Classical psychedelics in psychiatry - renaissance of interest and therapeutic perspectives. / Klasyczne psychodeliki w psychiatrii ­ renesans zainteresowania i perspektywy terapeutyczne.

Substances that change the states of consciousness have been used in the therapeutics of traditional cultures for hundreds of years. In the Western cultural circle, scientific curiosity and hope for a breakthrough in the treatment of various mental disorders constituted the basis of the first wave of research on humans with the use of psychedelics. After synthesizing LSD, psychedelic substances aroused intense but short-term interest among mental health specialists at the beginning of the second half of the 20th century. In the preliminary studies, substances such as psilocybin or LSD, used as a supplement to psychotherapy, showed promising therapeutic effects, however, due to legal and political reasons, all research work was stopped in the 1970s. The last two decades have been a period of renaissance in the interest in using sychedelic substances in psychiatry. Despite the early stage of work, the clinical research conducted so far has indicated the potential benefits of using psychedelics in the treatment of anxiety, affective disorders, or addictions. Moreover, so far, no serious side effects of this form of therapy have been reported. However, due to a number of barriers of both medical and legal nature, the creation of the first psychiatric drug with psychedelic properties appears to be extremely complicated. Further, precisely constructed studies on large groups of patients are needed to determine whether psychedelics can find practical applications in psychiatric therapy (or even become a long-awaited breakthrough in the treatment of mental disorders).

Neuroimaging in psychedelic drug development: past, present, and future.

Psychedelic therapy (PT) is an emerging paradigm with great transdiagnostic potential for treating psychiatric disorders, including depression, addiction, post-traumatic stress disorder, and potentially others. 'Classic' serotonergic psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), which have a key locus of action at the 5-HT2A receptor, form the main focus of this movement, but substances including ketamine, 3,4-Methylenedioxymethamphetamine (MDMA) and ibogaine also hold promise. The modern phase of development of these treatment modalities in the early 21st century has occurred concurrently with the wider use of advanced human neuroscientific research methods; principally neuroimaging. This can potentially enable assessment of drug and therapy brain effects with greater precision and quantification than any previous novel development in psychiatric pharmacology. We outline the major trends in existing data and suggest the modern development of PT has benefitted greatly from the use of neuroimaging. Important gaps in existing knowledge are identified, namely: the relationship between acute drug effects and longer-term (clinically-relevant) effects, the precise characterisation of effects at the 5-HT2A receptor and relationships with functional/clinical effects, and the possible impact of these compounds on neuroplasticity. A road-map for future research is laid out, outlining clinical studies which will directly address these three questions, principally using combined Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) methods, plus other adjunct techniques. Multimodal (PET/MRI) studies using modern PET techniques such as the 5-HT2A-selective ligand [11 C]Cimbi-36 (and other ligands sensitive to neuroplasticity changes) alongside MRI measures of brain function would provide a 'molecular-functional-clinical bridge' in understanding. Such results would help to resolve some of these questions and provide a firmer foundation for the ongoing development of PT.

Psychosis and psychedelics: Historical entanglements and contemporary contrasts.

Experiences of psychedelics and psychosis were deeply entangled in scientific practices in the mid-20th century, from uses of psychedelic drugs that could model psychosis, to detailed phenomenological comparisons of endogenous and drug-induced madness. After the moral panic of the 1960s shut down psychedelic research, however, these two phenomena became disentangled. In the decades following, the science of psychosis transformed, shedding the language of psychoanalysis, and adopting the new scientific veneer of psychiatry. Today, as psychedelic science re-emerges, the research programs surrounding psychosis and psychedelics now stand in stark contrast. Here, I look closely at how these research programs respond to questions related to what is worth measuring, what is worth investigating, and how we ought to respond to these experiences. This comparison reveals radically different assumptions and values that guide each research paradigm and shape clinical practice. While psychedelic research often includes scales that seek to capture experiences of mysticism, meaningfulness, and ego dissolution, research related to psychosis focuses on the measurement of pathological symptoms and functioning. Research into psychosis primarily seeks universal and reductionist causal explanations and interventions, while psychedelic research embraces the importance of set and setting in shaping unique experiences. Responses to psychedelic crisis involve warmth, compassion, and support, while responses to psychotic experiences often involve restraint, seclusion, and weapons. I argue that these differences contain important lessons for psychiatry. However, as psychedelic research struggles to meet regulatory requirements and fit within the paradigm of evidence-based medicine, these differences may quickly dissolve.

Modalities of the psychedelic experience: Microclimates of set and setting in hallucinogen research and culture.

Mid-20th-century American research on psychedelics evinced a stunning diversity of interpretations of hallucinogenic effects. While some researchers viewed psychedelics as invaluable tools for psychotherapy, others persisted in treating them as psychosis-inducing agents. As some groups considered psychedelics as catalysts for artistic creativity, others investigated their potential use as psychochemical weapons in the battlefield, or conversely as tools for spiritual ecstasy and revelation. This bewildering array of perceptions regarding the nature of hallucinogenic effects led to stark contrasts in the contexts (set and setting) of psychedelic research and experimentation, leading to wildly divergent outcomes and reports on the effects of the drugs, and strident disagreements between the actors in the field. Examining this remarkable historical moment of epistemological unclarity regarding psychedelics and their effects, this article describes how distinct scientific and cultural trends and moments of mid-20th-century America contributed to the creation of diverse microclimates of set and setting that reproduced investigator beliefs and attitudes and brought about a beguiling Pygmalion effect that left researchers befuddled and perplexed. I propose the concept of psychedelic modality to describe how distinct sociocultural microclimates lead to thematic aggregates in which distinct types of expectations, intentions as well as physical, social, and cultural environments all tend to cluster, producing characteristic outcomes and results. By exploring the historical context and consequences of the emergence of seven psychedelic modalities (psychotomimetic, military, psychotherapeutic, spiritual, artistic-creative, tech-innovative, and political) in mid-20th-century America, this article outlines the varieties of psychedelic experiences in their relationship with culture at large, and subcultures in particular.

Psilocybin Conspectus: Status, Production Methods, and Considerations.

Psilocybin is a psychoactive alkaloid that is produced naturally by approximately 200 species of mushrooms. The potential medical use of this molecule for the treatment of mental illness is gaining renewed momentum. As demand grows and clinical trials progress, appropriate methods for producing a quality pharmaceutical product are needed. This review highlights the methods currently available, such as the prominent synthetic method and its biosynthetic alternatives, as well as others on the near horizon. This article further seeks to discuss the rapid and evolving nature of the psilocybin industry in the 21st century.

¿Es posible desarrollar investigaciones clínicas utilizando sustancias psicodélicas en Uruguay?: pasado y presente de las investigaciones sobre el potencial medicinal de los psicodélicos / Is it possible to develop clinical research using psychedelic substances in Uruguay ?: past and present of research on the medicinal potential of psychedelics

Los psicodélicos son sustancias capaces de alterar la conciencia, a través de su efecto sobre la transmisión serotoninérgica en el sistema nervioso central. En sus formas de ingesta tradicional son utilizados en rituales, con fines espirituales y medicinales. En el campo científico, dichas sustancias fueron estudiadas para posibles aplicaciones psicoterapéuticas en el período 1950-1970, y luego fueron excluidas de la investigación clínica durante las posteriores décadas. Sin embargo, desde 1990 asistimos a un «renacimiento de los estudios sobre psicodélicos¼, donde estas sustancias están siendo estudiadas en su potencial clínico para el tratamiento de distintos trastornos menta-les. El presente artículo describe y reflexiona sobre la historia de estas investigaciones en Uruguay y en el mundo, tanto en su primera etapa (1950-1970) como en su renacimiento posterior (1990-actualidad), dejando planteado un escenario en el que sea posible avanzar en el campo de las investigaciones clínicas con psicodélicos en nuestro país.

Psychedelics are substances capable of altering consciousness, through their effect on serotonergic transmission within the central nervous system. In their traditional uses, psychedelics are consumed during rituals, for spiritual and medicinal purposes. In the scientific field, these substances were studied because of their possible psychotherapeutic applications in the period 1950-1970. Afterwards, psychedelics were banned from clinical research for decades. Nevertheless, since 1990 we are witnessing a "renaissance of psychedelic studies", where these substances are being studied because of their clinical potential applications for the treatment of different mental disorders. The current article describes and analyzes the history of these research in Uruguay and in the world, both in its first stage (1950-1970) and in the present "renaissance" (1990-present). The article suggests a future scenario, where Uruguay could play a major role in the field of psychedelic research.

Psychedelic-Assisted Therapy: Emerging Treatments in Mental Health Disorders

Psychedelics are a class of psychoactive substances that were studied extensively between 1943 and 1970 as potential therapies for treating a host of mental health disorders, including addiction. Despite promising early results, U.S. psychedelic research was halted in the early 1970s with the enactment of the Controlled Substances Act. As the field of psychedelic-assisted therapy develops, nurses can decide the role they will play in the continuing clinical and scholarly research of these substances, which may soon be used in controlled settings to treat some of the most widespread mental health disorders. To prepare for this task, this article proposes that nurses * become familiar with the history, relevant language, and scientific findings related to the field of psychedelic research. * learn about existing psychedelic-assisted therapy and research resources. * examine their thoughts, judgments, and opinions about therapeutic psychedelic use. * consider the potential role of nursing in psychedelic-assisted therapies going forward.

Supporting the Patient on LSD Day.

Editor's note: From its first issue in 1900 through to the present day, AJN has unparalleled archives detailing nurses' work and lives over more than a century. These articles not only chronicle nursing's growth as a profession within the context of the events of the day, but also reveal prevailing societal attitudes about women, health care, and human rights. Today's nursing school curricula rarely include nursing's history, but it's a history worth knowing. To this end, From the AJN Archives highlights articles selected to fit today's topics and times. During the 1960s, the therapeutic effects of lysergic acid diethylamide (LSD) were studied in psychiatric clinical settings. In this February 1964 article, nurse Kay Parley writes enthusiastically about this work at one such research hospital. She describes the benefits of LSD therapy for patients with alcoholism, as well as the richness of the experience for the nurse who guides the patient through treatment. "No role is so welcomed on our psychiatric unit than that of 'sitting' with a patient during LSD therapy." Parley vividly describes the nurse's role in these treatments. Her own long hospitalization for "manic-depressive psychosis" and treatment with LSD undoubtedly framed her approach to this therapy. Today there is renewed interest in the therapeutic use of psychoactive substances such as LSD. Penn and colleagues provide an update in "Psychedelic-Assisted Therapy" in this issue.-Betsy Todd, MPH, RN.

Psilocybin: from ancient magic to modern medicine.

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.

A dangerous method? Psychedelic therapy at Modum Bad, Norway, 1961-76.

After many years of disregard, the use of psychedelic drugs in psychiatric treatment has re-emerged in recent years. The prospect that psychedelics may again be integrated into mainstream psychiatry has aroused interest in long-forgotten research and experience from the previous phase of psychedelic therapy, which lasted from the late 1940s to the 1970s. This article will discuss one large-scale psychedelic therapy programme at Modum Bad Nervesanatorium, a psychiatric clinic which treated 379 inpatients with psychedelic drugs during the years 1961-76. The psychiatrists there initially regarded the psychedelic treatment as efficacious and without serious negative reactions, but reports of long-term harm have since surfaced. This article discusses how insights from Modum Bad might benefit the new generation of psychedelic treatment efforts.

Las alucinaciones visuales en la obra de Oliver Sacks / Visual hallucinations in the works of Oliver Sacks

Introducción: Las alucinaciones visuales constituyen una de las manifestaciones más singulares de diversas situaciones clínicas, ya sea en el ámbito de las enfermedades mentales, de las alteraciones físicas o del consumo de drogas. Sin embargo, el análisis detallado de su vivencia en relación con las causas que pueden producirlas es poco frecuente. Objetivo: Considerar la representación de las alucinaciones visuales en las publicaciones del neurólogo y escritor Oliver Sacks, con especial atención a su obra Hallucinations. Desarrollo: Las alucinaciones han llamado la atención de la cultura, la religión y el arte, lo que ha conllevado múltiples interpretaciones. El interés de Sacks por la percepción de las sensaciones le llevó a investigar los mecanismos por los que se producen las alucinaciones, debido al escaso conocimiento que se tenía sobre el tema. Las alucinaciones aparecieron ya en obras como Migraine, Awakenings o A leg to stand on. En Musicophilia abordó las alucinaciones auditivas, y en Hallucinations las consideró de forma monográfica. En esta última obra, Sacks analizó especialmente las presentes en el síndrome de Charles Bonnet, en situaciones de privación sensorial y en pacientes con epilepsia, las precipitadas por la levodopa y las causadas por drogas de abuso. Conclusiones: Hallucinations es una de las obras de Oliver Sacks con mayor contenido neurooftalmológico. La descripción de las alucinaciones de sus pacientes o las experimentadas en su propia piel y la reflexión sobre el mundo de la percepción hacen de Hallucinations una de las obras más fascinantes de Sacks

Introduction: Hallucinations are one of the most bizarre experiences in several diseases. They appear in mental diseases as well as in physical illnesses and may be the consequence of the usage of drugs of abuse. However, a detailed analysis of how patients feel under hallucinations caused by different diseases is uncommon. Aim: This article analyses how visual hallucinations are considered in the works of the neurologist and writer Oliver Sacks, with special attention to his book Hallucinations. Development: Hallucinations have been under consideration by culture, religion and arts, which has led to multiple interpretations. Sackss interest in perception of sensations led him to work on the analysis of hallucinations, given the limited knowledge on the topic. References to hallucinations appeared in several of his books like Migraine, Awakenings and A leg to stand on. In Musicophilia Sacks approached the auditory hallucinations and in Hallucinations he considered them in depth. In the latter work, Sacks analyses especially those present in Charles Bonnet syndrome, in situations of sensory deprivation, in patients with epilesy, those present during treatment with levodopa and those caused by drug of abuse. Conclusions: Hallucinations is one of Sacks’s books with greater neuroophthalmological content. The descriptions of the hallucinations of his patients or those experienced by himself, as well as the reflective analysis on the world of perception make this book one of the most fascinating works of Oliver Sacks

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

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.

The Past and Future of Psychedelic Science: An Introduction to This Issue.

Psychedelic plants and fungi have been used in indigenous medicinal traditions for millennia. Modern psychedelic research began when Albert Hofmann first synthesized lysergic acid diethylamide (LSD-25) in 1938. Five years later, became the first person to ingest LSD. Hofmann was unaware of the significance of his actions, and the effects they would set in motion. After a burgeoning period of scientific and cultural exploration in the1950s and '60s, psychedelic research was slowed to a near halt. Throughout the 1970s and '80s governmental interventions severely hampered global psychedelic research, despite evidence of the limited medical risks and therapeutic potential of psychedelics. After decades of persistent education and advocacy, rigorous research employing psychedelics as tools of discovery and healing are abundant today. Studies are taking place in research institutions and in private practice sites supported by non-profit and for-profit organizations, as well as individual investigators. This research includes clinical trials with MDMA-assisted therapy for the treatment of PTSD, alcoholism, and social anxiety, and psilocybin clinical studies for depression and addiction, as well as the ability of psychedelics to catalyze spiritual or mystical experiences and inspire creativity, and into the neuroscientific understanding the effects of psychedelic substances on our nervous system.

Psychedelic-assisted therapies: The past, and the need to move forward responsibly.

Recent clinical studies illustrate that psychedelics such as LSD and psilocybin may represent much-needed new treatment options for mood disorders and alcohol and other drug use disorders. More clinical studies are required to confirm the safety and efficacy of psychedelic-assisted therapies, but the cultural stigma that has surrounded psychedelics since the 1960s has hindered research. This problem is amplified in Australia. There has been a complete absence of research into psychedelic therapies, and Australian-based research advocates claim to have encountered a number of barriers. In this commentary, we provide a brief account of the historical stigma associated with psychedelics, and an overview of the contemporary context of research into psychedelic-assisted therapies, including the purported barriers to research in Australia. In light of the complex history of psychedelics, we identify a number of pressing questions relating to the social and legal context that need to be addressed so that clinical studies can proceed. Research is needed to address such questions so that the nature and extent of purported barriers to clinical studies with psychedelics can be properly elucidated, and strategies developed - with practitioners, patients, families and other stakeholders - to responsibly address these barriers. This is important because it will enable Australian researchers to contribute robust evidence about the possible efficacy and safety of psychedelic therapies, and to facilitate local expertise needed to implement psychedelic-assisted therapies, should they prove efficacious.

Psychedelics and Dying Care: A Historical Look at the Relationship between Psychedelics and Palliative Care.

This article examines the historical relationship between psychedelics and palliative care. Historians have contributed to a growing field of studies about how psychedelics have been used in the past, but much of that scholarship focused on interrogating questions of legitimacy or proving that psychedelics had therapeutic potential. Palliative care had not yet developed as medical sub-specialty, more often leaving dying care on the margins of modern, pharmaceutical-based treatments. As psychedelic researchers in the 1950s began exploring different applications for psychoactive substances such as LSD and mescaline, however, dying care came into clearer focus as a potential avenue for psychedelics. Before that application gained momentum in clinical or philosophical discussions, psychedelics were criminalized and some of those early discussions were lost. This article looks back at historical discussions about LSD's potential for easing the anxiety associated with dying, and considers how those early conversations might offer insights into today's more articulated discussions about psychedelics in palliative care.

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

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.

The Role of the Journal of Psychedelic Drugs in the Evolution of Psychedelic Medicine.

A review of the primary role that this journal (and by extension, Dr. David Smith) has played in bearing witness to the second wave of psychedelic research as our modern-day culture embraces the current third wave of the psychedelic revival, exploring through research its therapeutic uses.