A review of the clinical effects of psychotomimetic agents

This early review from 1957 details the clinical effects of what was back then still called “psychotomimetics,” i.e., psychedelics.

Abstract

From the summary: “After indicating that there are a number of substances at present subsumed as psychotomimetic agents I have indicated that these are not yet clearly defined, and I have suggested that while mimicking psychoses is one aspect of these agents, it is not the only or even the most important one. 1 have discussed their great antiquity and have shown how they have attracted man since the dawn of history. Since many drugs produce changes in both body and mind, I consider that some working definition is required that will exclude anesthetics, hypnotics, alcohol, and the derivatives of morphine, atropine, and cocaine. I have suggested as a definition: “psychotomimetic agents are substances that produce changes in thought, perception, mood and sometimes posture, occurring alone or in concert, without causing either major disturbances of the autonomic nervous system or addictive craving, and although, with overdosage, disorientation, memory disturbance, stupor, and even narcosis may occur, these reactions are not characteristic.” “

Author: Humphry Osmond

Summary

The Psychotominiefic rlgepzls

Until recently, science has shown only sporadic interest in compounds that mimic the mental illnesses called psychoses, but it is only recently that the relationship between psychotomimetics and schizophrenia has become somewhat clearer.

Psychotomimetic agents are substances that cause changes in thought, perception, mood and posture, occurring alone or in concert, without causing major disturbances of the autonomic nervous system or addictive craving.

This rough and ready guide excludes morphine, cocaine, atropine, and their derivatives, as well as anesthetics, analgesics, and hypnotics. It also includes the still-unidentified soma?’ imported from central Asia into India several thousand years ago.

There are many different substances that have been used to treat pain, including soma, hashish, cohoba, ololiuqui, peyote, the Syrian rue, the caapi vine, the fungus teonanacatl, the iboga bean, and the fierce virola snuff. Modern synthetics have been developed that may help with these conditions.

We know little about the most familiar of these agents, and there are only vague correlations between the physical and mental changes that they cause. These agents are of more than medical significance, and we must remediate our ignorance of them.

Nearly everyone who works with psychotomimetics and allied compounds agrees there is something special about them. However, few workers have emphasized that the unique qualities of these substances must be investigated in many directions at the same time, a consideration that makes work in this field all the more difficult.

These drugs are useful in training and educating those who work in psychiatry and psychology, especially in understanding strange ways of the mind. They also have social, philosophical, and religious implications.

The Model Psychoses

Over a century ago B. A. Morel used hashish to show his students the sort of world that might be endured by some mentally ill people. We still do not know for certain the exact differences between experiences produced by hashish, peyote, mescaline and LSD.

The isolation and synthesis of mescaline by HeffteP encouraged further work, which was justified by the introduction of LSD by HoffmanGg. The question of how the drug continues to act after it is excreted from the body is an unsolved mystery.

It is curious that the difference between an artificially induced, experimental state and a prolonged, insidious, creeping illness was not recognized until 195152.

There is one golden rule that should be applied in working with model psychoses: one cannot expect to make sense of someone else’s communications unless one has taken LSD themselves.

After Smythie@ rediscovered the similarities in the structural formula of mescaline and adrenalin, FabingI7 and colleagues started to hunt for substances that might be psychotomimetic. They found adrenochrome and adrenolutin, which they think are psychotomimetic.

422 Annals New York Academy of Sciences

The causes of the difficulties in detecting, measuring, and classifying indolic derivatives of adrenalin are not yet clear. They are more subtle and less florid than those induced by mescaline or LSD, but are excellent prospects for use as natural psychotomimetic agents.

The more our psychotomimetics resemble the hypothetical endotoxin that Carl Jng called toxin-X, the harder they will be to test, and the more attention they will require in experimental design. However, the rewards are large.

Model psychoses are induced chemically and by other means, and the use of specialized environments raises a host of questions.

Most people can adjust themselves to small changes in perception quickly enough to not be concerned, but in some situations even small changes can be dangerous. High-speed flying and flight into outer space can cause major psychophysiological and psychochemical changes in men.

A steady drinking of alcoholic liquor would damage the liver, low blood sugar and inadequate niacin intake would increase these tendencies, and coffee and tobacco, in excess, would increase the danger. Atropine derivatives especially should be avoided by men flying planes.

I do not know if such changes actually occur, but I have never been able to relate time to distance after taking adrenochrome.

Uses in Psychotherapy I have read several accounts of the use of LSD-25 and mescaline in psychotherapy, but I have not been able to find any reports of Busch and Johnson’s work.

Abramson gives small doses of LSD-25 in repeated sessions to resolve early conflicts, Sandison gives a varying dose to chronic neurotic patients in a mental hospital, and FrederkinglZ3 compares mescaline and LSD-25 and discusses about 200 treatments.

Hubbard treated a number of gravely ill alcoholics, and it is hard not to agree with the appraisal these patients gave of themselves. The substances in question can be used to develop very high degrees of empathy, and this may help the therapist better help his patients.

Psychotomimetics ad Trainiitg

No study has dealt specifically with the application of these substances to the training of workers engaged in many different disciplines who work together in psychiatry.

The Model Therapies ad the Reverse

Schueler gave mescalinized medical students sodium succinate by vein, which reduced their symptoms briefly, but the symptoms recurred when the succinate was excreted, which happened quickly. Mayer-Gross used the LSD 25 model, and Elkes used chlorpromazine and sodium amytal.

Schueler’s work has never been used in psychiatric treatment on any scale, although Meyer-Gros’s work may have a bearing on insulin therapy. A radical change in technique seems indi- cated.

Ways of aggravating model psychoses are equally important, though we know little about them. Atropine and its derivatives increase perceptual disorders and paranoid trends, and dhatura on hashish produces temporary madness in its victims.

Psychotomimetic Agents and Psychology

Heinrich Kliier pioneered many trails in psychology, and his book on mescaline is now out of print. The advances he considered could be made by studying the effects of mescaline and similar experiences are still undone.

When empathy is lacking to any great degree, something essentially human is lost. Saints have experienced empathy sustained for a lifetime, but for the rest of us a few moments of it are ever remembered as supreme exaltation.

42 6 Annals New York Academy of Sciences

Synesthesia is a strange fusing of 2 or more sensory modalities. Bleuler7 gives a hint of the possibilities here.

I have noticed 3 different varieties of this phenomenon, in which associations rupture the chain of thought, illusions and even hallucinations distract one’s attention, and thought fades out. The effects are strange and impressive, and we have almost no language suitable for communicating them.

Other Inquiries drising from This Work

It is encouraging that many are joining in the hunt for psychotomimetic indoles, but we need more detailed information about these derivatives of adrenalin and other related compounds, and we need a means of temporarily enhancing the effect of psychotomimetics.

If we are to succeed, we must encourage people from distant and often hostile groups to meet, talk, and listen together.

In history, men have pursued certain experiences that they considered valuable above all others, from dervish dancing to prayerful contemplation, from chewing peyote to prolonged starvation.

William James endured much uncalled-for criticism for suggesting that inhalations of nitrous oxide allowed a psychic disposition that is always potentially present to manifest itself briefly. This has led to a comparative neglect of these experiences, which have rendered psychology stale and savorless.

There was another stream of psychological thought in Europe and the United States that is more suitable for the work that I shall discuss next. Its great figures include James, Sedgwick, Myers, and Gurney, and Carl Jung.

The effect of these agents, which include many authors, artists, a junior cabinet minister, scientists, a hero, philosophers, and businessmen, is unique, and is often described as beyond verbal description. The brain acts more subtly and complexly than when it is normaI, yet one must undergo the experience himself.

The phenomenon of chemically induced mental aberration is not something new, and has been studied since the earliest times. Visionaries and mystics have experienced similar states, and it is foolish to expect a single exploration to bring back as much information as 20.

The reader should reflect that something unusual ought to seem irrational, because it transcends fashionable ruts of thinking. Psychoanalysts claim that their ideas cannot be fully understood without a personal analysis, but can one ever understand something one has never done?

Psychoanalysis resembles Galileo’s telescope, and psychotomimetic agents are more like radar telescopes, which are being built to scan the deeps of outer, invisible space. They raise more questions than answers, and we must invent new languages to understand them.

I believe Freud and his pupils tried to extrapolate from his data far beyond its proper limit, and this was magnificent bravado. Jung, using inadequate tools, has shown such skill and dexterity.

Splendid rashness should be avoided, but calculated risks must be taken to understand the mind. Freud has told us much about many important matters, but there have always been risks in discovery.

How Should We Name Them?

These agents mimic mental illness, but they do much more than that. They are not pathological, and children are infinitely potential rather than polymorphously perverse.

I have tried to find an appropriate name for the agents under discussion, but psychedelic, mind-manifesting, is clear, euphonious, and uncontaminated by other associations.

Epilogue

One clinician sees psychedelics as helping people explore their own nature. People can perceive themselves in many different ways, including as stampings of an automatic socioeconomic process, highly plastic and conditionable animals, congeries of instinctive strivings ending in loss of sexual drive and death, or even as semantic conundrums.

The Ames9 demonstrations in perception* show that our beliefs greatly influence the world in which we live. If we can divest ourselves of our acquired assumptions, we can see the universe again with an innocent eye, and perhaps learn how to rebuild our world in another and better image.

While we are learning, we may hope that dogmatic religion and authoritarian science will keep away from each other’s throats. Few of us can accept or understand the mind that emerges from these studies.

In a few years, psychedelics will seem as crude as our ways of using them, but they can enlarge our experience greatly. Whether we use them for good or ill depends on the courage, intelligence, and humanity of many of us working in the field today.

The techniques for developing spontaneous experience are often faulty, uncertain, clumsy, objectionable, and even dangerous. I believe that the psychedelics provide a chance for homo jaber to merge into homo sapiens, the wise, the understanding, the compassionate.

Summary

I have indicated that there are a number of substances at present subsumed as psychotomimetic agents, but that they are not yet clearly defined. I have also suggested a working definition that excludes anesthetics, hypnotics, alcohol, and the derivatives of morphine, atropine, and cocaine.

Lack of information has delayed the development of the sort of inquiry that has recently led to work with adrenochrome, adrenolutin, and bufotenin. I have suggested that “psychotomimetic” is far too narrow a generic term, and have suggested several that imply alterations in the normal mind.

Notes

Humphrey Osmond offers us a definition of psychotomimetic agents, a term preceding (his and Aldous Huxley‘s coined) psychedelics.

“Psychotomimetic agents are substances that produce changes in thought, perception, mood and, sometimes, in posture, occurring alone or in concert, without causing either major disturbances of the autonomic nervous system or addictive craving, and although, with overdosage, disorientation, memory disturbance, stupor, and even narcosis may occur, these reactions are not characteristic.“

He recognizes that his work is built on more than 5000 years of history:

“… think upon those nameless discoverers and rediscoverers, Aztec and Assassin, Carib and berserker, Siberian and Red Indian, Brahmin and African, and many others of whose endeavors even scholars do not know. We inherit their secrets and profit by their curiosity, their courage, and even from their errors and excesses, Let us honor them. They do not appear in any list of references.”

At the time of writing (1957) we knew very little about psychedelics, yet still we are only at the beginning of understanding them and the potential they have:

“Surely we are woefully ignorant of these agents and this ignorance must be remedied.”

Osmond also muses on which word to use for psychedelics.

“I have tried to find an appropriate name for the agents under discussion: a name that will include the concepts of enriching the mind and enlarging the vision. Some possibilities are: psychephoric, mind-moving ; psychehormic, mind-rousing ; and psycheplastic, mind-molding . Psychezymic, mind-fermenting, is indeed appropriate. Psycherhexic, mind bursting forth, though difficult, is memorable. Psychelytic, mind-releasing, is satisfactory. My choice, because it is clear, euphonious, and uncontaminated by other associations, is psychedelic, mind-manifesting. one of these terms should serve.”