Michael A. Sherer

Cardiovascular responses to cocaine placebo in humans: A preliminary report

Cardiovascular responses after placebo-cocaine injections were in the same direction as the effect of cocaine iv in 22 male volunteers. Subjects received iv placebo in a room where they had been given repeated doses of iv cocaine. The placebo response consisted of an increase from baseline values of systolic and diastolic blood pressure and pulse rate. The control group, 8 subjects, which was not exposed to a conditioning phase, showed a smaller increase in the pulse rate and systolic blood pressure after the placebo injection. The results, in accordance with animal literature, suggest the existence of cocaine-conditioned effects in humans.

Effects of S-adenosyl-methionine on plasma norepinephrine, blood pressure, and heart rate in healthy volunteers

S-adenosyl-methionine (SAMe) is currently undergoing trials as a possible antidepressant. Because SAMes mechanism of action is obscure and norepinephrine (NE) is often implicated in affective disorders, we studied the effects of SAMe on this neurotransmitter in volunteers. Plasma NE and 3-methoxy-4-hydroxyphenylglycol (MHPG) in the supine and standing position were studied before and after acute placebo or a single 400 mg dose of SAMe and following seven daily administrations; concomitant measures were heart rate (HR) and blood pressure. Subjects were unable to distinguish acute drug from placebo, and although chronic SAMe administration was open, they reported no behavioral effects. Standing HR and plasma NE were reduced following chronic SAMe. Qualitatively similar changes are obtained following chronic treatment with monoamine oxidase inhibitors (MAOIs). However, unlike MAOIs, chronic SAMe treatment was not associated with changes in plasma MHPG. Exaggerated standing NE is found in depressed patients; SAMe may reduce this abnormal response, providing a clue for its mechanism of action in depression.

Acute noradrenergic effects of desipramine in depression

As a probe of the noradrenergic system in depression, single oral doses of the tricyclic antidepressant desipramine (100 mg) and placebo were administered to unipolar and bipolar depressed patients and healthy volunteers. Plasma concentrations of norepinephrine (NE) were determined 2-3 hours after dosing, with subjects in supine and upright positions. On the placebo day plasma NE was low in a subset of bipolar patients; both groups of depressives demonstrated an exaggerated increase in plasma NE upon standing. After desipramine dosing, the orthostatic procedure resulted in even greater relative increments in plasma NE in both patient groups, with no change in volunteers. These data are consistent with noradrenergic dysregulation in depression.

Noradrenergic and Cardiovascular Effects of Chronic S-Adenyosyl-Methionine in Healthy Volunteers

S-Adenosyl-Methionine (SAMe), the universal methyl donor in methylation reactions, has been extensively studied over the past twenty Years in a variety of neuropsychiatric conditions (Agnoli et al., 1976; Fazio et al., 1974; Carney et al., 1983). Following early case reports indicating that SAMe might have a mood-elevating effect, studies were conducted in Italy (Agnoli et al., 1976; Del Vecchio et al., 1978; Miccoli et al., 1978; Muscettola et al., 1982; Salvadorini et al., 1980), Germany (Kufferle et al., 1982) and in the United States (Lipinski et al., 1984); these provide evidence that parenterally administered SAMe can produce clinical improvement in depressed patients. In comparison to standard antidepressants, SAMe is claimed to be as effective as the tricyclics while producing fewer side effects.