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.

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.

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.

Supple bodies, healthy minds: yoga, psychedelics and American mental health.

Much discussion about mental health has revolved around treatment models. As interdisciplinary scholarship has shown, mental health knowledge, far from being a neutral product detached from the society that generated it, was shaped by politics, economics and culture. By drawing on case studies of yoga, religion and fitness, this article will examine the ways in which mental health practices-sometimes scientific, sometimes spiritual-have been conceived, debated and applied by researchers and the public. More specifically, it will interrogate the relationship between yoga, psychedelics, South Asian and Eastern religion (as understood and practiced in the USA) and mental health.

"Bunanje": XX Century Abuse of Atropa Belladonna Halucinogenic Berries in Continental Croatia.

BACKGROUND: Atropa belladonna (Engl. deadly nightshade, Cro. velebilje, bunika) is a plant containing pharmacologically active, potentially toxic alkaloids: atropine, hyocyamine and scopolamine. The risk of poisoning in children is important because of possible confusion of black/dark blue belladonna fruit berries with other edible berries. There are many reports in literature of accidental intoxication but no report on traditional intentional usage to achieve hallucinogenic effects. SUBJECTS AND METHODS: Here we report purposeful ingestion of Atropa belladonna berries for hallucinatory effects among adolescents in Bjelovar region in north part of Croatia. This has been happening among children/adolescents while they were grazing animals. We visited a dozen villages in the region and spoke to the oldest mostly to the elderly residents. RESULTS: The existence of such abuse of Atropa belladonna berries in the first part of XX century was confirmed by eight narrators from five distinct places in the region. Interestingly this type of behavior had a specific name "bunanje", unknown in Croatian language, but clearly associated with local plant name bun or bunika. According to informants consumers of berries would develop delirium or hallucinations associated behavior, incoherent and meaningless speech. However nobody remembers any severe case of poisoning. At the regional hospital in Bjelovar in the Pediatric department, there is no record of poisoning with Atropa belladonna. To our knowledge this is the first report of intentional consumption of belladonna berries to achieve the hallucinogenic effect. CONCLUSIONS: The fact that the custom was observed in five distinct spots and it had its specific name "bunanje" suggest that those are not isolated random events but the type of practices; seasonal abuse of hallucinogenic berries of Atropa belladonna, among rural adolescents in the first part of XX century.

The History of MDMA as an Underground Drug in the United States, 1960-1979.

MDMA (3,4-methylenedioxy-methylamphetamine, a.k.a. "ecstasy") was first synthesized in 1912 and resynthesized more than once for pharmaceutical reasons before it became a popular recreational drug. Partially based on previously overlooked U.S. government documentation, this article reconstructs the early history of MDMA as a recreational drug in the U.S. from 1960 to 1979. According to the literature, MDMA was introduced as a street drug at the end of the 1960s. The first forensic detection of MDMA "on the street" was reported in 1970 in Chicago. It appears that MDMA was first synthesized by underground chemists in search of "legal alternatives" for the closely related and highly sought-after drug MDA, which was scheduled under the Controlled Substances Act (CSA) in 1970. Until 1974, nearly all MDMA street samples seized came from the U.S. Midwest, the first "hot region" of MDMA use. In Canada, MDMA was first detected in 1974 and scheduled in 1976. From 1975 to 1979, MDMA was found in street samples in more than 10 U.S. states, the West Coast becoming the major "hot region" of MDMA use. Recreational use of MDMA spread across the U.S. in the early 1980s, and in 1985 it was scheduled under the CSA.

Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration.

Over the 1950s and early 1960s, the use of the hallucinogenic drug lysergic acid diethylamide (LSD) to facilitate psychotherapy was a promising field of psychiatric research in the USA. However, during the 1960s, research began to decline, before coming to a complete halt in the mid-1970s. This has commonly been explained through the increase in prohibitive federal regulations during the 1960s that aimed to curb the growing recreational use of the drug. However, closely examining the Food and Drug Administration's regulation of LSD research in the 1960s will reveal that not only was LSD research never prohibited, but that the administration supported research to a greater degree than has been recognized. Instead, the decline in research reflected more complex changes in the regulation of pharmaceutical research and development.

Hallucinogenic drugs in pre-Columbian Mesoamerican cultures.

INTRODUCTION: The American continent is very rich in psychoactive plants and fungi, and many pre-Columbian Mesoamerican cultures used them for magical, therapeutic and religious purposes. OBJECTIVES: The archaeological, ethno-historical and ethnographic evidence of the use of hallucinogenic substances in Mesoamerica is reviewed. RESULTS: Hallucinogenic cactus, plants and mushrooms were used to induce altered states of consciousness in healing rituals and religious ceremonies. The Maya drank balché (a mixture of honey and extracts of Lonchocarpus) in group ceremonies to achieve intoxication. Ritual enemas and other psychoactive substances were also used to induce states of trance. Olmec, Zapotec, Maya and Aztec used peyote, hallucinogenic mushrooms (teonanacatl: Psilocybe spp) and the seeds of ololiuhqui (Turbina corymbosa), that contain mescaline, psilocybin and lysergic acid amide, respectively. The skin of the toad Bufo spp contains bufotoxins with hallucinogenic properties, and was used since the Olmec period. Jimson weed (Datura stramonium), wild tobacco (Nicotiana rustica), water lily (Nymphaea ampla) and Salvia divinorum were used for their psychoactive effects. Mushroom stones dating from 3000 BC have been found in ritual contexts in Mesoamerica. Archaeological evidence of peyote use dates back to over 5000 years. Several chroniclers, mainly Fray Bernardino de Sahagún, described their effects in the sixteenth century. CONCLUSIONS: The use of psychoactive substances was common in pre-Columbian Mesoamerican societies. Today, local shamans and healers still use them in ritual ceremonies in Mesoamerica.

History and future of the Multidisciplinary Association for Psychedelic Studies (MAPS).

This article describes the teenage vision of the founder of the Multidisciplinary Association for Psychedelic Studies (MAPS) that humanity's future would be aided by the therapeutic and spiritual potential of psychedelic substances. The article traces the trajectory of MAPS from inception in 1986 to its present, noting future goals with respect to research, outreach, and harm reduction. MAPS was created as a non-profit psychedelic pharmaceutical company in response to the 1985 scheduling of 3,4-methylenedioxymethamphetamine (MDMA). Overcoming many hurdles, MAPS developed the first double-blind, placebo-controlled trial of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) and plans for FDA prescription approval in 2021. MAPS' program of research expanded to include a trial of lysergic acid diethylamide (LSD)-assisted psychotherapy for anxiety when facing life-threatening illness, observational studies of ibogaine in the treatment of addiction, and studies of MDMA for social anxiety in people with autism spectrum disorders. MAPS meets the challenges of drug development through a clinical research team led by a former Novartis drug development professional experienced in the conduct, monitoring, and analysis of clinical trials. MAPS' harm-reduction efforts are intended to avoid backlash and build a post-prohibition world by assisting non-medical users to transform difficult psychedelic experiences into opportunities for growth.

Why psychiatry needs psychedelics and psychedelics need psychiatry.

Without researching psychedelic drugs for medical therapy, psychiatry is turning its back on a group of compounds that could have great potential. Without the validation of the medical profession, the psychedelic drugs, and those who take them off-license, remain archaic sentiments of the past, with the users maligned as recreational drug abusers and subject to continued negative opinion. These two disparate groups--psychiatrists and recreational psychedelic drug users--are united by their shared recognition of the healing potential of these compounds. A resolution of this conflict is essential for the future of psychiatric medicine and psychedelic culture alike. Progression will come from professionals working in the field adapting to fit a conservative paradigm. In this way, they can provide the public with important treatments and also raise the profile of expanded consciousness in mainstream society.

From Hofmann to the Haight Ashbury, and into the future: the past and potential of lysergic acid diethlyamide.

Since the discovery of its psychedelic properties in 1943, lysergic acid diethylamide (LSD) has been explored by psychiatric/therapeutic researchers, military/intelligence agencies, and a significant portion of the general population. Promising early research was halted by LSD's placement as a Schedule I drug in the early 1970s. The U.S. Army and CIA dropped their research after finding it unreliable for their purposes. NSDUH estimates that more than 22 million (9.1% of the population) have used LSD at least once in their lives. Recently, researchers have been investigating the therapeutic use of LSD and other psychedelics for end-of-life anxiety, post-traumatic stress disorder (PTSD), cancer, and addiction treatment. Adverse psychedelic reactions can be managed using talkdown techniques developed and in use since the 1960s.

AA, Bill Wilson, Carl Jung and LSD.

Alcoholics Anonymous (AA) is an established resource for people suffering from alcohol use disorder (AUD). However, Bill Wilson, the co-founder of AA, in his second letter to Jung referred to its low success rate. One evidence-based alternative, dating back to the 1950s, is the clinical use of lysergic acid diethylamide (LSD) for treating AUD. Bill Wilson was a strong advocate of using LSD as a preparation for alcoholics who had difficulty grasping the spiritual aspect of the 12-step programme. Bill Wilson wrote a "secret" four-page letter to Carl Jung detailing his own use of LSD and the success two psychiatrists in Canada had in treating alcoholics and asked for his advice on using LSD to help alcoholics. Aniela Jaffé, a Jungian analyst and co-worker of Jung, replied to Wilson on May 29, 1961, "… as soon as Dr. Jung feels better and has enough strength to begin again his mail, I will show it to him." Jung died a week later. This article quotes Jung's previous hostile opinions on psychedelics and asks: Just as Jung overcame his negative views on groups when giving "complete instructions" on extending the 12-step programme of AA to "general neurotics", might he similarly have changed his mind when he saw the documented success of using LSD with recalcitrant alcoholics?

Alcooliques Anonymes (A.A.) est une ressource reconnue pour les personnes souffrant du Trouble de l'Usage de l'Alcool (TUA). Bill Wilson, co­fondateur des AA, dans sa deuxième lettre à Jung, a fait référence à son faible taux de réussite. Une alternative fondée sur des preuves, et qui remonte aux années 1950, est l'utilisation médicale de l'acide lysergique diéthylamide (LSD) pour le traitement du TUA. Bill Wilson a fortement préconisé l'utilisation du LSD pour la préparation des alcooliques qui avaient des difficultés à saisir l'aspect spirituel du programme en douze étapes. Bill Wilson écrivit à Carl Jung une lettre de quatre pages, « secrète ¼, exposant en détails sa propre utilisation du LSD et le succès de deux psychiatres canadiens dans le traitement de personnes alcooliques avec le LSD. Il demandait conseil à Jung sur l'utilisation du LSD pour aider les alcooliques. Aniela Jaffé, une analyste jungienne et collaboratrice de Jung répondit à Wilson le 29 mai 1961 : « … dès que le Dr Jung se sentira mieux et aura suffisamment de force pour recommencer à s'occuper de son courrier, je lui montrerai. ¼ Jung est mort une semaine plus tard. Cet article cite les opinions antérieures négatives de Jung concernant les drogues psychédéliques et pose la question suivante: tout comme Jung avait dépassé ses perspectives négatives sur les groupes en donnant des « instructions complète ¼ sur l'extension du programme en douze étapes pour les « névrosés de base ¼, aurait­il de la même manière changé d'avis s'il avait vu les résultats probants de l'utilisation du LSD avec les alcooliques récalcitrants?

Alcohólicos Anónimos (A.A.) es un recurso establecido para las personas que padecen Trastorno por Consumo de Alcohol (AUD). Sin embargo, Bill Wilson, cofundador de AA, en su segunda carta a Jung se refirió a su baja tasa de éxito. Una alternativa basada en la evidencia, que se remonta a la década de 1950, es el uso clínico de la dietilamida del ácido lisérgico (LSD) para tratar el AUD. Bill Wilson era un firme defensor del uso del LSD como preparación para los alcohólicos que tenían dificultades para captar el aspecto espiritual del programa de 12 pasos. Bill Wilson escribió una carta "secreta" de cuatro páginas a Carl Jung en la que detallaba su propio uso del LSD y el éxito que habían tenido dos psiquiatras en Canadá en el tratamiento de alcohólicos con LSD y le pedía consejo a Jung sobre el uso del LSD para ayudar a los alcohólicos. Aniela Jaffé, analista Junguiana y compañera de trabajo de Jung, respondió a Wilson el 29 de mayo de 1961: "…tan pronto como el Dr. Jung se sienta mejor y tenga fuerzas suficientes para mirar de nuevo su correo, se lo mostraré". Jung murió una semana después. Este artículo cita las anteriores opiniones hostiles de Jung sobre los psicodélicos y pregunta: Del mismo modo que Jung superó sus opiniones negativas sobre los grupos al dar "instrucciones completas" sobre la extensión del programa de 12 pasos de A.A. a los "neuróticos en general", ¿podría haber cambiado de opinión de forma similar cuando vio el éxito documentado del uso del LSD con alcohólicos recalcitrantes?

Jung, the Rebirth Motif and Psychedelics I: Documenting Jung's Contact with the British Pioneers.

C. G. Jung wrote very little about psychedelic drugs and he took a sceptical view of them. However, he was sufficiently impressed by Aldous Huxley's 1954 account of taking mescaline, The Doors of Perception, to invite Huxley to visit him in Switzerland. Huxley declined Jung's invitation but Huxley's collaborator Humphry Osmond met Jung instead. This paper documents Jung's contact with the British pioneers of psychedelics research and presents the scant material illuminating his views about these drugs. It also determines the efforts of British psychiatrist Ronald Sandison, who was the first to develop an "explicitly Jungian approach" to psychedelic-assisted psychotherapy (Hill, 2013), and it highlights a connection between Sandison's initiative and the Society of Analytical Psychology (SAP) through the involvement of two SAP members: Margot Cutner, Sandison's colleague, and Michael Fordham, who supervised a trainee working with one of Sandison's former patients. Despite Jung's objections to the use of psychedelics, Sandison and Cutner developed ground-breaking protocols during the 1950s and they were among the first to document the phenomenon of "spiritual rebirth symbolized in the birth experience known to many LSD therapists" (Sandison, 2001). In two companion papers, I consider Jung's treatment of the rebirth motif in his commentary on The Tibetan Book of the Dead, which later became a central text in the psychedelic movement, and I chart the evolution in psychedelics research from an association with schizophrenia during the 1950s to the mystical paradigms of the 1960s and beyond.

C.G. Jung a très peu écrit sur les drogues psychédéliques et il avait à leur égard une attitude sceptique. Cependant il fut suffisamment impressionné par le récit d'Aldous Huxley de son expérience avec la mescaline en 1954, Les Portes de la Perception, pour inviter Huxley à lui rendre visite en Suisse. Huxley déclina l'invitation de Jung mais son collaborateur Humphry Osmond rencontra Jung à sa place. Cet article rend compte des contacts de Jung avec les recherches des pionniers britanniques en matière de drogues psychédéliques. Il présente aussi le peu de matériel qui illustre ses opinions concernant ces drogues. L'article explore les efforts du psychiatre britannique Ronald Sandison ­ qui fut le premier à développer une « approche spécifiquement jungienne ¼ à la psychothérapie assistée par des drogues psychédéliques ­ et il souligne un lien entre l'initiative de Sandison et The Society of Analytical Psychology (SAP) par l'implication de deux de ses membres : Margot Cutner, collègue de Sandison, et Michael Fordham, qui supervisa un candidat sur son travail avec un des anciens patients de Sandison. Malgré les objections de Jung sur l'utilisation des drogues psychédéliques, Sandison et Cutner ont développé des protocoles très innovants durant les années 1950 et furent parmi les premiers à documenter le phénomène de la « renaissance spirituelle symbolisée par l'expérience de naissance, bien connue par la plupart des thérapeutes utilisant le L.S.D. ¼ (Sandison, 2001). Dans deux articles apparentés j'examine la manière dont Jung a traité le motif de la renaissance dans son commentaire sur Le Livre des Morts Tibétain, qui devint par la suite un texte central dans le mouvement psychédélique, et je retrace l'évolution dans la recherche sur les drogues psychédéliques à partir d'une association avec la schizophrénie dans les années 1950 et jusqu'aux paradigmes mystiques des années 1960 et au­delà.

C. G. Jung escribió muy poco sobre las drogas psicodélicas y adoptó una postura escéptica hacia ellas. Sin embargo, quedó lo suficientemente impresionado por el relato, Las Puertas de la Percepción, que Aldous Huxley hizo en 1954 en referencia a su consumo de mescalina, como para invitar a Huxley a visitarle en Suiza. Huxley declinó la invitación, pero en su lugar Jung se reunió con Humphry Osmond, colaborador de Huxley. Este artículo documenta el contacto de Jung con los pioneros británicos en investigación psicodélica y presenta el escaso material que da cuenta de las opiniones de estos, sobre dichas drogas. También determina los esfuerzos del psiquiatra británico Ronald Sandison, que fue el primero en desarrollar un "enfoque explícitamente Junguiano" de la psicoterapia asistida por psicodélicos (Hill, 2013), y destaca una conexión entre la iniciativa de Sandison y la Sociedad de Psicología Analítica (SAP) a través de la participación de dos miembros de la SAP: Margot Cutner, colega de Sandison, y Michael Fordham, quien supervisaba a un candidato a analista que trabajaba con uno de los antiguos pacientes de Sandison. A pesar de las objeciones de Jung al uso de psicodélicos, Sandison y Cutner desarrollaron innovadores protocolos durante la década de 1950 y fueron los primeros en documentar el fenómeno del "renacimiento espiritual simbolizado en la experiencia del nacimiento conocida por muchos terapeutas del LSD" (Sandison, 2001). En dos artículos complementarios, considero el tratamiento que Jung da al motivo del renacimiento en su comentario sobre El Libro Tibetano de los Muertos, que más tarde se convirtió en un texto central del movimiento psicodélico, y trazo la evolución de la investigación sobre psicodélicos desde su asociación con la esquizofrenia durante la década de 1950 hasta los paradigmas místicos de la década de 1960 y posteriores.

Altered states: psychedelics and anesthetics.

The psychedelic experience has been reported since antiquity, but there is relatively little known about the underlying neural mechanisms. A recent neuroimaging study on psilocybin revealed a pattern of decreased cerebral blood flow and functional disconnections that is surprisingly similar to that caused by various anesthetics. In this article, the authors review historical examples of psychedelic experiences induced by general anesthetics and then contrast the mechanisms by which these two drug classes generate altered states of consciousness.

Cannabinoids and hallucinogens for headache.

Hallucinogens and most cannabinoids are classified under schedule 1 of the Federal Controlled Substances Act 1970, along with heroin and ecstacy. Hence they cannot be prescribed by physicians, and by implication, have no accepted medical use with a high abuse potential. Despite their legal status, hallucinogens and cannabinoids are used by patients for relief of headache, helped by the growing number of American states that have legalized medical marijuana. Cannabinoids in particular have a long history of use in the abortive and prophylactic treatment of migraine before prohibition and are still used by patients as a migraine abortive in particular. Most practitioners are unaware of the prominence cannabis or "marijuana" once held in medical practice. Hallucinogens are being increasingly used by cluster headache patients outside of physician recommendation mainly to abort a cluster period and maintain quiescence for which there is considerable anecdotal success. The legal status of cannabinoids and hallucinogens has for a long time severely inhibited medical research, and there are still no blinded studies on headache subjects, from which we could assess true efficacy.

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).

The Varieties of Psychedelic Expertise in 1960s Canada: The Psychiatrists behind the Addiction Research Foundation's Study of LSD Therapy.

In 1962, Ontario's Addiction Research Foundation launched the first double-blind randomized controlled trial of LSD therapy as a treatment for alcoholism. The study, which found that LSD was not effective, was heavily criticized by other therapists working with the drug. These critics argued that the Toronto researchers who carried out the study were biased against LSD and used an anti-therapeutic method that was destined to produce negative results. Instead of creating a comfortable and supportive environment, they stressed, the Toronto group restrained patients to a bed in a hospital ward, used an unusually large dose of LSD, and hardly provided any careful therapeutic support. Some even compared this method to a "form of torture." Historians have paid little attention to the study, mentioning it only as an example of flawed or naïve LSD therapy that contrasted with the more advanced "psychedelic" approach developed in Saskatchewan. In this paper, I take a closer look at the Toronto psychiatrists who carried out the study and created the unique method that was employed. I show that they were actually quite excited about LSD and were more sophisticated in their approach to its use than has been appreciated by historians and critics. In many ways, they had their own brand of LSD expertise that differed from that of the Saskatchewan group. Some of the problems with the ARF study, then, did not stem from negative bias or a lack of competency, but instead resulted from the awkward relationship between LSD therapy and controlled trials.

Résumé. En 1962, la Fondation pour la recherche sur la toxicomanie de l'Ontario lançait son premier test aléatoire et contrôlé en double aveugle de thérapie par le LSD pour traiter l'alcoolisme. L'étude, qui concluait que le LSD n'était pas efficace, a fait l'objet de critiques sévères de la part d'autres thérapeutes qui utilisaient cette drogue. Ces thérapeutes soutenaient que le groupe de recherche torontois avait un parti pris défavorable au LSD et avait employé des méthodes antithérapeutiques dans le but de produire des résultats négatifs. Ainsi, selon eux, au lieu de créer un environnement offrant un réel soutien, le groupe de Toronto attachait les patients à leur lit d'hôpital, employait des doses inhabituellement élevées de LSD et ne fournissait à peu près aucun soutien thérapeutique. La méthode a même été comparée à « une forme de torture ¼. Les historiennes et les historiens ont accordé peu d'attention à l'étude, sauf pour la citer comme exemple déficient ou naïf de thérapie par le LSD, en l'opposant à l'approche « psychédélique ¼ plus avancée mise au point en Saskatchewan. Dans cet article, je m'intéresse aux psychiatres qui ont mené l'étude de Toronto et conçu la méthode originale employée à la Fondation. Je montre que l'usage du LSD suscitait beaucoup d'enthousiasme dans le groupe et que son utilisation de cette drogue était plus complexe que l'ont reconnu jusqu'ici l'histoire et la critique. À plusieurs égards, le groupe de Toronto disposait de sa propre expertise en matière de LSD, différente de celle de ses collègues de la Saskatchewan. J'en conclus qu'une partie des problèmes attribués à l'étude conduite par la Fondation ne provient pas d'un préjugé défavorable ou d'un manque de compétence, mais plutôt des liens complexes entre la thérapie par le LSD et les essais cliniques.

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.

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.