Lektüreliste 1

für Neulinge in der psychedelischen Forschung 

 

Diese Liste wurde von Jagoda Mackowiak in Zusammenarbeit mit Blossom erstellt und gemeinsam veröffentlicht.

Um einen Einstieg in die psychedelische Forschung zu erleichtern, haben wir für Studierende, Forscher*innen und anderweitig Interessierte 10 wissenschaftliche Veröffentlichungen zusammengestellt.

Die folgenden Artikel geben Ihnen eine solide Grundlage, um Ihre psychedelische Forschungsreise zu beginnen. Sie erhalten mit ihnen einen Überblick über den aktuellen Stand, die Geschichte, und die zahlreichen Anwendungsmöglichkeiten psychedelischer Substanzen in Forschung und Therapie.

Um mit der wachsenden Popularität der psychedelischen Forschung Schritt halten zu können, präsentieren wir aktuelle Publikationen zur Neuropharmakologie von Psychedelika, zu ihren akuten sowie langfristigen psychologischen Effekten und schließlich zu ihrem Potenzial in der Behandlung psychiatrischer Erkrankungen. Neben den Forschungsergebnissen stellen wir dabei auch die wichtigsten Vertreter der heutigen psychedelischen Forschung vor.

Obwohl unsere Auswahl insbesondere auf Neulinge abzielt, enthält sie Artikel, die tief in die psychedelische Wissenschaft eintauchen. Sie umfasst eine Vielzahl von Disziplinen: Artikel aus den Neurowissenschaften und der Psychologie, aber auch philosophische, und sozialwissenschaftliche Publikationen und und Fachartikel aus der Chemie. Diese Einführung, in Kombination mit unserem Drug Science Programm und den uniMIND-Diskussionsgruppen, bereitet Sie optimal darauf vor der Erforschung von Psychedelika weiter nachzugehen.

Alle Artikel sind in englischer Sprache verfasst.

Einen groben Überblick über die psychedelische Forschung verschaffen Sie sich mit diesem Artikel von Prof. Dr. Robin Carhart-Harris vom Imperial College, London. Carhart-Harris ist seit mehr als einem Jahrzehnt einer der Pioniere der psychedelischen Forschung. In „Wie wirken Psychedelika?“ (2019) fasst er  Einsichten aus neurobiologischer, psychologischer und psychiatrischer Forschung zusammen.

Carhart-Harris, R. L. (2018). How do psychedelics work? Current Opinion in Psychiatry, 32(1):16-21.

Purpose of review

Psychedelics are reawakening interest from psychiatry, cognitive neuroscience and the general public with impressive outcomes in small-scale clinical trials, intriguing human brain imaging work and high-impact journalism.

Recent findings

This brief opinion piece offers a perspective on how psychedelics work in the brain that may help contextualize these developments. It attempts to link various scales of action, from the molecular (serotonin 2A receptor agonism) through to the anatomical and functional (heightened plasticity) and up to the dynamic (increased brain entropy), systems level (network disintegration and desegregation) and experiential.

Summary

It is proposed that psychedelics initiate a cascade of neurobiological changes that manifest at multiple scales and ultimately culminate in the relaxation of high-level beliefs. The purpose of psychedelic therapy is to harness the opportunity afforded by this belief-relaxation to achieve a healthy revision of pathological beliefs.

Im September 2020 veröffentlichten Prof. Dr. Franz X. Vollenweider und Dr. Katrin H. Preller einen umfassenden, aber dennoch zugänglichen Überblick über die neurobiologischen Wirkmechanismen von Psychedelika. Insbesondere die visuelle Darstellung der Auswirkungen psychedelischer Drogen auf die neuronalen Vernetzungen des Gehirns im Artikel sind hilfreich um ein Verständnis für die Komplexen Prozesse zu erhalten. „Psychedelische Drogen: Neurobiologie und Potenzial für die Behandlung psychiatrischer Störungen” fasst mehrere Jahrzehnte der psychedelischen Forschung zusammen.  

Vollenweider, F. X. and Preller, K. H. (2020). Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders. Nature Reviews Neuroscience, 21:611-624

Renewed interest in the use of psychedelics in the treatment of psychiatric disorders warrants a better understanding of the neurobiological mechanisms underlying the effects of these substances. After a hiatus of about 50 years, state-of-the art studies have recently begun to close important knowledge gaps by elucidating the mechanisms of action of psychedelics with regard to their effects on receptor subsystems, systems-level brain activity and connectivity, and cognitive and emotional processing. In addition, functional studies have shown that changes in self-experience, emotional processing and social cognition may contribute to the potential therapeutic effects of psychedelics. These discoveries provide a scientific road map for the investigation and application of psychedelic substances in psychiatry.

Wenn Sie nach dem vorherigen Artikel Lust auf mehr neurowissenschaftliche Forschung bekommen haben, sollten Sie auf diesen weiteren Artikel von Robin Carhart-Harris lesen, der in Zusammenarbeit mit Prof. Karl J. Friston verfasst wurde. „REBUS und das anarchische Gehirn: Auf dem Weg zu einem vereinheitlichten Modell der Hirnaktion von Psychedelika” wird ein Modell namens “gelockerte Annahmen unter Psychedelika” (RElaxed Beliefs Under pSychedelics – REBUS) vorgeschlagen. Dieses beschreibt wie die globale Hirnaktivität unter Psychedelika-Einfluss verstärkt durch “Bottom-up” Informationen aus Hirnregionen weiter unten in der kortikalen Hierarchie beeinflusst wird.

Mehr zu diesem Thema finden Sie in diesem MIND-Blog-post von Andy Meijer.

Carhart-Harris, R. L. and Friston K. J. (2019) REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics
Pharmacological Reviews, 71(3):316-344

This paper formulates the action of psychedelics by integrating the free-energy principle and entropic brain hypothesis. We call this formulation relaxed beliefs under psychedelics (REBUS) and the anarchic brain, founded on the principle that—via their entropic effect on spontaneous cortical activity—psychedelics work to relax the precision of high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as the limbic system. We assemble evidence for this model and show how it can explain a broad range of phenomena associated with the psychedelic experience. With regard to their potential therapeutic use, we propose that psychedelics work to relax the precision weighting of pathologically overweighted priors underpinning various expressions of mental illness. We propose that this process entails an increased sensitization of high-level priors to bottom-up signaling (stemming from intrinsic sources), and that this heightened sensitivity enables the potential revision and deweighting of overweighted priors. We end by discussing further implications of the model, such as that psychedelics can bring about the revision of other heavily weighted high-level priors, not directly related to mental health, such as those underlying partisan and/or overly-confident political, religious, and/or philosophical perspectives.

Dieser Review-Artikel von Link R. Swanson (2018) setzt sich kritisch mit „Vereinheitlichende[n] Theorien zur Wirkung psychedelischer Drogen” auseinander. Er arbeitet sich durch über ein Jahrhundert an Theorien der Effekte psychedelischer Substanzen. Swanson resümiert, dass der gemeinsame Nenner dieser Theorien ist, dass  Gehirnprozesse unter dem Einfluss von Psychedelika dahingehend verändert sind, dass der Gedankenfluss ungehemmter ist.

Swanson, L. R. (2018) Unifying theories of psychedelic drug effects. Frontiers in Pharmacology, 9:172

How do psychedelic drugs produce their characteristic range of acute effects in perception, emotion, cognition, and sense of self? How do these effects relate to the clinical efficacy of psychedelic-assisted therapies? Efforts to understand psychedelic phenomena date back more than a century in Western science. In this article I review theories of psychedelic drug effects and highlight key concepts which have endured over the last 125 years of psychedelic science. First, I describe the subjective phenomenology of acute psychedelic effects using the best available data. Next, I review late 19th-century and early 20th-century theories—model psychoses theory, filtration theory, and psychoanalytic theory—and highlight their shared features. I then briefly review recent findings on the neuropharmacology and neurophysiology of psychedelic drugs in humans. Finally, I describe recent theories of psychedelic drug effects which leverage 21st-century cognitive neuroscience frameworks—entropic brain theory, integrated information theory, and predictive processing—and point out key shared features that link back to earlier theories. I identify an abstract principle which cuts across many theories past and present: psychedelic drugs perturb universal brain processes that normally serve to constrain neural systems central to perception, emotion, cognition, and sense of self. I conclude that making an explicit effort to investigate the principles and mechanisms of psychedelic drug effects is a uniquely powerful way to iteratively develop and test unifying theories of brain function.

Keywords: psychedelic drugs, LSD, psilocybin, ego dissolution, cognitive flexibility, entropic brain theory, integrated information theory, predictive processing

Psychedelika. (2016)                                                                                                                

Prof. Dr. David Nichols, der auch einer der Gründer des Heffter-Forschungsinstituts ist und den Begriff “Entaktogene” geprägt hat, veröffentlichte mit diesem Artikel einen umfrangreichen Überblick über die Chemie psychedelischer Substanzen. „Psychedelika” (2016) ist eine fast 100-seitige Zusammenfassung der Forschung über das Serotoninsystem. Dabei wird erklärt, wie serotonerge Halluzinogene die Serotonin-2A-Rezeptoren beeinflussen und was das für Patienten und Therapeuten bedeutet.

Nichols, D. E. (2016) Psychedelics. Pharmacological Reviews, 68(2):264-355

Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD)-25 and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action. Today there is a consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A receptors, with particular importance on those expressed on apical dendrites of neocortical pyramidal cells in layer V. Several useful rodent models have been developed over the years to help unravel the neurochemical correlates of serotonin 5-hydroxytryptamine 2A receptor activation in the brain, and a variety of imaging techniques have been employed to identify key brain areas that are directly affected by psychedelics. Recent and exciting developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer-related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two small pilot studies of psilocybin-assisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level–dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain’s default mode network.

Da die molekularen Grundlagen psychedelischer Wirkweisen nur eines der Forschungsgebiete innerhalb der Erforschung psychedelischer Substanzen ist, versuchten Forscher des “Center for Psychedelic and Consciousness Research an der Johns Hopkins University School of Medicine” unter der Leitung von Roland Griffiths, unser bisheriges Wissen über die akute Veränderung der subjektiven Wahrnehmung durch psychedelische Substanzen zusammenzufassen. „Klassische Psychedelika: Ein integrativer Überblick über Epidemiologie, mystische Erfahrung, Gehirnnetzwerkfunktion und Therapeutika“ trägt dabei Einsichten aus der psychiatrischen Erforschung von Psychedelika zusammen und setzt dabei die genutzten Forschungsmethoden in ihren jeweiligen historischen Kontext.

Johnson, M. W., Hendricks, P. S., Barrett, F. S., and Griffiths, R. R. (2018) Classic Psychedelics: An integrative review of epidemiology, mystical experience, brain network function, and therapeutics. Pharmacology & Therapeutics, 197:83-102

The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are serotonin 2A receptor (5-HT2AR) agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times. They were of prominent interest within psychiatry and neuroscience in the 1950s to 1960s, and during this time contributed to the emergence of the field of molecular neuroscience. Promising results were reported for treatment of both end-of-life psychological distress and addiction, and classic psychedelics served as tools for studying the neurobiological bases of psychological disorders. Moreover, classic psychedelics were shown to occasion mystical experiences, which are subjective experiences reported throughout different cultures and religions involving a strong sense of unity, among other characteristics. However, the recreational use of classic psychedelics and their association with the counterculture prompted an end to human research with classic psychedelics in the early 1970s. We provide the most comprehensive review of epidemiological studies of classic psychedelics to date. Notable among these are a number of studies that have suggested the possibility that nonmedical naturalistic (non-laboratory) use of classic psychedelics is associated with positive mental health and prosocial outcomes, although it is clear that some individuals are harmed by classic psychedelics in non-supervised settings. We then review recent therapeutic studies suggesting efficacy in treating psychological distress associated with life-threatening diseases, treating depression, and treating nicotine and alcohol addictions. We also describe the construct of mystical experience, and provide a comprehensive review of modern studies investigating classic psychedelic-occasioned mystical experiences and their consequences. These studies have shown classic psychedelics to fairly reliably occasion mystical experiences. Moreover, classic-psychedelic-occasioned mystical experiences are associated with improved psychological outcomes in both healthy volunteer and patient populations. Finally, we review neuroimaging studies that suggest neurobiological mechanisms of classic psychedelics. These studies have also broadened our understanding of the brain, the serotonin system, and the neurobiological basis of consciousness. Overall, these various lines of research suggest that classic psychedelics might hold strong potential as therapeutics, and as tools for experimentally investigating mystical experiences and behavioral-brain function more generally.

In diesem Artikel untersucht Prof. Dr. Robin Carhart-Harris zusammen mit Guy M. Goodwin die Herausforderungen (z.B. die Subjektivität der Effekte) sowie die Chancen (z.B. die umfangreichen positiven Ergebnisse) der Therapie mit adjuvanter Gabe psychedelischer Substanzen. In „Das therapeutische Potenzial psychedelischer Drogen: Vergangenheit, Gegenwart und Zukunft“ (2017) diskutieren die beiden Forscher die “Renaissance  der Erforschung der Effekte von Psychedelika auf Menschen” und die Möglichkeit, dass die Therapie mit Psilocybin zu einer der wichtigsten Behandlungsmöglichkeiten für Depressionen werden könnte.

Carhart-Harris, R. L. and Goodwin, G. M. (2017) The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology, 42(11):2105-2113

Plant-based psychedelics, such as psilocybin, have an ancient history of medicinal use. After the first English language report on LSD in 1950, psychedelics enjoyed a short-lived relationship with psychology and psychiatry. Used most notably as aids to psychotherapy for the treatment of mood disorders and alcohol dependence, drugs such as LSD showed initial therapeutic promise before prohibitive legislature in the mid-1960s effectively ended all major psychedelic research programs. Since the early 1990s, there has been a steady revival of human psychedelic research: last year saw reports on the first modern brain imaging study with LSD and three separate clinical trials of psilocybin for depressive symptoms. In this circumspective piece, RLC-H and GMG share their opinions on the promises and pitfalls of renewed psychedelic research, with a focus on the development of psilocybin as a treatment for depression.

Es wird oft angenommen, dass die therapeutische Wirkung psychedelischer Substanzen abhängig von den subjektiven Effekten, wie z.B. “peak-experiences” (mystische Erfahrung) oder “Afterglow-phänomenen”, ist. In „Peak-Erlebnisse und das Phänomen des “Afterglows”: Wann und wie hängen therapeutische Effekte von Halluzinogenen von psychedelischen Erfahrungen ab?“ (2015) untersucht Dr. med. Tomislav Majić zusammen mit seinen Kollegen Dr. Timo Torsten Schmidt und Prof. Dr. med. Jürgen Gallinat, wie die subjektiven Effekte von Psychedelika ihre therapeutische Wirkung beeinflussen.

Majić, T., Schmidt, T. T., and Gallinat, J. (2015). Peak experiences and the afterglow phenomenon: When and how do therapeutic effects of hallucinogens depend on psychedelic experiences? Journal of Psychopharmacology, 29(3):241-253

Interest in the therapeutic potential of psychedelic substances has recently resumed. During an early phase of human psychedelic research, their therapeutic application in different pathologies had been suggested, and the first evidence for efficacy was provided. The range of recent clinical applications of psychedelics spans from cluster headaches and obsessive-compulsive disorder to addiction and the treatment of fear and anxiety in patients suffering from terminal illness, indicating potentially different therapeutic mechanisms. A variety of approaches in psychotherapy emphasize subjective experiences, such as so-called peak experiences or afterglow phenomena, as differentially mediating therapeutic action. This review aims to re-evaluate earlier and recent concepts of how psychedelic substances may exert beneficial effects. After a short outline of neurophenomenological aspects, we discuss different approaches to how psychedelics are used in psychotherapy. Finally, we summarize evidence for the relationship between subjective experiences and therapeutic success. While the distinction between pharmacological and psychological action obviously cannot be clear-cut, they do appear to contribute differently from each other when their effects are compared with regard to pathologies.

Die bisherigen Artikel waren alle Review Artikel, die große Teile der psychedelischen Forschung zusammenfassen. Wesentlich für unsere Einsichten in die Effekte von Psychedelika sind dabei Placebo-kontrollierte, randomisierte Studien zur Therapie mit Psychedelika. Luoma und Kollegen (2020) führten „Eine Meta-Analyse von Placebo-kontrollierten Studien zur psychedelisch-assistierten Therapie” durch. Diese Zusammenarbeit von mehreren Arbeitsgruppen hat einen detaillierten Vergleich der seit 1994 veröffentlichten Studien zur Therapie mit Psychedelika hervorgebracht. Die Analyse der Autoren legt nahe, dass die psychedelisch-assistierte Therapie bei allen vier untersuchten psychischen Gesundheitszuständen wirksam ist.

 Luoma, J. B., Chwyl, C., Bathje, G. J., Davis, A.K. and Lancelotta, R. (2020) A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy, Journal of Psychoactive Drugs, 52(4):289-299

After a two-decade hiatus in which research on psychedelics was essentially halted, placebo-controlled clinical trials of psychedelic-assisted therapy for mental health conditions have begun to be published. We identified nine randomized, placebo-controlled clinical trials of psychedelic-assisted therapy published since 1994. Studies examined psilocybin, LSD (lysergic acid diethylamide), ayahuasca (which contains a combination of N,N-dimethyltryptamine and harmala monoamine oxidase inhibitor alkaloids), and MDMA (3,4-methylenedioxymethamphetamine). We compared the standardized mean difference between the experimental and placebo control group at the primary endpoint. Results indicated a significant mean between-groups effect size of 1.21 (Hedges g), which is larger than the typical effect size found in trials of psychopharmacological or psychotherapy interventions. For the three studies that maintained a placebo control through a follow-up assessment, effects were generally maintained at follow-up. Overall, analyses support the efficacy of psychedelic-assisted therapy across four mental health conditions – post-traumatic stress disorder, anxiety/depression associated with a life-threatening illness, unipolar depression, and social anxiety among autistic adults. While study quality was high, we identify several areas for improvement regarding the conduct and reporting of trials. Larger trials with more diverse samples are needed to examine possible moderators and mediators of effects, and to establish whether effects are maintained over time.

Nicht zuletzt möchten wir einen Artikel empfehlen, der sich mit der Mikrodosierung befasst. Mikrodosierung ist die Verabreichung sub-halluzinogener Dosen psychedelischer Substanzen, mit der Hoffnung, dadurch die Stimmung, Konzentration und Kreativität gesunder Probanden zu steigern. Diese Praktik erregt aufgrund Ihrer Verbreitung außerhalb der klinischen Anwendung psychedelischer Substanzen. Es gibt jedoch noch keine ausreichenden Nachweise für ihren Nutzen. Die von Vince Polito und Richard J. Stevenson (2019) durchgeführte “Systematische Studie über die Mikrodosierung von Psychedelika” analysiert zwei Studien, welche die subjektiven Effekte von Mikrodosen psychedelischer Substanzen auf das Wohlbefinden untersuchen.

Polito, V. and Stevenson, R. J. (2019) A systematic study of microdosing psychedelics. PLoS ONE 14(2):e0211023

The phenomenon of ‘microdosing’, that is, regular ingestion of very small quantities of psychedelic substances, has seen a rapid explosion of popularity in recent years. Individuals who microdose report minimal acute effects from these substances yet claim a range of long-term general health and wellbeing benefits. There have been no published empirical studies of microdosing and the current legal and bureaucratic climate makes direct empirical investigation of the effects of psychedelics difficult. In Study One we conducted a systematic, observational investigation of individuals who microdose. We tracked the experiences of 98 microdosing participants, who provided daily ratings of psychological functioning over a six week period. 63 of these additionally completed a battery of psychometric measures tapping mood, attention, wellbeing, mystical experiences, personality, creativity, and sense of agency, at baseline and at completion of the study. Analyses of daily ratings revealed a general increase in reported psychological functioning across all measures on dosing days but limited evidence of residual effects on following days. Analyses of pre and post study measures revealed reductions in reported levels of depression and stress; lower levels of distractibility; increased absorption; and increased neuroticism. To better understand these findings, in Study Two we investigated pre-existing beliefs and expectations about the effects of microdosing in a sample of 263 naïve and experienced microdosers, so as to gauge expectancy bias. All participants believed that microdosing would have large and wide-ranging benefits in contrast to the limited outcomes reported by actual microdosers. Notably, the effects believed most likely to change were unrelated to the observed pattern of reported outcomes. The current results suggest that dose controlled empirical research on the impacts of microdosing on mental health and attentional capabilities are needed.