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Self-Experiments with Psychoactive Substances: A Historical Perspective

November 27, 2018 / History, New substances, Other subjects, Other substances, Papers, Psychopharmacology, Publications / By / ,

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.”

Passie, T., & Brandt, S. D. (2018). Self-Experiments with Psychoactive Substances: A Historical Perspective., 10.1007/164_2018_177
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Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions

November 13, 2018 / History, LSD, Mushrooms / Psilocybin, Neuroscience, Other subjects, Other substances, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Safety / By / ,

Abstract

Humans have used serotonergic hallucinogens (i.e. psychedelics) for spiritual, ceremonial, and recreational purposes for thousands of years, but their administration as part of a structured therapeutic intervention is still a relatively novel practice within Western medical and psychological frameworks. In the mid-20th century, considerable advances were made in developing therapeutic approaches integrating administration of low (psycholytic) and high (psychedelic) doses of serotonergic hallucinogens for treatment of a variety of conditions, often incorporating psychoanalytic concepts prevalent at that time. This work contributed seminal insights regarding how these substances may be employed with efficacy and safety in targeted therapeutic interventions, including the importance of optimizing set (frame of mind) and setting (therapeutic environment). More recently, clinical and pharmacological research has revisited the effects and therapeutic potential of psychedelics utilizing a variety of approaches. The current article provides an overview of past and present models of psychedelic therapy, and discusses important considerations for future interventions incorporating the use of psychedelics in research and clinical practice.

Garcia-Romeu, A., & Richards, W. A. (2018). Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions. International Review of Psychiatry, 30(4), 291-316., 10.1080/09540261.2018.1486289.
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Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine

July 12, 2018 / Chemistry, History, MDMA, Medicine, Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Safety, Toxicology / By / , ,

Abstract

Better known as “ecstasy”, 3,4-methylenedioxymethamphetamine (MDMA) is a small molecule that has played a prominent role in defining the ethos of today’s teenagers and young adults, much like lysergic acid diethylamide (LSD) did in the 1960s. Though MDMA possesses structural similarities to compounds like amphetamine and mescaline, it produces subjective effects that are unlike any of the classical psychostimulants or hallucinogens and is one of the few compounds capable of reliably producing prosocial behavioral states. As a result, MDMA has captured the attention of recreational users, the media, artists, psychiatrists, and neuropharmacologists alike. Here, we detail the synthesis of MDMA as well as its pharmacology, metabolism, adverse effects, and potential use in medicine. Finally, we discuss its history and why it is perhaps the most important compound for the future of psychedelic science-having the potential to either facilitate new psychedelic research initiatives, or to usher in a second Dark Age for the field.

Dunlap, L. E., Andrews, A. M., & Olson, D. E. (2018). Dark classics in chemical neuroscience: 3, 4-Methylenedioxymethamphetamine. ACS chemical neuroscience, 9(10), 2408-2427., 10.1021/acschemneuro.8b00155
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Dark Classics in Chemical Neuroscience: Mescaline

June 8, 2018 / Cacti / Mescaline, Ethnobotany, History, Indigenous use, Neuroscience, Other subjects, Papers, Psychology, Publications / By / ,

Abstract

Archeological studies in the United States, Mexico, and Peru suggest that mescaline, as a cactus constituent, has been used for more than 6000 years. Although it is a widespread cactus alkaloid, it is present in high concentrations in few species, notably the North American peyote ( Lophophora williamsii) and the South American wachuma ( Trichocereus pachanoi, T. peruvianus, and T. bridgesii). Spanish 16th century chroniclers considered these cacti “diabolic”, leading to their prohibition, but their use persisted to our days and has been spreading for the last 150 years. In the late 1800s, peyote attracted scientific attention; mescaline was isolated, and its role in the psychedelic effects of peyote tops or “mescal buttons” was demonstrated. Its structure was established by synthesis in 1929, and alternative routes were developed, providing larger amounts for pharmacological and biosynthetic research. Although its effects are attributed mainly to its action as a 5-HT2Aserotonin receptor agonist, mescaline binds in a similar concentration range to 5-HT1A and α2A receptors. It is largely excreted unchanged in human urine, and its metabolic products are apparently unrelated to its psychedelic properties. Its low potency is probably responsible for its relative neglect by recreational substance users, as the successful search for structure-activity relationships in the hallucinogen field focused largely on finding more potent analogues. Renewed interest in the possible therapeutic applications of psychedelic drugs may hopefully lead to novel insights regarding the commonalities and differences between the actions of individual classic hallucinogens.
Cassels, B., & Sáez-Briones, P. (2018). Dark Classics in Chemical Neuroscience: Mescaline. ACS chemical neuroscience. 10.1021/acschemneuro.8b00215
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Plant Knowledges: Indigenous Approaches and Interspecies Listening Toward Decolonizing Ayahuasca Research

April 29, 2018 / Ayahuasca, Ethnobotany, History, Indigenous use, Papers, Publications, Religious studies / By /

Abstract

The ayahuasca research community is familiar with the concept of plant intelligences; however, they have yet to be adequately accounted for by commonly used research practices. This chapter is a call to examine the ontological and epistemological assumptions that underlie research practices and how these practices and assumptions may reinforce hierarchies of knowledge and animacy. The first part of this chapter describes some absences created by following a “methods as usual” approach when researching ayahuasca, based on ethnographic fieldwork at the World Ayahuasca Conference in 2016 (AYA2016). This highlights the need for researchers to acknowledge the methodological, disciplinary, and identity-based limitations on our abilities to produce and represent certain knowledges. Secondly, this chapter is a call to seriously and humbly engage with Indigenous sciences and epistemologies. This requires an honest reckoning with how research has contributed to colonial appropriation and marginalization of Indigenous knowledges. Indigenous ways of knowing have precedent for collaborating with teacher plants in producing knowledge and have much to contribute to discourse on multispecies perspectives. Lastly, I discuss possibilities for including multispecies sensibilities and Indigenous standpoints in research practices to create more collaborative and decolonial knowledges.

Dev, L. (2018). Plant Knowledges: Indigenous Approaches and Interspecies Listening Toward Decolonizing Ayahuasca Research. Plant Medicines, Healing and Psychedelic Science: Cultural Perspectives, 185-204. 10.1007/978-3-319-76720-8_11
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Who Is Keeping Tabs? LSD Lessons from the Past for the Future

April 29, 2018 / Ayahuasca, History, LSD, Mushrooms / Psilocybin, Other subjects, Papers, Psychology, Psychotherapy, Publications / By /

Abstract

Psychedelics fell from medical grace nearly half a century ago, but recent activity suggests that some researchers are optimistic about their return. Are they at risk, however, of facing the same historic challenges with a new generation of psychedelic enthusiasts, or have the circumstances changed sufficiently to allow for a new path forward? The twenty-first-century incarnation of psychedelic research resurrects some anticipated hypotheses and explores some of the same applications that clinicians experimented with 50 years ago. On the surface then, the psychedelic renaissance might be dismissed for retreading familiar ground. A deeper look at the context that gave rise to these questions, though, suggests that while some of the questions are common, the culture of neuroscience and the business of drug regulation have changed sufficiently to warrant a retrial. A close look at the history of psychedelics encourages us to think carefully about the roles of regulators, the enthusiasm of researchers, and our cultural fascination and/or repulsion with mind-altering molecules.

Dyck, E. (2018). Who Is Keeping Tabs? LSD Lessons from the Past for the Future. Plant Medicines, Healing and Psychedelic Science: Cultural Perspectives, 1-17. 10.1007/978-3-319-76720-8_1
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Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)

March 1, 2018 / History, LSD, Papers, Psychology, Psychotherapy, Publications / By /

Abstract

Lysergic acid diethylamide (LSD) is one of the most potent psychoactive agents known, producing dramatic alterations of consciousness after submilligram (≥20 μg) oral doses. Following the accidental discovery of its potent psychoactive effects in 1943, it was supplied by Sandoz Laboratories as an experimental drug that might be useful as an adjunct for psychotherapy, or to give psychiatrists insight into the mental processes in their patients. The finding of serotonin in the mammalian brain in 1953, and its structural resemblance to LSD, quickly led to ideas that serotonin in the brain might be involved in mental disorders, initiating rapid research interest in the neurochemistry of serotonin. LSD proved to be physiologically very safe and nonaddictive, with a very low incidence of adverse events when used in controlled experiments. Widely hailed by psychiatry as a breakthrough in the 1950s and early 1960s, clinical research with LSD ended by about 1970, when it was formally placed into Schedule 1 of the Controlled Substances Act of 1970 following its growing popularity as a recreational drug. Within the past 5 years, clinical research with LSD has begun in Europe, but there has been none in the United States. LSD is proving to be a powerful tool to help understand brain dynamics when combined with modern brain imaging methods. It remains to be seen whether therapeutic value for LSD can be confirmed in controlled clinical trials, but promising results have been obtained in small pilot trials of depression, anxiety, and addictions using psilocybin, a related psychedelic molecule.
Nichols, D. E. (2018). Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD). ACS chemical neuroscience. 10.1021/acschemneuro.8b00043
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Amanita muscaria (fly agaric): from a shamanistic hallucinogen to the search for acetylcholine

March 1, 2018 / History, Mushrooms / Psilocybin, Other subjects, Other substances, Papers, Psychopharmacology, Psychotherapy, Publications / By / , ,

Abstract

The mushroom Amanita muscaria (fly agaric) is widely distributed throughout continental Europe and the UK. Its common name suggests that it had been used to kill flies, until superseded by arsenic. The bioactive compounds occurring in the mushroom remained a mystery for long periods of time, but eventually four hallucinogens were isolated from the fungus: muscarine, muscimol, muscazone and ibotenic acid. The shamans of Eastern Siberia used the mushroom as an inebriant and a hallucinogen. In 1912, Henry Dale suggested that muscarine (or a closely related substance) was the transmitter at the parasympathetic nerve endings, where it would produce lacrimation, salivation, sweating, bronchoconstriction and increased intestinal motility. He and Otto Loewi eventually isolated the transmitter and showed that it was not muscarine but acetylcholine. The receptor is now known variously as cholinergic or muscarinic. From this basic knowledge, drugs such as pilocarpine (cholinergic) and ipratropium (anticholinergic) have been shown to be of value in glaucoma and diseases of the lungs, respectively.

Lee, M. R., Dukan, E., & Milne, I. (2018). Amanita muscaria (fly agaric): from a shamanistic hallucinogen to the search for acetylcholine. The journal of the Royal College of Physicians of Edinburgh, 48(1), 85-91.,  10.4997/JRCPE.2018.119
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Psychedelics: Where we are now, why we got here, what we must do

February 21, 2018 / History, LSD, Other subjects, Papers, Psychology, Psychotherapy, Publications, Sociology / By / ,

Abstract

The purpose of this commentary is to provide an introduction to this special issue of Neuropharmacology with a historical perspective of psychedelic drug research, their use in psychiatric disorders, research-restricting regulatory controls, and their recent emergence as potential breakthrough therapies for several brain-related disorders. It begins with the discovery of lysergic acid diethylamide (LSD) and its promising development as a treatment for several types of mental illnesses during the 1940s. This was followed by its abuse and stigmatization in the 1960s that ultimately led to the placement of LSD and other psychedelic drugs into the most restrictively regulated drug schedule of the United States Controlled Substances Act (Schedule I) in 1970 and its international counterparts. These regulatory controls severely constrained development of psychedelic substances and their potential for clinical research in psychiatric disorders. Despite the limitations, there was continued research into brain mechanisms of action for psychedelic drugs with potential clinical applications which began during the 1990s and early 2000s. Finding pathways to accelerate clinical research in psychedelic drug development is supported by the growing body of research findings that are documented throughout this special issue of Neuropharmacology. Accumulated research to date suggests psychedelic drug assisted psychotherapy may emerge as a potential breakthrough treatment for several types of mental illnesses including depression, anxiety, post-traumatic stress disorder, and addiction that are refractory to current evidenced based therapies. This research equally shows promise in advancing the understanding of the brain, brain related functioning, and the consequential effects of untreated brain related diseases that have been implicated in causing and/or exacerbating numerous physical disease state conditions. The authors conclude that more must be done to effectively address mental illnesses and brain related diseases which have become so pervasive, destructive, and whose treatments are becoming increasingly resistant to current evidenced based therapies.
Belouin, S. J., & Henningfield, J. E. (2018). Psychedelics: Where we are now, why we got here, what we must do. Neuropharmacology. 10.1016/j.neuropharm.2018.02.018
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Regulation of human research with LSD in the United States (1949-1987)

November 17, 2017 / History, LSD, Other disciplines, Other subjects, Papers, Publications, Safety / By /

Abstract

Human research with hallucinogens such as lysergic acid diethylamide (LSD) has been ongoing in the USA since 1949. During the 1960s, LSD was investigated for a variety of psychiatric indications, including the following: as an aid in treatment of schizophrenia; as a means of creating a “model psychosis”; as a direct antidepressant; and as an adjunct to psychotherapy. Studies with all drugs, including LSD, have always been conducted under federal regulatory controls, including the 1938 Food Drug and Cosmetic Act (FDCA; which ensured the safety of drugs) and the 1962 Kefauver-Harris Amendments to the FDCA (which described appropriate scientific methodology and ensured drug efficacy). This paper details how the 1962 Amendments introduced numerous safety and efficacy requirements that must be in satisfied during clinical drug research-and how human studies conducted with LSD in the 1960s struggled with their fulfillment. Information is provided from Senate hearings, case law, and interviews with key investigators. Examples are also drawn from scientific papers and symposia published during and since that period, with a focus on information from clinical studies conducted with LSD by psychiatrist Albert Kurland at the Spring Grove State Hospital, near Baltimore, MD. While Kurland largely conformed with these new regulations, other investigators often fell short of complying with scientific standards and federal requirements. Thus, the human hallucinogen studies of the 1960s are best understood as providing pilot data on safety and efficacy, as well as testable hypotheses for current hallucinogen studies conducted under modern scientific and regulatory standards.
Bonson, K. R. (2017). Regulation of human research with LSD in the United States (1949-1987). Psychopharmacology, 1-14. 10.1007/s00213-017-4777-4
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30 April - Q&A with Rick Strassman

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