OPEN Foundation

History

The rise, fall, and possible rise of LSD

Abstract

LSD and other hallucinogens or psychedelics have been therapeutically used in psychiatry in the period between the Second World War and the late 1980s. In the past years renewed interest in the medical sciences for research and therapeutic use of these substances has evolved. AIM: A discussion of contemporary lsd research in the context of earlier research. METHOD: A systematic survey of the literature on the psychiatric use of lsd and the reactions towards lsd use in society. RESULTS: Since 1947 lsd has been therapeutically used in the treatment of anxiety, depression, addiction, post traumatic disorders, and other conditions. Since the early 1960s this use has been criticized because of the danger of evoking psychoses in patients, and because of the rise of a widespread non-medical use. However, there is no consolidated evidence-base for either the positive or the negative outcomes of lsd therapy. CONCLUSION: At this moment it is unpredictable whether lsd will make a comeback in psychiatry. Contemporary research attempts to evade all public controversy and to build up a solid evidence-base. Nevertheless it demonstrates a direct continuity with earlier research.

Snelders, S., & Pieters, T. (2020). The rise, fall, and possible rise of LSD. Tijdschrift Voor Psychiatrie62(8), 707-712.
Link to full text

The Current Status of Psychedelics in Psychiatry

Abstract

In the 1950s, the Swiss pharmaceutical company Sandoz, which employed the chemist Albert Hofmann, who discovered lysergic acid diethylamide (LSD) and the similar serotonergic psychedelic psilocybin, made these drugs available to the psychiatric research community as the products Delysid and Indocybin, respectively. By the 1960s, these drugs had caused a revolution in brain science and psychiatry because of their widespread use by researchers and clinicians in many Western countries, especially the US. Before LSD was banned, the US National Institutes of Health funded more than 130 studies exploring its clinical utility, with positive results in a range of disorders but particularly anxiety, depression, and alcoholism. However, the displacement of LSD into recreational use and eventual association with the anti-Vietnam war movement led to all psychedelics being banned in the US. This ban became ratified globally under the 1971 UN Convention on narcotics. Since then, research funding, drug production, and the study of psychedelics as clinical agents has been virtually stopped. Until very recently, no companies would manufacture medical-grade psychedelics, which made getting regulatory approval for clinical research—especially clinical trials—very difficult and in some countries (eg, Germany) impossible.

Nutt, D., & Carhart-Harris, R. (2021). The current status of psychedelics in psychiatry. JAMA psychiatry78(2), 121-122.; 10.1001/jamapsychiatry.2020.2171
Link to full text

Psilocybin occasioned mystical-type experiences

Abstract

Objective: Research into psychedelic therapy models has shown promise for the treatment of specific psychiatric conditions. Mystical-type experiences occasioned by psilocybin have been correlated with therapeutic benefits and long-term improvements in positive mental outlook and attitudes. This article aims to provide an overview of the topic, highlight strengths and weaknesses in current research, generate novel perspectives and discussion, and consider future avenues for research.

Design: This narrative review was designed to summarise and assess the state of research on psilocybin occasioned mystical-type experiences and applications for the treatment of specific psychiatric conditions.

Results: Contemporary methods on the quantification of mystical-type experiences and their acute subjective effects are discussed. Recent studies provide some understanding of the pharmacological actions of psychedelics although the neurological similarities and differences between spontaneous and psychedelic mystical-type experiences are not well described. Applicability to modern clinical settings is assessed. Potential novel therapeutic applications include use in positive psychology interventions in healthy individuals.

Conclusions: Since 2006 significant advancements in understanding the therapeutic potential of psilocybin-assisted psychotherapy have been made; however, more work is required to understand the neuromechanistic processes and applicability in modern clinical settings. Despite promising results in recent studies, funding issues for clinical trials, legal concerns and socio-cultural resistance provide a counterpoint to experimental evidence.

James, E., Robertshaw, T. L., Hoskins, M., & Sessa, B. (2020). Psilocybin occasioned mystical‐type experiences. Human Psychopharmacology: Clinical and Experimental35(5), e2742; 10.1002/hup.2742
Link to full text

Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments

Abstract

Introduction: Combinations of psychotherapy with antidepressants are gold-standard psychiatric treatments. They operate through complex and interactional mechanisms, not unlike the reemergent paradigm of psychedelic-assisted psychotherapy, which promising research suggests may also be highly effective in even challenging populations.
Areas covered: We review the therapeutic mechanisms behind both conventional and psychedelic paradigms, including the evolution of this knowledge and the associated explanatory frameworks. We explore how psychedelics have provided insights about psychiatric illnesses and treatments over the past decades. We discuss limitations to early explanatory models while highlighting and comparing the psychological and biological mechanisms underlying many psychiatric treatments.
Methods: A narrative review was conducted based on a search in Medline/Pubmed up to January 1st, 2020, and iterative retrieval of references from recent reviews and clinical trials.
Expert opinion: The contextual model of the common factors of psychotherapy provides a powerful perspective on psychotherapy, antidepressants, and psychedelics, as well as 3,4-methylenedioxymethamphetamine (MDMA) and ketamine. It aligns well with key tenets of psychedelic-assisted psychotherapy. Conventional antidepressants and especially psychedelics may improve the efficacy of psychotherapy via neurochemical changes and increased environmental sensitivity. Combined treatments hold significant promise for advancing the knowledge and treatment of many forms of psychopathology.

Keywords: Psychedelics; antidepressants; ketamine; ketamine-assisted psychotherapy; lsd; mdma; mdma-assisted psychotherapy; psilocybin; psychedelic-assisted psychotherapy; psychiatry; psychotherapy.
Greenway, K. T., Garel, N., Jerome, L., & Feduccia, A. A. (2020). Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments. Expert Review of Clinical Pharmacology, 1-15., https://doi.org/10.1080/17512433.2020.1772054
Link to full text

Psilocybin: from ancient magic to modern medicine

Abstract

Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is an indole-based secondary metabolite produced by numerous species of mushrooms. South American Aztec Indians referred to them as teonanacatl, meaning “god’s flesh,” and they were used in religious and healing rituals. Spanish missionaries in the 1500s attempted to destroy all records and evidence of the use of these mushrooms. Nevertheless, a 16th century Spanish Franciscan friar and historian mentioned teonanacatl in his extensive writings, intriguing 20th century ethnopharmacologists and leading to a decades-long search for the identity of teonanacatl. Their search ultimately led to a 1957 photo-essay in a popular magazine, describing for the Western world the use of these mushrooms. Specimens were ultimately obtained, and their active principle identified and chemically synthesized. In the past 10–15 years several FDA-approved clinical studies have indicated potential medical value for psilocybin-assisted psychotherapy in treating depression, anxiety, and certain addictions. At present, assuming that the early clinical studies can be validated by larger studies, psilocybin is poised to make a significant impact on treatments available to psychiatric medicine.

Nichols, D. E. (2020). Psilocybin: from ancient magic to modern medicine. The Journal of Antibiotics, 1-8., doi.org/10.1038/s41429-020-0311-8
Link to full text

The Psychedelic Renaissance and Its Forensic Implications

Abstract

Recent years have seen a renaissance of research into the use of psychedelic compounds to address various psychiatric conditions. The study of these substances went dormant in 1970 when the United States government passed the Controlled Substances Act, which categorized lysergic acid diethylamide, commonly known as LSD or acid, as a Schedule I drug. The rise of psychedelics in research settings raises questions regarding their risks outside of clinical trials. The available data on the impact of psychedelic use on interpersonal violence and other criminal behavior remain scant. Although Timothy Leary’s work of the 1960s failed to clearly demonstrate a reduction in criminal recidivism with psychedelic-assisted psychotherapy, recent studies suggest that the use of psychedelics may reduce individuals’ risk of interpersonal violence. Forensic psychiatrists should be aware of this research, as well as the role that psychedelics may play in various forensic assessments. This article summarizes basic information that the forensic practitioner should know about psychedelic substances, including their various effects and proposed mechanism of action; describes historical and recent research into psychedelics and criminal behavior; and offers evaluators a practical means by which to assess individuals’ psychedelic use in forensic contexts.

Holoyda, B. (2020). The Psychedelic Renaissance and Its Forensic Implications. The journal of the American Academy of Psychiatry and the Law48(1), 87-97., 10.29158/JAAPL.003917-20
Link to full text

[From Adam to ecstacy; legal use of MDMA in the 1970s and 1980s]

Abstract

MDMA is currently a controversial psychedelic in the Netherlands: it is banned under the Opium Act, but widely used as a recreational drug. According to the government, the normalization of MDMA must be combated, others argue in favour of legalization. Meanwhile, in recent years psychiatry has become interested in renewed therapeutic use of MDMA.<br/> AIM: To place the current discussion of MDMA in the context of recent history. What can we learn from the way MDMA was used in America and Western Europe in the period between the (re)discovery of the drug in the 1970s and its legal prohibition in the 1980s?<br/> METHOD: Survey of the literature on the history of MDMA, and additional source research.<br/> CONCLUSION: In the period before MDMA became illegal, its use was closely linked to the pursuit of self-actualisation in therapeutic, spiritual and recreational contexts. History shows that the meaning that people attach to a psychoactive substance like MDMA is highly dependent on the context of use. Like all drugs, MDMA also has multiple functionalities and ‘framings’. The psychoactive substance cannot be reduced to one valuation or essence.
Blok, G. (2020). From Adam to ecstacy; legal use of MDMA in the 1970s and 1980s. Tijdschrift Voor Psychiatrie62(8), 702-706., https://pubmed.ncbi.nlm.nih.gov/32816299/
Link to full text

Psychedelics in Western culture: unnecessary psychiatrisation of visionary experiences

Abstract

Historical research about the use of psychedelics in specific religious contexts can provide rational explanations for visionary experiences that could otherwise be cause to question the mental health of religious actors. Reversely, if historians ignore or overlook empirical evidence for the use of psychedelics, the result can be that normal and even predictable reactions of healthy subjects to the effects of psychedelic substances are arbitrarily interpreted as ‘irrational’.

AIM: To describe the meaning of the psychedelic factor in historical visionary experiences.

METHOD: Discussion based on three examples of selective use of historical sources on psychedelics.

RESULTS: This theme is of broader relevance to cultural history and scientific theory because we are typically dealing with religious practices that have traditionally been categorized as ‘magic’ and thereby classified in advance as irrational and potentially pathological. The article discusses three historical examples: the so-called Mithras Liturgy from Roman Egypt, early modern witches’ ointments, and spiritual use of hashish in the nineteenth century.

CONCLUSION: Established academics often deny the significance of psychedelics in visionary experiences. Discussion of pre-Enlightenment source material appears to be of considerable importance for the correct interpretation of important religious and cultural traditions. Critical empirical source research without prejudices or implicit agendas is the appropriate method.

Hanegraaff, W. J. (2020). Psychedelics in Western culture: unnecessary psychiatrisation of visionary experiences. Tijdschrift Voor Psychiatrie62(8), 713-720.
Link to full text

Psychedelic crossings: American mental health and LSD in the 1970s.

Abstract

This article places a spotlight on lysergic acid diethylamide (LSD) and American mental health in the 1970s, an era in which psychedelic science was far from settled and researchers continued to push the limits of regulation, resist change and attempt to revolutionise the mental health market-place. The following pages reveal some of the connections between mental health, LSD and the wider setting, avoiding both ascension and declension narratives. We offer a renewed approach to a substance, LSD, which bridged the gap between biomedical understandings of ‘health’ and ‘cure’ and the subjective needs of the individual. Garnering much attention, much like today, LSD created a cross-over point that brought together the humanities and arts, social sciences, health policy, medical education, patient experience and the public at large. It also divided opinion. This study draws on archival materials, medical literature and popular culture to understand the dynamics of psychedelic crossings as a means of engendering a fresh approach to cultural and countercultural-based healthcare during the 1970s.
Richert, L., & Dyck, E. (2019). Psychedelic crossings: American mental health and LSD in the 1970s. Medical Humanities, medhum-2018., https://doi.org/10.1136/medhum-2018-011593
Link to full text

Beyond LSD: A Broader Psychedelic Zeitgeist during the Early to Mid-20 th Century

Abstract

During the 1950s and 1960s, there was a tremendous surge in research into the effects of psychedelic drugs. When discussing this period of research, the discovery of the psychoactive properties of LSD in 1943 is often presented as the main, and sometimes only, driving force of the boom in research. This “Great Person,” or “Great Chemical,” historiographical lens fails to acknowledge other factors that were fundamental in setting the stage for the research. In particular, other psychedelic drugs, such as mescaline, were already being probed for their uses in psychotherapy and as models for psychosis before the effects of LSD had been discovered. Psilocybin and other classical psychedelics had also been discovered by Western researchers around the same time as the synthesis of LSD. Additionally, many of the dominant zeitgeists (e.g., pharmacological, psychoanalytic, and humanistic) in psychology during this period were congruent with psychedelic research. This article argues that while the discovery of LSD may have been a catalyst for psychedelic research in the 1950s and ’60s, there was a broader psychedelic zeitgeist that deserves acknowledgement for setting the stage.
Aday, J. S., Bloesch, E. K., & Davoli, C. C. (2019). Beyond LSD: A broader psychedelic zeitgeist during the early to mid-20th century. Journal of psychoactive drugs51(3), 210-217., https://doi.org/10.1080/02791072.2019.1581961
Link to full text