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.

  • Correspondence
  • Published:

Reply to Gattuso et al.: “Comments on ‘Striking long-term beneficial effects of single-dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming’ by Brownstien et al. (2024)”

Molecular Psychiatry volume 30, pages 6075–6076 (2025) Cite this article

Subjects

We thank Gattuso and colleagues [1] for their kind comments about our paper [2]. However, we wish to note several inaccuracies in statements made about our research and respond to some of their observations:

  1. 1)

    The contention that we did not take sex into account in our analyses is incorrect. On the contrary, we compared self-grooming and head-body twitches in male and female SAPAP3-KO mice as the first step in our data analysis. We then analyzed the effect of psilocybin treatment on these variables in males and females separately. The results are shown in Supplementary Tables 1 and 2. There were no differences between males and females at baseline, nor in the effect of psilocybin treatment. Therefore, males and females were combined for further analyses. Sex was also taken into account in our analysis of the behavioral tests.

  2. 2)

    Our study was designed and executed as would a clinical trial in patients. In patients with OCD and other disorders, clinical trials do not include an arm in which individuals who do not suffer from the disorder receive the treatment. Therefore, the non-inclusion of such an arm in our study cannot be seen as a shortcoming. Furthermore, compulsive behaviors are, frequently, normal behaviors carried out in an exaggerated way. This is true of the excessive self-grooming of SAPAP3-KO mice. It is of interest that in their own paper on the effect of psilocybin on self-grooming, Gattusso et al. [3] found evidence for a reduction of self-grooming in wild type mice administered psilocybin. However, the absence of a wild type group treated with psilocybin does not detract from the validity of our findings. In the same way, finding that fluoxetine reduces the frequency of hand-washing in individuals without OCD does not in any way detract from a finding that fluoxetine reduces compulsive handwashing.

  3. 3)

    Gattuso et al. [1] note that excessive self-grooming increased substantially over the 42 days of our study in SAPAP3-KO mice. A progressive increase in self-grooming after the age of 6 months is by no means idiosyncratic as Gattuso et al. [3] appear to imply and has been noted by other authors. Thus, Glorie et al. [4] examined SAPAP3-KO mice from 6–9 months and reported an “increase in grooming duration with ageing.” Similarly, Manning et al. [5] reported a progressive increase in self-grooming up to the age of 8 months.

  4. 4)

    Comments made by Gattuso et al. [1] regarding our study, rest significantly on the findings of their own study on the effect of psilocybin on self-grooming in SAPAP3-KO mice [3]. We are gratified that this work replicated our findings reported in Brownstien et al. [2]. However, we note that in their study Gattuso et al. [3] performed a very limited assessment of self-grooming, quantifying the behavior for only 10 min following 10-min acclimatization. In our study [2] we scored self-grooming over a full hour in each mouse. To determine the validity of a 10-min assessment of self-grooming, we evaluated the correlation between self-grooming scores in the second 10 min of a 1-h assessment and self-grooming scores over the full hour in 60 mice. The results show a positive correlation (r = 0.53, p < 0.0001); however, this falls short of an r of 0.80 which would provide confidence as to the validity of the shorter assessment.

  5. 5)

    We fully agree with Gattuso et al. [1] that mechanistic assessments as to the receptors involved in mediating the remarkable effects of psilocybin on excessive self-grooming in SAPAP3-KO mice are highly indicated. Such assessments were not included in their own paper either [3]. In our case, these studies are currently in progress in our laboratory.

The contention that we did not take sex into account in our analyses is incorrect. On the contrary, we compared self-grooming and head-body twitches in male and female SAPAP3-KO mice as the first step in our data analysis. We then analyzed the effect of psilocybin treatment on these variables in males and females separately. The results are shown in Supplementary Tables 1 and 2. There were no differences between males and females at baseline, nor in the effect of psilocybin treatment. Therefore, males and females were combined for further analyses. Sex was also taken into account in our analysis of the behavioral tests.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

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

References

  1. Gattuso JJ, Wilson C, Hannan AJ, Renoir T. Letter to the editor: comments on ‘Striking long-term beneficial effects of single-dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming’ by Brownstien et al. (2024). Mol Psychiatry. 2025;30:3829–32.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Brownstien M, Lazar M, Botvinnik A, Shevakh C, Blakolmer K, Lerer L, et al. Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming. Mol Psychiatry. 2025;30:1172–83.

    Article  PubMed  CAS  Google Scholar 

  3. Gattuso JJ, Wilson C, Hannan AJ, Renoir T. Psilocybin reduces grooming in the SAPAP3 knockout mouse model of compulsive behaviour. Neuropharmacology. 2025;262:110202.

    Article  PubMed  CAS  Google Scholar 

  4. Glorie D, Verhaeghe J, Miranda A, De Lombaerde S, Stroobants S, Staelens S. Sapap3 deletion causes dynamic synaptic density abnormalities: a longitudinal [11C]UCB-J PET study in a model of obsessive–compulsive disorder-like behaviour. EJNMMI Res. 2020;10:140.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Manning EE, Wang AY, Saikali LM, Winner AS, Ahmari SE. Disruption of prepulse inhibition is associated with compulsive behavior severity and nucleus accumbens dopamine receptor changes in Sapap3 knockout mice. Sci Rep. 2021;11:9442.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Funding

This work was supported in part by Parow Entheobiosciences (ParowBio) and Negev Labs.

Author information

Authors and Affiliations

  1. Hadassah BrainLabs Center for Psychedelic Research, Hebrew University, Jerusalem, Israel

    Michal Brownstien, Michal Lazar, Alexander Botvinnik, Ilana Pogodin, Tzuri Lifschytz & Bernard Lerer

Authors
  1. Michal Brownstien
    View author publications

    Search author on:PubMed Google Scholar

  2. Michal Lazar
    View author publications

    Search author on:PubMed Google Scholar

  3. Alexander Botvinnik
    View author publications

    Search author on:PubMed Google Scholar

  4. Ilana Pogodin
    View author publications

    Search author on:PubMed Google Scholar

  5. Tzuri Lifschytz
    View author publications

    Search author on:PubMed Google Scholar

  6. Bernard Lerer
    View author publications

    Search author on:PubMed Google Scholar

Contributions

MB - Revising the manuscript critically for important intellectual content; Reviewing and approving the version of the manuscript to be published. ML - Reviewing and approving the version of the manuscript to be published. AB - Revising the manuscript critically for important intellectual content; Reviewing and approving the version of the manuscript to be published. IP - Revising the manuscript critically for important intellectual content; Reviewing and approving the version of the manuscript to be published. TL - Reviewing and approving the version of the manuscript to be published. BL - Drafting the article and revising it critically for important intellectual content: Final approval of the version to be published.

Corresponding author

Correspondence to Bernard Lerer.

Ethics declarations

Competing interests

The Hadassah BrainLabs Center for Psychedelic Research is supported in part by Negev Labs.

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

Brownstien, M., Lazar, M., Botvinnik, A. et al. Reply to Gattuso et al.: “Comments on ‘Striking long-term beneficial effects of single-dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming’ by Brownstien et al. (2024)”. Mol Psychiatry 30, 6075–6076 (2025). https://doi.org/10.1038/s41380-025-03173-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41380-025-03173-z

Search

Advanced search

Quick links