Gaddum and LSD: the birth and growth of experimental and clinical neuropharmacology research on 5‐HT in the UK

Abstract

The vasoconstrictor substance named serotonin was identified as 5-hydroxytryptamine (5-HT) by Maurice Rapport in 1949. In 1951, Rapport gave Gaddum samples of 5-HT substance allowing him to develop a bioassay to both detect and measure the amine. Gaddum and colleagues rapidly identified 5-HT in brain and showed that lysergic acid diethylamide (LSD) antagonized its action in peripheral tissues. Gaddum accordingly postulated that 5-HT might have a role in mood regulation. This review examines the role of UK scientists in the first 20 years following these major discoveries, discussing their role in developing assays for 5-HT in the CNS, identifying the enzymes involved in the synthesis and metabolism of 5-HT and investigating the effect of drugs on brain 5-HT. It reviews studies on the effects of LSD in humans, including Gaddum's self-administration experiments. It outlines investigations on the role of 5-HT in psychiatric disorders, including studies on the effect of antidepressant drugs on the 5-HT concentration in rodent and human brain, and the attempts to examine 5-HT biochemistry in the brains of patients with depressive illness. It is clear that a rather small group of both preclinical scientists and psychiatrists in the UK made major advances in our understanding of the role of 5-HT in the brain, paving the way for much of the knowledge now taken for granted when discussing ways that 5-HT might be involved in the control of mood and the idea that therapeutic drugs used to alleviate psychiatric illness might alter the function of cerebral 5-HT.British Journal of Pharmacology (2008Pharmacology ( ) 154, 1583Pharmacology ( -1599 doi:10.1038/bjp.2008 published online 26 May 2008 Keywords: 5-hydroxytryptamine; lysergic acid diethylamide; depression; brain; antidepressant drugs; monoamines; history; platelets; monoamine oxidase inhibitors; tricyclic antidepressants Abbreviations: 5-HIAA, 5-hydroxyindole acetic acid; 5-HTP, 5-hydroxytryptophan; NIH, National Institutes of Health; MAO, monoamine oxidase IntroductionThe history of recent science can be evaluated in two ways, not necessarily exclusively. One approach examines the published literature, primarily journals, to give an accurate time line of the primacy of presentation of new knowledge to the world, although this does not always indicate primacy of discovery. Consequently, the information gained does not always give a clear idea of how the investigator became involved in a specific research project or the way in which ideas developed. The other approach is to talk to the scientists involved in the research, or to colleagues or friends of those involved in the research, to obtain their personal views of events, people and priority. This latter approach has been used recently in the area of psychopharmacology (Healy, 1996(Healy, , 1998(Healy, , 1999 and is of course the basis of many personal reviews published in major journals. However, such reviews can be biased by personal memory and even, it has to be said, personal prejudice. Goodfield, a scientific...

Psychedelics

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