death; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects; D004298:Dopamine / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000378:metabolism; D011699:Putamen / Q000737:chemistry / Q000187:drug effects
D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D004298:Dopamine