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A close relationship exists between the activity of the pituitary—adrenal system and the psychological state of a subject. For example, marked mood changes occur in Cushing's syndrome and in Addison's disease (Michael & Gibbons, 1963) and severe depression may increase the plasma cortisol concentration and abolish its physiological diurnal rhythm (Gibbons & McHugh, 1962; Besser & Butler, 1967). Other forms of stress such as surgical operations (Estep, Island, Ney & Liddle, 1963) have similar effects as does hypoglycaemia (Landon, Wynn & James, 1963). We now report the effect on the plasma cortisol level in man of two centrally acting drugs: dexamphetamine, which has predominantly stimulant actions, and chlordiazepoxide, a benzodiazepine which is now much used in the treatment of anxiety instead of small doses of barbiturates. The drugs were given separately and in combination.

Forty-four healthy volunteers (aged 18–32, 32 male) were randomly divided into four equal groups. All subjects