https://science.sciencemag.org/content/sci/184/4143/1243.full.pdf

Drugs, neurotransmitters, and schizophrenia.

The production of head-twitches in mice appears to be a suitable laboratory test for predicting whether a compound is likely to be hallucinogenic in man. This is based on the following findings:
 A potent antiserotonin, methysergide, antagonised the head-twitches induced by a wide variety of chemically different hallucinogens. This gives support to the idea that hallucinogens may act by mimicking, releasing or potentiating serotonin centrally.

A possible correlation between drug-induced hallucinations in man and a behavioural response in mice.

Background: To begin applying basic neuropharmacological hypotheses of hallucinogenic drug actions to humans, we generated dose-response data for intravenously administered dimethyltryptamine fumarate's (DMT) neuroendocrine, cardiovascular, autonomic, and subjective effects in a group of experienced hallucinogen users. Methods: Dimethyltryptamine, an endogenous mammalian hallucinogen and drug of abuse, was administered intravenously at 0.05,0.1,0.2, and 0.4 mg/kg to 11 experienced hallucinogen users, in a double-blind, saline placebo—controlled, randomized design. Treatments were separated by at least 1 week. Results: Peak DMT blood levels and subjective effects were seen within 2 minutes after drug administration, and were negligible at 30 minutes. Dimethyltryptamine dose dependently elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of β-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected. Threshold doses for significant effects relative to placebo were also hallucinogenic (0.2 mg/kg and higher). Subjects with five or more exposures to 3,4-methylenedioxymethamphetamine demonstrated less robust pupil diameter effects than those with two or fewer exposures. Conclusions: Dimethyltryptamine can be administered safely to experienced hallucinogen users and dose-response data generated for several measures hypothesized under serotonergic modulatory control. Additional studies characterizing the specific mechanisms mediating DMT's biological effects may prove useful in psychopharmacological investigations of drug-induced and endogenous alterations in brain function.

https://jamanetwork.com/journals/PSYCH/articlepdf/496494/archpsyc_51_2_001.pdf

Dose-Response Study of N,N-Dimethyltryptamine in Humans: I. Neuroendocrine, Autonomic, and Cardiovascular Effects

Preferential action of 5-methoxytryptamine and 5-methoxydimethyltryptamine on presynaptic serotonin receptors: A comparative iontophoretic study with LSD and serotonin

TANIMUKAI et al.1, using gas-liquid separation, correlated the appearance of a bufotenin-like substance in urine and the onset of psychosis in latent schizophrenics brought on by administration of a monoamine oxidase inhibitor with amino-acid precursors of indoleamines and methyl groups. Serious doubt about endogenous bufotenin as the cause of psychiatric disturbance was cast by research demonstrating that intravenously administered bufotenin produced nothing but bizarre cardiovascular symptoms in man2, 3. One objection to such work is that bufotenin may not easily cross the blood-brain barrier. Recent preliminary evidence gathered in our laboratories from rats infused intraventricularly with bufotenin has suggested that this substance is at least as potent as its powerfully hallucinogenic 5-methoxy congener (unpublished results of D. Segal and A. J. M.).

Indole(ethyl)amine N-methyltransferase in human brain.

Throughout an arc described by the islands of the Caribbean, the shores of the Amazon, and as far as the western ridges of the Andes, in Colombia and Peru, there has been used since pre-Columbian times a snuff variously known ascohoba, niopo, parica, andyopo, among other designations.1-11With minor variations, this snuff is prepared from seeds of Piptadenia peregrina by grinding with calcined clam shells or wood ashes. It is inhaled or is forcibly blown into the nostrils of the person to be intoxicated by it. Descriptions of the action of the snuff vary somewhat, but the one we have previously reported,12given us by Dr. Jacques Fourcand, is typical. The inhalation of the snuff is quickly followed by rigidity and staring and, at times, a convulsion. This gives way to an excited state, which may last an hour more or less and in which there

Effect of some indolealkylamines on man.

A study of the rates of admission, therapy and outcome of depressed patients at Central Islip State Hospital for the two years 1955 and 1960 is reported. A drop in the admission rate for the more severely psychotic depressions has been balanced by a rise in admission rate of reactive and neurotic depressions. The high value of EST in the severe depressions is again revealed by our data. There is evidence for high value of phenothiazines in the agitated and in the neurotic depressions. There has been surprisingly little use of the MAO inhibitors and of imipramine, despite the reported value of these drugs. The hopeful, protective and supportive attitude of admission services is in itself highly therapeutic. All in all, the present prognosis for a depressed patient admitted to hospital is highly favorable and constantly improving.

The treatment of depression in hospitalized patients before and since the introduction of antidepressant drugs.

A table is presented showing the relationship of EEG before treatment to outcome of electric shock therapy, in 187 schizophrenics, of whom 95 percent were young men. One-fourth of those with a normal pattern left the hospital much improved or "quiescent." None of these with abnormal records was able to leave the hospital. Of 19 patients who had previously had insulin therapy 3 left the hospital much improved.[See Table 1 in source Pdf]

The correlation of pre-electroshock electroencephalogram and therapeutic result in schizophrenia.

The evaluation of psychotropic drugs presents special problems to the pharmacologist and clinician. In such evaluation, the severity of the patient's anxiety is a useful parameter, but it is not the only one that needs to be considered. The best therapy may be to learn more about the circumstances of the patient and to resolve difficulties when possible. Drugs are prescribed only when this fails. Some properties of 25 drugs now used to relieve anxiety are given. In severe anxiety, potent drugs are used initially despite their inherent dangers. If an office patient drives a car, takes care of a home, cooks, watches children, or competes in business, parameters other than anxiety are obviously important. The problems of psychopharmacology are therefore complex, but the principles here outlined provide orientation.

William J. Turner

Papers

Effect of some indolealkylamines on man.

The treatment of depression in hospitalized patients before and since the introduction of antidepressant drugs.

The correlation of pre-electroshock electroencephalogram and therapeutic result in schizophrenia.

Drug evaluation and practical psychiatric therapeutics.

Alcoholism, Homosexuality, and Bipolar Affective Disorder