Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Matters Arising
  • Published:

Caution at psychiatry’s psychedelic frontier

Nature Medicine volume 27, pages 1687–1688 (2021)Cite this article

Subjects

Matters Arising to this article was published on 11 October 2021

The Original Article was published on 10 May 2021

arising from J. M. Mitchell et al. Nature Medicine https://doi.org/10.1038/s41591-021-01336-3 (2021)

At a time when new psychiatric treatments are needed more than ever, a promising line of psychedelic treatment options has emerged, and there is a palpable buzz surrounding them. While there are many unique considerations for this field moving forward, recent clinical trials of psychedelics are forcing psychiatry to carefully contemplate the way it views and weighs blinding and placebo effects. Historically, blinding has been a foundational component that ensures the validity of placebo-controlled clinical trial results. The main purpose of blinding is to avoid introducing bias from study personnel and to ensure equal distribution of placebo effects (i.e., beneficial effects associated with positive expectation and other contextual factors surrounding treatment rather than the treatment itself) across the trial arms. However, what happens when the treatment you are studying makes it challenging (if not impossible) to properly blind participants? Can we interpret trial results in line with the previous frameworks? Or should we simply focus on whether or not patients get better?

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Mitchell, J. M. et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat. Med. https://doi.org/10.1038/s41591-021-01336-3 (2021).

  2. Colloca, L. & Barsky, A. J. Placebo and nocebo effects. N. Engl. J. Med. 382, 554–561 (2020). 6.

    Article  CAS  Google Scholar 

  3. Ashar, Y. K., Chang, L. J. & Wager, T. D. Brain mechanisms of the placebo effect: an affective appraisal account. Annu Rev. Clin. Psychol. 13, 73–98 (2017).

    Article  Google Scholar 

  4. Burke, M. J., Kaptchuk, T. J. & Pascual-Leone, A. Challenges of differential placebo effects in contemporary medicine: the example of brain stimulation. Ann. Neurol. 85, 12–20 (2019).

    Article  Google Scholar 

  5. Feder, A. et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry 71, 681–688 (2014).

    Article  CAS  Google Scholar 

  6. Mithoefer, M. C. et al. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology 236, 2735–2745 (2019).

    Article  CAS  Google Scholar 

  7. Carhart-Harris, R. et al. Trial of psilocybin versus escitalopram for depression. N. Engl. J. Med. 384, 1402–1411 (2021).

    Article  CAS  Google Scholar 

  8. Schulz, K. F., Altman, D. G., Moher, D. & Fergusson, D. CONSORT 2010 changes and testing blindness in RCTs. Lancet 375, 1144–1146 (2010).

    Article  Google Scholar 

  9. Colagiuri, B. & Benedetti, F. Testing for blinding is the only way to determine whether a trial is blind. Br. Med. J. 340, c332 (2010).

    Article  Google Scholar 

  10. Olson, J. A., Suissa-Rocheleau, L., Lifshitz, M., Raz, A. & Veissière, S. P. Tripping on nothing: placebo psychedelics and contextual factors. Psychopharmacology 237, 1371–1382 (2020).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The content of this article is the opinion of the authors. It does not necessarily represent the official views of the University of Toronto or Harvard Medical School (and their affiliated academic health care centers).

Author information

Authors and Affiliations

  1. Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada

    Matthew J. Burke & Daniel M. Blumberger

  2. Division of Neurology, Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada

    Matthew J. Burke

  3. Harquail Centre for Neuromodulation and Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada

    Matthew J. Burke

  4. Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Matthew J. Burke

  5. Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Canada

    Daniel M. Blumberger

Authors
  1. Matthew J. Burke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel M. Blumberger
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M. J. B., concept/design, drafting manuscript; D. M. B., concept/design, critical revision of manuscript.

Corresponding author

Correspondence to Matthew J. Burke.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Burke, M.J., Blumberger, D.M. Caution at psychiatry’s psychedelic frontier. Nat Med 27, 1687–1688 (2021). https://doi.org/10.1038/s41591-021-01524-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41591-021-01524-1

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing