Schizophrenia mescaline

LSD, mescaline and other psychedelic drugs cause psychosis, but their perceptual and cognitive changes do not resemble schizophrenia. 

Psychedelics (LSD) and other psy-chotomimetics such as mescaline and psilocybin can induce states of altered awareness, or induce hallucinations and anxiety, probably mediated by 5-HT2A receptors. Overactivity of these receptors may also play a role in the genesis of negative symptoms in schizophrenia (p. 238) and sleep disturbances. 

The transmethylation hypothesis depended on the psychosis of mescaline as an example of how methylated compounds similar in structure to the monoamine neurotransmitters could be psychotogenic, and demonstrated how methionine, the precursor of the methyl donor S-adenosylmethionine, could exacerbate the psychotic symptoms of schizophrenia in patients. This theory was fed by studies of the now notorious pink spot, an amine found in paper chromatography of urine extracts from schizophrenics and thought to be 3,4-dimethoxyphenylethylamine (i.e., O-methylated dopamine). Subsequent studies eventually identified this as another compound or compounds, primarily of dietary origin. Another methylated derivative erroneously proposed to be found in higher quantities in schizophrenia was dimethyltryptamine. This compound is similar in structure to LSD, the hallucinogenic nature of which was the key to the serotonin deficiency hypothesis, which proposed that the known antagonism of serotonin (5-HT) by LSD indicated that psychotic disorders such as schizophrenia may result from a hypofunction of 5-HT. 

Like LSD, mescaline has been used in animal models of schizophrenia. Both produce effects on 5HT2 receptors. 

We are reminded of the fascinating role of catalytic selectivity in human behavior by J. R. Smythies discussion of the possible generation of schizophrenia as a result of a slight aberration in catalytic selectivity in a methoxylation reaction, as illustrated by the creation of a molecule manyfold more hallucinogenic than mescaline when methoxylation occurs in the para- as compared to the meta-position of amphetamines. 

The psychotomimetic (hallucinogenic, psychedelic, psychodysleptic) activity reported to be shown by adrenochrome and some of its derivatives, in particular, adrenolutin, and its possible role in the etiology of some forms of mental illness, particularly schizophrenia, have been the subjects of much controversy since the adrenochrome hypothesis of schizophrenia was first proposed by Hoffer, Osmond and Smythies in 1954 [342]. This hypothesis, which developed from an earlier suggestion by Osmond and Smythies, states that schizophrenia results from a defect in the normal metabolism of adrenaline in the body, with the in vivo formation of a psychotoxic metabolite of adrenaline, referred to as M-substance (i.e. mescaline-like substance) [343]. In their 1954 publication Hoffer, Osmond and Smythies postulated that adrenochrome was the endogenous psychotoxin (i.e. M-substance ) [342]. This suggestion was based on their observations after... 

O-methylation of catecholamines was suggested by the reported presence of 3,4-dimethyoxyphenylethylamine (which is structurally very similar to mescaline) in schizophrenic urine [388]. The relationship between this substance, dietary factors and the so-called pink spot detected on urinary chromatograms [389] is somewhat confused. The latter is probably a complex mixture which may or may not contain 3,4-dime thoxyphenylethylamine [163, 390, 391]. Furthermore clear evidence that this substance is either a product of endogenous metabolism or that its excretion is elevated in schizophrenia is lacking [392]. 

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