Differential Effects of Two Amphetamine‐barbiturate Mixtures in Man

Abstract

Mixtures of amphetamine and a barbiturate continue to be fairly widely used in psychiatry, especially in the treatment of mild anxiety and depression (Lancet, 1962; British Medical Journal, 1962;Ornstein & Whitman, 1963), but relatively little is known about the effects of such mixtures from laboratory experiments on man. In a previous investigation (Legge & Steinberg, 1962) a mixture of 15 mg of amphetamine sulphate and 300 mg of cyclobarbitone and the two ingredients separately were studied in normal human subjects, and it was found that the mixture produced a different pattern of effects from the separate ingredients: it impaired the efficiency of the performance of three simple tasks less than did the barbiturate alone; it produced almost as big a rise in the pulse rate as did amphetamine alone; and it produced spontaneous reports suggesting " elation " from more subjects than did either drug separately, though there was no corresponding increase in reports of other feelings and sensations. The mixture used contained proportionally several times as much barbiturate as a widely used commercial preparation, Drinamyl (Smith, Kline & French), which contains dexamphetamine sulphate and amylobarbitone sodium in a ratio of 1: 6.5. In the experiments to be reported the earlier mixture was therefore compared with a mixture which contained the two drugs in approximately the same proportions as Drinamyl, except that for practical reasons amphetamine sulphate and cyclobarbitone were again the compounds used. Since the main clinical aim of using these drug mixtures appears to be to induce favourable changes in subjective reactions, especially in moods, a standardized and detailed method was adopted to elicit reports of the subjects' feelings. Otherwise the test methods were similar to those previously used. METHODSThe subjects were preclinical medical students in their fourth term, and the experiments were carried out in the course of practical classes in which the students learned simple ways of assessing in man effects of drugs acting on the central nervous system. Before the experiment it was explained that each student would receive a tablet containing either amphetamine, or cyclobarbitone, or one of two mixtures of the two, or lactose as a control; the main effects of amphetamine and barbiturate drugs were described in general terms. Regarding the mixtures, the subjects were told that combinations of depressant and stimulant drugs were fairly widely used in medicine, and that the effects would be discussed at the end of the class. The following were studied:

A comparison of bupropion hydrochloride with dexamphetamine and amitriptyline in healthy subjects.

“…Reaction time, short term memory and tapping were impaired by amitriptyline as previously reported by the authors. Only the brief tapping test, however, was improved by dexamphetamine, indicating its sensitivity to stimulant drugs (Dickens, Lader & Steinberg, 1965).…”

Institute of Psychiatry Clinical Psychopharmacology Research Team

“…Other depressant drugs which have been evaluated include the barbiturates and barbiturateamphetamine mixtures (Dickins et a!., 1965). The effects of cyclobarbitone were found to be quite marked with respect to physiological measures such as the pulse rate and the activity of palmar sweat glands (Lader, 1965a, b).…”

Conversation with Ian Stolerman

“…We discussed the next step, and I thought it was important to work in a better‐controlled environment and also to determine whether the mecamylamine was actually blocking nicotine. I proposed an adaptation of the experimental situation used by Hannah Steinberg for studies of amphetamine–barbiturate mixtures [4], where experimental subjects sat around a table work in pairs carrying out psychomotor tests and each one would score the performance of the other. The psychomotor tests were there in part to disguise the main purpose of the work, which was to score smoking behaviour.…”