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Post-Psychedelic Reductions in Experiential Avoidance Are Associated With Decreases in Depression Severity and Suicidal Ideation
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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.
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“Second, although two of these studies employed prospective designs, their use of naturalistic, volunteer samples with high rates of attrition (> 50%) may have contributed self-selection and sample biases that limit generalizability (Close et al., 2020; Zeifman et al., 2020).”
From Prospective examination of the therapeutic role of psychological flexibility and cognitive reappraisal in the ceremonial use of ayahuasca (2022) · cites this paper as Zeifman et al., 2020
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“In particular, across three prospective samples, psychological flexibility showed signs of increasing and covarying over time with clinical outcomes including depression and suicidality (Close et al., 2020; Zeifman et al., 2020).”
From Prospective examination of the therapeutic role of psychological flexibility and cognitive reappraisal in the ceremonial use of ayahuasca (2022) · cites this paper as Zeifman et al., 2020
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“It has been proposed that they exert their effects through the stimulation of psychological flexibility processes that decrease emotional avoidance and increase approach-oriented emotional coping (Davis et al., 2020; Kashdan et al., 2020; Zeifman et al., 2020)”
From Prospective examination of the therapeutic role of psychological flexibility and cognitive reappraisal in the ceremonial use of ayahuasca (2022) · cites this paper as Zeifman et al., 2020
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“A few recent studies, including three prospective studies, have suggested that psychological flexibility is a key component in psychedelic-induced outcomes (Close et al., 2020; Davis et al., 2020; Zeifman et al., 2020).”
From Prospective examination of the therapeutic role of psychological flexibility and cognitive reappraisal in the ceremonial use of ayahuasca (2022) · cites this paper as Zeifman et al., 2020
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“Reductions in experiential avoidance were significantly associated with decreases in depression and suicidality scores [55].”
From The psychological processes of classic psychedelics in the treatment of depression: a systematic review protocol (2022) · cites this paper as [55]
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“Through prospective surveys, Zeifman and colleagues [55] found experiential avoidance (the attempt to avoid or ignore negative or unwanted emotions or cognitions [56];) to be significantly reduced at 2 and 4 weeks after psychedelic use.”
From The psychological processes of classic psychedelics in the treatment of depression: a systematic review protocol (2022) · cites this paper as [55]
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“…and Soar, 2020; Smigielski et al., 2019), increased cognitive flexibility (Murphy-Beiner and Soar, 2020) and reduced experiential avoidance (Zeifman et al., 2020) have been proposed, as well as increased acceptance and processing of traumatic autobiographical memories (Sloshower et al.,…”
Combining Psychedelic and Mindfulness Interventions: Synergies to Inform Clinical Practice
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BackgroundResultThe Psychedelic Future of Post-Traumatic Stress Disorder Treatment
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“Such traits have been demonstrated to change following a meaningful psychedelic experience where the experience of intense emotional states is an important part of the therapeutic process (25, 41, 50, 51).”
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“Thus, although the risk of adverse psychological responses did appear to be appreciably elevated in those with self-reported histories of PD in the present study, this does not also imply that they cannot stand to benefit from psychedelic therapy (Müller et al., 2020; Zeifman et al., 2020).”
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“Furthermore, following classic psychedelic use, increases in psychological flexibility have been found to be associated with improvements in mental health, including depressive symptoms 22,36 , anxious/depressive symptoms 21 , positive and negative affect 37 , and grief 38 .”
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“Observational and experimental studies in healthy individuals (Smigielski et al., 2019; Soler et al., 2016, 2018) as well as online surveys (Davis et al., 2020a, 2021; Zeifman et al., 2020) suggest that the acceptance-promoting effects of psychedelics are not restricted to their clinical uses.”
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Psilocybin for Trauma-Related Disorders
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Ledwos, N., Rodas, J. D., Husain, M. I., Feusner, J. D., & Castle, D. J. (2022) · Journal of Psychopharmacology · doi:10.1177/02698811221140009 · Cited by 28
“Classic psychedelics may be able to disrupt rigid thought patterns biochemically, through 5-HT binding, and psychologically through spiritual and mystical experiences and/or the confrontation of challenging emotions (Murphy-Beiner and Soar, 2020; Roseman et al., 2019; Zeifman et al., 2020).”
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“…through which classic psychedelics might have effects on final outcomes such as depression and anxiety (Davis et al. 2020; Roseman et al. 2018; Zeifman et al. 2020), well-being (Roseman et al. 2019), positive mood (Forstmann et al. 2020), narcissism (van Mulukom et al. 2020), or partner…”
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Rabeyron, T. (2021) · The International Journal of Psychoanalysis · doi:10.1080/00207578.2021.1932514 · Cited by 23
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“Early results suggest psychedelics may effectively reduce experiential avoidance, depression severity, and SI.(86) Further research should explore mechanisms of this intervention technique, as well as expand upon broader implications for SI treatment.”
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BackgroundPsilocybin as a Novel Pharmacotherapy for Treatment-Refractory Anorexia Nervosa
Rodan, S.-C., Aouad, P., McGregor, I. S., & Maguire, S. (2021) · OBM Neurobiology · doi:10.21926/obm.neurobiol.2102102 · Cited by 12
“(2020) found that individuals with mild to very severe depression had significant reductions in suicidal ideation 4 weeks following psilocybin [36].”
BackgroundInfluentialHealy, C. J., Frazier, A., Kirsch, S., Sanford, A., Garcia‐Romeu, A., Todman, M., Varon, J. P., & D'Andrea, W. M. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111361 · Cited by 9
“…or other emotional memories (Roseman et al., 2019; Zeifman et al., 2023; Sarris et al., 2021; Perkins et al., 2021; Feduccia and Mithoefer, 2018; Healy, 2021; Davis et al., 2021; Agin-Liebes et al., 2022; Weiss et al., 2021b; Davis et al., 2020b; Gonz ´ alez et al., 2020; Zeifman et al., 2020).”
Psychedelic medicine: mechanisms, evidence, and translation to practice
Jacobs, E., Zahid, Z., Hinkle, J. T., Nayak, S. M., & Yaden, D. B. (2026) · BMJ · doi:10.1136/bmj-2024-081723 · Cited by 9
“58 59 REBUS model: computational perspective The REBUS (relaxed beliefs under psychedelics) model provides a computational framework for understanding psychedelic therapeutic effects.”
Bouso, J. C., Révész, D., Oña, G., Rossi, G. N., Rocha, J. M., SANTOS, R. G. D., Hallak, J. E. C., & Alcázar‐Córcoles, M. Á. (2023) · Scientific Reports · doi:10.1038/s41598-023-41199-x · Cited by 9
Zhang, Y., Yang, L., Zhang, Q., Li, C., Mao, F., & Zhuo, C. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03410-7 · Cited by 9
“Future studies, including clinical trials, are essential to con fi rm the mechanisms and therapeutic potential of psilocybin in suicide prevention.”
Psychedelics and psychological strengths
Brasher, T. J., Rosen, D., & Spinella, M. (2023) · International Journal of Wellbeing · doi:10.5502/ijw.v13i1.2325 · Cited by 10
A suicide attempt following psilocybin ingestion in a patient with no prior psychiatric history
Kramer, E. N., Reddy, K., & Shapiro, B. B. (2023) · Psychiatry Research Case Reports · doi:10.1016/j.psycr.2023.100118 · Cited by 8
Psychedelics and Suicide-Related Outcomes: A Systematic Review
Meshkat, S., Malik, T., Zeifman, R. J., Swainson, J., Zhang, Y., Burback, L., Winkler, O., Greenshaw, A. J., Reichelt, A. C., Vermetten, E. H. G. J. M., et al. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14051416 · Cited by 7
Self-citationRoseby, W., Kettner, H., Roseman, L., Spriggs, M. J., Lyons, T., Peill, J., Giribaldi, B., Erritzøe, D., Nutt, D. J., & Carhart-Harris, R. L. (2025) · Frontiers in Psychology · doi:10.3389/fpsyg.2025.1580663 · Cited by 8
Self-citationWahba, M., Hayes, C., Kletter, M., & McAllister-Williams, H. (2024) · BJPsych Open · doi:10.1192/bjo.2024.768 · Cited by 7
“26 The lack of immediate response, however, raises the question of whether other elements are necessary, e.g. emotional breakthrough, which was correlated with improvement in this trial.”
Irrmischer, M., Puxty, D. J., Yıldırım, B. O., Deijen, J. B., & Engelbregt, H. (2025) · Psychopharmacology · doi:10.1007/s00213-024-06733-3 · Cited by 7
“The release of (deep held, or sometimes hard to access) emotions was a major contributor to the changes in the form of reduced experience avoidance (Zeifman et al. 2020).”
Jones, J. L. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1565852 · Cited by 6
Gold, N. D., Mallard, A. J., Hermann, J. C., Zeifman, R. J., Pagni, B. A., Bogenschutz, M. P., & Ross, S. (2023) · Journal of Palliative Medicine · doi:10.1089/jpm.2022.0604 · Cited by 6
“, 39, 64, 65 In addition to supporting those with life-threatening illness, evidence also suggests that both the serotonergic psychedel-ics 39,68,69 and ketamine 70–72 may reduce suicidality across various populations and settings, including those with major and treatment-resistant depression.”
Self-citationVilca-Melendez, S., Uthaug, M. V., & Griffin, J. L. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.742856 · Cited by 5
Rodan, S.-C., Meez, N., Lloyd-Hurwitz, S., Bedoya‐Pérez, M. A., Suraev, A. S., Sommer, N., Greenstien, K., Maguire, S., & McGregor, I. S. (2025) · Journal of Eating Disorders · doi:10.1186/s40337-025-01328-5 · Cited by 4
“The current literature is mixed on the effect of psychedelics on suicidality, for the most part predominantly indicating that psychedelics may be protective against suicide [97, 98].”
Bevione, F., Lacidogna, M. C., Lavalle, R., Daga, G. A., & Preti, A. (2025) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-025-01771-y · Cited by 4
Exploring serotonergic psychedelics as a treatment for personality disorders
Carrithers, B. M., Roberts, D. E., Weiss, B., King, J. D., Carhart-Harris, R. L., Gordon, A. R., Pagni, B. A., Moreau, M., Ross, S., & Zeifman, R. J. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110413 · Cited by 4
Self-citationExperiential Avoidance, Pain, and Suicide Risk in a National Sample of Gulf War Veterans
Grove, J. L., Young, J. R., Chen, Z., Blakey, S. M., Beckham, J. C., Calhoun, P. S., Dedert, E. A., Goldston, D. B., Pugh, M. J., & Kimbrel, N. A. (2022) · Archives of Suicide Research · doi:10.1080/13811118.2022.2160681 · Cited by 5
“Moreover, reduction of EA in treatment is associated with reductions in depression and suicidal ideation (Ellis & Rufino, 2016; Zeifman et al., 2020).”
BackgroundPsychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice
Hu, X., Gorman, I., & Nielson, E. M. (2024) · Current topics in behavioral neurosciences · doi:10.1007/7854_2024_529 · Cited by 4
(Dis)connectedness, suicidality and group psychedelic therapies.Preprint
McAlpine, R. G., & Blackburne, G. (2024) · doi:10.31234/osf.io/haeqs · Cited by 3
Gordon, A. R., Carrithers, B. M., Pagni, B. A., Kettner, H., Marrocu, A., Nayak, S. M., Weiss, B. J., Carhart-Harris, R. L., Roberts, D. E., & Zeifman, R. J. (2024) · Research Square · doi:10.21203/rs.3.rs-4203641/v1 · Cited by 3
Self-citationAcupuncture for treating adolescent depression: Study protocol for a randomized controlled trial
Jiang, J., Liang, F., Xu, Z., Jin, W., Ji, B., & Li, L. (2023) · Medicine in Novel Technology and Devices · doi:10.1016/j.medntd.2023.100273 · Cited by 2
Zeifman, R. J., Hernandez, K. M., Song, J., Liebman, R. E., Ip, J., Burdo, J., Johnson, C. M., Stirman, S. W., & Monson, C. M. (2024) · European Journal of Psychotraumatology · doi:10.1080/20008066.2024.2434315 · Cited by 2
Self-citationDahka, S. M., Ganjari, M. G., Sarparast, M., Kenarsari, H. E., Hassanpour, A., Morteza-Nejad, S. H. R. F., & Delpasand, K. (2021) · Journal of Guilan University of Medical Sciences · doi:10.32598/jgums.30.2.1700.1 · Cited by 2
“[27] Zeifman RJ, Wagner AC, Watts R, Kettner H, Mertens LJ, Carhart-Harris RL.”
Strika-Bruneau, L., Fauvel, B., Dupuis, D., & Benyamina, A. (2023) · L Évolution Psychiatrique · doi:10.1016/j.evopsy.2023.01.003 · Cited by 1
Saifullah, K., Zaffar, W., Qureshi, H. S., Ullah, R., & Laraib (2025) · Journal of Political Stability Archive · doi:10.63468/jpsa.3.3.23 · Cited by 1
Mehmood, M., Bremler, R., Spriggs, M. J., Kettner, H., Roseman, L., Damgaard, L., Carhart-Harris, R. L., Erritzøe, D., & Zeifman, R. J. (2025) · Psychedelic Medicine · doi:10.1177/28314425251392251 · Cited by 2
“36 It is possible that ceremonial psyche-delic use may help to improve mental health outcomes among those with ACEs.”
Self-citationRao, M., Dai, Q., Li, F., & Ye, B. (2026) · Journal of Adolescence · doi:10.1002/jad.70120 · Cited by 2
Erdmann, L., Breitenstein, B., Badanova, M., Telschow, L., Havenith, M. N., & Dziobek, I. (2026) · Frontiers in Psychology · doi:10.3389/fpsyg.2026.1777341 · Cited by 1
“…EA does not mediate the relationship between ASCs and mental well-being, contrasting with psy-chedelic research in which increases in psychological flexibility or reductions in EA predict improvements in mental well-being, depression, and anxiety (e.g., Davis et al., 2020; Zeifman et al., 2020).”
Rabeyron, T. (2023) · In Analysis · doi:10.1016/j.inan.2023.100331 · Cited by 1
Baldour-Wang, M., Kotov, R., Gámez, W., Chmielewski, M. S., Ruggero, C. J., & Eaton, N. R. (2024) · Journal of Psychopathology and Behavioral Assessment · doi:10.1007/s10862-024-10159-8 · Cited by 2
“Further, experiential avoidance was reported to be associated with risk symptoms such as suicidality and NSSI (Chapman et al., 2005; Nielsen et al., 2016; Zeifman et al., 2020).”
Psychedelic-assisted grief therapy: a mixed-method case study
Sabucedo, P., Evans, C., Nicolson, D., Farré, M., & González, D. (2024) · Mortality · doi:10.1080/13576275.2024.2434456 · Cited by 2
“…research into psychological processes of change tied to these modalities, such as psychological flexibility (Davis et al., 2020; Luoma et al., 2019; Zeifman et al., 2020, 2023) and cognitive change (Wolff et al., 2020), that could potentially be applied both to the psychedelic experience and the…”
Imany, M., Mohammadkhani, S., Atashipour, H. S., & Pourhosseini, P. (2025) · BMC Psychology · doi:10.1186/s40359-025-03364-x · Cited by 1
Journey To The Centre Of The Mind: Psychedelic Treatment of Mental Health in Aotearoa
Lutyens, D. (2023) · Open Access Victoria University of Wellington | Te Herenga Waka (Figshare) · doi:10.26686/wgtn.21904854 · Cited by 2
Phenylketonuria with mental retardation and valproate-induced hyperammonemia
Sterpu, D. (2020) · Romanian Journal of Psychiatry & Psychotherapy · doi:10.37897/rjpp.2020.4.5
“The hyper-frontal metabolic pattern that results from psilocybin treatment and 5-HT2A recep-ABSTRACT tor activation is considered to be comparable to metabolic patterns seen during acute psychotic episodes in chronic schizophrenics [10].”
Breeksema, J. J. (2024) · University of Groningen research database (University of Groningen / Centre for Information Technology) · doi:10.33612/diss.912040905
Zeifman, R. J. (2024) · doi:10.32920/26052859.v1 · Cited by 1
Self-citationAlshayea, A. K. (2024) · Journal of Contextual Behavioral Science · doi:10.1016/j.jcbs.2024.100807
Integrating the Gestalt Model of Self With Psychedelic‐Assisted Psychotherapy
Fox, T. R. (2025) · The Journal of Humanistic Counseling · doi:10.1002/johc.70026
Gordon, A. R., Carrithers, B. M., Pagni, B. A., Kettner, H., MRes, A. M., Nayak, S. M., Weiss, B., Carhart-Harris, R. L., Roberts, D. E., Erritzøe, D., et al. (2025) · Psychedelic Medicine · doi:10.1177/28314425251382930
Self-citationPredictors of the Effectiveness of Psychedelics in Treating Depression—A Scoping Review
Chmiel, J., & Rybakowski, F. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27052202 · Cited by 1
“…(Study 1 d = 0.9–1.5; Study 2 d = 0.7–0.9) alongside sharp QIDS reductions (Study 1 d ≈ 1.4–2.6; Study 2 d = 1.0–2.1), with decreases in avoidance correlating with decreases in depression ( ρ = 0.32–0.52) and suicidal ideation ( ρ = 0.15–0.46); no rebound occurred between 2 and 4 weeks [58].”
InfluentialCarhart-Harris, R. L., Zeifman, R. J., Pasquini, L., Nandi, B., Rohani-Shukla, C., Suseelan, S., Mediano, P. A. M., Rosas, F. C. W., Timmermann, C., Kettner, H., et al. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1875339
“In such scenarios, PCP becomes centrally relevant, as does the notion of maladaptive learning, including maladaptive avoidance (Dymond, 2019; Deane et al., 2024; Zeifman et al., 2020), and learned helplessness (Maier and Seligman, 2016).”
Self-citationEffectiveness of Acceptance and Commitment Therapy in Patients With Depression
Sarwar, I., Raza, M. A., & Majeed, A. (2026) · Counselling and Psychotherapy Research · doi:10.1002/capr.70157
Modlin, N. L., Elek, Z., Maggio, C., Agrawal, M., Lepow, L., Rucker, J., Stubley, J., & Guss, J. R. (2026) · Psychodynamic Psychiatry · doi:10.1521/pdps.2026.54.2.338
Clark, T. A. (2025) · The Therapeutic Conversation · doi:10.66330/100520252
Psychedelic therapy at the end of life: unexplored alternative to assisted suicide in the UK
Zinchenko, R. (2026) · The British Journal of Psychiatry · doi:10.1192/bjp.2026.10729
Metadata
- Authors
- Zeifman, R. J., Wagner, A. C., Watts, R., Kettner, H., Mertens, L. J., & Carhart-Harris, R. L.
- Affiliations
- Imperial College London (GB)
- Heidelberg University (DE)
- Corresponding author
- Zeifman, Richard J.
- Venue
- Frontiers in Psychiatry
- Publisher
- Frontiers Media SA
- Published
- 2020-08-07
- Volume
- 11
- Pages
- 782-782
- ISSN
- 1664-0640 (ISSN-L)
- PMC
- PMC7438781
- OpenAlex
- W3047886920
- Cited by
- 106
- References
- 98
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 17 · 2023: 17 · 2022: 18 · 2021: 20 · 2020: 4
- FWCI
- 5.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- Canadian Institutes of Health Research
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Social Sciences › Psychology › Clinical Psychology › Mindfulness and Compassion Interventions
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- psychedelics, experiential avoidance, depression severity, suicidal ideation, acceptance and commitment therapy, transdiagnostic mechanisms, psychedelic therapy, treatment outcomes
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