Lithium does not attenuate the effects of D-amphetamine in healthy volunteers

It has previously been suggested that an acute dose of 20 mg D-amphetamine can be a good model of mania. In the present study we attempted to validate this model by determining if subacute administration of lithium (for 7 days) would attenuate the effects of 20 mg D-amphetamine in human volunteers. Sixteen healthy volunteers were enrolled in this double-blind, placebo-controlled study. Subjects received either oral lithium at night for 7 nights (1200 mg) (n = 10) or matching placebo (n = 6). On day 8, subjects were assessed at baseline and then once each hour for 3 h following an oral dose of D-amphetamine (20 mg). Subjective states were measured with visual analog scales, and pulse, systolic and diastolic blood pressure were also repeatedly assessed. The results showed that D-amphetamine alone produced a number of subjective and cardiovascular changes, as expected. However, lithium did not attenuate any of these subjective or cardiovascular changes, as would be predicted if D-amphetamine were a valid model of mania. It is suggested that whilst D-amphetamine may produce effects similar to mania, its mechanism of action is different from that which occurs in mania, and therefore the usefulness of the amphetamine model of mania is called into question.