...there had been interest in reports that adrenalin that had become old and discolored seemed to elicit central effects in man. The oxidation products were identified as the deeply colored indolic compound adrenochrome and the colorless analogue adrenolutin. The controversy that these reports created just sort of died away, and the adrenochrome family has never been accepted as being psychedelic. No one in the scientific community today is looking in and about the area, and at present this is considered as an interesting historical footnote.

Connection To Schizophrenia
For example, two of these metabolic neurotoxins--adrenolutin and adrenochrome--breakdown products from the body's own epinephrine. Both are associated with biochemically based schizophrenia. Adrenochrome is a hallucinogen which also inhibits nerve cell transmission. If the body is making an excess of adrenochrome, from either stress or a poor biochemical ability to break it down into harmless by-products, we have the potential for brain dysfunction. A slowly emerging awareness from the scientific literature suggests there are a number of brain disturbances that are related to the accumulation of various neurotoxins in the brain.

More is known about adrenochrome which inhibits a number of enzymes (COMT, hexokinase, succinic dehydrogenase) and stimulates prostaglandin synthesis and guanylcyclase activity. Adrenochrome has also been shown to be a psychotomimetic agent and to produce EEG abnormalities.

We showed many years ago (Hoffer et al. 1954) that one catecholamine o-quinone (adrenochrome) is a psychotomimetic agent. This finding was confirmed by three other groups. Adrenochrome also produces behavioral and EEG disturbances in animals. The other catecholamine o-quinones derived respectively from dopamine and noradrenaline have never so been tested.

ADRENOCHROME SEMICARBAZONE -- 3-hydroxy-1-methyl-5,6-indolinedione semicarbazone.
Material: Oxidized epinephrine (adrenaline) with semicarbazide.
Usage: 100 mg is thoroughly dissolved in just enough alcohol, melted fat (butter), or vegetable oil and ingested. Because of its poor solubility in water these must be used to aid absorption.
Effects: Physical stimulating, feeling of well-being, slight reduction of thought processes.
Contraindications: None noted.
Acts as a systemic hemostatic preventing capillary bleeding during injury. Adrenochrome causes chemically induced schizophrenia. Its semicarbazone does not.
Supplier: CS.

Dr. Abram Hoffer, a world-renowned psychiatrist in Victoria, reports on the successful treatment of six patients with atrial fibrillation. One 76 year old physician who suffered from atrial fibrillation was completely cured after starting a vitamin supplementation program which included megadoses of niacin and folic acid. Other patients report complete disappearance of their irregular heart beat symptoms after supplementing with high doses of niacin, folic acid, and vitamin B-12. Dr. Hoffer believes that one of the main causes of atrial fibrillation is excessive stress. High levels of stress release large amounts of adrenalin which in turn is oxidized to adrenochrome. Adrenochrome is known to cause fibrillation and other cardiac dysfunctions. Adrenochrome is a natural free radical and is primarily produced in the heart tissue, but circulates in the blood throughout the body. It can cross the blood-brain barrier and excessive amounts of it are believed to be a main cause of schizophrenia. Antioxidants protect against the formation of excessive amounts of adrenochrome and schizophrenics have been successfully treated with large amounts of niacin and ascorbic acid. Penicillamine has also been successfully used in the treatment of schizophrenia. Dr. Hoffer points out that adrenochrome is not all bad. He believes that the leucocytes use adrenochrome to destroy abnormal cells like cancer cells and that we therefore need a certain amount of adrenochrome in order to control cancer. The fact that schizophrenics rarely develop cancer supports this hypothesis. Dr. Hoffer concludes that we need a certain amount of stress in order to produce enough adrenochrome to enable our leucocytes to kill bacteria and tumor cells. However, we also need an adequate supply of natural antioxidants such as vitamins C and E and beta-carotene in order to neutralize an excess of adrenochrome after its work is done. (51 references)
Hoffer, A. Schizophrenia: an evolutionary defence against severe stress. Journal of Orthomolecular Medicine, Vol. 9, No. 4, Fourth Quarter, 1994, pp. 205-21

The question of religious chemistry has been underscored recently by the wide attention given to the theories, already mentioned, of Dr. Abram Hoffer and Humphry Osmond. Their adrenochrome-adrenolutin hypothesis suggests that schizophrenia may be caused at least in part by defective adrenal metabolism. Very briefly, the adrenal gland secretes the hormone adrenaline, which helps coordinate biological mechanisms in emergency situations--for example, a fist fight or a threatened traffic accident. Heart rate is increased, the blood is sugared up and pumped to the necessary muscles. Adrenaline also may affect the emotions, contributing to anxiety and depression. In the body it turns into a toxic hormone called adrenochrome, which in turn can be converted into either of two other compounds: dihydroxyindole or adrenolutin. It is possible that dihydroxyindole balances off adrenaline to reduce tension and irritability; in schizophrenics, however, adrenochrome is converted primarily into adrenolutin, which also is toxic, and the combination of adrenochrome-adrenolutin results in a poisonous disruption of the brain's chemical processes. That is the theory. And the prescribed antidotes are nicotinic acid (niacin) or nicotinamide (Vitamin B-3). Discussing one of the villains in the piece, the scientists write: "There are few who doubt that adrenochrome is active in animals or in man, and it is now included among the family of compounds known as hallucinogens--compounds like mescaline and LSD-2 5 capable of producing psychological changes in man."
The Hoffer-Osmond studies are far from conclusive, and similar theories have been advanced in the past. But the studies hold promise, and they are receiving serious consideration--due in part, no doubt, to the significance they have in other areas of current debate, including religion. The line dividing insanity and mysticism has never been too sharply drawn, and the biochemical theory of schizophrenia makes it all the more tenuous. Vitamin B-3 actually has cured cases of schizophrenia, according to Dr. Hoffer and Osmond. But Vitamin B-3 also has proved effective in terminating LSD experiences, and the implications of this must be obvious. As we asked earlier: Are insanity, mysticism, and the psychedelic experience in some way related?

There matters rested until, two or three years ago, a new and perhaps highly significant fact was observed.* Actually the fact had been staring everyone in the face for several decades; but nobody, as it happened, had noticed it until a Young English psychiatrist, at present working in Canada, was struck by the close similarity, in chemical composition, between mescalin and adrenalin. Further research revealed that lysergic acid, an extremely potent hallucinogen derived from ergot, has a structural biochemical relationship to the others. Then came the discovery that adrenochrome, which is a product of the decomposition of adrenalin, can produce many of the symptoms observed in mescalin intoxication. But adrenochrome probably occurs spontaneously in the human body. In other words, each one of us may be capable of manufacturing a chemical, minute doses of which are known to cause Profound changes in consciousness. Certain of these changes are similar to those which occur in that most characteristic plague of the twentieth century, schizophrenia. Is the mental disorder due to a chemical disorder? And is the chemical disorder due, in its turn, to psychological distresses affecting the adrenals? It would be rash and premature to affirm it. The most we can say is that some kind of a prima facie case has been made out. Meanwhile the clue is being systematically followed, the sleuths--biochemists , psychiatrists, psychologists--are on the trail.
"Schizophrenia: A New Approach." By Abram Hoffer, Humphry Osmond and John Smythies. Journal of Mental Science. Vol. C. No. 418. January, 1954.