Skip to main content
Log in

The adrenochrome hypothesis of schizophrenia revisited

  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

This paper reviews the current status of the adrenochrome theory of schizophrenia. An account is first given of all the experiments in which adrenochrome was reported to induce psychotomimetic effects in normal volunteers. Then the evidence is presented that adrenochrome may actually occur in the brain as a metabolite of adrenaline in the C2 group of adrenergic neurons in the medulla, together with an account of current ideas of the function of these neurons in higher limbic functions. Lastly the recent evidence is reviewed that the gene for the enzyme glutathione S-transferase is defective in schizophrenia. This enzyme detoxifies adrenochrome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Carlsson, A., Waters, A. and Hansson, L.O. (1994) “Neurotransmitter aberrations in schizophrenia: new findings”, In: Fog, R., Gerlach, J. and Hemmingston, R., eds, Schizophrenia. An Integrated View (Munksgard, Copenhagen), pp 332–343.

    Google Scholar 

  • Fornstedt, B., Brun, A., Rosengren, E. and Carlsson, A. (1989) “The apparent autoxidation rate of catechols in dopamine-rich areas of the brain increases with the degree of depigmentation of substantia nigra”, J. Neural. Trans. Park. Dis. Den. Sect. 1, 279–295.

    Article  CAS  Google Scholar 

  • Gai, W.P., Geffen, L.B., Denoroy, L. and Blessing, W.W. (1993) “Loss of C1 and C3 epinephrine-synthesizing neurons in the medulla oblongata in Parkinson’s disease”, Ann. Neurol. 33, 357–367.

    Article  PubMed  CAS  Google Scholar 

  • Gertz, H-J. and Schmidt, L.G. (1991) “Low melanin content of substantia nigra in a case of neuroleptic malignant syndrome”, Pharmacopsychiatry 24, 93–95.

    Article  PubMed  CAS  Google Scholar 

  • Greiner, A.C. and Nicholson, G.A. (1965) “Schizophrenia-melanism”, Lancet ii, 1165.

    Article  Google Scholar 

  • Grof, S., Vojtechovsky, M., Vitek, V. and Prankova, S. (1963) “Clinical and experimental study of central effects of adrenochrome”, J. Neuropsychiatr. 5, 33–50.

    Google Scholar 

  • Harada, S., Tachikawa, H. and Kawanishi, Y. (2001) “Glutathione S-transferase M1 gene deletion may be associated with susceptibility to certain forms of schizophrenia”, Biochem. Biophys Res. Comm. 281, 267–271.

    Article  PubMed  CAS  Google Scholar 

  • Herbert, H. and Saper, C.B. (1992) “Organization of medullary adrenergic and noradrenergic projections to medullary periacqueductal gray matter in the rat”, J. Comp. Neurol. 315, 34–52.

    Article  PubMed  CAS  Google Scholar 

  • Hoffer, A. (1957) “Adrenochrome in blood plasma”, Am. J. Psychiat. 114, 0.

    Google Scholar 

  • Hoffer, A., Osmond, H. and Smythies, J. (1954) “Schizophrenia: a new approach part 2”, J. Ment. Sci. 100, 29–45.

    PubMed  CAS  Google Scholar 

  • Kaiya, H. (1980) “Neuromelanin, neuroleptics and schizophrenia”, Neuropsychobiology 6, 241–248.

    Article  PubMed  CAS  Google Scholar 

  • Lew, J.Y., Matsumoto, Y., Pearson, J., Goldstein, M., Hokfelt, T. and Fuxe, K. (1977) “Localization and characterization of phenylethanolamine-N-methyltransferase in the brain of various mammalian species”, Brain Res. 119, 199–210.

    Article  PubMed  CAS  Google Scholar 

  • Lindemann, E. (1935) “The psychopathological effects of drugs affecting the vegetative system”, Am. J. Psychiat. 91, 983–1008.

    Google Scholar 

  • Macarthur, H., Westfall, T.C., Riley, D.P., Misko, T.P. and Salvemini, D. (2000) “Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock”, Proc. Natl Acad. Sci. USA 97, 9753–9758.

    Article  PubMed  CAS  Google Scholar 

  • Nagutsu, I., Ikemoto, K., Takeuchi, T., Arai, T., Karasawa, N., Fujii, T. and Nagatsu, T. (1996) “Phenylethanolamine-N-methyltransferase-immunoreactive nerve terminals afferent to the mouse substantia nigra”, Neurosci. Lett. 245, 41–44.

    Article  Google Scholar 

  • Osmond, H. and Smythies, J. (1952) “Schizophrenia: a new approach”, J. Ment. Sci. 98, 309–320.

    PubMed  CAS  Google Scholar 

  • Otake, K., Ruggiero, D.A. and Nakamura, Y. (1995) “Adrenergic innervation of forebrain neurons that project to the paraventricular thalamic nucleus in the rat”, Brain Res. 697, 17–26.

    Article  PubMed  CAS  Google Scholar 

  • Rico, B. and Cavada, C. (1998) “Adrenergic innervation of the monkey thalamus; an immunohistochemical study”, Neuroscience 84, 839–847.

    Article  PubMed  CAS  Google Scholar 

  • Rinkel, M. and Solomon, A.C. (1957) “Chemical theories of psychosis”, J. Clin. Exp. Psychopath. 18, 323–334.

    PubMed  CAS  Google Scholar 

  • Schwartz, B.E., Sem-Jacobsen, C. and Petersen, M.C. (1956) “Effects of mescaline, LSD-25 and adrenochrome on depths electrograms in man”, Arch. Neurol. Psychiat. 75, 579–587.

    Google Scholar 

  • Smythies, J. (1996) “On the function of neuromelanin” Proc. R Soc. London B 263, 487–489.

    Article  CAS  Google Scholar 

  • Smythies, J. (1999) “The neurotoxicity of glutamate, dopamine, iron and reactive oxygen species: functional interrelationships in health and disease: a review” Neurotox. Res. 1, 27–39.

    Article  PubMed  CAS  Google Scholar 

  • Smythies, J. and Galzigna, L. (1998) “The oxidative metabolism of catecholamines in the brain: a review”, Biochim. Biophys Acta 1380, 19–162.

    Google Scholar 

  • Smythies, J.R., Morin, R.D. and Brown, G.B. (1979) “Identification of dimethyltryptamine and o-methylbufotenin in human cerebrospinal fluid by combined gas chromatography/mass spectrometry”, Biol. Psychiatr. 14, 549.

    CAS  Google Scholar 

  • Szara, S., Axelrod, J. and Perlin, S. (1958) “Is adrenochrome present in the blood?”, Am. J. Psychiatr. 115, 162–163.

    PubMed  CAS  Google Scholar 

  • Szatmari, A., Hoffer, A. and Schneider, R. (1955) “The effect of adrenochrome and niacin on the electroencephalogram in epilepsy”, Am. J. Psychiat. 111, 603–616.

    PubMed  CAS  Google Scholar 

  • Taubman, G. and Jantz, H. (1957) “Untersuchung über die dem adrenochrom zugeschrieben psychotoxischen wirkungen”, Nervenartz 28, 485–488.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John Smythies.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smythies, J. The adrenochrome hypothesis of schizophrenia revisited. neurotox res 4, 147–150 (2002). https://doi.org/10.1080/10298420290015827

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/10298420290015827

Keywords

Navigation