A Pilot Study of Pathogenic Mechanisms in Amphetamine Psychosis Utilizing Differential Effects of D and L Amphetamine^*

Summary

This preliminary investigation is, to a great extent, based on the prior work of two investigators, Griffith (12, 13) who has demonstrated the safety and feasibility of inducing amphetamine psychoses under experimental conditions, and Taylor and Snyder (28), who have demonstrated differential effects of the d and 1 isomers of amphetamine on noradrenergic and dopaminergic mechanisms and their respective animal behavioral correlates, hyperactivity and stereotypy.

In an attempt to ascertain which of these mechanisms was more crucial in amphetamine psychotogenesis, a volunteer subject who was non-schizophrenic and an experienced amphetamine user, was administered large doses of d, racemic and 1 amphetamine under controlled conditions, in three separate experiments. Cardiovascular effects and hyperactivity, (as measured by a pedometer were greater with d amphetamine. Disoganization of thought and perception that critical disparaging attitudes were being taken toward him by the nursing staff were also somewhat greater with d than with 1 amphetamine. However, his characteristic psychotic syndrome (established in prior experiments) consisting primarly of referential ideation, ideas of smelling badly, and olfactory hallucinations, was more pronounced with 1 than with d amphetamine and loss of insight and fear were greater at this time.

While these studies are preliminary and require extensive replication, the comparative psychotogenic potencies of d vs 1 amphetamine observed in this study suggests that attention be directed to the possible role of dopaminergic mechanisms in amphetamine psychosis.

Zusammenfassung

Es wird die Reaktion freiwilliger Versuchspersonen auf die Verabreichung Psychosen erzeugender Dosen Amphetamin beschrieben. Der Effekt pharmakologischer Vorbehandlungen, welche Synthese und Ablagerung von Monoaminen im Gehirn und das Verhalten unter Amphetamin beeinflussen, wird diskutiert. Resultate in bezug auf gewisse Tierstudien über die Wirkung von Amphetamin, Cocain und L-DOPA bei Hunden werden ebenfalls diskutiert.