Capsule 17

17. Adrenochrome hypothesis of schizophrenia and treatment with nicotinic acid
The hypothesis, that schizophrenia is the outcome of stress-induced anxiety in which a failure of epinephrine metabolism results in highly toxic mescaline-like (“M”) compounds was formulated by Osmond and Smythies, in 1952. The hypothesis was based on Cannon’s recognition, in 1915, that adrenal hormones play an important role in the adaptation to stress. In 1954, Hoffer, Osmond and Smythies suggested that adrenochrome, a toxic oxidation product of epinephrine, is the “M” substance. In 1957, Hoffer and his associates, administered mega dose of nicotinic acid to patients with schizophrenia to prevent the excessive amount of epinephrine production  from which the psychotoxic aminochrome is formed and reported favorable findings in some patients. Their rationale for this treatment was that nicotinic acid converts into nicotinamide, a substance that competes with norepinephrine for methyl groups. Hoffer and his associates’ favorable findings with mega doses of nicotinic acid in schizophrenia could not be replicated in the Canadian Mental Health Association Collaborative Studies, conducted, in the late 1960s and early, 1970s. Nevertheless, treatment with mega doses of nicotinic acid of patients with schizophrenia, refractory to conventional treatment, was lingering on by “orthomolecular psychiatrists” until the end of the 20th century and even beyond.