Self-Experiments with Psychoactive Substances: A Historical Perspective

This book chapter (2018) presents a historic overview of self-experimentation with psychoactive substances whose scientific documentation began in the mid-1850s and continuously expanded over the next 125 years while stimulating scientific (and therapeutic) advances and becoming increasingly widespread amongst layperson with the rise of New Psychoactive Substances. While psychologists like William James and Sigmund Freud drew significant inspiration from their drug experiences, other examples may serve as cautionary tales, such as John C. Lilly’s account of ketamine dependence that developed out of self-experimentation.

Abstract

“The purpose of this chapter is to highlight the rich tradition of self-experiments (SEs) with psychoactive substances carried out by scientists and therapists for more than a century. Scientifically inspired controlled SEs dominated until the end of the twentieth century, when ethical requirements minimized controlled SEs and “wild” SEs expanded particularly with the emergence of new psychoactive substances. The review focuses on laughing gas (nitrous oxide), cannabis, cocaine, hallucinogens, entactogens, and dissociative hallucinogens. This is due to the fact that substances that induce “complex” effects such as alteration of space/time experience, ego dissolution, and increased feelings and insights (e.g., hallucinogens, entactogens) represent by far the majority of SEs, whereas SEs with substances inducing “simple” effects such as euphoria, anxiolysis, dissociation, or emotional blunting (e.g., cocaine, opioids) are much rarer or even absent (e.g., benzodiazepines). Complex drug effects are much harder to describe, thus allowing SEs to fulfill a more important function. SEs with psychoactive drugs appeared to emerge in the mid-eighteenth century, which triggered a long-standing tradition throughout the nineteenth and early twentieth century. SEs have been de facto performed for a variety of reasons, ranging from establishing scientific knowledge and gaining philosophical insights to compensating for personal deficits. Self-experimenters can be divided into two general types. Besides their scientific intentions, “exploratory” self-experimenters intend to expand awareness and insight, whereas “compensatory” self-experimenters might aim for coping with psychiatric symptoms or personality deficits. Scientific limitations of SEs are obvious when compared to double-blind, randomized, placebo-controlled trials. Whereas the former might lead to more “realistic” detailed description of subjective effects, the latter lead to more solid results in respect to objectively measurable “average” effects. Possible adverse effects of SEs were identified that resulted in loss of scientific objectivity and decreased control over substance use and addiction, development of isolation, problematic group dynamics, and “social autism.“”

Authors: Torsten Passie & Simon D. Brandt

Summary

Abstract

This chapter highlights the rich tradition of self-experiments (SEs) with psychoactive substances carried out by scientists and therapists for more than a century. SEs with substances inducing “complex” effects such as alteration of space/time experience, ego dissolution, and increased feelings and insights are much rarer.

SEs with psychoactive drugs appeared in the mid-eighteenth century, and were performed for a variety of reasons, ranging from establishing scientific knowledge to gaining philosophical insights. SEs have several disadvantages, however, such as loss of scientific objectivity and decreased control over substance use and addiction.

1 Introduction

Since ancient times, humans have experimented on other humans and themselves. The ancient Greeks and Romans did not experiment much on healthy or sick people, but since the medieval ages, medical and other investigators have begun to experiment on fellow humans and on themselves.

Claude Bernard emphasized the importance of self-experiments, saying that morals do not forbid making experiments on one’s neighbor or on one’s self.

After World War II, a code of ethics was established for medical experiments, but it was found that Nazi doctors had defiled it. This led to lower safety standards for self-experiments when performed by physicians or other scientists.

2 Self-Experimentation in Medicine

In the eighteenth and nineteenth century, a broader discussion on the issue of self-experimentation emerged, and many medical and psychological researchers carried out SEs. However, the topic has received little attention in the scientific literature.

SEs are conducted by medical doctors for many reasons, including to observe, to assess therapeutic benefits to accumulate data, to study physiological processes, to explore mechanisms associated with the transfer of infections, to test newly developed instruments, to minimize risks of harm to patients, and/or to explore resilience.

Henry K. Beecher wrote that a willingness to experiment on oneself is evidence of good faith, and Sir George Pickering said that the experimenter should have one golden rule to guide him.

Leo Alexander, who was a major figure in writing the Nuremberg Code, differentiated this point of view: “Scientific experimenters may use subjects in significant risk to themselves” (quoted by Altman 1986, p. 17). However, some medical institutions permit SEs only in certain cases.

John Scott Haldane experimented on himself to gain knowledge that could save other men’s lives. His studies were referred to as the “most fundamental studies and far-reaching contributions to physiology”.

3 Self-Experimentation with Psychoactive Substances

The first systematic descriptions of self-experiments with psychoactive substances were published by Horace Wood (1869) and Weir Mitchell (1896), who used the mescaline-containing peyote cactus to study its psychological effects.

Animal experiments are of limited value when assessing psychological effects, so researchers, chemists, and therapists self-experimented with hallucinogens, entactogens, and dissociative drugs.

4 Defining the Topic

This chapter highlights the rich tradition of self-experimentation in the field of psychoactive substance research, which has not been considered in the authoritative review on medical self-experimentation published by Altman (1986).

Specific types of psychoactive substances that produce relatively easily predictable psychological effects were excluded, such as benzodiazepines, antidepressants, simple amphetamine-like stimulants, and (synthetic) opioids/opiates. These substances produce more interesting, complex, and challenging effects, which include large interindividual variation.

This review will be restricted to SEs performed by physicians, psychologists, or medicinal chemists. There is an abundance of information available about other groups of researchers who carried out SEs.

4.1.1 Controlled Self-Experiments

SEs are usually conducted in a controlled environment, with an exactly defined dose, and are intended to facilitate some form of systematic self-observation. They are usually performed by a physician or a scientist, and a written self-report is provided by the experimenter.

4.1.2 Uncontrolled Self-Experiments

Uncontrolled self-experiments (SEs) are experiments in which a scientist tests a substance on himself, without giving much detail and documentation on what was specifically done and experienced. SEs might be considered useful for certain purposes, but suffer from the possibility of obtaining irreproducible results.

4.1.3 “Wild” Self-Experiments

“Wild” SEs are not intended to lead to scientifically relevant knowledge and are therefore somewhat beyond the scope of this chapter. They can be conducted by problematic drug users in search for another “high” or by people with more serious scientific or therapeutic interests.

5 Self-Experimentation with New Psychoactive Substances (NPS)

From the mid-1960s onwards, “wild” drug self-experimentation carried out by laymen became a mass phenomenon. However, the earliest origins can be traced back to the 1950s, when artists and writers began to experiment with drugs.

During the last four decades, legislation, adapted medical treatment, and harm reduction through informal learning processes of user groups have taken place. This has led to the emergence of so-called designer drugs in the early 1980s.

In the late 1990s, a new market of uncontrolled substances started to emerge. These substances include psychostimulants, synthetic cannabinoid receptor agonists, entactogens, hallucinogens, dissociative drugs, synthetic opioids, and benzodiazepines.

Self-experimentation is a way for substance users to learn about unknown effects and potential dangers of substances by exchanging information with others. There is no explicit design for the experiment, no formal professional education in scientific observation and methodology, and no knowledge of identity and purity of substances involved.

The time span covering the use of NPS is relatively small compared to other psychoactive substances, and the clinical and experimental environment of today does not easily allow for SEs with NPS. However, some information about effects of some NPS has been extracted and published using qualitative analysis tools.

SEs with NPS are rare, but some notable exceptions exist where controlled self-experiments (category 1) have provided valuable information. For example, oral administration of the SCRA AM-2201 showed that the compound was not psychoactive at the dose tested (5 mg).

Meyer 2018) have been noted to form metabolites that are both pharmacologically active and medicines in their own right. These experiments revealed important contributions to understanding these mechanisms.

The use of non-standardized reports from non-standardized experiments in online forums for knowledge exchange and harm reduction can be important pillars of a drug discourse, but their use in the scientific domain is at best limited to extractions from many reports to gain a rough “mean” impression.

A recent online survey found that motivations for NPS users vary depending on the substance of choice, with many users trying to cope with symptoms and clinical features associated with psychiatric disorders including opioid dependence.

6.1 Nitrous Oxide

Nitrous oxide was discovered in 1772 by Joseph Priestley. Thomas Beddoes, a British physician from Bristol, opened a small experimental clinic and laboratory, where Humphrey Davy experimented on himself and wrote on the subjective experiences.

After having a hard time producing pure nitrous oxide, Davy self-experimented with the gas, and felt an immediate desire to increase the pleasurable feelings. He first described the pain-relieving properties of nitrous oxide in his book, although its potential use as an anesthetic was not discovered until 40 years later.

Benjamin P. Blood (1832 – 1919) claimed to have gained revelatory insights following experiments with anesthetics other than nitrous oxide. He concluded that the Kingdom is within us, and there can be no climacteric purpose of eternity, nor any scheme of the whole.

William James experienced SEs with nitrous oxide and described them as “revelations of significant metaphysical insights”, but found himself unable to remember the exact contents of the experience. He strongly urged others to repeat the experiment to gather experiences with this extraordinary state of consciousness. James was frustrated with attempts to measure consciousness and concluded that there were other forms of consciousness apart from rational consciousness.

6.2 Cannabis

Fitzhugh Ludlow was an early nonmedical self-experimenter with cannabis resin, who noted correctly the relation between dose and effect, inter- and intraindividual variations in response, and the influence of set and setting.

In the mid-1920s, German physicians Ernst Jol and Fritz Fränkel conducted SEs with cannabis extracts. The SEs revealed a state of intoxication characterized by a steady change between a dreamy and nearly usual waking state, with altered mood and affects, as well as dysfunctional memory.

6.3 Cocaine

The first scientist to report on SEs with cocaine was Paolo Mantegazza. He felt isolated from the external world, deeply joyful, and intensely alive, and sneered at the poor mortals condemned to live in this valley of tears.

In 1884, Sigmund Freud conducted SEs with cocaine to study its physiological effects. He concluded that cocaine could easily be applied in cases of “neurasthenia” and melancholia, but 2 years later he discovered cocaine’s dependence potential.

Aleister Crowley was a former medical student and British magician who used hashish and cocaine on a regular basis and sometimes mescaline. He experienced the full spectrum of cocaine’s effects, including unpleasant hallucinations, paranoia, and dependence.

Ernst Jol and Fritz Fränkel published a significant monograph on the effects of cocaine in the late 1920s. They were very aware of the dependence-producing potential of the drug and fought against the black market and illegal distribution.

6.4.1 Mescaline

The prominent American neurologist Weir Mitchell performed a SE with two and a half buttons of the mescaline-containing peyote cactus in 1896, and reported that he experienced an endless display of richly finished Gothic towers, statues, spinning hoops laden with jewels, and other marvels when he closed his eyes.

Louis Lewin and Arthur Heffter were the first researchers to self-experiment with extracts from the mescaline-containing peyote cactus. They established the Heffter Research Institute in 1898.

In the 1920s, many human studies with mescaline were conducted by physicians. Knauer and Maloney gave mescaline to nine physicians to compare inter- and intraindividual drug-induced effects, and Guttmann conducted SEs with mescaline to get a grip on “abnormal psychological processes”.

Kurt Beringer, a prominent German psychiatrist, conducted experiments on doctors who took mescaline and reported exhilarating nirvana-like experiences. The doctors became irritable and other doctors tried to “talk them down” (Passion 2005).

In the early 1930s, Hans Friedrichs conducted experiments with mescaline at Bonn University in Germany. His dissertation represents the most detailed psychological study on the mescaline intoxication up to now.

In 1925, Heinrich Klüver ingested some peyote buttons in his laboratory at the University of Minnesota to test a new tool for studying perception.

Roland Fischer began his hallucinogen research with a SE with mescaline in 1945, Norbert Matussek conducted SEs with mescaline in 1952, and Humphrey Osmond performed SEs with peyote in 1956.

6.4.2 Lysergic Acid Diethylamide (LSD)

LSD was discovered in 1943 by Albert Hofmann in the laboratories of the pharmaceutical company Sandoz in Basle (Switzerland). Later, several clinical studies were performed with LSD on physicians located at the Psychiatric Clinic at the University of Zürich (Switzerland).

LSD was discovered to have psychoactive effects, and Humphry Osmond let Aldous Huxley take mescaline under his supervision. Huxley became a major spokesman for the intelligent use of psychedelics.

Max Rinkel and Sidney Cohen were the first researchers to experiment on themselves with LSD. Cohen described feeling elevated peacefulness and a “majestic, sunlit, heavenly inner quietude” after taking the drug, and turned to his friend Gerald Heard for more articulate reports.

Oscar Janiger, a psychiatrist, set up a naturalistic study involving 875 people who had been introduced to LSD, including Anais Nin, Cary Grant, and Jack Nicholson.

Stanislav Grof was one of the first subjects to self-administer LSD at the Psychiatric Research Institute in Prague. He led the last research center for the therapeutic use of psychedelic drugs in Baltimore, Maryland, until 1976.

In 1959, LSD was at its peak of medical acceptance, but Cohen detected trends of going lax in controlling the drug and its use. In 1960, Cohen felt very much “uncomfortably unscientific” and wrote to his sponsor that he got enough “of the fringy goings on with this group of drugs”.

Practically every LSD investigator in the nation had taken LSD at least once, and many had taken it innumerable times.

Van Dusen conducted SEs with LSD at the Mendocino State Hospital in Talmage, California, USA, and concluded that LSD facilitates the discovery of this experience.

A group of psychologists conducted social experiments with psilocybin in 1961, and later opened a “psychedelic center” in Zihuatanejo (Mexico) where they explored regular psychedelic drug use and experimental social ways of life. They soon attracted the attention of the media, the world, and finally the police.

In the 1950s, John C. Lilly began experimenting with the isolation tank, and later conducted SEs with LSD. His books became classics in the “consciousness expansion” and “spiritual search” literature.

Dozens of Czech psychology students underwent LSD experiments at the psychiatric hospital at Kromeriz in 1966. The experiments were aimed at understanding some mental states occurring during psychosis.

6.4.3 Nightshade Hallucinogens

When it comes to the traditional plant hallucinogens of the nightshade family, SEs have been rarely reported. However, in the early 1950s, a German ethnologist prepared an ointment using these plants and reported experiencing wild dreams and flying through the air.

6.4.4 Fly Agaric (Amanita muscaria)

In 1967, Swiss pharmacologist Peter G. Waser and psychiatrist Jules Angst performed SEs with compounds isolated from the fly agaric mushroom. They reported experiencing hallucinations, disturbances of consciousness, and time and space perception.

6.4.5 Salvia divinorum

Mexican sage Salvia divinorum has hallucinogenic effects that were first reported by the Swedish anthropologist Jean Bassett Johnson in 1938. In the late 1950s, ethnomycologist Robert G. Wasson and LSD discoverer Albert Hofmann took part in a shamanic ceremony by chewing the leaves. Salvia divinorum effects enter with an irresistibly powerful force that takes the user in a dissociative trance state. The user is catapulted into strange realms of experiences, sometimes involving the most cosmic, wonderful, and detailed universes, while at other times, memories might not be recalled.

6.4.6 N,N-Dimethyltryptamine (DMT)

Self-experiments with DMT and closely related substances were performed in the 1950s and 1960s to explore the “psychopathological” effects of these substances.

Szára took mescaline in 1955 and discovered that DMT was inactive when given orally. He experimented with different modes of administration and found that the intensity of effects was significantly linked to the route of administration, with nasal insufflation and smoking leading to the most drastic experiences.

Timothy Leary got some intramuscular injections of DMT in 1965 and described being transfigured, seeing the delicate, wondrous body machinery of each person, all joined as one organism.

The state of consciousness experienced during the initial intoxication is characterized by amazing visual effects, but this is just a prelude to a profound state in which subjects report contacts with “another realm of reality”.

Administrations via intravenous, inhalation, or nasal routes lead to experiences usually so bizarre and dramatic that an inexperienced person might feel like being catapulted out of any known realm of consciousness.

Jonathan Ott carried out hundreds of SEs to explore the possibilities of producing an orally active DMT-containing inebriant. Ott also explored the psychoactive effect of bufotenine (5-HO-DMT).

6.4.7 Synthetic Hallucinogenic Phenethylamines

Daniel Trachsel, a Swiss chemist, published various contributions on new psychoactive substances and their effects, but distanced himself from any SEs.

Myron Stolaroff conducted SEs with a series of new psychoactive substances developed by Shulgin, including 2C-B, 2C-E, 2C-T-2, 2C-T-7, 2C-T4, 2C-T-21, and MEM. He understood his research as an attempt to make the unconscious conscious.

6.5 Entactogens/Empathogens

Gordon A. Alles, a Californian chemist and pharmacologist, accidentally ingested 3,4-methylenedioxyamphetamine (MDA) in 1934, which marks the first human entactogenic trip. He did not make this discovery public because of interest from the military.

Alexander T. Shulgin started his research on the synthesis and self-administration of psychedelic drugs after experiencing the effects of mescaline in 1960. He synthesized and tested hundreds of new psychoactive substances and developed a simple rating scale to measure their subjective effects.

Shulgin was not able to detect the special entactogenic effects of MDE and MDMA in his (self-)experiments, but was informed about the effects of MDMA by another student in 1976. He commenced with SEs but named its effects as “an alcohol-like intoxication” in his laboratory notebook.

Andrew Weil conducted SEs with MDA, psilocybin mushrooms, and the DMT-containing “Yage” plant concoction before Shulgin’s books were published, and SEs inspired the therapeutic work of many physicians and psychologists.

6.6 Dissociatives (Ketamine)

John C. Lilly described his SEs with ketamine and spread the word about its effects. He also combined the use of ketamine with the flotation tank and believed in an “Earth Coincidence Control Office”.

Howard Alltounian and Marcia Moore began exploring the psychedelic effects of ketamine, and later designed a psychospiritual treatment technique called “samadhi therapy”. However, Marcia Moore was found dead and frozen months later thought to be a consequence of an accident.

Karl Jansen’s research on ketamine addiction was inspired by his own SEs, but did not prevent him from becoming ketamine dependent. This points to the dangers of losing control without external control mechanisms in place in situations where self-generated SE gets “uncontrolled”.

7 Discussion

Shamans were the first “proto-scientists” who systematically navigated the complex space linked to the use of psychoactive substances. However, after World War II, SEs with psychoactive drugs became less frequent and better controlled.

In the mid-1850s, self-experimentation with psychoactive substances began. The motivations, intentions, “experimental procedures”, as well as the trajectories related to these SEs were quite different.

Scientists have found that substances with a comparatively “simple” spectrum of effects (e.g., benzodiazepines and opioids/opiates) have invited less self-experimentation compared to drugs with more “complex” effects that impact on many spheres of the human experience.

The prospect of potentially confronting unpleasant effects makes it less likely to engage in self-experimentation unless specific purposes have been identified. However, the classic hallucinogens radiated some form of appeal, at least to some experimenters, in spite of the possibility of experiencing psychological effects that might be challenging to cope with.

7.1 Motives for Self-Experimentation

To explore the effects of unknown substances, to learn about drug effects, to gain knowledge from the effects of substances, to cope with psychological problems, to gather power over others, to explore possible risks, to escape.

Some substances are more conducive to escapism than others, and LSD was advocated as having a purpose other than simply “getting high”. It was rarely abused, but controlled and specific conditions might be specifically sought after and useful.

7.2 Goals of Self-Experiments with Psychoactive Substances

The review of the literature indicates that a number of goals were associated with self-experimental use.

To learn more about LSD, you need to identify the psychoactive constituent(s) in extracts obtained from a plant matrix, evaluate the general effects of the substance, investigate the metabolism and pharmacokinetics of a substance, explore risk potential, evaluate some specific effects of the substance, and hold social LSD parties.

7.3 Ethical Issues in Self-Experimentation with Psychoactive Substances

Most investigations into self-experimentation with psychoactive substances were triggered by curiosity or were part of larger scientific studies that included SEs.

SEs with psychoactive substances have to be reviewed and permitted by institutional review boards. Essential toxicological data are also required.

Ethical considerations might have played a role in SEs designed to gain insights into the condition of the mentally ill, or to develop more empathy for people experiencing psychotic states.

Other SEs were thought to provide insights into the treatment of patients who were treated with hallucinogen-assisted psychotherapy.

SEs with LSD were consistent with recommendations made by the Sandoz pharmaceutical company and were well integrated among psychiatrists and psychologists. They were also used to deepen the understanding of reaction patterns and identify “blind spots” in the therapeutic process.

Passie (2002) performed controlled scientific experiments with psychoactive drugs prior to performing clinical studies. The experiences resulting from such SEs informed the design of the studies and provided optimal circumstances to avoid “bad trips”.

7.4 Kinds and Consequences of Self-Experiments

The majority of the presented SEs reviewed in this chapter belonged to the first category, while some examples seemed to fit into the second category (e.g., Crowley, the Los Angeles group of psychotherapists, and Leary’s group at Harvard).

Experimentation with certain types of psychoactive drugs can be associated with unique features and results, such as changes of personality, social attitudes, and value system, and in some cases, alterations of group dynamics.

7.5 Dangers of Self-Experimentation

The pursuit of self-experimentation has been repeatedly criticized for overenthusiasm, positive bias involving data interpretation, and lack of ability to evaluate the findings critically. When performing a surgical procedure or treating an experimentally induced infection, this might be considered a much smaller issue.

Another important point is that no basic toxicology data exist for many substances used for SEs. This puts the user at risk of overdoses, complications, and psychiatric sequelae.

Self-experimentation may result in psychological complications, physical complications, overdose, development of dependence, group dynamics becoming dysfunctional, and proliferating of certain substances.

Most SEs in the fields of medicine seemed relatively simple and harmless, but there were exceptions to this rule, such as the neurotoxic effects of MPTP, a synthesis by-product found in the synthetic opioid MPPP, which led to irreversible precipitation of Parkinsonism in users exposed to this by-product.

Other complications can occur during self-experimentation, such as unrealistic behavior, hypocritical attitude, and feelings of megalomania, which can even lead to dependence.

The “Los Angeles group” was a group of highly qualified psychotherapists who began using LSD and SEs in the late 1950s. Their enthusiasm soon extended to other substances and the establishment of “LSD social parties”.

8.1 What Can Be Learned from the History of Self-Experimentation?

SEs with psychoactive substances have a varied history. They have led to a deeper understanding of patients with psychotic illnesses and neurotic patients, and have even inspired new therapeutic methods for the effective treatment of post-traumatic stress disorder.

Under certain circumstances, it may be impossible to avoid posing risk to others when exploring new terrain. However, the risks should not be underestimated and have to be evaluated for every substance in its own right.

Psychologists like William James and Sigmund Freud have been inspired significantly by their self-experiments, but others have been confronted with serious dangers when their self-experimentation got out of control, especially with substances with more simple and reliable euphoric effects that also carry a higher dependence liability.

The psychological state of the experimenter will predict a preference for substances with properties that allow for compensation of psychological deficits, whereas substances with more complex effects are not particularly usable for coping with psychiatric symptoms.

If self-experimentation appears unavoidable or necessary, it is advantageous to work in the framework of controlled SEs where environmental circumstances are carefully controlled and characteristics of the substance used are known. This provides sufficient safety and a more reliable outcome, documentation, and instruction.

Recent scientific and ethical restrictions do not allow for much scientifically driven SEs anymore, and the future might see a further expansion of the spectrum and range of NPS and “self-experimentation” with them by curious laypersons, “para-professional” experimenters, or users with drug dependence.