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Review
Peer-Review Record

Critical Windows of Vulnerability: Behavioral Dysregulation After Prenatal vs. Adolescent THC Exposure

Psychoactives 2025, 4(3), 29; https://doi.org/10.3390/psychoactives4030029
by Erica Holliday 1,2,*,†, Kawsar Ullah Chowdhury 2,†, Kai Chen 2, Bilal Saleem 2, Abhinav Yenduri 2,3 and Vishnu Suppiramaniam 2
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Psychoactives 2025, 4(3), 29; https://doi.org/10.3390/psychoactives4030029
Submission received: 3 July 2025 / Revised: 7 August 2025 / Accepted: 8 August 2025 / Published: 20 August 2025

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript reviews the neurodevelopmental and behavioral effects of THC exposure during prenatal and adolescent periods. Overall, it makes a valuable and scientific contribution to the field of neurotoxicology. However, there are some issues to be addressed.

1. The abstract needs revision for clarity and completeness. It does not adequately summarize the manuscript's scope and lacks clear statements of the review's purpose, methodology, and structure.

2. The introduction is relevant and informative, but would benefit from a more explicit statement of the review's goal. Some sentences are long or syntactically complex, which may affect readability.

3. Figure 1 should be improved by using clearer, more informative labels to enhance interpretability.

4. The conclusion is somewhat lengthy, and I recommend that the authors reorganize the discussion and conclusion sections for the final version.

5. The manuscript is generally well-written, and the references are current and appropriate. However, there are a few typographical errors, such as "tetrahyrdocannabinol," which should be corrected to "tetrahydrocannabinol." 

Author Response

Reviewer one
This manuscript reviews the neurodevelopmental and behavioral effects of THC exposure during prenatal and adolescent periods. Overall, it makes a valuable and scientific contribution to the field of neurotoxicology. However, there are some issues to be addressed.

  1. The abstract needs revision for clarity and completeness. It does not adequately summarize the manuscript's scope and lacks clear statements of the review's purpose, methodology, and structure.

We have rewritten the abstract to emphasize the purpose, general methodology and structure.

  1. The introduction is relevant and informative, but would benefit from a more explicit statement of the review's goal. Some sentences are long or syntactically complex, which may affect readability.

We have included an explicit goal for the review at the end of the introduction that now reads “This review aims to systematically synthesize preclinical evidence on the behavioral consequences of cannabinoid exposure during key developmental periods: prenatal and adolescence. By delineating the similarities and differences in long-term outcomes resulting from prenatal versus adolescent THC exposure, this review provides a translational framework for informing public health policy and guiding targeted interventions.”

  1. Figure 1 should be improved by using clearer, more informative labels to enhance interpretability.

Figure has been updated with more descriptive, and accurate, labels.

  1. The conclusion is somewhat lengthy, and I recommend that the authors reorganize the discussion and conclusion sections for the final version.

A separate conclusion section is included that summarized the article goal and overall conclusions from the literature synthesis. Further, the discussion section was edited for clarity and flow.

5. The manuscript is generally well-written, and the references are current and appropriate. However, there are a few typographical errors, such as "tetrahyrdocannabinol," which should be corrected to "tetrahydrocannabinol." 

These have been corrected and the manuscript edited for typos.

Reviewer 2 Report

Comments and Suggestions for Authors

The aim of this review is to examine how exposure to cannabinoids, particularly delta-9-tetrahydrocannabinol (THC), during two critical developmental periods—prenatal and adolescence—differentially affects neurodevelopment and behavior. The study emphasizes the vulnerability of the endocannabinoid system during these developmental windows and the long-term consequences of its disruption.

Considering the recent legalization of cannabis in some countries and the increase in THC usage, I believe this study is highly compelling and will attract considerable interest from many readers. I believe this review is exceptionally well-organized and of high quality, as it comprehensively covers a wide range of relevant literature. I will provide only the following two minor comments.

(1) In paragraph 3, the authors describe both prenatal THC exposure and adolescent THC exposure. It might improve readability for the reader if this section were divided into two separate paragraphs—one for prenatal THC exposure and another for adolescent THC exposure (e.g., “3. Prenatal THC Exposure” and “4. Adolescent THC Exposure”).

(2) The conclusion section feels slightly long. While the content itself is appropriate, some parts—such as the detailed mechanisms at the synaptic level—might be better placed in the Discussion section. Some readers tend to read only the abstract and conclusion, keeping this section concise is important.

Author Response

  • In paragraph 3, the authors describe both prenatal THC exposure and adolescent THC exposure. It might improve readability for the reader if this section were divided into two separate paragraphs—one for prenatal THC exposure and another for adolescent THC exposure (e.g., “3. Prenatal THC Exposure” and “4. Adolescent THC Exposure”).

We have reorganized components of the introduction to increase readability. However, this suggestion on the third paragraph refers to a paragraph on the endocannabinoid system and discusses the developmental changes in the endocannabinoids.

(2) The conclusion section feels slightly long. While the content itself is appropriate, some parts—such as the detailed mechanisms at the synaptic level—might be better placed in the Discussion section. Some readers tend to read only the abstract and conclusion, keeping this section concise is important.

The original conclusion has been divided into a discussion and conclusion section. The most critical information has been preserved in the designated conclusion section.

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