Therapist-rated predictors of response to psychedelic-assisted therapy – Nature Mental Health

therapist-rated-predictors-of-response-to-psychedelic-assisted-therapy-–-nature-mental-health
  • Yao, Y. et al. Efficacy and safety of psychedelics for the treatment of mental disorders: a systematic review and meta-analysis. Psychiatry Res. 335, 115886 (2024).

    Article  PubMed  Google Scholar 

  • Romeo, B., Hermand, M., Pétillion, A., Karila, L. & Benyamina, A. Clinical and biological predictors of psychedelic response in the treatment of psychiatric and addictive disorders: a systematic review. J. Psychiatr. Res. 137, 273–282 (2021).

    Article  PubMed  Google Scholar 

  • Viljoen, G., Walter, H., Bendau, A., Koslowski, M. & Betzler, F. Predictors of therapeutic response to psychedelic-assisted therapy: a systematic review. J. Psychopharmacol. https://doi.org/10.1177/02698811251389581 (2025).

    Article  PubMed  Google Scholar 

  • Haijen, E. C. H. M. et al. Predicting responses to psychedelics: a prospective study. Front. Pharmacol. 9, 897 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  • Johnson, M. W., Garcia-Romeu, A. & Griffiths, R. R. Long-term follow-up of psilocybin-facilitated smoking cessation. Am. J. Drug Alcohol Abuse 43, 55–60 (2017).

    Article  PubMed  Google Scholar 

  • Roseman, L., Nutt, D. J. & Carhart-Harris, R. L. Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression. Front. Pharmacol. 8, 974 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  • Acevedo, E. C., Uhler, S., White, K. P. & Al-Shawaf, L. What predicts beneficial outcomes in psychedelic use? A quantitative content analysis of psychedelic health outcomes. J. Psychoactive Drugs 56, 1–10 (2024).

    Google Scholar 

  • Smigielski, L., Scheidegger, M., Kometer, M. & Vollenweider, F. X. Psilocybin-assisted mindfulness training modulates self-consciousness AND brain default mode network connectivity with lasting effects. Neuroimage 196, 207–215 (2019).

    Article  PubMed  Google Scholar 

  • Carhart-Harris, R. L. et al. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology 235, 399–408 (2018).

    Article  PubMed  Google Scholar 

  • Davis, A. K. et al. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry 78, 481 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  • Van Oorsouw, K., Toennes, S. W. & Ramaekers, J. G. Therapeutic effect of an ayahuasca analogue in clinically depressed patients: a longitudinal observational study. Psychopharmacology 239, 1839–1852 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  • Holze, F., Gasser, P., Müller, F., Dolder, P. C. & Liechti, M. E. Lysergic acid diethylamide–assisted therapy in patients with anxiety with and without a life-threatening illness: a randomized, double-blind, placebo-controlled phase II study. Biol. Psychiatry 93, 215–223 (2023).

    Article  PubMed  Google Scholar 

  • Bogenschutz, M. P. et al. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J. Psychopharmacol. 29, 289–299 (2015).

    Article  PubMed  Google Scholar 

  • Griffiths, R. R. et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J. Psychopharmacol. 30, 1181–1197 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  • Ross, S. et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J. Psychopharmacol. 30, 1165–1180 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  • Agin-Liebes, G. et al. Reports of self-compassion and affect regulation in psilocybin-assisted therapy for alcohol use disorder: an interpretive phenomenological analysis. Psychol. Addict. Behav. 38, 101–113 (2024).

    Article  PubMed  Google Scholar 

  • Mian, M. N., Altman, B. R. & Earleywine, M. Ayahuasca’s antidepressant effects covary with behavioral activation as well as mindfulness. J. Psychoactive Drugs 52, 130–137 (2020).

    Article  PubMed  Google Scholar 

  • Zeifman, R. J., Wagner, A. C., Monson, C. M. & Carhart-Harris, R. L. How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change. J. Affect. Disord. 334, 100–112 (2023).

    Article  PubMed  Google Scholar 

  • Davis, A. K., Xin, Y., Sepeda, N. & Averill, L. A. Open-label study of consecutive ibogaine and 5-MeO-DMT assisted-therapy for trauma-exposed male Special Operations Forces Veterans: prospective data from a clinical program in Mexico. Am. J. Drug Alcohol Abuse 49, 587–596 (2023).

    Article  PubMed  Google Scholar 

  • Sloshower, J. et al. Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial. Sci. Rep. 14, 8833 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  • Jungwirth, J., Von Rotz, R., Dziobek, I., Vollenweider, F. X. & Preller, K. H. Psilocybin increases emotional empathy in patients with major depression. Mol. Psychiatry 30, 2665–2672 (2025).

    Article  PubMed  Google Scholar 

  • Dakwar, E. et al. A sub-set of psychoactive effects may be critical to the behavioral impact of ketamine on cocaine use disorder: results from a randomized, controlled laboratory study. Neuropharmacology 142, 270–276 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  • Romeo, B. et al. The intensity of the psychedelic experience is reliably associated with clinical improvements: a systematic review and meta-analysis. Neurosci. Biobehav. Rev. 172, 106086 (2025).

    Article  PubMed  Google Scholar 

  • Dahan, J. D. C., Dadiomov, D., Bostoen, T. & Dahan, A. Meta-correlation of the effect of ketamine and psilocybin induced subjective effects on therapeutic outcome. npj Ment. Health Res. 3, 45 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  • Levin, A. W. et al. The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder. PLoS ONE 19, e0300501 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  • Liebnau, J., Betzler, F. & Kerber, A. Catalyst for change: psilocybin’s antidepressant mechanisms—a systematic review. J. Psychopharmacol. 39, 397–415 (2025).

    Article  PubMed  PubMed Central  Google Scholar 

  • Murphy, R. et al. Therapeutic alliance and rapport modulate responses to psilocybin assisted therapy for depression. Front. Pharmacol. 12, 788155 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  • Koslowski, M., Johnson, M. W., Gründer, G. & Betzler, F. Novel treatment approaches for substance use disorders: therapeutic use of psychedelics and the role of psychotherapy. Curr. Addict. Rep. 9, 48–58 (2021).

    Article  Google Scholar 

  • Russ, S. L., Carhart-Harris, R. L., Maruyama, G. & Elliott, M. S. Replication and extension of a model predicting response to psilocybin. Psychopharmacology 236, 3221–3230 (2019).

    Article  PubMed  Google Scholar 

  • Wolff, M. et al. Learning to let go: a cognitive-behavioral model of how psychedelic therapy promotes acceptance. Front. Psychiatry 11, 5 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  • Aday, J. S., Davis, A. K., Mitzkovitz, C. M., Bloesch, E. K. & Davoli, C. C. Predicting reactions to psychedelic drugs: a systematic review of states and traits related to acute drug effects. ACS Pharmacol. Transl. Sci. 4, 424–435 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou, K. et al. Prediction of hallucinogen persisting perception disorder and thought disturbance symptoms following psychedelic use. PNAS Nexus 4, 560 (2025).

    Article  Google Scholar 

  • Ko, K., Carter, B., Cleare, A. & Rucker, J. Predicting the intensity of psychedelic-induced mystical and challenging experience in a healthy population: an exploratory post-hoc analysis. Neuropsychiatr. Dis. Treat. 19, 2105–2113 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  • Viljoen, G. & Betzler, F. Anxiety and affective symptoms related to the use of classic psychedelics: a systematic review. Curr. Top. Behav. Neurosci. 2024, 1–30 (2024).

    Google Scholar 

  • Zilcha-Mano, S. et al. The relationship between alliance and outcome: analysis of a two-person perspective on alliance and session outcome. J. Consul. Clin. Psychol. 84, 484–496 (2016).

    Article  Google Scholar 

  • Marquett, R. M. et al. Psychosocial predictors of treatment response to cognitive-behavior therapy for late-life depression: an exploratory study. Aging Ment. Health 17, 830–838 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  • Solomonov, N. et al. Modifiable predictors of nonresponse to psychotherapies for late-life depression with executive dysfunction: a machine learning approach. Mol. Psychiatry 26, 5190–5198 (2021).

    Article  PubMed  Google Scholar 

  • Bagby, R. M., Ryder, A. G. & Cristi, C. Psychosocial and clinical predictors of response to pharmacotherapy for depression. J. Psychiatry Neurosci. 27, 250–257 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  • Flückiger, C., Böhme, M., Schweizer, A.-M., Gómez Penedo, J.-M. & Wampold, B. E. In psychedelic-assisted therapy, the alliance in the psychotherapy component is as important as the drug. Psychother. Psychosom. 94, 304–305 (2025).

    Article  PubMed  Google Scholar 

  • Thal, S., Engel, L. B. & Bright, S. J. Presence, trust, and empathy: preferred characteristics of psychedelic carers. J. Humanist. Psychol. https://doi.org/10.1177/00221678221081380 (2022).

    Article  Google Scholar 

  • Stauffer, C. S., Anderson, B. T., Ortigo, K. M. & Woolley, J. Psilocybin-assisted group therapy and attachment: observed reduction in attachment anxiety and influences of attachment insecurity on the psilocybin experience. ACS Pharmacol. Transl. Sci. 4, 526–532 (2021).

    Article  PubMed  Google Scholar 

  • Wolff, M. et al. Common factors in altered states: understanding psychedelic therapy through the lens of Grawe’s general change mechanisms. Psychol. Rev. 132, 1467–1492 (2025).

    Article  PubMed  Google Scholar 

  • Erritzoe, D. et al. Effects of psilocybin therapy on personality structure. Acta Psychiatr. Scand. 138, 368–378 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  • Barrett, F. S., Johnson, M. W. & Griffiths, R. R. Neuroticism is associated with challenging experiences with psilocybin mushrooms. Pers. Individ. Differ. 117, 155–160 (2017).

    Article  Google Scholar 

  • Holas, P. & Kamińska, J. Mindfulness meditation and psychedelics: potential synergies and commonalities. Pharmacol. Rep. 75, 1398–1409 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  • Lewis-Healey, E., Tagliazucchi, E., Canales-Johnson, A. & Bekinschtein, T. A. Breathwork-induced psychedelic experiences modulate neural dynamics. Cereb. Cortex https://doi.org/10.1093/cercor/bhae347 (2024).

  • Von Rotz, R. et al. Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial. eClinicalMedicine 56, 101809 (2023).

    Article  Google Scholar 

  • Nygart, V. A. et al. Antidepressant effects of a psychedelic experience in a large prospective naturalistic sample. J. Psychopharmacol. 36, 932–942 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  • Low, Z. L. F. Intention-Setting among Recreational Psychedelic Users: Associated Acute Effects and Changes in Well-being. PhD thesis, Univ. at Albany, State Univ. of NY (2025); https://scholarsarchive.library.albany.edu/etd/134

  • Joyce, P. R. et al. Patterns and predictors of remission, response and recovery in major depression treated with fluoxetine or nortriptyline. Aust. N. Z. J. Psychiatry 36, 384–391 (2002).

    Article  PubMed  Google Scholar 

  • Garcia-Romeu, A. et al. Cessation and reduction in alcohol consumption and misuse after psychedelic use. J. Psychopharmacol. 33, 1088–1101 (2019).

    Article  PubMed  Google Scholar 

  • Garcia-Romeu, A. et al. Persisting reductions in cannabis, opioid, and stimulant misuse after naturalistic psychedelic use: an online survey. Front. Psychiatry 10, 955 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  • Xin, Y., Armstrong, S. B., Averill, L. A., Sepeda, N. & Davis, A. K. Predictors of psychedelic treatment outcomes among special operations forces veterans. Psychol. Conscious. https://doi.org/10.1037/cns0000374 (2023).

    Article  Google Scholar 

  • Beard, J. I. L. & Delgadillo, J. Early response to psychological therapy as a predictor of depression and anxiety treatment outcomes: a systematic review and meta-analysis. Depress. Anxiety 36, 866–878 (2019).

    Article  PubMed  Google Scholar 

  • Nordmo, M., Monsen, J. T., Høglend, P. A. & Solbakken, O. A. Investigating the dose–response effect in open-ended psychotherapy. Psychother. Res. 31, 859–869 (2021).

    Article  PubMed  Google Scholar 

  • Rost, F. et al. The complexity of treatment-resistant depression: a data-driven approach. J. Affect. Disord. 358, 292–301 (2024).

    Article  PubMed  Google Scholar 

  • Foltin, R. W., Luba, R., Chen, Y., Wang, Y. & Evans, S. M. Impulsivity in cocaine users compared to matched controls: effects of sex and preferred route of cocaine use. Drug Alcohol Depend. 226, 108840 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  • Stellern, J. et al. Emotion regulation in substance use disorders: a systematic review and meta-analysis. Addiction 118, 30–47 (2023).

    Article  PubMed  Google Scholar 

  • Johnson, M. W. Consciousness, religion, and gurus: pitfalls of psychedelic medicine. ACS Pharmacol. Transl. Sci. 4, 578–581 (2021).

    Article  PubMed  Google Scholar 

  • Mion, G. & Villevieille, T. Ketamine pharmacology: an update. CNS Neurosci. Ther. 19, 370–380 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  • Mathai, D. S., Meyer, M. J., Storch, E. A. & Kosten, T. R. The relationship between subjective effects induced by a single dose of ketamine and treatment response in patients with major depressive disorder: a systematic review. J. Affect. Disord. 264, 123–129 (2020).

    Article  PubMed  Google Scholar 

  • Machado-Vieira, R., Salvadore, G., DiazGranados, N. & Zarate, C. A. Jr. Ketamine and the next generation of antidepressants with a rapid onset of action. Pharmacol. Ther. 123, 143–150 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  • Passie, T., Seifert, J., Schneider, U. & Emrich, H. M. The pharmacology of psilocybin. Addict. Biol. 7, 357–364 (2002).

    Article  PubMed  Google Scholar 

  • Holze, F., Becker, A. M., Kolaczynska, K. E., Duthaler, U. & Liechti, M. E. Pharmacokinetics and pharmacodynamics of oral psilocybin administration in healthy participants. Clin. Pharmacol. Ther. 113, 822–831 (2023).

    Article  PubMed  Google Scholar 

  • Studerus, E., Kometer, M., Hasler, F. & Vollenweider, F. X. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. J. Psychopharmacol. 25, 1434–1452 (2011).

    Article  PubMed  Google Scholar 

  • Mertens, L. J. et al. Methodological challenges in psychedelic drug trials: efficacy and safety of psilocybin in treatment-resistant major depression (EPIsoDE)—rationale and study design. Neurosci. Appl. 1, 100104 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  • Aday, J. S. et al. Personal psychedelic use is common among a sample of psychedelic therapists: implications for research and practice. Psychedelic Med. 1, 27–37 (2023).

    Article  Google Scholar 

  • Braun, V. & Clarke, V. Using thematic analysis in psychology. Qual. Res. Psychol. 3, 77–101 (2006).

    Article  Google Scholar 

  • Viljoen, G. et al. Predictors of psychedelic-assisted therapy response (PREPARE-study): the therapist’s perspective. figshare https://doi.org/10.6084/m9.figshare.30218056 (2026).

  • Comments

    Leave a Reply

    Your email address will not be published. Required fields are marked *