Lektüreliste 2

Einführung in die Psychedelisch-Assistierte Therapie

 

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

Die positiven Wirkungen serotonerger Halluzinogene sind von Freizeitkonsumenten seit langem anerkannt. Die Geschichte der akademischen Forschung über das therapeutische Potenzial von Psychedelika war jedoch, um es vorsichtig auszudrücken, turbulent.

Seit mehr als einem Jahrzehnt lässt sich eine psychedelische Renaissance – ein wachsendes Interesse an der Erforschung des Potenzials von Psychedelika bei der Behandlung von psychischen Gesundheitsstörungen – beobachten. Substanzen wie Psilocybin, LSD und Ayahuasca werden auf der ganzen Welt untersucht, von universitären Forschungsgruppen bis hin zu vorrausschauenden Therapeutenbüros. All dies in der Hoffnung, für die Gesellschaft als Ganzes wirksame Methoden zur Verbesserung der globalen psychischen Gesundheit zu etablieren.

In dieser Liste stellen wir die Geschichte und den aktuellen Stand der Forschung zur psychedelisch-assistierten Therapie vor, sowie ihre Herausforderungen und Zukunftsperspektiven.

Dr. Ben Sessa’s Artikel ist eine zugängliche Zusammenfassung des Überschnitts von Psychedelika und psychiatrischer Forschung. Er argumentiert, dass man sich von der naiven Vorstellung, durch den Einsatz von Psychedelika eine utopische Gesellschaft erschaffen zu können, verabschieden muss. Stattdessen sollten sich Forscher, sowie ÄrztInnen und PsychotherapeutInnen darauf konzentrieren, das Potential von Psychedelika in der Psychiatrie kritisch zu erfassen.

Sessa, B. (2014). Why Psychiatry Needs Psychedelics and Psychedelics Need Psychiatry. Journal of Psychoactive Drugs, 46(1):57-62.

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.

In dem Artikel von Belouina & Henningfield wird der historische Kontext der Erforschung von Psychedelika ausführlich diskutiert.  Die Forscher beleuchten den Aufstieg, den Fall und die gegenwärtige Renaissance von Psychedelika in der Psychiatrie. Aufbauend auf einer historisch-politischen Perspektive präsentieren die Autoren einen Kurs für die systematische Erforschung des therapeutischen Potentials von Psychedelika.

Belouin, S. J. and Henningfeld, J. E. (2018). Psychedelics: Where we are now, why we got here, what we must do. Neuropharmacology, 142:7-19.

The purpose of this commentary is to provide an introduction to this special issue of Neuropharmacology with a historical perspective of psychedelic drug research, their use in psychiatric disorders, research-restricting regulatory controls, and their recent emergence as potential breakthrough therapies for several brain-related disorders. It begins with the discovery of lysergic acid diethylamide (LSD) and its promising development as a treatment for several types of mental illnesses during the 1940s. This was followed by its abuse and stigmatization in the 1960s that ultimately led to the placement of LSD and other psychedelic drugs into the most restrictively regulated drug schedule of the United States Controlled Substances Act (Schedule I) in 1970 and its international counterparts. These regulatory controls severely constrained development of psychedelic substances and their potential for clinical research in psychiatric disorders. Despite the limitations, there was continued research into brain mechanisms of action for psychedelic drugs with potential clinical applications which began during the 1990s and early 2000s. Finding pathways to accelerate clinical research in psychedelic drug development is supported by the growing body of research findings that are documented throughout this special issue of Neuropharmacology. Accumulated research to date suggests psychedelic drug assisted psychotherapy may emerge as a potential breakthrough treatment for several types of mental illnesses including depression, anxiety, post-traumatic stress disorder, and addiction that are refractory to current evidenced based therapies. This research equally shows promise in advancing the understanding of the brain, brain related functioning, and the consequential effects of untreated brain related diseases that have been implicated in causing and/or exacerbating numerous physical disease state conditions. The authors conclude that more must be done to effectively address mental illnesses and brain related diseases which have become so pervasive, destructive, and whose treatments are becoming increasingly resistant to current evidenced based therapies.

Eine streng medizinische Perspektive bieten Prof. Dr. David Nichols, Prof. Dr. Matthew Johnson und Dr. Charles Nichols in ihrem Fachartikel von 2016. Sie vergleichen verschiedene klinische Studien mit diversen Patientenpopulationen und beleuchten parallel die Wirkungsmechanismen von Psychedelika auf zellulärer Ebene.

Nichols, D. E., Johnson, M. W., and Nichols, C. D. (2017). Psychedelics as Medicines: An Emerging New Paradigm. Clinical Pharmacology and Therapeutics, 101(2):209-219.

Scientific interest in serotonergic psychedelics (e.g., psilocybin and LSD; 5‐HT2A receptor agonists) has dramatically increased within the last decade. Clinical studies administering psychedelics with psychotherapy have shown preliminary evidence of robust efficacy in treating anxiety and depression, as well as addiction to tobacco and alcohol. Moreover, recent research has suggested that these compounds have potential efficacy against inflammatory diseases through novel mechanisms, with potential advantages over existing antiinflammatory agents. We propose that psychedelics exert therapeutic effects for psychiatric disorders by acutely destabilizing local brain network hubs and global network connectivity via amplification of neuronal avalanches, providing the occasion for brain network “resetting” after the acute effects have resolved. Antiinflammatory effects may hold promise for efficacy in treatment of inflammation‐related nonpsychiatric as well as potentially for psychiatric disorders. Serotonergic psychedelics operate through unique mechanisms that show promising effects for a variety of intractable, debilitating, and lethal disorders, and should be rigorously researched.

Vier Jahre später schlossen sich zwei Pioniere der psychedelischen Forschung in Brasilien zusammen und veröffentlichten eine detaillierte Analyse des  therapeutischen Potenzials von LSD, Psilocybin und Ayahuasca. Diese Studie untersucht die Auswirkungen von Psychedelika bei Störungen des Substanzkonsums sowie bei Angstzuständen und Depressionen im Zusammenhang mit Krebs und anderen lebensbedrohlichen Krankheiten.

dos Santos, R. G. and Hallak, J. E. C. (2019). Therapeutic use of serotoninergic hallucinogens: a review of the evidence and of the biological and psychological mechanisms. Neuroscience & Biobehavioral Reviews, 108:423-434.

Serotoninergic hallucinogens include drugs such as lysergic acid diethylamide (LSD), dimethyltryptamine (DMT) and psilocybin. Recent trials with single/few doses of these compounds show that they induce rapid and sustained antidepressive, anxiolytic, and antiaddictive effects. These effects are also observed in religious groups using the DMT-containing brew ayahuasca. The agonist action of these substances on 5-HT2A receptors expressed in frontal and limbic areas increase glutamatergic transmission and neuroplasticity. These neurochemical effects are associated with acute alterations on self-perception and increases in introspection and positive mood, and with subacute and long-term decreases in psychiatric symptoms, increases in some personality traits such as openness, improvements in emotional processing, and increases in empathy. These are preliminary but promising results that should be further explored in controlled trials with larger sample sizes, especially considering that these compounds could be beneficial in the treatment of treatment-resistant psychiatric disorders.

Mit einer lebensbedrohlichen Krankheit zu leben kann viele psychische Probleme mit sich bringen. Generalisierte Angst, Einsamkeit, die Angst im Bezug auf unaufgelöste interpersonelle Konflikte und die Bewältigung von Schmerzen sind nur einige dieser Probleme. Im Jahr 2014 haben sich Forscher aus der Schweiz und den USA in einer klinischen Studie die Sicherheit und Wirksamkeit LSD-unterstützter Psychotherapie bei Angstzuständen im Zusammenhang mit lebensbedrohlichen Krankheiten untersucht. Die Studie, die teilweise von MAPS finanziert wurde, zeigte bereits nach zwei LSD-unterstützten Therapiesitzungen einen positiven Trend zur Verringerung von Angstzuständen. In einer Folgestudie stellten sie fest, dass die positiven Effekte auch 12 Monate danach anhielten.

Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., and Brenneisen, R. (2014). Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. Journal of Nervous and Mental Disease, 202(7):513-520.

A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.

Key Words: LSD, psychedelic, psycholytic therapy, hallucinogen, anxiety disorder

Parallel zu LSD wurde auch getestet ob Psilocybin zur Verringerung von Depressionen und Angstzuständen bei Patienten beitragen kann, die an lebensbedrohlichem Krebs leiden. Wissenschaftler von der Johns Hopkins University, School of Medicine, stellten in ihrer randomisierten Doppelblindstudie  2016 fest, dass Psilocybin bei Patienten mit lebensbedrohlichem Krebs eine erhebliche und anhaltende Verringerung von Depressionen und Angstzuständen bewirken kann. Dabei traten keine unerwünschten Wirkungen auf. Verbesserungen der Lebensqualität, des Lebenssinns, der Akzeptanz des Todes und des Optimismus hielten für mindestens sechs Monate nach der Verabreichung von Psilocybin an.

Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., and Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology, 30(12):1181-1197.

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.

Die Untersuchung der Auswirkungen von Psychedelika bei PatientInn im Kontext der palliativen Behandlung ist jedoch äußerst anspruchsvoll, nicht nur wegen dem gesundheitlichen Zustand der PatientInnen, sondern auch wegen des Studiendesigns und der Stichprobengröße. Der Artikel über serotonerge Psychedelika bei der Behandlung von Angstzuständen und Depressionen bei PatientInnen, die an einer lebensbedrohlichen Krankheit leiden, verfasst von Simon Reiche und Kollegen (darunter Dr. Henrik Jungaberle – einer der Gründer der MIND Foundation), analysiert dafür über 50 Jahre klinischer Studien zum Thema.

Reiche, S., Hermle, L., Gutwinski, S., Jungaberle, H.,Gasser, P., and Majic, T. (2018). Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 81:1-10.

Anxiety and depression are some of the most common psychiatric symptoms of patients suffering with life-threatening diseases, often associated with a low quality of life and a poor overall prognosis. 5-HT2A-receptor agonists (serotonergic hallucinogens, ‘psychedelics’) like lysergic acid diethylamide (LSD) and psilocybin were first investigated as therapeutic agents in the 1960s. Recently, after a long hiatus period of regulatory obstacles, interest in the clinical use of these substances has resumed. The current article provides a systematic review of studies investigating psychedelics in the treatment of symptoms of existential distress in life-threatening diseases across different periods of research, highlighting how underlying concepts have developed over time. A systematic search for clinical trials from 1960 to 2017 revealed 11 eligible clinical trials involving a total number of N = 445 participants, of which 7 trials investigated the use of lysergic acid diethylamide (LSD) (N = 323), 3 trials investigated the use of psilocybin (N = 92), and one trial investigated the use of dipropyltryptamine (DPT) (N = 30). The 4 more recent randomized controlled trials (RCTs) (N = 104) showed a significantly higher methodological quality than studies carried out in the 1960s and 1970s. Evidence supports that patients with life threatening diseases associated with symptoms of depression and anxiety benefit from the anxiolytic and antidepressant properties of serotonergic hallucinogens. Some studies anecdotally reported improvements in patients´ quality of life and reduced fear of death. Moreover, low rates of side effects were reported in studies that adhered to safety guidelines. Further studies are needed to determine how these results can be transferred into clinical practice.

In der Therapie mit Psychedelika werden nicht nur LSD und Psilocybin, sondern auch Ayahuasca genutzt. Obwohl es ursprünglich nur im Dschungel des Amazonasgebietes im Rahmen schamanistischer Rituale genutzt wurde, wird es heutzutage nahezu weltweit konsumiert. Im Jahr 2017 füllten 527 Teilnehmer, die Ayahuasca genutzt hatten eine Umfrage eines internationalen Forscherteam aus. Die Umfrage fand insbesondere Veränderungen in der subjektiven Zufriedenheit und den Trinkgewohnheiten von Ayahuasca Konsumenten.

Lawn, W., Hallak, J. E. C., Crippa, J. A. S., dos Santos, R. G., Pory, L., Barratt, M. J., Ferris, J. A., Winstock, A. R., and Morgan, C. J. (2017). Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: A large, international, self-selecting online survey. Scientific Reports, 7:15201.

Ayahuasca is a natural psychedelic brew, which contains dimethyltryptamine (DMT). Its potential as a psychiatric medicine has recently been demonstrated and its non-medical use around the world appears to be growing. We aimed to investigate well-being and problematic alcohol use in ayahuasca users, and ayahuasca’s subjective effects. An online, self-selecting, global survey examining patterns of drug use was conducted in 2015 and 2016 (n = 96,901). Questions were asked about: use of ayahuasca, lysergic acid diethylamide (LSD) and magic mushrooms; demographics, current well-being and past-year problematic alcohol use of past-year ayahuasca users and comparison drug users; and subjective effects of ayahuasca and comparison drugs. Ayahuasca users (n = 527) reported greater well-being than both classic psychedelic users (n = 18,138) and non-psychedelic drug-using respondents (n = 78,236). Ayahuasca users reported less problematic drinking than classic psychedelic users, although both groups reported greater problematic drinking than the other respondents. Ayahuasca’s acute subjective effects usually lasted for six hours and were most strongly felt one hour after consumption. Within our online, self-selecting survey, ayahuasca users reported better well-being than comparison groups and less problematic drinking than classic psychedelic users. Future longitudinal studies of international samples and randomised controlled trials are needed to dissect the effects of ayahuasca on these outcomes.

Inspiriert durch das von Prof. Dr. Robin Carhart-Harris vorgeschlagene REBUS-Modell konstruierten Dr. rer. nat. Max Wolff et al. (2020) ein kognitiv-behaviorales Modell, um die Mechanismen der positiven Effekte bei psychedelischen Interventionen zu erklären. Die Forscher schlugen vor, dass vermeidungsbezogene Annahmen während einer Psychedelika-assistierten Therapiesitzung gelockert werden können. Dies ermöglicht Patienten emotionale Durchbrüche zu erreichen und damit Vermeidungsmuster aufzulösen.

Wolff, M., Evens, R., Mertens, L. J., Koslowski, M., Betzler, F., Grunder, G., and Jungaberle, H. (2020). Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance. Frontiers in Psychiatry, 11:5.

The efficacy of psychedelic-assisted therapies for mental disorders has been attributed to the lasting change from experiential avoidance to acceptance that these treatments appear to facilitate. This article presents a conceptual model that specifies potential psychological mechanisms underlying such change, and that shows substantial parallels between psychedelic therapy and cognitive behavioral therapy: We propose that in the carefully controlled context of psychedelic therapy as applied in contemporary clinical research, psychedelic-induced belief relaxation can increase motivation for acceptance via operant conditioning, thus engendering episodes of relatively avoidance-free exposure to greatly intensified private events. Under these unique learning conditions, relaxed avoidance-related beliefs can be exposed to corrective information and become revised accordingly, which may explain long-term increases in acceptance and corresponding reductions in psychopathology. Open research questions and implications for clinical practice are discussed.

Dieser Artikel beurteilt die ‘cost-effectiveness’ von MDMA-unterstützter Psychotherapie zur Behandlung chronischer, therapieresistenter posttraumatischer Belastungsstörung. Der Artikel begutachtet hierzu die Kosten der medizinischen Versorgung von PatientInnen, die an PTBS leiden – einer Erkrankung, von der fast 12 Millionen Amerikaner betroffen sind und von denen viele chronisch oder rezidivierend erkranken. Die Effektivität der Standardbehandlung ist dabei oft unzureichend. Die Analyse legt nahe, dass die MDMA-unterstützte Psychotherapie, trotz der hohen Kosten der Substanz-assistierten Sitzungen, sehr kosteneffektiv und daher nicht nur für die PatientInnen, sondern auch für die Gesellschaft und das Gesundheitssystem von Vorteil ist.

Marseille, E., Kahn, J.G., Yazar-Klosinski, B. and Doblin, R. (2020) The cost-effectiveness of MDMA-assisted psychotherapy for the treatment of chronic, treatment-resistant PTSD. PLoS ONE 15(10):e0239997

To assess the cost-effectiveness of MDMA-assisted psychotherapy (MAP) from the health care payer’s perspective, we constructed a decision-analytic Markov model to portray the costs and health benefits of treating patients with chronic, severe, or extreme, treatment-resistant PTSD with MAP. In six double-blind phase 2 trials, MAP consisted of a mean of 2.5 90-minute trauma-focused psychotherapy sessions before two 8-hour sessions with MDMA (mean dose of 125 mg), followed by a mean of 3.5 integration sessions for each active session. The control group received an inactive placebo or 25–40 mg. of MDMA, and otherwise followed the same regimen. Our model calculates net medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Efficacy was based on the pooled results of six randomized controlled phase 2 trials with 105 subjects; and a four-year follow-up of 19 subjects. Other inputs were based on published literature and on assumptions when data were unavailable. We modeled results over a 30-year analytic horizon and conducted extensive sensitivity analyses. Our model calculates expected medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Future costs and QALYs were discounted at 3% per year. For 1,000 individuals, MAP generates discounted net savings of $103.2 million over 30 years while accruing 5,553 discounted QALYs, compared to continued standard of care. MAP breaks even on cost at 3.1 years while delivering 918 QALYs. Making the conservative assumption that benefits cease after one year, MAP would accrue net costs of $7.6 million while generating 288 QALYS, or $26,427 per QALY gained.