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The present study investigated the effects of intravenous injections of 2,5-dimethoxy-4-methylamphetamine (DOM) on central serotonergic and dopaminergic function in humans. Fourteen healthy subjects received saline, 0.4, 0.8, or 2.0 mg/kg DOM on separate days. Symptoms of drug-induced excitement, nervousness, or tension were reported by 11 subjects at all doses, and all subjects reported one or more positive effects of DOM. Only one subject reported nausea at 0.8 mg/kg, and all subjects reported only mild to moderate dizziness and/or slowness at 2.0 mg/kg. Subjects were not aware of any symptoms of drug-induced excitement after DOM administration. The subjective effects of DOM were of little clinical importance. DOM reduced growth hormone (GH) responses and increased prolactin (PRL) responses to synthetic GHRH (1-29)-NH2. GH responses returned to preinjection values by 2 h after DOM injection. PRL responses did not change following DOM administration. DOM induced an increase in the 5-HIAA/5-HT ratio in cerebrospinal fluid and thus displaced CSF 5-HT from presynaptic 5-HT storage pools into the extracellular space. However, DOM did not significantly affect the CSF 5-HIAA/5-HIAA+5-HT ratio, suggesting that DOM did not increase 5-HT reuptake. The DOM-induced increased 5-HIAA/5-HT ratio was also found in the CSF of subjects who received 2.0 mg/kg DOM before the administration of synthetic 5-HT. DOM, however, did not change the PRL response to 10 micrograms/kg 5-HT or the PRL response to the somatostatin analog SMS 201-995. DOM did not change the PRL response to saline challenge. These results provide further evidence that DOM does not increase 5-HT reuptake in the human CNS. Since DOM
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