Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

A report of a thematic analysis of all Reddit links and metadata over one year extracted on 07/03/2025 to determine the use of ketamine in self-described therapeutic contexts.

 

The strengths are (1) the study is novel, (2) the Title is a succinct summary of the manuscript content, (3) the Introduction contextualizes the problem, defines terms, and presents the aim, (4) the Materials and Methods are sufficiently descriptive for study replication, (5) the Results pertain to the aim of the study, (6) the Discussion elaborates on research regarding the Results, and includes a limitations paragraph, and (7) the Conclusion correspond to the Results.

 

The weaknesses are (1) some claims lack citations, (2) some of the citations in the Introduction and Discussion are outdated without the support of additional citations to research published in the previous five years, (3) the information on Reddit belongs in the Introduction rather than the Materials and Methods, (4) there is no hypothesis, (5) the Tables are missing a column of the thematic, category, or class count, (6) there is no paragraph on future research directions, and (7) the Informed Consent Statement is missing.

 

Line-by-line suggested edits

Please attend to the following:

13–31 Reduce the length of the Abstract to 200 words.

35 Cite research published since 2022 to support the claim that “Ketamine is a fast-acting general anesthetic”.

40, 51–52, 55, 57–58, 60, 66 Improve the currency of the citations in the Introduction. These line numbers have outdated citations that require support of citations to research published since 2022. Do not delete the current citation—add to it.

44–45 Cite research published since 2022 to support the claim that “The term ketamine is often used vaguely in both clinical and public discourse”.

95 Include a hypothesis after this line.

98 Include a citation to seminal research and research published since 2022 to demonstrate the continued relevance in the field of employing qualitative content analysis.

115 Clarify when “the last year” began and ended.

124 Delete this heading.

125–133 Move this paragraph after line 84.

133–134 Increase the size of Figure 1 to fill the space from left margin to right margin. Its current size makes some of the text illegible.

171–173 Delete this text. It is instructions from the template.

185–186 Add a right-most column to Table 1 to be titled “Thematic Count” and list the total counts for the themes. Additionally, although the Theme column is justified vertically to the top, the other columns are vertically justified to the middle. All columns should correspond in their vertical justification. All the following Tables should be consistent regarding whether their columns are top- or middle-justified.

194–195 Add a right-most column to Table 2 to be titled “Thematic Count” and list the total counts for the themes.

204–205 Add a right-most column to Table 3 to be titled “Thematic Count” and list the total counts for the themes.

215–216 Add a right-most column to Table 4 to be titled “Category Count” and list the total counts for the themes.

241–242 Add a right-most column to be titled “Class Count” and list the total counts for the themes.

278–279, 291, 293, 300, 307, 319, 343, and 208 Improve the currency of the citations in the Discussion. These line numbers have outdated citations that require support of citations to research published since 2022. Do not delete the current citation—add to it.

333 Change “observation” to “observations”.

374 Add a paragraph on future research directions.

376 After adding the hypothesis to the Introduction, please refer to it in the opening line of the Conclusions and state the extent of its corroboration by the Results.

403 Add an Informed Consent Statement.

Author Response

Please see attached

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The current study analyzed 500 Reddit threads from r/TherapeuticKetamine to examine self-reported ketamine use for therapeutic purposes. The researchers found that mood-related concerns (particularly depression) were the primary motivation for use, with most users reporting positive emotional effects. However, 70% of users reported doses exceeding 149mg (far above clinical standards), intravenous administration was common despite lack of medical supervision, and polydrug use with other psychoactive substances was frequently described. The study is an original one and needs revisions from my view of point.

1. The title of the study is misleading as self-selected Reddit users could not be representative of "real-world" clinical populations. They are mostly unregulated/self-directed users. Title should be changed accordingly.
2. Authors should add some information about ketamine misuse potential, complications and addiction liability in the introduction as there are such reports in results.
3. While claiming that Reddit "reduces barriers to disclosure", authors should also consider that such platforms enable fabrication, exaggeration, and role-playing. Add such perspectives also.
4. It is hard to assume that analyzing r/TherapeuticKetamine captures "therapeutic use" profile of cases. This community likely attracts users seeking validation for non-prescribed use or recreational use. It should be mentioned in intro.
5. Not possible to say that included threads are representative of experiences. Sorting by "Reddit score" selects for popular, agreeable content rather than representative experiences. Included ones could be controversial or sensational content rather than typical experiences or the ones with most clinically relevant. These factors should also be added to limitations.
6. Clarify who were independent coders, what were their coder training, background, or qualifications. Were there any actual inter-rater reliability statistics (Kappa coefficients, percentage agreement).
7. Describe the determination of dose data. Did users explicitly state mg amounts, or were these inferred?.
8. How did you avoid duplicate or multientry users. Are there any mechanisms in reddit to avoid this issue?
9. Altered experiences (dissociation, hallucinations) have been considered as **positive effects** (28%). This challenges clinical literature where these are typically adverse effects. Auhtors should reconsider this grouping.
10. Define what is meant by Reduced Substance Use, or as data shows concurrent substance use is common.
11. Is there any finding regarding sustainability of positive effects, are they acute effect only? Same for Improved interpersonal relationships, is this only during intoxication?
12. Addictive effects reports is a major concern given ketamine’s abuse potential. This should be detailed.
13. Authors should mention about safety concerns of IV ketamine outside medical settings like infection, overdose, and cardiovascular events without monitoring equipment
14. In discussion authors should focus more on addictive nature and withdrawal effects of ketamine based on reports. They should avoid to normalize dangerous use patterns by framing as "therapeutic". They should repeatedly indicate legal status of ketamine and flag misuse and addictive nature.

Author Response

Please see attached

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for the changes to the manuscript. All have improved it. A few remain.

 

Line-by-line suggested edits

Please make the following changes.

83-84 and 84–85 Cite research published since 2022 to support these claims.

101 Cite research published since 2022 to support the claim that Reddit is the premier anonymous social networking form.

103 Support (Miller, 2019) with a citation to research published since 2022.

103–110 This information on Reddit needs research support. Here is a Google Scholar search of the topic for research published since 2022 that may be helpful in this regard: https://scholar.google.ca/scholar?as_ylo=2022&q=features+of+Reddit&hl=en&as_sdt=0,5.

127–128 Cite research published since 2022 to support the claim that it is those individuals who present to medical providers who are “often those experiencing clinically salient concerns or adverse outcomes”.

143 Change “from the last year (07/03/2024-07/03/2025)” to “from 07 March 2024 to 07 March 2025”.

405 Cite research published since 2022 to support what is standard medical practice.

424 Support (Muetzelfeldt et al., 2008) with a citation to research published since 2022.

430 Support (Liu et al., 2016) with a citation to research published since 2022.

441 Support (Jansen, 1990, 2000) with a citation to research published since 2022.

465–466 For each of “selection bias”, “unverifiable clinical status”, “incomplete reporting of dose”, “formulation”, “route of administration”, and “timing”, cite the seminal research that recognizes these as limitations and a citation to research published since 2022 demonstrating that these remain limitations in the field.

473–475 For each of “fabricate or exaggerate ketamine experiences”, “precludes verification of therapeutic credibility”, and “compromises the internal validity of the date” cite the seminal research that recognizes these as limitations and a citation to research published since 2022 demonstrating that these remain limitations in the field.

481–482 For “leaving uncertainty in whether certain positive or negative effects were experienced acutely or as a later effect,” cite the seminal research that recognizes this as a limitation and a citation to research published since 2022 demonstrating that this remains a limitation in the field.

485–486 For each of “causal inference”, “prevalence estimation”, and “longitudinal outcome assessment”, cite the seminal research that recognizes these as limitations and a citation to research published since 2022 demonstrating that these remain limitations in the field.

495 Support (Lankenau et al., 2008) with a citation to research published since 2022.

506 Delete (Lankenau et al., 2008). Conclusions should avoid citations. The focus should be on summarizing the Results.

Author Response

Please see attached.

Author Response File: Author Response.pdf

Round 3

Reviewer 1 Report

Comments and Suggestions for Authors

Improvements regarding all concerns of this manuscript are sufficient to recommend the acceptance of this submission.