Composition Vendor Newgen KnowledgeWorks (P) Ltd. PLoS One plos plosone PLOS One 1932-6203 Public Library of Science San Francisco, CA USA 10.1371/journal.pone.0329897 PONE-D-25-19383 Research Article Medicine and health sciencesClinical medicineSigns and symptomsPain Medicine and health sciencesClinical medicineSigns and symptomsPainLower back pain Medicine and health sciencesPharmacologyBehavioral pharmacologyRecreational drug useCannabis Medicine and health sciencesMental health and psychiatry Medicine and health sciencesMental health and psychiatryMental health therapies Medicine and health sciencesPublic and occupational healthGlobal health Medicine and health sciencesSurgical and invasive medical procedures Medicine and health sciencesPain management Discontinuation rates and predictors of Medical Cannabis cessation for chronic musculoskeletal pain Medical Cannabis discontinuation in musculoskeletal pain Khak Mohammad Conceptualization Data curation Formal analysis Methodology Project administration Software Writing – original draft Writing – review & editing 1 ¤ https://orcid.org/0000-0001-5197-6204 Ramtin Sina Conceptualization Data curation Formal analysis Writing – review & editing 1 ¤ * Chung Juliet Data curation 1 ¤ Ilyas Asif M. Conceptualization Methodology Supervision Writing – review & editing 1 2 3 ¤ Greis Ari Conceptualization Supervision Writing – review & editing 1 2 3 ¤ Rothman Institute Foundation for Opioid Research & Education, Philadelphia, Pennsylvania, United States of America Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America Mitra Souparno Editor NYU Grossman School of Medicine: New York University School of Medicine, UNITED STATES OF AMERICA

The authors have declared that no competing interests exist.

¤¤ Department of Orthopaedic Surgery, Rothman Orthopaedic Institute, Philadelphia, Pennsylvania, United States of America

 * E-mail: sina.ramtin@austin.utexas.edu 782025 2025 20 8 e0329897 2142025 2272025 2025 Khak et al This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Medical cannabis (MC) is increasingly used as a treatment for chronic musculoskeletal pain, but there is limited data on factors influencing its discontinuation. This study aims to investigate the rates of MC discontinuation and explore factors influencing it in patients with chronic musculoskeletal pain. A retrospective analysis was conducted on 78 patients certified for medical cannabis over a 2 year period. Patient demographics, pain origin, and Global Physical Health (GPH) and Global Mental Health (GMH) scores were collected before intervention. Discontinuation rates were measured at three-month and one-year follow-up. Statistical analyses, including Fisher’s Exact Test and two-sample t-tests, were performed to assess associations between variables and discontinuation. The overall discontinuation rate of MC use was 57.9% at one year, with 44.7% of patients discontinuing within the first three months. Older age was significantly associated with higher discontinuation rates. Pain origin categories did not significantly differ between those who discontinued and continued MC use, although a higher proportion of patients in the discontinued group reported low back pain. No significant differences were observed in baseline GPH and GMH scores between the two groups. This study demonstrates a high discontinuation rate of MC use in patients for chronic musculoskeletal pain. The absence of significant differences in pain origin or baseline health scores suggests that factors beyond pain location or general health may contribute to the decision to discontinue MC. Further research is needed to explore the long-term effects of MC on pain management and patient outcomes.

 The author(s) received no specific funding for this work. Data Availability The data used in this study were obtained from the Rothman Orthopaedic Cannabis Data Repository (ROCDR), a third-party dataset managed by the Rothman Institute Foundation for Opioid Research & Education. The authors do not have permission to publicly share the full dataset. However, interested researchers may apply for access by contacting the Rothman Institute Foundation via email (Lilly.Caso@rothmanopioid.org). The authors did not receive any special privileges in accessing this dataset. Introduction

Chronic musculoskeletal pain is a prevalent condition that affects the quality of life of millions of individuals worldwide. Despite advancements in pharmacologic and non-pharmacologic therapies, many patients continue to experience persistent pain and disability. As a result, there has been growing interest in alternative treatments, including medical cannabis (MC), for managing chronic pain. The therapeutic application of MC has gained global attention due to its potential to alleviate pain. Cannabis and its derivatives are believed to act on CB1 receptors in the brain, modulating pain signals, and CB2 receptors in the dorsal root ganglion, which influence pain integration in nerve pathways [1]. While MC has shown promise in providing significant relief from chronic pain, often surpassing 50% improvement compared to a placebo [2], its effects on cognition, particularly executive function remain a concern. Short-term memory impairment is commonly associated with MC use, and chronic use can exacerbate cognitive deficits, leading to slower processing and reduced attention. Furthermore, long-term and early-age use of MC has been linked to neurocognitive deficits, with neuroimaging studies showing reduced hippocampal volume and density [3].

Despite the growing acceptance of MC as a therapeutic option for chronic musculoskeletal pain, significant gaps remain in understanding its long-term efficacy. While some patients report significant pain relief, others experience dissatisfaction, intolerance, or prefer more definitive treatments, such as surgery or joint injections [4,5]. These factors contribute to the complexity of integrating MC into routine clinical practice. Furthermore, limited research exists on the reasons for MC discontinuation, which is crucial for optimizing its clinical use.

This study aims to address these gaps by investigating the discontinuation of medical cannabis in patients with chronic musculoskeletal pain. We focus on factors such as age, pain origin, and baseline health status. Understanding the predictors of discontinuation will provide valuable insights into the factors that influence patient decisions regarding MC use, helping guide clinical recommendations and treatment strategies.

 Materials and methods

Patient outcome measures in this study were derived from the Rothman Orthopaedic Cannabis Data Repository (ROCDR), which was established with approval from the Institutional Review Board at Thomas Jefferson University, Philadelphia, Pennsylvania (protocol number 19D.159). Consent was obtained or waived by all participants in this study. Physicians participating in MC certification completed a mandatory four-hour continuing medical education course and sought accreditation from the Pennsylvania Department of Health. The patient certification process involved verifying the presence of one of the 23 state-approved medical conditions, confirming Pennsylvania residency, and reviewing the patient’s mental health and pain management history. Eligible individuals underwent a chart review to identify any significant history of substance abuse or any other mental health disorders, with those patients being excluded from the certification process. Additionally, a review of controlled substance use history was conducted using the Pennsylvania Prescription Drug Monitoring Program. If a patient was currently prescribed opioids, their prescribing physician was consulted to discuss the integration of MC into the treatment plan. During the certification visit, patients were provided comprehensive information on the chemical composition of MC, available delivery methods, optimal dosing guidelines, and recommended formulations by the certifying physicians. Upon certification, patients were issued a medical cannabis identification card by the Pennsylvania Department of Health, enabling them to purchase cannabis at authorized dispensaries within the state.

The medical records of 78 patients diagnosed with chronic musculoskeletal noncancer pain who were certified for MC at the Medical Cannabis Department of the Rothman Orthopaedic Institute between October 2022 and December 2024 were analyzed. These patients, previously described in a prior publication on short-term outcomes [6], were reviewed for a minimum follow-up period of one year to assess MC discontinuation rates. Following their initial MC certification, patients were scheduled to attend follow-up visits at three months and subsequently on an annual basis. To further evaluate the continuity of MC use among these patients, we accessed the Pennsylvania Medical Marijuana Program’s patient registry. This registry allows practitioners to verify patients’ certification statuses and identify whether they have obtained recertifications through other healthcare providers. By cross-referencing our patient cohort with this database, we determined the recertification status of each individual, providing insights into their ongoing engagement with MC treatment across different medical practices.

Patient demographics were obtained through electronic medical records for all patients. At the initial visit, we collected data on pain in specific regions, including low back, neck, shoulder, and foot and ankle pain, as well as the Patient-Reported Outcomes Measurement Information System (PROMIS) global health scale. Due to the variability in the site of musculoskeletal pain, we utilized global pain outcome measures rather than site-specific disability measures. The PROMIS global health scale provided two key scores: Global Physical Health (GPH) and Global Mental Health (GMH) quality of life (QoL) T-scores (available online at https://www.healthmeasures.net/). Statistical analysis for GPH and GMH was conducted using the Shapiro-Wilk test to assess normality. The relationship between explanatory variables and GPH and GMH was tested using T-tests, as the outcome variables were normally distributed. Due to limitations in retrospective chart review, specific details regarding the THC:CBD ratio, delivery method (e.g., vaporized, tincture), and formulation types were not uniformly recorded and could not be analyzed. A p-value of <0.05 was considered statistically significant in the analysis.

 Results

The 3-month and 1-year follow-up data was available for the 76 of 78 patients. By the first 3-month period, 44.7% (34 patients) had discontinued MC. Reasons for discontinuation included dissatisfaction with MC, joint or epidural injections, and surgical intervention. After the 3-month follow-up, an additional 13.2% (10 patients) ceased MC use, resulting in a total discontinuation rate of 57.9% (44 patients) at 1 year. The 1-year study cohort of MC tolerance thus consisted of 32 patients among which 11 patients (14.5%) continued treatment with other physicians outside of our practice (Fig 1).

10.1371/journal.pone.0329897.g001Patient retention and cannabis use over time.

We compared the characteristics of patients who continued MC use after one year with those who discontinued its use. There was a statistically significant difference in age between the two groups (p = 0.04) (Fig 2). Patients who discontinued MC were older, with a mean age of 71.5 ± 9.8 years compared to those who continued MC, who had a mean age of 64.5 years ± 10.2. There was no significant difference in insurance type between the two groups. Of the 44 patients who discontinued MC, 47.7% were on Medicare and 52.3% were on HMO/PPO insurance, while 37.5% of those who continued MC were on Medicare and 62.5% were on HMO/PPO. Race distribution did not differ significantly between the groups with 97.7% of patients who discontinued MC being White compared to 90.6% of those who continued MC. Of the patients who discontinued MC, 61.4% were female and 38.6% were male, compared to 65.6% female and 34.4% male in the group that continued MC with no significant difference.

10.1371/journal.pone.0329897.g002Comparison of age between patients who discontinued vs. Continued Medical Cannabis (MC) use after 1 Year.

Regarding health outcomes, there were no significant differences in GPH or GMH scores between the two groups. The mean GPH score for patients who discontinued MC was 43.6 ± 9.8, while those who continued MC had a mean GPH score of 43.9 ± 10.2. Similarly, the mean GMH score for patients who discontinued MC was 46.7 ± 7.5, compared to 47.2 ± 9.3 for those who continued MC (Table 1).

10.1371/journal.pone.0329897.t001Bivariate analysis of discontinued vs. continued Medical Cannabis use.
Variable Continued MC (n = 32) Discontinued MC (n = 44) P-value
Age (Median) 64.5 years 71.5 years 0.04
Insurance Type 0.3
  Medicare 37.5% 47.7%
  HMO/PPO/O 62.5% 52.3%
Race 0.1
  White 90.6% 97.7%
  Other 9.4% 2.3%
Gender 0.7
  Female 65.6% 61.4%
  Male 34.4% 38.6%
GPH Score 43.9 ± 10.2 43.6 ± 9.8 0.8
GMH Score 47.2 ± 9.3 46.7 ± 7.5 0.7

The distribution of pain origin was analyzed between patients who discontinued MC and those who continued its use. The following categories were reported: low back pain, neck pain, Foot/Ankle pain, shoulder pain, and knee pain. We combined all categories associated with low back pain (low back pain only, low back and neck pain, low back and Foot/Ankle pain, and low back and shoulder pain) and compared the occurrence of low back pain between the two groups. There was no significant difference in the occurrence of low back pain between the 30 patients (68.2%) who discontinued MC and 18 patients (56.3%) who continued MC after 1 year (p = 0.3). For all other pain origin categories, Fisher’s Exact Test was applied, and none of the results were statistically significant (all p-values > 0.05) suggesting that the distribution of pain origins between the two groups remained relatively similar across all categories (Fig 3).

10.1371/journal.pone.0329897.g003Pain origin distribution between discontinued and continued Medical Cannabis users. Discussion

This study aimed to investigate the rate of cessation and factors influencing the discontinuation of MC use in patients with chronic musculoskeletal pain. A key finding in this study was the high discontinuation rate, with 57.9% of patients ceasing MC use within one year. This suggests that a large proportion of patients may experience dissatisfaction, intolerance, or prefer alternative treatments such as surgery or joint injections for managing chronic musculoskeletal pain. However, it is important to note that 42.1% of patients either continued MC use or sought recertification, indicating that a subset of patients perceive sustained benefits from MC. These results are consistent with previous studies, which have shown mixed responses to MC treatment in chronic pain patients. While some patients report significant relief, others may not find sufficient therapeutic benefit, leading to early discontinuation [7,8].

By the three-month follow-up, 44.7% had already discontinued MC, reflecting a considerable early drop-off. This early discontinuation could point to initial expectations not being met, potential side effects, or insufficient symptom relief, which are common reasons for discontinuation in medical treatments. The relatively high early discontinuation rate indicates that MC may not provide immediate or sustained relief for all patients and highlights the need for better patient selection and management strategies in the early stages of treatment. To address the high discontinuation rates observed in medical cannabis treatment for chronic pain, recent studies have utilized machine learning models to predict therapy dropout and identify influential factors. Visibelli et al [9] employed a random forest classifier to predict dropout in a cohort of 542 patients undergoing cannabis-based treatment for chronic pain. The study found that high final VAS scores and elevated THC dosages were the most significant predictors of discontinuation, while factors like baseline therapeutic benefits and CBD dosages were associated with improved adherence.

The age of patients was found to be significantly associated with the likelihood of discontinuing MC. Older patients were more likely to cease MC use, which aligns with findings from other studies suggesting that older adults may be more cautious in using alternative therapies like MC due to concerns about long-term effects or a preference for more conventional treatments [10]. Although our study did not collect detailed data on adverse effects, this trend may be partially explained by age-related concerns such as increased susceptibility to cognitive side effects, dizziness, or drug interactions. One possible explanation for the higher discontinuation rates observed in the elderly population is the presence of more advanced musculoskeletal conditions, such as degenerative changes (radiculopathies, stenosis) or chronic wear and tear (osteoarthritis, tendinopathies), which may not respond well to medical cannabis [10–11]. As patients age, chronic pain often becomes more complex and severe, leading them to seek more definitive treatments such as joint replacements or surgical interventions. Furthermore, the progression of chronic diseases and the presence of comorbidities in older adults may also influence their decision to stop MC, as they may be more inclined to rely on treatments with well-established outcomes while younger individuals tend to continue exploring newer treatment options, including MC. Haug et al. [11] examined cannabis use patterns and motives among medical cannabis dispensary patients of different age groups. They suggest that age-related factors may influence medical cannabis use patterns and the likelihood of discontinuation, which is consistent with our observation that older patients were more likely to discontinue MC treatment.

The origin of pain was also assessed to determine if certain pain conditions influenced MC discontinuation rates over a one-year period. While no significant differences were observed between pain origin categories, we did combine all categories related to low back pain and found that a higher proportion of patients in the Discontinued MC group reported low back pain (68.18%) compared to the Continued MC group (56.25%). Although no statistical significance was reached, this difference suggests that low back pain, as a common and complex chronic condition, may contribute to patients’ decisions to discontinue MC. The higher prevalence of low back pain in the Discontinued MC group may reflect the difficulties in managing pain of this nature with MC alone, as patients with chronic low back pain often seek more definitive treatments, such as joint injections or surgical interventions. However, the absence of significant findings points to the multifactorial nature of treatment adherence, where factors beyond pain location, such as psychological, social, and healthcare system-related variables, likely play a more substantial role in the decision to discontinue treatment. Previous studies have suggested that pain-related factors, including the chronicity and intensity of pain, are often associated with patients’ decisions to either persist with or discontinue treatment [12–14].

The distribution of other pain origins, such as neck pain, shoulder pain, and knee pain, did not reveal significant differences between the two groups. These findings suggest that, overall, pain origin does not appear to be a determining factor in whether patients continue or discontinue MC use. This supports the hypothesis that MC may be used as an adjunctive treatment for multiple pain conditions, with its effectiveness varying based on individual patient responses rather than specific pain etiologies. However, this does not negate the importance of individualized treatment plans for patients with complex, multidimensional pain, where factors such as the patient’s psychological status, comorbidities, and social support systems are equally important considerations in determining treatment adherence.

While the present study could not capture THC/CBD ratios, specific administration methods, or cognitive effects due to its retrospective design, a recent prospective study of medical cannabis users with chronic musculoskeletal pain has addressed these variables. Another study, which followed patients over a one-year period, reported that most patients used topical formulations, experienced high levels of perceived efficacy, and noted minimal cognitive or motor side effects. In addition, nearly 80% maintained stable usage patterns [15]. These findings offer complementary insights into long-term MC use and may help contextualize the discontinuation patterns observed in this analysis.

Baseline GPH and GMH scores were measured but did not show significant differences between patients who discontinued and those who continued MC use. This suggests that at the time of MC certification, the two groups did not differ substantially in their overall physical or mental health status. However, it is important to recognize that these scores reflect only the baseline health status and do not capture the potential changes in physical and mental health outcomes over time as a result of MC use. Since MC is primarily used to manage chronic pain, it is likely that over time, changes in pain levels and functional status may influence GPH and GMH scores, potentially leading to improved or worsened outcomes that could affect a patient’s decision to continue or discontinue treatment [16,17]. Future studies should examine how these scores evolve throughout the course of MC treatment to provide more comprehensive insights into the impact of MC on both physical and mental well-being. This study has several limitations. First, the data on important variables such as THC:CBD ratios, formulation types, and side-effect profiles were not consistently documented and therefore not analyzed. Second, patient-reported outcomes on pain severity, functional improvement, or subjective satisfaction over time were not collected, limiting our ability to understand the underlying reasons for discontinuation (e.g., improvement vs. adverse effects). Third, external factors like cost, dispensary access, and product consistency, known to affect treatment adherence, were not assessed. We also did not evaluate patient expectations or attitudes at baseline, which are known predictors of adherence. Finally, potential confounders such as comorbid cognitive impairment, polypharmacy, or other geriatric syndromes were not included and may have influenced discontinuation, particularly among older adults. The sample was also limited to a specific cohort of patients who sought treatment at a single Medical Cannabis Department, which may not be representative of the broader population of individuals using MC for chronic pain management. Future prospective studies with larger, more diverse populations and more comprehensive data collection on these variables would help to clarify the factors influencing MC use and discontinuation.

 Conclusions

This study highlights the importance of discontinuation rate of MC use in patients with chronic musculoskeletal pain, with over half of patients discontinuing treatment within one year. Age was identified as a key factor influencing discontinuation, with older patients being more likely to stop using MC. While pain origin did not significantly affect discontinuation rates, a higher proportion of patients in the discontinued group reported low back pain, suggesting that the complexity of managing chronic pain conditions with MC alone may contribute to treatment cessation. Additionally, baseline Global Physical Health and Global Mental Health scores did not show significant differences between the two groups, indicating that overall health status at the time of MC certification did not influence the decision to discontinue or continue treatment. These findings suggest that while MC may offer benefits for some patients, further research is needed to better understand the long-term effects of MC on pain management and patient satisfaction, as well as the factors influencing treatment adherence.

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29 May 2025

PONE-D-25-19383 Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain PLOS ONE

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Reviewer #1: The study titled “Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain” addresses a timely and important question on medical cannabis (MC) use in chronic musculoskeletal pain, a condition with significant public health burden. This study uniquely examines discontinuation rates and potential predictors, filling a knowledge gap. Data is collected from a clinical MC program, reflecting real-world usage and discontinuation patterns in a regulated environment. Analysis at 3 months and 1 year provides insight into early attrition versus sustained engagement, which is valuable for guiding clinical expectations and patient counseling.

However some of the limitations have not been addressed or mentioned in the study:

1. Discontinuation may vary by THC/CBD ratio, method of administration (e.g., tincture vs. vaporized), and side-effect profiles. These key variables were not collected or analyzed.

2. Without tracking pain severity or functional status over time, it's unclear whether discontinuation reflects symptom improvement, lack of efficacy, or adverse effects.

3. Patient expectations and subjective satisfaction are strong predictors of treatment adherence, but these were not assessed.

4. Financial barriers and cannabis availability (e.g., dispensary access, product consistency) may influence discontinuation but are not addressed.

5. Other comorbid conditions (e.g., cognitive impairment, polypharmacy) in older adults could influence discontinuation but were not explored.

Please address these limitations in the study.

Reviewer #2: Well written article.

Please explain and further expand on the various complications arising as a result of medical cannabis use which led to discontinuation of use mainly in the older population.

Also an explanation of the types of Medical Cannabis used by the subjects in the study , with mention of the THC:CBD ratio would give a broader understanding of what types of Medical Cannabis were tolerated and which ones were discontinued more.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Nikhil Tondehal

Reviewer #2: Yes: Arun Prasad

**********

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While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Submitted filename: Discontinuation of medical cannabis.pdf

 10.1371/journal.pone.0329897.r002 Author response to Decision Letter 1 Submission Version 1

8 Jun 2025

Dear Editor-in-Chief of PLOS ONE,

We sincerely thank you for the opportunity to revise and resubmit our manuscript titled:

"Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain."

We appreciate the thoughtful comments provided by the editorial team and peer reviewers. We have revised the manuscript accordingly and addressed each point as detailed below. All changes have been incorporated into the main text per PLOS ONE guidelines.

Please find our detailed responses below:

Editorial Comments

1. Style and Formatting:

Please ensure that your manuscript meets PLOS ONE's style requirements…

Response:

We have reviewed and revised the manuscript to align with the PLOS ONE formatting style, including the title page, abstract structure, and section headings.

2. Ethics Statement:

Please include your full ethics statement in the ‘Methods’ section…

Response:

We have added the following ethics statement in the “Methods” section:

“Patient outcome measures in this study were derived from the Rothman Orthopaedic Cannabis Data Repository (ROCDR), which was established with approval from the Institutional Review Board at Thomas Jefferson University, Philadelphia, Pennsylvania (protocol number 19D.159). Verbal consent was obtained from all participants prior to data collection.”

3. Data Availability – Third-Party Data:

Please describe the data source, confirm usage permission, disclose any special access, and provide contact info for data access.

Response:

We have included the following statement in the Data Availability section:

“The data used in this study were obtained from the Rothman Orthopaedic Cannabis Data Repository (ROCDR), a third-party dataset managed by the Rothman Institute Foundation for Opioid Research & Education. The authors do not have permission to publicly share the full dataset. However, interested researchers may apply for access by contacting the Rothman Institute Foundation at mohammad.khak@rothmanopioid.org. The authors did not receive any special privileges in accessing this dataset.”

4. Data Anonymization:

Remove personal information and re-upload an anonymized dataset.

Response:

As outlined in our Data Availability Statement (Editorial Comment #3), the dataset used in this study is part of the Rothman Orthopaedic Cannabis Data Repository (ROCDR), a third-party database we do not have legal rights to publicly share. Therefore, no dataset has been uploaded.

5. Missing Table Reference:

Refer to Table 1 in the text.

Response:

We have added a reference to Table 1 in the Results section.

Reviewer Comments

Reviewer #1

We appreciate the reviewer’s valuable feedback. We have added a new paragraph in the Discussion section addressing the following limitations. We also added a reference to a similar recently published article addressing part of these limitations in a prospective study.

Reviewer #2 Comment 1:

Please expand on complications in older patients that may have led to discontinuation.

Response:

We added the following paragraph to the Discussion section:

“Although our study did not collect detailed data on adverse effects, this trend may be partially explained by age-related concerns such as increased susceptibility to cognitive side effects, dizziness, or drug interactions. One possible explanation for the higher discontinuation rates observed in the elderly population is the presence of more advanced musculoskeletal conditions, which may not respond well to medical cannabis.”

________________________________________

Reviewer #2 Comment 2:

Explain types of cannabis used and include THC:CBD ratios.

Response:

We acknowledge this limitation. Unfortunately, detailed data on product formulation and THC:CBD ratios were not consistently available in patient records. We have noted this as a limitation in the Methods and Discussion and highlighted the need for future research that includes specific product characteristics to better understand their impact on treatment adherence.

Submitted filename: long-term, stable access to study data contact.docx

 10.1371/journal.pone.0329897.r003 Decision Letter 1 Mitra Souparno Academic Editor 2025 Souparno Mitra This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 1

3 Jul 2025

PONE-D-25-19383R1 Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain PLOS ONE

Dear Dr. Ramtin,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

  Please address reviewer comments and resubmit to reconsider for publication.

Please submit your revised manuscript by Aug 17 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Souparno Mitra, M.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Partly

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Thank you for addressing the suggested edits for "Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain."

Reviewer #3: “scores were collected at baseline”. Recommend substituting Baseline with before intervention.

“Executive function” includes Working Memory and selective attention

“history of substance abuse or severe mental health disorders”. Substance abuse is mental health disorder when they meet criteria per DSM-V

Include PROMIS 10 questionnaires using 5-point Likert scales. Rating is “limited to the past 7 days” before intervention.

“There was a significant difference in age between the two groups” Statistically significant

Reference for “advanced musculoskeletal conditions which may not respond well to medical cannabis”

“Advanced musculoskeletal conditions in the elderly” such as degenerative changes (radiculopathies, stenosis) or chronic wear and tear(OA, tendinopathies etc)

“That study.” Please reference the study here

“due to its retrospective design”. Does 2-year follow-up after an intervention(MC) make it a prospective rather than a retrospective study?

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: Arun Prasad

Reviewer #3: Yes: Anoop Narahari

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

 10.1371/journal.pone.0329897.r004 Author response to Decision Letter 2 Submission Version 2

8 Jul 2025

Dear Editor-in-Chief of PLOS ONE,

We sincerely thank you for the opportunity to revise and resubmit our manuscript titled:

"Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain."

We appreciate the thoughtful comments provided by the editorial team and peer reviewers. We have revised the manuscript accordingly and addressed each point as detailed below. All changes have been incorporated into the main text per PLOS ONE guidelines.

Please find our detailed responses below:

Reviewer#2 Comments:

1. “scores were collected at baseline”. Recommend substituting Baseline with before intervention.

Response:

Corrected. The term “baseline” has been replaced with “before intervention” throughout the manuscript.

2. “Executive function” includes Working Memory and selective attention

Response:

We have revised the manuscript to remove specific mentions of “working memory” and “selective attention” under “executive function” to improve clarity and accuracy.

3. “history of substance abuse or severe mental health disorders”. Substance abuse is a mental health disorder when it meets DSM-V criteria

Response:

Thank you for the clarification. The sentence has been updated to: “significant history of substance abuse or any other mental health disorders” to align with DSM-V definitions.

4. Include PROMIS 10 questionnaires using 5-point Likert scales. Rating is “limited to the past 7 days” before intervention.

Response:

We have added a reference to the questionnaire, which is available online at https://www.healthmeasures.net/.

5. “There was a significant difference in age between the two groups” – Statistically significant

Response:

We have updated the sentence to read: “There was a statistically significant difference in age between the two groups.”

6. Reference for “advanced musculoskeletal conditions which may not respond well to medical cannabis”

Response:

A supporting reference has been added to the manuscript to substantiate this statement.

7. “Advanced musculoskeletal conditions in the elderly” such as degenerative changes (radiculopathies, stenosis) or chronic wear and tear (OA, tendinopathies etc)

Response:

We have incorporated these specific examples—radiculopathies, stenosis, osteoarthritis (OA), and tendinopathies—into the manuscript to provide clarity.

8. “That study.” Please reference the study here

Response:

The study has been referenced as citation [15], and the sentence has been rephrased accordingly.

9. “due to its retrospective design”. Does 2-year follow-up after an intervention (MC) make it a prospective rather than a retrospective study?

Response:

To eliminate confusion, we have removed this sentence from the manuscript.

Submitted filename: point by point response 2nd.docx

 10.1371/journal.pone.0329897.r005 Decision Letter 2 Mitra Souparno Academic Editor 2025 Souparno Mitra This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 2

23 Jul 2025

Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain

PONE-D-25-19383R2

Dear Dr. Ramtin,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Souparno Mitra, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Thank you for making the suggested edits. Best of luck on publication of "Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain.

Reviewer #3: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: Arun Prasad

Reviewer #3: Yes: Anoop Narahari

**********

 10.1371/journal.pone.0329897.r006 Acceptance letter Mitra Souparno Academic Editor 2025 Souparno Mitra This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PONE-D-25-19383R2

PLOS ONE

Dear Dr. Ramtin,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

* All relevant supporting information is included in the manuscript submission,

* There are no issues that prevent the paper from being properly typeset

You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps.

Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

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Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Souparno Mitra

Academic Editor

PLOS ONE