Lektüreliste 3

Psychedelika in der Behandlung von Depressionen

 

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

 

Eine Depression ist eine psychische Störung, die durch Symptome wie Stimmungsstörungen, anhaltender Unfähigkeit Freude zu empfinden, und Suizidalität gekennzeichnet ist. Im Jahr 2017 waren weltweit etwa 264 Millionen Menschen von Depressionen betroffen.1 Studien legen nahe, dass bis zu 20% der Mitglieder der amerikanischen Gesellschaft im Laufe ihres Lebens depressive Episoden erleben werden.2 Angststörungen treten in etwa 50% der Fälle parallel zur klinischen Depression auf.3

Mainstream-Antidepressiva haben eine wichtige Rolle bei der Verringerung der Symptome bei depressiven Patienten gespielt. Ihre Wirkung tritt jedoch oft verzögert ein, unerwünschte Nebenwirkungen sind häufig, und einige Patienten sind von der Behandlung nicht betroffen.4 Die verbundenen sozioökonomischen Kosten sind hoch,5 und viele Patienten erleiden nach Beendigung der Behandlung einen Rückfall6 (um mehr über die Wirksamkeit von SSRIs und ihre Wechselwirkungen mit anderen Substanzen zu erfahren, lesen Sie diesen MIND-Blog-Post von Camile Bahi).

Psychedelika bieten einen neuen Weg in der Behandlung von Depressionen. Die Studien, die wir hervorgehoben haben, zeigen ein Potenzial, das von keiner der gegenwärtigen Alternativen erreicht wird. Doch gleichzeitig sollte sich die wissenschaftliche Gemeinschaft davor hüten, einen zu frühen Erfolg zu verkünden.

Obwohl vielversprechend, wurde die Forschung dieser Liste meist mit einer kleinen Stichprobengröße, mit sorgfältig konzipierten Settings, und Therapeuten mit langjähriger Erfahrung durchgeführt. Die “therapeutische Allianz” – die Beziehung zwischen Patienten und Therapeuten – und Placebo-Effekte sind definitiv im Spiel. Darüber hinaus können Psychedelika die grundlegenden (familiären, gesellschaftlichen, wirtschaftlichen) Ursachen von Depressionen vermutlich nicht direkt beeinflussen.

Unter Berücksichtigung all dessen fassen die folgenden Publikationen die wichtigsten Studien der letzten Jahre zusammen, die das Potenzial von Psychedelika bei der Behandlung von Depressionen und Angstzuständen untersuchen.

1. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017
https://ourworldindata.org/grapher/number-of-people-with-depression
2. Hasin DS, Sarvet AL, Meyers JL, et al. (2018) Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the United States. JAMA Psychiatry 75(4):336–346. doi:10.1001/jamapsychiatry.2017.4602
3. Kircanski, K., LeMoult, J., Ordaz, S. and Gotlib, I. H. (2017) Investigating the nature of co-occurring depression and anxiety: Comparing diagnostic and dimensional research approaches. Journal of Affective Disorders 216:123-135
4. Penn, E., & Tracy, D. K. (2012). The drugs don’t work? antidepressants and the current and future pharmacological management of depression. Therapeutic Advances in Psychopharmacology, 2(5):179–188.
5. Whiteford, H. A., Degenhardt, L., Rehm, J., Baxter, A. J., … and Vos, T. (2013). Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet, 382(9904):1575–1586
6. Geddes, J., Carney, S., Davies, C., Furukawa, T., Kupfer, D., Frank, E.. (2003) Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet, 361(9358):653–661.

Vor ihrer Prohibition in den 1960er Jahren wurden umfangreiche Forschungsarbeiten über Psychedelika bei der Behandlung psychiatrischer Erkrankungen durchgeführt. Eine systematische Übersicht von Rucker und Kollegen (2016) untersucht Studien, die zwischen 1949 und 1973 veröffentlicht wurden. Die Autoren stellten fest, dass LSD erfolgreich zur Behandlung von Depressionen eingesetzt worden war, wobei in 19 Studien bei fast 80% der 423 Teilnehmer eine Verbesserung festgestellt wurde. Obwohl die Forschungsstandards des 20. Jahrhunderts nicht annähernd so streng waren wie heute, wurde das Potenzial von Psychedelika in der Behandlung von Gemütsstörungen bereits vor mehr als 50 Jahren erkannt.

Rucker, J. J., Jelen, L. A., Flynn, S., Frowde, K. D. and Young, A. H. (2016). Psychedelics in the treatment of unipolar mood disorders: a systematic review. Journal of Psychopharmacology, 30(12):1220-1229.

Unipolar mood disorders, including major depressive disorder and persistent depressive disorder (dysthymia), confer high rates of disability and mortality and a very high socioeconomic burden. Current treatment is suboptimal in most cases and there is little of note in the pharmaceutical development pipeline. The psychedelic drugs, including lysergic acid diethylamide and psilocybin, were used extensively in the treatment of mood disorders, and other psychiatric conditions, before their prohibition in the late 1960s. They are relatively safe when used in medically controlled environments, with no reported risk of dependence. Here, we present a systematic review of published clinical treatment studies using psychedelics in patients with broadly defined UMD, and consider their place in psychiatry. Whilst all of the included studies have methodological shortcomings, of 423 individuals in 19 studies, 335 (79.2%) showed clinician-judged improvement after treatment with psychedelics. A recently completed pilot study in the UK favours the use of psilocybin with psychological support in treatment resistant depressive disorder. The evidence overall strongly suggests that psychedelics should be re-examined in modern clinical trials for their use in unipolar mood disorders and other non-psychotic mental health conditions.

Dieser Bericht behandelt die wichtigsten Entdeckungen aus den 2010er Jahren (und einen Artikel aus 2007). Die ausgewählten Studien deuten auf ein hohes Potenzial von LSD, Psilocybin und Ayahuasca bei der Behandlung von Depressionen und Angstzuständen sowie bei Alkohol- und Tabakabhängigkeit hin. Die Autoren diskutieren die Einschränkungen der analysierten Studien und erörtern mögliche zukünftige Verbesserungen des Studiendesigns. Zusammen mit dem vorhergehenden Artikel gibt dieser Artikel dem Leser einen soliden Überblick über das, was bisher in der Forschung über Psychedelika bei Depressionen gefunden wurde.

dos Santos, R.G, Bouso, J.C., Alcázar-Córcoles, M.A. and Hallak, J.E.C. (2018) Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews. Expert Review of Clinical Pharmacology, 11(9):889-902

Introduction: Mood, anxiety, and substance-use disorders are among the most prevalent psychiatric disorders in the population. Although several pharmacological treatments are available, they are not effective for a significant proportion of patients and are associated with several adverse reactions. Therefore, new treatments should be explored. Recent studies suggest that serotonergic hallucinogens/psychedelics including ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) have anxiolytic, antidepressive, and antiaddictive effects.

Areas Covered: A systematic review of systematic reviews assessing the efficacy, safety, and tolerability of serotonergic hallucinogens/psychedelic was performed using the PubMed data base until 11 April 2018. Systematic reviews with or without meta-analysis were analyzed, but only reviews that described at least one randomized controlled trial (RCT) were included.

Expert Commentary: Psilocybin and LSD reduced anxiety and depression in cancer patients and symptoms of alcohol and tobacco dependence, and ayahuasca reduced depression symptoms in treatment-resistant depression. Although the results are promising, several studies were open label, and only few were RCTs, and most had small sample sizes and a short duration. Single or few doses of these drugs seem to be well tolerated, but long-term studies are lacking. New RCTs with bigger samples and longer duration are needed to replicate these findings.

Einer der möglichen Mechanismen, durch die Psychedelika langfristige positive Auswirkungen auf Depressionen zu erzielen, ist eine Verringerung der Erlebnisvermeidung. Die Umfragestudie von Zeifman et al. (2020), fand heraus, dass die Teilnehmer nach der Einnahme von Psychedelika weniger Erlebnisvermeidung aufzeigten. Erlebnisvermeidung ist definiert als ein Versuch, Gedanken, Gefühle, Erinnerungen und andere (negative) innere Erfahrungen zu vermeiden. Darüber hinaus stützen die Ergebnisse die Hypothese, dass die positiven Auswirkungen von Psychedelika über das gesamte Spektrum der Depressionsschwere, einschließlich des milden Endes der Depression, beobachtet werden können.

Zeifman, R. J., Wagner, A. C., Watts, R., Kettner, H., Mertens, L. J. and Carhart-Harris, R. L. (2020). Post-psychedelic reductions in experiential avoidance are associated with decreases in depression severity and suicidal ideation. Frontiers in Psychiatry, 11:782

Psychedelic therapy shows promise as a novel intervention for a wide range of mental health concerns but its therapeutic action is incompletely understood. In line with acceptance and commitment therapy’s (ACT’s) transdiagnostic model, qualitative research has suggested that reductions in experiential avoidance are an important component of therapeutic outcomes associated with psychedelics. However, limited research has quantitatively explored the association between decreases in experiential avoidance and therapeutic outcomes associated with psychedelics. Therefore, in two prospective studies, using convenience samples of individuals with plans to use a psychedelic, we explored the impact of psychedelic use on experiential avoidance, depression severity, and suicidal ideation, as well as relationships between changes in these outcomes. Participants (Study 1, N=104; Study 2, N=254) completed self-report questionnaires of depression severity, suicidal ideation, and experiential avoidance: 1) before using a psychedelic (in ceremonial and non-ceremonial contexts), as well as 2) 2-weeks and 3) 4-weeks after psychedelic use. Across both studies, repeated measures ANOVAs indicated significant decreases in experiential avoidance, depression severity, and suicidal ideation after psychedelic use. Furthermore, decreases in experiential avoidance were significantly associated with decreases in depression severity and suicidal ideation. These results suggest that psychedelics may lead to significant decreases in experiential avoidance, depression severity, and suicidal ideation. Additionally, these findings imply that reduced experiential avoidance may be a transdiagnostic mechanism mediating treatment success within psychedelic therapy. We conclude that integrating psychedelics with psychotherapeutic interventions that target experiential avoidance (e.g. ACT) may enhance therapeutic outcomes.

Eine andere Theorie wurde von Alan Davis, Frederick Barrett und Roland Griffiths vorgeschlagen. Sie vermuten, dass erhöhte psychologische Flexibilität einer der Mechanismen sein könnte, die bei der Symptomlinderung von Depressionen eine Rolle spielen. Nach der Befragung von fast 1000 Benutzern von Psychedelika fanden die Forscher heraus, dass die psychologische Flexibilität die Beziehungen zwischen akuten psychedelischen Effekten und der subjektiven Abnahme von Depressionen und Angstzuständen vermittelt. Mit anderen Worten, die psychologische Einsicht und das Auftreten mystischer Erfahrungen während einer psychedelischen Erfahrung führen zu einer Zunahme der psychologischen Flexibilität, die mit einer Abnahme der Depressions- und Angstsymptome einhergeht.

Davis, A. K., Barrett, F. S., and Griffiths, R. R. (2020). Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety. Journal of Contextual Behavioral Science, 15:39-45.

Prior research has shown that acute subjective psychedelic effects are associated with both spontaneous and intended changes in depression and anxiety. Psychedelics are also theorized to produce increases in psychological flexibility, which could explain decreases in depression and anxiety following a psychedelic experience. Therefore, the present cross-sectional survey study sought to examine whether psychological flexibility mediated the relationship between acute psychedelic experiences and spontaneous or intended changes in depression and anxiety among a large international sample of people who reported having used a psychedelic (n = 985; male = 71.6%; Caucasian/white = 84.1%; Mage = 32.2, SD = 12.6). A regression analysis showed that acute effects (i.e., mystical and insightful effects) were significantly associated with decreases in depression/anxiety following a psychedelic experience. A path analysis revealed that, while controlling for age and sex, increases in psychological flexibility fully mediated the effect of mystical and insightful experiences on decreases in depression and anxiety following a psychedelic experience. This suggests that psychological flexibility may be an important mediator of the therapeutic effects of psychedelic drugs. Future prospective experimental studies should examine the effect of psychedelic drug administration on psychological flexibility in order to gain a better understanding of the psychological processes that predict therapeutic effects of psychedelics.

Dieselbe Forschungsgruppe des Johns Hopkins Center for Psychedelic and Consciousness Research untersuchte die Auswirkungen der Verabreichung von Psilocybin bei 24 Teilnehmern mit schwerer Depression. Dies war die erste randomisierte kontrollierte Studie, bei der die Patienten nach der ersten und vierten Behandlungswoche eine klinisch signifikante Reaktion auf die Intervention zeigten. Obwohl Studieneinschränkungen unvermeidlich waren, tragen diese Ergebnisse zu der zunehmenden Beweislage zu großen, schnellen und anhaltenden Wirkungen von Psilocybin bei der Behandlung von Depression bei.

Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2020). Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA psychiatry, e203285

Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression.

This randomized, waiting list–controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population).

The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR).

Leor Roseman, David Nutt und Robin Carhart-Harris (2017) untersuchten die Aspekte der psychedelischen Erfahrung, die möglicherweise die wichtigsten Vermittler langfristiger Verbesserungen der psychischen Gesundheit sein können. In ihrem Artikel  legen sie nahe, dass das Ausmaß der “ozeanischen Grenzenlosigkeitserfahrung” der wichtigste Prädiktor für die positiven Ergebnisse ist. Ein Aspekt, der sich als völlig unabhängig vom klinischen Ergebnis herausstellte, war das Ausmaß der visuellen Bilder, die von den Teilnehmern während der psychedelischen Erfahrung gesehen wurden. Diese Ergebnisse bedeuten, dass im Gegensatz zu herkömmlichen Antidepressiva “die therapeutischen Effekte von Psilocybin nicht einfach ein Produkt einer isolierten pharmakologischen Wirkung sind, sondern vielmehr erfahrungsabhängig.”

Roseman, L., Nutt, D. J. and Carhart-Harris, R. L. (2018). Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression. Frontiers in Pharmacology, 8:974.

Introduction: It is a basic principle of the “psychedelic” treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would have negligible predictive value.

Materials and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10 and 25 mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25 mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-Time and DED-by-Time interactions were the primary outcomes of interest.

Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson's correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05).

Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety.

Das vielversprechende Paradigma der Psilocybin-unterstützten Therapie für behandlungsresistente depressive Patienten wurde von Robin Carhart-Harris et al. untersucht (2018). In ihrem Studie untersuchten sie, wie 20 Teilnehmer nach zwei Sitzungen mit einer moderaten (10 mg) und einer hohen Dosis (25 mg) Psilocybin abschnitten. Die Behandlung wurde im Allgemeinen von den Patienten gut vertragen, und es traten keine schwerwiegenden Nebenwirkungen auf. Die Daten deuteten darauf hin, dass die Suizidalitäts-Werte signifikant reduziert wurden und maximale Effekte wurden fünf Wochen nach der Behandlung beobachtet. Die Studie hob auch die Bedeutung der psychologischen Unterstützung, während und nach der Verabreichung von Psilocybin hervor.

Carhart-Harris, R. L., Bolstridge, M., Day, C. M. J., Rucker, J., Watts, R., Erritzoe, D. E., Kaelen, M., Giribaldi, B., Bloomfield, M., Pilling, S., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Curran, H. V. and Nutt, D. J. (2018). Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology, 235(2):399-408.

Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy.

Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression.

Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure.

Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen’s d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen’s d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience.

Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.

Eine funktionelle Magnetresonanztomographie (fMRI)-Studie von Robin Carhart-Harris et al. (2017) untersuchte die neurologischen Grundlagen der Reaktion auf Psychedelika. Die Studie untersuchte die zerebrale Blutversorgung im Gehirn nach der Behandlung mit Psilocybin. Die Daten zeigten eine Abnahme in mehreren Bereichen der Temporal- und Frontallappen, und es wurde ein Zusammenhang zwischen verminderter Blutversorgung des Gehirns und der Verringerung der depressiven Symptome festgestellt. Die Ergebnisse legen nahe, dass “die Veränderungen der Hirnaktivität, die nur einen Tag nach einer psychedelischen Erfahrung mit einer hohen Dosis beobachtet wurden, sich sehr von denen unterscheiden, die während des akuten psychedelischen Zustands gefunden wurden”. Darüber hinaus beobachteten die Autoren nach der Behandlung eine erhöhte funktionelle Konnektivität im Ruhezustand innerhalb des Standardmodus-Netzwerks (Default Mode Network, DMN). Dies stimmt mit früheren Befunden überein, die darauf hindeuteten, dass Veränderungen der DMN-Integrität mit Stimmungsverbesserungen verbunden sind.

Carhart-Harris, R. L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, J. N., Wall, M. B., Tanner, M., Kaelen, M., McGonigle, J. Murphy, K., Leech, R., Curr, H. V. and Nutt, D. J. (2017). Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific reports, 7(1):1-11.

Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.

Lea Mertens et al. (2020) untersuchten die funktionelle Konnektivität zwischen der Amygdala, einer Hirnstruktur, die an der Expression von Angst beteiligt ist, und dem ventromedialen präfrontalen Kortex, der an der sozialen Entscheidungsfindung beteiligt ist. Hierzu wurden 19 Forschungsteilnehmer während einer Gesicht-Verarbeitungs-Aufgabe im Vergleich zu einer Ruhephase vor und nach der Behandlung mit Psilocybin beobachtet. Der Artikel legt nahe, dass die Aktivität der Nervenbahnen, die an der emotionalen Reaktionsfähigkeit beteiligt sind, nach einer hohen Dosis Psilocybin erhöht ist. Es wurde ferner die Hypothese aufgestellt, dass die vorgeschlagenen funktionellen Konnektivitätsveränderungen in der Amygdala und im ventromedialen präfrontalen Kortex mit Verbesserungen bei Depressionen und Angstzuständen zusammenhängen.

Lea Mertens diskutierte die Ergebnisse dieser Studie im Interview mit Lukas Basedow. Sie ist auch an unserer Psilocybin-Depressionsstudie beteiligt.

Mertens, L. J., Wall, M. B., Roseman, L., Demetriou, L., Nutt, D. J., and Carhart-Harris, R. L. (2020). Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression. Journal of Psychopharmacology, 34(2):167-180.

Background: Psilocybin has shown promise as a treatment for depression but its therapeutic mechanisms are not properly understood. In contrast to the presumed actions of antidepressants, we recently found increased amygdala responsiveness to fearful faces one day after open-label treatment with psilocybin (25 mg) in 19 patients with treatment-resistant depression, which correlated with treatment efficacy.

Aims: Aiming to further unravel the therapeutic mechanisms of psilocybin, the present study extends this basic activation analysis. We hypothesised changed amygdala functional connectivity, more precisely decreased amygdala-ventromedial prefrontal cortex functional connectivity, during face processing after treatment with psilocybin.

Methods: Psychophysiological interaction analyses were conducted on functional magnetic resonance imaging data from a classic face/emotion perception task, with the bilateral amygdala and ventromedial prefrontal cortex time-series as physiological regressors. Average parameter estimates (beta weights) of significant clusters were correlated with clinical outcomes at one week.

Results: Results showed decreased ventromedial prefrontal cortex-right amygdala functional connectivity during face processing post- (versus pre-) treatment; this decrease was associated with levels of rumination at one week. This effect was driven by connectivity changes in response to fearful and neutral (but not happy) faces. Independent whole-brain analyses also revealed a post-treatment increase in functional connectivity between the amygdala and ventromedial prefrontal cortex to occipital-parietal cortices during face processing.

Conclusion: These results are consistent with the idea that psilocybin therapy revives emotional responsiveness on a neural and psychological level, which may be a key treatment mechanism for psychedelic therapy. Future larger placebo-controlled studies are needed to examine the replicability of the current findings.

Keywords: Amygdala; depression; emotional processing; functional connectivity; psilocybin; psychophysiological interaction; ventromedial prefrontal cortex.

Eine weitere Alternative zu klassischen Antidepressiva könnte Ayahuasca sein – ein botanisches Halluzinogen, das von den Eingeborenenstämmen des Amazonas im rituellen und medizinischen Kontext verwendet wird. Die Untersuchung der antidepressive Wirkung Ayahuascas bei behandlungsresistenten Depressionen zeigt, dass auch Ayahuasca das Potential hat, die Werte des Depression Rating Scale’s (MARDS) signifikant zu verbessern. Die Autoren zeigten, dass an einem Tag und an sieben Tagen nach der Behandlung mit Ayahuasca die MARDS-Werte der Depression (aber nicht die Remissionsraten) signifikant niedriger waren. Es hat sich gezeigt, dass das Gebräu aus Banisteriopsis caapi im Vergleich zu einem Placebo nicht nur eine schnelle antidepressive Wirkung hat, sondern auch ein hohes Sicherheits- und Verträglichkeitsprofil aufweist.

Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M. M., Pessoa, J. A., Mota-Rolim, S. A., Osório, F. L., Sanches, R., Dos Santos, R. G., … and Araújo, D. B. (2019). Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychological medicine, 49(4):655–663.

Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.

To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.

We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054).

To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).

Key words: Ayahuasca, depression, HRS, MEQ, psychedelics, randomized controlled trial (RCT)

Obwohl sich Joost Breeksema et al. (2020) nicht ausschließlich auf Depressionen konzentrierten, überprüften sie die qualitativen Erfahrungen von Patienten bei der Behandlung von psychischen Gesundheitsstörungen. In ihrer Studie suchte die Gruppe nach Mustern in den Erfahrungen der Patienten, wobei sowohl die Erfahrungen über spezifische Störungen hinweg als auch die therapeutischen Prozesse und gewonnene Erkenntnisse berücksichtigt wurden. Die Patienten berichteten häufig über die Vorteile der psychedelisch-assistierten Therapie gegenüber Mainstream-Ansätzen und betonten dabei die positive Rolle von Vertrauen, Sicherheit, Aufmerksamkeit und von Musik. Die Studie fand auch heraus, dass Psychedelika überlappende therapeutische Wirkungen bei verschiedenen Krankheiten aufweisen, darunter auch introspektive Einsichten und das Gefühl der Verbundenheit. Die Autoren kommen zu dem Schluss, dass das Verständnis der Faktoren, die während einer Therapiesitzung ins Spiel kommen, “zur Optimierung des Behandlungskontextes beitragen und zu verbesserten klinischen Reaktionen und persönlichen Vorteilen führen kann.”

Breeksema, J. J., Niemeijer, A. R., Krediet, E., Vermetten, E., and Schoevers, R. A. (2020). Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies. CNS drugs, 34:925–946.

Interest in the use of psychedelic substances for the treatment of mental disorders is increasing. Processes that may affect therapeutic change are not yet fully understood. Qualitative research methods are increasingly used to examine patient accounts; however, currently, no systematic review exists that synthesizes these findings in relation to the use of psychedelics for the treatment of mental disorders.

To provide an overview of salient themes in patient experiences of psychedelic treatments for mental disorders, presenting both common and diverging elements in patients’ accounts, and elucidating how these affect the treatment process.

We systematically searched the PubMed, MEDLINE, PsycINFO, and Embase databases for English-language qualitative literature without time limitations. Inclusion criteria were qualitative research design; peer-reviewed studies; based on verbalized patient utterances; and a level of abstraction or analysis of the results. Thematic synthesis was used to analyze and synthesize results across studies. A critical appraisal of study quality and methodological rigor was conducted using the Critical Appraisal Skills Programme (CASP).

Fifteen research articles, comprising 178 patient experiences, were included. Studies exhibited a broad heterogeneity in terms of substance, mental disorder, treatment context, and qualitative methodology. Substances included psilocybin, lysergic acid diethylamide (LSD), ibogaine, ayahuasca, ketamine and 3,4-methylenedioxymethamphetamine (MDMA). Disorders included anxiety, depression, eating disorders, post-traumatic stress disorder, and substance use disorders. While the included compounds were heterogeneous in pharmacology and treatment contexts, patients reported largely comparable experiences across disorders, which included phenomenological analogous effects, perspectives on the intervention, therapeutic processes and treatment outcomes. Comparable therapeutic processes included insights, altered self-perception, increased connectedness, transcendental experiences, and an expanded emotional spectrum, which patients reported contributed to clinically and personally relevant responses.

This review demonstrates how qualitative research of psychedelic treatments can contribute to distinguishing specific features of specific substances, and carry otherwise undiscovered implications for the treatment of specific psychiatric disorders.