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Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety
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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%; M age=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.
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“First, two of the relevant studies used cross-sectional designs that inherently preclude analysis of process-level psychedelic changes and may be impacted by retrospective bias (Davis et al., 2020; Thiessen et al., 2018).”
From Prospective examination of the therapeutic role of psychological flexibility and cognitive reappraisal in the ceremonial use of ayahuasca (2022) · cites this paper as Davis et al., 2020
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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 Davis et al., 2020
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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 Davis et al., 2020
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Assessing the subjective effects of psychedelics is essential since much research has indicated an association between the characteristic psychedelic experience and a positive effect on the symptomatology of several psychiatric illnesses.”
From Assessment of the acute subjective psychedelic experience: A review of patient-reported outcome measures in clinical research on classical psychedelics (2024) · cites this paper as Davis et al., 2020
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Most of this research has been carried out with the Revised Mystical Experience Questionnaire 30 (MEQ30), where a high score correlates with and has been suggested as a predictor of long-term positive therapeutic outcomes in various clinical and naturalistic studies of psychedelics.”
From Assessment of the acute subjective psychedelic experience: A review of patient-reported outcome measures in clinical research on classical psychedelics (2024) · cites this paper as Davis et al., 2020
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“Two retrospective survey studies suggest that increased psychological flexibility might mediate the therapeutic effects of the quality of the psychedelic experience on depression and anxiety on the one hand [59] and of psychedelic therapy on alcohol consumption and posttraumatic stress symptoms on the other hand [60].”
From Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial (2024) · cites this paper as [59]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Music and a supportive environment during PAP facilitate this process, increasing psychological and cognitive flexibility, which is the main mediator of psilocybin benefits in mood disorders. 53”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [53]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Current research points toward specific traits of the psychedelic experience as relevant mediators of the therapeutic outcomes of PAP, such as acceptance-related experiences, the presence of mystical experiences, or the reappraisal of negative emotion (52–55).”
From Ayahuasca-assisted meaning reconstruction therapy for grief: a non-randomized clinical trial protocol (2025) · cites this paper as [54]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Other prospective surveys have found psychological flexibility (a set of processes which allow one to adapt to various demands, maintain balance across various domains and be open to and committed to behaviours congruent to their values) to be negatively correlated with depression scores post psychedelic use [58, 59].”
From The psychological processes of classic psychedelics in the treatment of depression: a systematic review protocol (2022) · cites this paper as [59]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“previous studies that have shown PF can predict the levels of psychological health problems, such as depressive symptoms, anxiety as well as sleep disturbance”
From The Psychological Flexibility in Epilepsy Questionnaire (PFEQ): Psychometric properties of the Persian version (2022) · cites this paper as [50]
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“PF is related to the quality of life outcomes [49–51]”
From The Psychological Flexibility in Epilepsy Questionnaire (PFEQ): Psychometric properties of the Persian version (2022) · cites this paper as [50]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In general, the results in the current study are in line with previous studies that have shown PF can predict the levels of psychological health problems, such as depressive symptoms, anxiety as well as sleep disturbance and PF is related to the quality of life outcomes [49–51]”
From The Psychological Flexibility in Epilepsy Questionnaire (PFEQ): Psychometric properties of the Persian version (2022) · cites this paper as [50]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In a recent cross-sectional study, increases in psychological flexibility were found to statistically mediate the relation between acute insight, mystical experience, and decreases in depression and anxiety (Davis 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 Davis et al., 2020
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“Consistent with prior studies (Griffiths et al., 2016; Ross et al., 2016; Davis et al, 2019), in the present study mystical experiences were associated with decreases in depression and anxiety.”
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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
The relationship between test anxiety, rumination, and psychological flexibility
Doğan, U. (2023) · Current Psychology · doi:10.1007/s12144-023-04411-9 · Cited by 12
Factors influencing employee’s quality of life during COVID-19 pandemic
Mulyani, I., Rahardjo, W., Andriani, I., & Qomariyah, N. U. (2020) · Indigenous Jurnal Ilmiah Psikologi · doi:10.23917/indigenous.v5i2.11086 · Cited by 9
Akcan, G., Bakkal, B. H., & Elmas, Ö. (2026) · OMEGA - Journal of Death and Dying · doi:10.1177/00302228241292381 · Cited by 9
Hu, S., Lin, C., Wang, H., & Wang, X. (2025) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.5c00094 · Cited by 8
Cyberdelics: Virtual reality hallucinations modulate cognitive-affective processes
Brizzi, G., Pupillo, C., Rastelli, C., Greco, A., Bernardelli, L., Natale, A. F. D., Pizzoli, S. F. M., Sajno, E., Frisone, F., Lernia, D. D., et al. (2025) · Dialogues in Clinical Neuroscience · doi:10.1080/19585969.2025.2499459 · Cited by 11
Klučková, T., Nikolič, M., Tylš, F., Viktorin, V., Vejmola, Č., Viktorinová, M., Bravermanová, A., Androvičová, R., Andrashko, V., Korčák, J., et al. (2025) · Pharmacological Reports · doi:10.1007/s43440-025-00742-5 · Cited by 10
Psilocybin with psychotherapeutic support for treatment-resistant depression: a pilot clinical trial
Meikle, S. E., Carter, O. L., Liknaitzky, P., Johansen, L., Iyer, R., Strauss, N. H. M., Williams, M. L., Castle, D. J., & Rossell, S. L. (2025) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253251377187 · Cited by 9
EMBARK Psychedelic Therapy for Depression
Brennan, B., & Belser, A. (2024) · doi:10.1093/9780197762622.001.0001 · Cited by 8
Hilal, F. F., Jeanblanc, J., Deschamps, C., Naassïla, M., Pierrefiche, O., & Hamida, S. B. (2024) · Journal of Neural Transmission · doi:10.1007/s00702-024-02757-3 · Cited by 8
Grob, C. S., Bossis, A. P., & Griffiths, R. R. (2022) · Springer eBooks · doi:10.1007/978-3-030-85702-8_5 · Cited by 10
Self-citationArnaud, K. O. S., & Sharpe, D. (2023) · Journal of Psychedelic Studies · doi:10.1556/2054.2023.00263 · Cited by 10
de Oliveira, D. S., Fontenele, R., Weleff, J., Sofuoglu, M., & Aquino, J. P. D. (2023) · International Review of Psychiatry · doi:10.1080/09540261.2023.2229430 · Cited by 8
Seragnoli, F., Picard, F., Thorens, G., Buchard, A., Geyer, M., Abatista, A., Ponomarenko, P., Petignat, C., Riccardi, M., Bisson, M. D., et al. (2025) · Cognitive Therapy and Research · doi:10.1007/s10608-025-10588-z · Cited by 8
Aesthetic quality of psychedelic experience is linked to insight and psychological outcomes
Hooper, J., Gyongyosi, E., Hutchison, K. E., & Mueller, R. L. (2025) · Frontiers in Psychology · doi:10.3389/fpsyg.2025.1533055 · Cited by 7
Psychedelics, With a Focus on Psilocybin: Issues for the Clinician
Garakani, A., Alexander, J. L., Sumner, C. R., Pine, J. H., Gross, L. S., Raison, C. L., Aaronson, S. T., & Baron, D. A. (2023) · Journal of Psychiatric Practice · doi:10.1097/pra.0000000000000729 · Cited by 7
Lancelotta, R., DellaCrosse, M. A., Quinn, D., Saniyah, S., Saniyah, M., Gukasyan, N., Narayan, S. K., Nikolaidis, A., Sevelius, J. M., & Davis, A. K. (2025) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2025.2520224 · Cited by 7
Self-citationRadyani, A. M., Indra, G. H., & Oriza, I. I. D. (2022) · KnE Social Sciences · doi:10.18502/kss.v7i1.10210 · Cited by 7
5-MeO-DALT: the freebase of N,N-diallyl-5-methoxytryptamine
Chadeayne, A. R., Pham, D. N. K., Golen, J. A., & Manke, D. R. (2020) · IUCrData · doi:10.1107/s2414314620004988 · Cited by 7
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
Roméo, B., Kervadec, E., Fauvel, B., Strika-Bruneau, L., Amirouche, A., Verroust, V., Piolino, P., & Benyamina, A. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111300 · Cited by 7
Gaughan, S. J., Wootton, A. R., Krantz, D., Davis, A. K., James, J. E., Rinaldi-Rose, R., Lancelotta, R., & Sevelius, J. M. (2025) · International Journal of Transgender Health · doi:10.1080/26895269.2025.2478112 · Cited by 7
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Psychedelika in der Psychiatrie – Entwicklungen und die Stellung in Deutschland
Herwig, U., Mertens, L. J., Rosal, S. P., Koller, G., Jungaberle, A., Borgwardt, S., & Gründer, G. (2023) · Fortschritte der Neurologie · Psychiatrie · doi:10.1055/a-1981-3152 · Cited by 7
Zheng, Y., Wang, X., & Xia, C. (2023) · World Journal of Psychiatry · doi:10.5498/wjp.v13.i10.753 · Cited by 6
Roméo, B., Kervadec, E., Fauvel, B., Strika-Bruneau, L., Amirouche, A., Verroust, V., Piolino, P., & Benyamina, A. (2024) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2024.2375720 · Cited by 6
New Insights Into the Clinical and Nonclinical Effects of Psychedelic Substances
Forstmann, M., & Sagioglou, C. (2021) · European Psychologist · doi:10.1027/1016-9040/a000447 · Cited by 7
Yavorsky, C., Ballard, E. D., Opler, M. G. A., Sedway, J. A., Targum, S. D., & Lenderking, W. R. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1135828 · Cited by 7
Luoma, J. B., Davis, A. K., Watts, R., & McCracken, L. M. (2020) · Journal of Contextual Behavioral Science · doi:10.1016/j.jcbs.2020.01.004 · Cited by 6
Self-citationSabucedo, P., Andión, O., Neimeyer, R. A., Soto-Angona, O., Javkin, J., Haro, J. M., Farré, M., & González, D. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1484736 · Cited by 6
Ontologically Challenging Psychedelic Experiences: Considerations for Managing Associated Distress
Argyri, E. K., & Evans, J. (2025) · Current topics in behavioral neurosciences · doi:10.1007/7854_2025_609 · Cited by 5
Predictors of therapeutic response to psychedelic-assisted therapy: A systematic review
Viljoen, G., Walter, H., Bendau, A., Koslowski, M., & Betzler, F. (2025) · Journal of Psychopharmacology · doi:10.1177/02698811251389581 · Cited by 8
Levin, A. W. (2024) · Journal of Psychopharmacology · doi:10.1177/02698811241303599 · Cited by 5
Kajonius, P., Sjöström, D., & Claesdotter‐Knutsson, E. (2025) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2024.2444892 · Cited by 8
Metadata
- Authors
- Davis, A. K., Barrett, F. S., & Griffiths, R. R.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Davis, Alan K.
- Venue
- Journal of Contextual Behavioral Science
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 15
- Pages
- 39-45
- ISSN
- 2212-1447 (ISSN-L)
- PMC
- PMC7451132
- OpenAlex
- W2987203272
- Cited by
- 375
- References
- 62
- Citations by year
- 2026: 47 · 2025: 61 · 2024: 75 · 2023: 76 · 2022: 58 · 2021: 38 · 2020: 19
- FWCI
- 33.55
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Contextual Behavioral Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Social Sciences › Psychology › Clinical Psychology › Mindfulness and Compassion Interventions
- Social Sciences › Health › Religion, Spirituality, and Psychology
- Keywords
- psychological flexibility, psychedelics, depression, anxiety, mystical experience, insight, mediating effect, psychedelic therapy, acceptance and commitment therapy
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