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 psychiatry, 78(2), 121-122.; 10.1001/jamapsychiatry.2020.2171 Link to full text
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 Experimental, 35(5), e2742; 10.1002/hup.2742 Link to full text
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 (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, 73(10), 679–686. https://doi.org/10.1038/s41429-020-0311-8
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
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 Law, 48(1), 87-97., 10.29158/JAAPL.003917-20 Link to full text
The Old World has had its own remarkable history concerning psychedelic research – it was after all the continent where Albert Hofmann first discovered LSD and where Dutch professor Jan Bastiaans treated the trauma of Holocaust survivors with the same substance for many decades. Now, the psychedelic wave has washed ashore again in Europe, and we’re here to witness it first-hand. In this piece, we have attempted to give the most complete overview of the current wave of psychedelic science that’s happening on the European continent.
The past decade has seen a new wave of academic research into psychedelics – a fledgling but true renaissance of this scientific frontier. Currently, phase 2 trials are underway for the study of MDMA-assisted psychotherapy in the treatment of PTSD in Europe, psilocybin studies are underway in more than one nation, and multiple academic hubs facilitate growth of the field.
Below we summarize the experimental psychedelic studies in the fields of (clinical) psychology, psychiatry and neuroscience in Europe. Many of these studies are still young, and will take years to complete. Still, this decade will likely harbor historic moments in moving psychedelics into the mainstream in Europe – because psychedelics science has only just started scratching the surface of what’s possible.
In addition to the research carried out at these universities, two multi-site trials – sponsored by the non-profit organisation MAPS (mdma) and the for-profit Compass Pathways (psilocybin) – are underway in Europe, thereby involving various academic treatment centers in Europe in psychedelics research.
There are a few main research hubs in Europe where most of the psychedelics research is concentrated. At these locations, multiple studies below are performed.
Experimental research
Below we summarize the current European research into three psychedelic substances: LSD, psilocybin or mdma3.
Experimental research can be broken down into two basic categories. The first are the clinical trials, in which psychedelics are administered to patient populations. The other is neurobiological research, in which the effect of psychedelics on healthy participants are studied.
Of course, the field of psychedelic research is much broader and includes naturalistic, historical and qualitative research methods such as used in the social sciences and humanities. For lack of a central registry in which such studies are enlisted, it is harder to keep track of ongoing non-experimental (social scientific) research.
Clinical Studies 👩🏫First, let’s look at all the clinical studies that are going on.
LSD studies in Switzerland
“LSD is a Baseler product,” said Matthias Liechti to the Guardian about the most famous product from Basel, Switzerland. Liechti – a professor in clinical pharmacology at University Hospital Basel and speaker at ICPR 2020 – studies the effects of LSD on the human mind and body. “It’s tied to Basel’s history as a centre of pharmacology and innovation.”
How fitting that almost all research with LSD is taking place in the substance’s ‘place of birth’, Basel.
LSD as Treatment for Cluster Headache – University Hospital Basel
Cluster headaches are the most painful and debilitating form of headache, for which available medication often does not work sufficiently. LSD has been reported to abort cluster headache attacks and to decrease their frequency. Headed by lead investigator Professor Matthias Liechti and conducted by Yasmin Schmid, MD, this double-blind, placebo-controlled crossover study will administer LSD (or a placebo) to 30 patients suffering from cluster headaches. They will receive three doses of 100 micrograms within a three week period.
LSD Therapy for Major Depression – University Hospital Basel.
This study will test the efficacy of LSD therapy in patients with Major Depressive Disorder and is recruiting 60 patients. The treatment group will undergo two sessions with LSD (100 & 200 μg) and the control group will undergo two sessions with an active placebo (25 μg and 50 μg LSD). This study is lead by Prof. Dr. med. Stefan Borgwardt and has just started recruiting. It is estimated to be completed by the summer of 2023.
LSD Treatment for Anxiety in Severe Somatic Diseases – University Hospital Basel
In this study, 40 patients with an Anxiety Disorder will be given a single dose of LSD. Due to its cross-over within-subjects design, all patients will receive both a placebo dose and an active dose: 200 μg LSD. This study is a collaboration between University Hospital Basel and the private practice of Peter Gasser, MD, who is also the study’s principal investigator.
Imperial College in London has recently founded the world’s first Centre for Psychedelics Research
Psilocybin studies in Europe
About a third of all experimental studies with psilocybin are happening in Europe. All of the European psychedelic research hubs – University of Zurich, University Hospital Basel and Imperial College London – are currently involved in clinical or neurobiological research with psilocybin. Europe also hosts 11 of the 21 sites of the clinical study on psilocybin therapy for treatment resistant depression – for which its sponsor Compass Pathways was granted a breakthrough therapy status by the FDA in 2018. Clinical studies with patients:
Psilocybin vs Escitalopram for Major Depressive Disorder – Imperial College, London
This study is recruiting 50 patients suffering from depression in order to compare the efficacy and mechanisms of action of psilocybin with the SSRI Escitalopram. Principal investigator of this study is Professor David Nutt.
Clinical and Mechanistic Effects of Psilocybin in Alcohol Addicted Patients – University of Zurich
This study will test the efficacy of psilocybin for treating alcohol use disorder and study its underlying neurobiological mechanisms in a randomized, placebo controlled, double blind study. 60 participants are recruited for this study. Six weeks after undergoing a withdrawal treatment, they will either receive a single dose of placebo or a single dose of psilocybin (25 mg, orally). Dr. Katrin Peller is the principal investigator in this study.
The Safety and Efficacy of Psilocybin in Participants with Treatment Resistant Depression. This is a multi-site clinical trial with 21 study locations in North America and Europe, sponsored by the (for profit) organization Compass Pathways. The following European sites are involved in this study:
Enhed for Psykiatrisk Forskning, Psykiatrien i Aalborg – Aalborg, Denmark Tallaght University Hospital – Dublin, Ireland Groningen University Medical Centre – Groningen, the Netherlands Leiden University Medical Centre – Leiden, the Netherlands Utrecht University Medical Centre – Utrecht, the Netherlands Hospital de Dia Numancia – Barcelona, Spain Institute Hospital del Mar of Medical Research (IMIM) – Barcelona, Spain Clinical Research and Imaging Centre – Bristol, United Kingdom Wolfson Research Centre, Campus for Ageing and Vitality – Newcastle Upon Tyne, United Kingdom Kings College London, Institute of Psychiatry, Psychology and Neurology – London, United Kingdom Greater Manchester Mental Health Foundation Trust – Manchester, United Kingdom MDMA studies by MAPS
The Multidisciplinary Association for Psychedelics Studies from the United States -and headed by Rick Doblin- is planning phase 2 and phase 3 clinical trials to develop MDMA-assisted psychotherapy into an approved treatment for PTSD. In order to conduct part of these trials in Europe, MAPS has created a European-based subsidiary.
Six study sites in five European countries are involved in the “Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Psychotherapy for Treatment of PTSD With Optional fMRI Sub-Study”:
Czechia – NUDZ – National Institute of Mental Health, Klecany
Norway – Sykehuset Østfold Hf, DPS Norder, Moss
Netherlands
Maastricht University, Dept of Neuropsychology and Psychopharmacology – Maastricht
Stichting Centrum ’45/Arq – Oestgeest
Portugal – Fundação de Anna de Sommer Champalimaud, Lisbon
United Kingdom – University Hospital of Wales – Research Facility, Cardiff
The University of Bristol and Imperial College London are collaborating in an ongoing study on mdma as a treatment for alcoholism. The “Bristol Imperial MDMA in Alcoholism Study (BIMA)” is an open label within-subject feasibility study in 20 patients with Alcohol Use Disorder who have recently undergone detoxification. The study is conducted by Ben Sessa, MD and its principal investigator is Professor David Nutt.
🧠 Studies into the psychedelic state itself
LSD AND PSILOCYBIN
Direct Comparison of Altered States of Consciousness Induced by LSD and Psilocybin – University Hospital Basel
Both LSD and psilocybin are used as pharmacological tools in neuroscience. However, there are no modern studies comparing these two substances directly within the same clinical study and using validated psychometric tools. In this study the researchers will compare the acute effects of LSD, psilocybin and placebo. 30 Healthy participants will be administered various dosages of these psychedelics, the effects of which will be measured with various assessment tools.The study is conducted by Friederike Holze and Professor Matthias Liechti.
Effects of Serotonin Transporter Inhibition on the Subjective Response to Psilocybin in Healthy Subjects – University Hospital Basel The aim of the study is to investigate the effects of psilocybin after Escitalopram and placebo pretreatment. Subjective and physiological effects as well as effects on gene expression will be assessed. This study is recruiting 24 healthy participants who will be pretreated with either Escitalopram or a placebo. On each of the 2 study days, participants will receive psilocybin 25 mg orally. Professor Matthias E. Liechti is the principal investigator in this study.
Comparative Acute Effects of LSD, Psilocybin and Mescaline –University Hospital Basel This study compares the acute effects of LSD, psilocybin, mescaline and placebo in a double-blind, placebo-controlled, 4-period cross-over design. In four separate sessions, the 25 healthy participants will receive 100 μg LSD, 20 mg psilocybin, 300 mg mescaline and a placebo. Professor Matthias E. Liechti is the principal investigator in all three of the above psilocybin studies taking place in Basel.
Beyond the Self and Back: Neuropharmacological Mechanisms Underlying the Dissolution of the Self – University of Zurich
In terms of the number of participants in a single study, this is currently the largest experimental study with psilocybin in Europe. 140 Healthy participants are divided into 4 groups, each with it’s own double-blind, placebo-controlled setup. One of the groups consists of long-term and short-term meditators during a 5-day group retreat. The aim of the study is to identify neural signatures, behavioral and phenomenological expressions of self-related processes.
Characterization of Altered Waking States of Consciousness in Healthy Humans– University of Zurich This study uses a combination of transcranial magnetic stimulation (TMS) and high density electroencephalography (hd-EEG) to measure the level of consciousness in a pharmacologically altered waking state of consciousness (induced by psilocybin).Lead investigator Professor Franz X. Vollenweider and his team are recruiting 25 healthy participants for this study.
MDMA and fear
University Hospital Basel is currently recruiting healthy participants for a study called “The Effect of MDMA (Serotonin Release) on Fear Extinction”. Fear extinction is a psychological process that plays a crucial role in treating disorders such as PTSD. Although MDMA has been shown to enhance the extinction of fear in animals, no data exists on the effect of MDMA on fear extinction in humans. The lead investigator in this study is Professor Matthias E. Liechti, MD.
Should you be interested in contributing to science by participating in a clinical/neuroimaging study: most of these studies are still recruiting. Look them up on this website to study their inclusion and exclusion criteria and to find out more.
This overview only covers the research that has been registered at clinicaltrials.gov and is therefore not exhaustive. Do you know of other ongoing experimental studies in Europe, feel free to reach out to us!
1 The FDA (Food and Drug Administration in the US) granted the label ‘breakthrough therapy’ to mdma-assisted psychotherapy for PTSD (sponsored by MAPS) in 2017. In 2018 the treatment of depression with psilocybin (sponsored by Compass Pathways) was granted the breakthrough therapy status, followed by a designation for the research by Usona in 2019, also for the treatment of major depression with psilocybin assisted therapy. 2 Of course there are other psychedelics, but for the scope of this article we focus on the most popular substances for clinical research. We also focus on trials that induce psychedelic effects – unlike for example many ketamine trials where sub-psychedelic dosages are used.
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 Psychiatrie, 62(8), 702-706., https://pubmed.ncbi.nlm.nih.gov/32816299/ Link to full text
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 Psychiatrie, 62(8), 713-720. Link to full text
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
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