BACKGROUND: In rats, amino acid mixtures lacking tyrosine and its precursor phenylalanine decrease the release of dopamine produced by the psychostimulant drug amphetamine. Amphetamine has been proposed as a model for clinical mania. AIMS: To assess whether dietary tyrosine depletion attenuates the psychostimulant effects of methamphetamine in healthy volunteers and diminishes the severity of mania in acutely ill patients. METHOD: Sixteen healthy volunteers received a tyrosine-free amino acid mixture and a control mixture in a double-blind crossover design 4 h before methamphetamine (0.15 mg/kg). Twenty in-patients meeting DSM-IV criteria for mania were allocated blindly and randomly to receive either the tyrosine-free mixture or the control mixture. RESULTS: The tyrosine-free mixture lowered both subjective and objective measures of the psychostimulant effects of methamphetamine. Ratings of mania were lower in the patients who received the tyrosine-free mixture. CONCLUSIONS; Decreased tyrosine availability to the brain attenuates pathological increases in dopamine neurotransmission following methamphetamine administration and putatively in mania.
Br J Psychiatry
356 - 360
Adult, Analysis of Variance, Bipolar Disorder, Brain, Central Nervous System Stimulants, Cross-Over Studies, Dopamine, Double-Blind Method, Female, Humans, Male, Methamphetamine, Middle Aged, Psychiatric Status Rating Scales, Tyrosine