Psycho- and immunopharmacological factors relevant to selection of volunteers in clinical studies

There are many well-known factors and variables which play a role in the evaluation of pharmacokinetic and pharmacodynamic results gained from healthy volunteers. The genetic constitution is influenced by age, sex, circadian and seasonal variations, dietary factors, immunological function, alcohol intake, smoking, etc. Vesell repeatedly pointed out these facts some time ago [Vesell 1982, Vesell and Passananti 1977]. Since Janke [1964], we have suspected that personality traits can also influence the drug response. The following overview is dedicated to this field designated as differential psychopharmacology which, from the point of view ofthe author, has been given too little attention by pharmacologists and clinical pharmacologists. It has been demonstrated that the effect of psychotropic drugs, including placebo, can be differentially influenced by personality traits, e.g. introversion/extroversion, high level neuroticism/low level neuroticism and success motivation/failure motivation. For example, relatively high doses of diazepam (0.3 mg/kg), when compared to placebo, only impaired the psychophysical performance of extroverted volunteers whereas introverted volunteers remained unaffected. Pharmacokinetic parameters, e.g. absorption, biotransformation, can also be affected by the level of neuroticism or by anxiety, as demonstrated for diazepam, caffeine, paracetamol and theophylline. The absorption kinetics of diazepam and caffeine clearly differ between volunteers with high neuroticism scores and those with low neuroticism scores. Emotionally unstable volunteers absorbed the substances more quickly and more completely than emotionally stable volunteers. There were surprising differences in various immunological indices between dominant and submissive subjects. In dominant volunteers the immune system was more activated than in submissive volunteers. In the future, it will become increasingly necessary to obtain results for such target groups and to avoid generalized data, which may conceal the actual events. Differential clinical psycho-neuro-immunopharmacology may be an approach which is helpful in the development of "volunteer models" for clinical research in Phase I.