Autism, Sleep, and Medicinal Cannabis: 18-Month Prospective Registry Outcomes on Efficacy and Safety

Autism, Sleep, and Medicinal Cannabis: 18-Month Prospective Registry Outcomes on Efficacy and Safety | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Autism, Sleep, and Medicinal Cannabis: 18-Month Prospective Registry Outcomes on Efficacy and Safety Mohsin Maqbool, MD., Diya Khullar, Izabella Jonhson, Taha Maqbool This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8689930/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Sleep disturbances are highly prevalent in children with autism and are associated with worsening daytime functioning and reduced family quality of life. Despite widespread real-world use of medicinal cannabis to address sleep difficulties, long-term prospective data on efficacy and safety in pediatric autism populations remain limited. This study evaluated 18-month efficacy and safety outcomes of medicinal cannabis use on sleep in children with autism using a prospective clinic registry. Methods This prospective observational study enrolled 68 children with autism initiating medicinal cannabis treatment within a specialty clinic registry. Cannabis products included tinctures and gummies. Caregiver-reported sleep duration was assessed before treatment initiation and after sustained exposure. Caregiver Global Impression of Change (CGIC) was recorded using a 7-point ordinal scale ranging from substantially improved to substantially worsened. Of the initial cohort of 68, 57 participants completed 18 months of follow-up: 11 discontinued treatment due to side effects (n = 7), cost (n = 2), or travel barriers (n = 2). Descriptive and paired analyses were conducted to evaluate sleep outcomes and caregiver-reported change. Results Among participants completing at least 18 months of follow-up, mean caregiver-reported sleep duration increased from 6.8 to 8.1 hours, corresponding to a mean increase of 1.3 hours (95% CI 0.8–1.7). Improvements were most pronounced among children with more severe baseline sleep deprivation, with those sleeping less than six hours per night demonstrating a mean increase of 2.2 hours. Across caregiver-reported sleep domains, approximately 70-75% of caregivers reported improvement in sleep onset, sleep maintenance, and overall sleep quality, with minimal reports of worsening. CGIC ratings also indicated improvement in both child and caregiver quality of life in the majority of participants. Caregivers additionally reported modest, variable improvements across several behavioral domains, including attention, sensory sensitivities, anxiety, and repetitive behaviors, which were assessed descriptively. Adverse effects were most commonly reported early in treatment and declined over time, with treatment discontinuation due to persistent adverse effects occurring in a minority of participants and no serious adverse events observed. Developmental Neuroscience Neurology Autism spectrum disorder Sleep disturbance Pediatric insomnia Medicinal cannabis Cannabidiol (CBD) Tetrahydrocannabinol (THC) Figures Figure 1 Figure 2 1. Introduction Autism spectrum disorder is a common neurodevelopmental condition, currently estimated to affect approximately 1 in 32 children in the United States (Zablotsky et al., 2019 ). Sleep disturbances are among the most prevalent and clinically significant co-occurring challenges in children with autism, with up to 80 percent experiencing chronic sleep difficulties (Courchesne, 2018, Esteban-Figuerola 2019). These commonly include sleep onset insomnia, sleep maintenance insomnia, and poor overall sleep quality (Hollway & Aman, 2011 ; Tchaconas & Adesman, 2017 ). Sleep difficulties in children with autism are multifactorial. Contributors include anxiety, sensory sensitivities, hyperactivity, circadian rhythm dysregulation, and neurobiological differences involving underdeveloped sleep regulatory circuitry (Sadeh et al., 2002 ; Malow et al., 2012 ). In addition, co-occurring but frequently underdiagnosed sleep disorders such as obstructive sleep apnea, periodic limb movement disorder, and restless sleep contribute to fragmented and insufficient sleep (Malow et al., 2012 ). Persistent sleep disruption is associated with worsening daytime behavior, increased emotional dysregulation, impaired attention, and substantial negative effects on family quality of life (Sadeh et al., 2002 ; Tchaconas & Adesman, 2017 ). Pharmacologic treatment options for sleep disturbances in autism remain limited. The only U.S. Food and Drug Administration–approved medications for children with autism spectrum disorder, risperidone and aripiprazole, are indicated for irritability rather than sleep and are associated with substantial metabolic, neurological, and behavioral adverse effects (Janssen Pharmaceuticals, Inc., 2020; Otsuka America Pharmaceutical, Inc., 2009; Hyman et al., 2020 ). Other commonly used medications, including selective serotonin reuptake inhibitors, stimulants, and non-stimulants, demonstrate inconsistent effects on sleep and may exacerbate insomnia or behavioral symptoms (Hollway & Aman, 2011 ). Stimulants, while sometimes improving daytime attention, often worsen sleep onset and maintenance (Malow et al., 2012 ). Melatonin is widely used and supported by evidence for improving sleep onset latency, yet its effects are frequently incomplete, particularly for sleep maintenance and long-term sleep quality (Gringras et al., 2017 ). In this context, families increasingly report the use of medicinal cannabis products to address sleep and behavioral challenges in children with autism. Caregivers commonly describe improvements in sleep duration, sleep continuity, and overall calmness (Aran et al., 2021 ; Poleg et al., 2019 ). Hemp-derived and cannabidiol-containing products are widely accessible through online and over-the-counter sources, and real-world use has rapidly outpaced the available clinical evidence, particularly regarding long-term efficacy and safety in pediatric populations (Volkow et al., 2017 ). In 2019, the legalization of medicinal cannabis for autism in Texas (Texas Department of Public Safety, 2019 ) created a unique opportunity to prospectively study real-world outcomes in a regulated clinical setting. Leveraging this policy change, the present study examines 18-month efficacy and safety outcomes of medicinal cannabis use in a prospective clinic registry of children with autism, with a focus on sleep duration and CGIC for sleep disturbance and quality of life. 2. Methods 2.1 Study Design and Setting This prospective observational study was conducted using a clinic-based registry of patients followed in a pediatric neurology and sleep medicine practice. The registry was established following the legalization of medicinal cannabis for autism in Texas in 2019 and was designed to capture real-world efficacy and safety outcomes associated with medicinal cannabis use. The study followed participants for a minimum of 18 months, with extended follow-up when available. 2.2 Participants Participants were children with autism receiving care in a specialty neurology and sleep clinic who elected to initiate medicinal cannabis as part of their clinical care. Inclusion criteria included a clinical diagnosis of autism spectrum disorder, the presence of severe sleep disturbance, and caregiver-reported concerns regarding sleep onset insomnia, sleep maintenance insomnia, or associated behavioral dysregulation. Participants included both medication-naïve patients and those who had previously failed multiple pharmacologic sleep interventions. Children with clinical features suggestive of obstructive sleep apnea (habitual snoring, witnessed apneas) or restless legs syndrome (caregiver-reported leg discomfort or urge to move) were excluded. These conditions were excluded a priori as they may independently disrupt sleep and act as mimickers or confounders of insomnia-related sleep disturbance. A total of 68 patients elected to enroll in the registry and initiate medicinal cannabis treatment. Of these, 57 participants completed at least 18 months of follow-up and were included in the primary efficacy analyses. Eleven participants discontinued treatment prior to 18 months due to side effects (n = 7), cost-related barriers (n = 2), or travel or technical constraints (n = 2). 2.3 Ethics and Data Handling This study was conducted using data collected as part of routine clinical care within a specialty clinic registry. Parents or legal guardians provided written informed consent for treatment and for inclusion of de-identified clinical data in research analyses. The study protocol was reviewed and determined to meet criteria for exempt research under applicable institutional policies, as it involved secondary analysis of de-identified clinical data. All data were stored within secure electronic medical records (eClinical Works v12.0.2) and the Texas Compassionate Use Registry (CURT), a state-maintained, HIPAA-compliant platform. No identifiable patient information was included in the analytic dataset. 2.4 Exposure Participants initiated medicinal cannabis following shared decision-making between caregivers and clinicians. Cannabis products included tinctures and gummies containing cannabidiol (CBD) and tetrahydrocannabinol (THC) in varying ratios, including 1:1, 3:1, and 4:1 formulations. THC dosing was titrated gradually, beginning at 1.25 mg twice daily and increased in weekly increments of 1.25 mg as tolerated, to a maximum dose of 5 mg twice daily. Final dosing was individualized based on clinical response and tolerability. No new pharmacological sleep agents were initiated during the follow-up period. Participants continued previously prescribed medications, melatonin, or supplements at the discretion of their treating clinicians and caregivers, without protocol-mandated stabilization. Among participants who completed follow-up, the mean duration of treatment was 22 months, with a range of 18 to 30 months. (INSERT TABLE 1 HERE) 2.5 Outcome Measures Sleep Outcomes: Sleep duration was assessed using a combination of caregiver-maintained two-week sleep logs. Measurements were obtained prior to treatment initiation and repeated at the 18-month follow-up timepoint. Caregivers recorded bedtime, wake time, and nighttime awakenings during the logging period. Sleep onset insomnia and sleep maintenance insomnia were evaluated using the Caregiver Global Impression of Change (CGIC), a 7-point ordinal scale ranging from 1 (substantially improved) to 7 (substantially worsened). Caregivers completed CGIC at 18 months anchored to baseline status. Quality of Life: Caregiver-perceived quality of life was assessed using the CGIC scale at 18 months, compared to the baseline. Caregivers were instructed to consider overall child functioning and family well-being when completing ratings. 2.6 Safety Assessment Caregivers prospectively recorded both initial and sustained adverse effects throughout the treatment period. Reasons for treatment discontinuation were documented. 3. Statistical Analysis Descriptive statistics were used to summarize participant characteristics, treatment exposure, and follow-up duration. Continuous variables are presented as means with standard deviations or medians with interquartile ranges, as appropriate, and categorical variables are presented as counts and percentages. Changes in sleep duration from baseline to 18 months were analyzed using paired statistical tests. Normality of sleep duration differences was assessed visually and using standard distributional assessments. A paired t-test was used for normally distributed data, and the Wilcoxon signed-rank test was applied when distributional assumptions were not met. CGIC outcomes were treated as ordinal variables and were summarized by distribution across all response categories. For interpretability, CGIC outcomes were additionally grouped into clinically meaningful categories: improved (scores 1–3), no change (score 4), and worsened (scores 5–7), with proportions reported for each group. Analyses were conducted among participants who completed at least 18 months of follow-up. Given the observational design and modest sample size, multivariable modeling was not performed. All statistical analyses were conducted using Microsoft Excel with embedded statistical functions. 4. Results 4.1 Sleep Duration Outcomes Among participants completing at least 18 months of follow-up, mean caregiver-reported sleep duration increased from 6.8 to 8.1 hours (mean change +1.3 h, 95% CI 0.8–1.7; paired t-test p < 0.001), with 56% of participants achieving a ≥1-hour increase. Among children sleeping less than 6.5 hours at baseline (n = 22, 38%), mean sleep duration increased by 2.20 hours (95% CI 1.43–2.98), corresponding to a large within-subject effect (Cohen’s dz = 1.25). (INSERT TABLE 2 HERE) (INSERT FIGURE 1 HERE) 4.2 Sleep Onset, Maintenance, and Quality Outcomes CGIC ratings indicated improvement across multiple sleep domains. Improvements in sleep onset were reported by 41 of 57 caregivers (71.9%), while 16 (28.1%) reported no change and none reported worsening. For sleep maintenance, 43 caregivers (75.4%) reported improvement, 13 (22.8%) reported no change, and one (1.8%) reported worsening. Improvements in overall sleep quality were reported by 40 caregivers (70.2%), with the remaining 17 (29.8%) reporting no change. In descriptive analyses, improvements in sleep onset, maintenance, and duration were observed across formulation types, including balanced CBD:THC ratios and CBN-containing products, without a clear pattern favoring any single formulation. (INSERT TABLE 3 HERE) 4.3 Quality of Life Outcomes CGIC ratings demonstrated improvements in both child and caregiver quality of life. Improvement in child quality of life was reported by 52 of 57 caregivers (91.2%), while 4 (7.0%) reported no change and 1 (1.8%) reported worsening. Similarly, improvement in caregiver quality of life was reported by 51 caregivers (89.5%), with 3 (5.3%) reporting no change and 3 (5.3%) reporting worsening. In addition to sleep and quality of life measures, caregivers reported changes across several behavioral domains, including attention and focus, sensory sensitivities, anxiety and obsessive-compulsive features, and repetitive behaviors. Across these domains, most caregivers reported mild to moderate improvement, with fewer reporting no change and a small number reporting worsening. Improvements were most described as incremental rather than transformative, and behavioral responses varied across individuals. As these behavioral domains were assessed using caregiver impression ratings rather than validated behavioral instruments, they were not analyzed as primary outcomes and should be interpreted as descriptive, hypothesis-generating findings. (INSERT TABLE 4 HERE) (INSERT FIGURE 2 HERE) 4.4 Safety Outcomes Caregiver-reported adverse effects were common during the initial treatment period but declined over time. Approximately half of participants reported at least one adverse effect within the first two weeks of initiating medicinal cannabis, decreasing to approximately 20% by two months and to fewer than 10% by six months of treatment. The most frequently reported adverse effects included irritability, aggression, drowsiness, changes in appetite, weight gain, and rash. Most adverse effects were mild to moderate in severity and resolved with dose adjustment or continued treatment. Seven participants discontinued medicinal cannabis between two and six months due to persistent adverse effects, including irritability (n = 3), changes in appetite (n = 2), lack of perceived benefit (n = 1), and rash (n = 1). Two additional participants discontinued due to unaffordability, as treatment costs were not covered by insurance, and two discontinued due to travel-related restrictions. No serious adverse events were reported. (INSERT TABLE 5 HERE) 5. Discussion In this prospective clinic registry, medicinal cannabis use was associated with sustained improvements in sleep duration over an 18-month period, with particularly pronounced gains among children with more severe baseline sleep restriction and deprivation. In addition, the majority of caregivers reported favorable global impressions of change across sleep onset, sleep maintenance, sleep quality, and both child and caregiver quality of life. Taken together, these findings suggest that medicinal cannabis may be associated with meaningful, durable improvements in sleep-related outcomes in children with autism when used in a real-world clinical setting. Sleep disturbances are among the most burdensome co-occurring challenges in autism, affecting not only daytime functioning and emotional regulation in children but also caregiver sleep, stress, and overall family well-being (Malow et al., 2012 ; Tchaconas & Adesman, 2017 ). Improvements in sleep duration and sleep continuity may therefore have downstream effects that extend beyond nighttime symptoms alone, including daytime behavior and family functioning (Sadeh et al., 2002 ). The high proportion of caregivers reporting improvements in both child and caregiver quality of life in this study underscores the clinical relevance of sleep as a treatment target in autism and highlights the potential family-level impact of interventions that meaningfully improve sleep (Malow et al., 2012 ). The findings of this study are consistent with prior reports suggesting potential benefits of cannabinoid-based interventions on sleep and global functioning in autistic populations, while extending the literature by providing longer-term follow-up. Shorter-duration studies have reported caregiver-reported improvements in sleep and behavior, including open-label and observational cohorts from Israel demonstrating improvements in sleep and global functioning over periods ranging from eight weeks to six months (Aran et al., 2021 ; Poleg et al., 2019 ). Randomized controlled trials, including studies evaluating cannabidiol-dominant formulations, have reported modest improvements in behavior and related domains over short treatment intervals (Aran et al., 2021 ). The present study aligns with these reports while adding longitudinal data over 18 months, addressing an important gap in the literature regarding durability of effects in real-world clinical use. Several limitations should be considered when interpreting these findings. As a specialty clinic–based registry, the study population may overrepresent families with more severe sleep concerns and higher treatment engagement, which may limit generalizability to broader autistic populations. The observational design precludes causal inference, and outcomes were primarily caregiver-reported rather than derived from blinded or clinician-rated instruments (Hollway & Aman, 2011 ). The absence of a control group limits the ability to distinguish treatment effects from placebo response, regression to the mean, or natural developmental change. In addition, caregiver-reported outcomes are vulnerable to expectancy effects and heterogeneity in cannabis formulations and individualized dosing reflects real-world practice but limits conclusions regarding optimal product composition (Volkow et al., 2017 ). Despite these limitations, the prospective design, extended follow-up, and consistent pattern of findings across sleep and quality-of-life domains provide a clinically meaningful signal that warrants further investigation in controlled, long-term studies. Declarations Statement of Ethics Approval: The study was reviewed and approved by the University of Texas at Dallas Office of Research Compliance, Institutional Review Board (IRB), with a waiver of informed consent due to the retrospective, de-identified nature of the registry data. All procedures were conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments. References American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Publishing Aran A, Cassuto H, Lubotzky A, Wattad N, Hazan E, Ben-Shalom E, Harel M (2021) Brief report: Cannabidiol-rich cannabis in children with autism spectrum disorder and severe behavioral problems - A retrospective feasibility study. J Autism Dev Disord 51(2):677–684. https://doi.org/10.1007/s10803-020-04500-5 Courchesne V, Bacon K, Courchesne E (2018) Sleep problems in autism spectrum disorder: Prevalence, nature, and possible biopsychosocial mechanisms. J Autism Dev Disord 48(6):1999–2015. https://doi.org/10.1007/s10803-017-3396-8 Esteban-Figuerola P, Canals J, Fernández-Cao JC, Val A, V (2019) Differences in sleep patterns between children with autism spectrum disorder and typically developing children: A meta-analysis. Autism Res 12(6):939–947. https://doi.org/10.1002/aur.2105 Gringras P, Nir T, Breddy J, Frydman-Marom A, Findling RL (2017) Efficacy and safety of pediatric prolonged-release melatonin for insomnia in children with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry 56(11):948–957e4. https://doi.org/10.1016/j.jaac.2017.09.414 Hollway JA, Aman MG (2011) Sleep correlates of pervasive developmental disorders: A review of the literature. Res Dev Disabil 32(5):1399–1421. https://doi.org/10.1016/j.ridd.2011.02.001 Hyman SL, Levy SE, Myers SM (2020) Identification, evaluation, and management of children with autism spectrum disorder. Pediatrics, 145(1), e20193447 Janssen Pharmaceuticals, Inc (2020) Risperidone prescribing information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020272s085,020588s072,021444s058lbl.pdf Malow BA, Byars K, Johnson K, Weiss SK, Bernal P, Goldman SE, Panzer R, Coury DL, Glaze DG (2012) A practice pathway for the identification, evaluation, and management of insomnia in children and adolescents with autism spectrum disorders. Pediatrics 130(Suppl 2):S106–S124. https://doi.org/10.1542/peds.2012-0900I Otsuka America Pharmaceutical, Inc (2009) Aripiprazole prescribing information. U S Food Drug Adm https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021436Orig1s027.pdf Poleg S, Golubchik P, Offen D, Weizman A (2019) Cannabidiol as a suggested candidate for treatment of autism spectrum disorder. Prog Neuropsychopharmacol Biol Psychiatry 89:90–96. https://doi.org/10.1016/j.pnpbp.2018.08.030 Sadeh A, Gruber R, Raviv A (2002) Sleep, neurobehavioral functioning, and behavior problems in school-age children. Child Dev 73(2):405–417. https://doi.org/10.1111/1467-8624.00414 Tchaconas A, Adesman A (2017) Sleep problems in children with autism spectrum disorders. Pediatr Clin North Am 64(3):563–579. https://doi.org/10.1016/j.pcl.2017.01.014 Texas Department of Public Safety (2019) Compassionate Use Program. Retrieved March 2025, from https://www.dps.texas.gov/section/compassionate-use-program Volkow ND, Hampson AJ, Baler RD (2017) Don’t worry, be happy: Endocannabinoids and cannabis at the intersection of stress and reward. Annu Rev Pharmacol Toxicol 57:285–308. https://doi.org/10.1146/annurev-pharmtox-010716-104615 Zablotsky B, Black LI, Maenner MJ, Schieve LA, Blumberg SJ (2019) Estimated prevalence of autism spectrum disorder among children aged 3–17 years in the United States. Natl Health Stat Rep 65(142):1–11 Tables Table 1 Demographics and Treatment Characteristics Age at enrollment (years) Mean (SD) 10.6 (5.4) Median (range) 10.0 (1–17) Sex, n (%) Male 44 (77.2%) Female 13 (22.8%) Primary formulation, n (%) Tincture only 26 (45.6%) Gummy only 23 (40.4%) Combination (tincture + gummy) 8 (14.0%) CBD:THC ratio category Balanced (1:1 to 4:1) 41 (71.9%) CBD-dominant (≥10:1) 10 (17.5%) Mixed / variable ratios over time 6 (10.5%) CBN-containing products, n (%) 12 (21.1%) Dosing frequency, n (%) Once daily 11 (19.3%) Twice daily 29 (50.9%) Three times daily 13 (22.8%) As needed 4 (7.0%) Duration of treatment, (months) Mean (range) 22 (18–30) Table 2 Sleep Duration Outcomes Before and After Medicinal Cannabis Exposure A. Overall Cohort (n = 57) Outcome Value Sleep duration at baseline, mean (SD), hours 6.81 (SD: 1.6) Sleep duration at follow-up, mean (SD), hours 8.07 (SD: 1.5) Mean change in sleep duration (hours) +1.26 95% CI for mean change 0.80 to 1.73 Paired t-test p-value < 0.001 Participants with ≥1-hour increase in total sleep time 32 / 57 (56%) B. Children With Baseline Sleep Duration <6.5 Hours (n = 22, 38%) Outcome Value Sleep duration at baseline, mean (SD), hours 4.84 (SD: 0.9) Sleep duration at follow-up, mean (SD), hours 7.05 (SD: 1.1) Mean change in sleep duration (hours) 2.2 95% CI for mean change (hours) 1.43–2.98 Within-subject effect size (Cohen’s dz) 1.25 (large) Table 3 Caregiver-Reported Sleep Outcomes (CGIC) After Medicinal Cannabis Exposure (n = 57) Sleep Domain Improved, n (%) No Change, n (%) Worsened, n (%) Sleep onset 41 (71.9%) 16 (28.1%) 0 (0.0%) Sleep maintenance 43 (75.4%) 13 (22.8%) 1 (1.8%) Overall sleep quality 40 (70.2%) 17 (29.8%) 0 (0.0%) Table 4 Caregiver Global Impression of Change (CGIC): Quality of Life Outcomes (n = 57) Outcome Improved, n (%) No Change, n (%) Worsened, n (%) Child quality of life 52 (91.2%) 4 (7.0%) 1 (1.8%) Caregiver quality of life 51 (89.5%) 3 (5.3%) 3 (5.3%) Table 5 Safety and Treatment Discontinuation Outcomes A. Caregiver-Reported Adverse Effects Over Time Outcome Percentage (%) Any adverse effect within first 0-2 weeks Approximately 50% Any adverse effect at 2 months Approximately 20% Any adverse effect at 6 months <10% B. Treatment Discontinuation Reason for Discontinuation n (%) Total discontinued (of 68 enrolled) 11 (16.2%) Due to adverse effects 7 (10.3%) Irritability 3 (4.4%) Changes in appetite 2 (2.9%) Lack of perceived benefit 1 (1.5%) Rash 1 (1.5%) Due to unaffordability (insurance coverage) 2 (2.9%) Due to travel-related restrictions 2 (2.9%) C. Serious Adverse Events Outcome n (%) Serious adverse events 0 (0.0%) Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8689930","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":579953869,"identity":"ee15c802-f080-4f6e-8675-4c1d95bd1348","order_by":0,"name":"Mohsin Maqbool, MD.","email":"data:image/png;base64,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","orcid":"","institution":"Texas Child Neurology","correspondingAuthor":true,"prefix":"","firstName":"Mohsin","middleName":"","lastName":"Maqbool","suffix":"MD."},{"id":579953870,"identity":"7d74c8c9-8de6-4779-beea-7787302fae5e","order_by":1,"name":"Diya Khullar","email":"","orcid":"","institution":"The University of Texas at Dallas","correspondingAuthor":false,"prefix":"","firstName":"Diya","middleName":"","lastName":"Khullar","suffix":""},{"id":579953871,"identity":"4fcc2332-dec1-49f5-92bf-da7a06c2caa6","order_by":2,"name":"Izabella Jonhson","email":"","orcid":"","institution":"The University of Texas at Dallas","correspondingAuthor":false,"prefix":"","firstName":"Izabella","middleName":"","lastName":"Jonhson","suffix":""},{"id":579953872,"identity":"4c794324-14b7-4b7a-827d-89f26863c544","order_by":3,"name":"Taha Maqbool","email":"","orcid":"","institution":"The University of Texas at Dallas","correspondingAuthor":false,"prefix":"","firstName":"Taha","middleName":"","lastName":"Maqbool","suffix":""}],"badges":[],"createdAt":"2026-01-25 03:38:04","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-8689930/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8689930/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101364671,"identity":"ce1de998-d180-47a2-8006-57065b76cc1d","added_by":"auto","created_at":"2026-01-29 00:51:18","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":54443,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of total sleep duration at baseline and follow-up among children with autism spectrum disorder receiving medicinal cannabis: overall cohort (n = 57, left) and short-sleep subgroup sleeping \u0026lt;6.5 hours per night at baseline (n = 22, right).\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8689930/v1/42ef339a68e8299eab896886.jpg"},{"id":101364672,"identity":"75de9c21-0633-4f4d-9cd9-5df95520b778","added_by":"auto","created_at":"2026-01-29 00:51:18","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":67503,"visible":true,"origin":"","legend":"\u003cp\u003eCaregiver Global Impression of Change (CGIC) outcomes across sleep and quality-of-life domains following ≥18 months of medicinal cannabis exposure. Stacked bars represent the proportion of participants rated as improved (CGIC 1–3), unchanged (CGIC 4), or worsened (CGIC 5–7) for sleep onset, sleep maintenance, overall sleep quality, child quality of life, and caregiver quality of life (n = 57).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8689930/v1/43d962cbb8176f2ef1db36ef.jpg"},{"id":102298531,"identity":"c1781424-da20-460a-b772-93c5e99590c4","added_by":"auto","created_at":"2026-02-10 10:43:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":841330,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8689930/v1/3bcd12da-9361-4620-8837-033426d47581.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eAutism, Sleep, and Medicinal Cannabis: 18-Month Prospective Registry Outcomes on Efficacy and Safety\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAutism spectrum disorder is a common neurodevelopmental condition, currently estimated to affect approximately 1 in 32 children in the United States (Zablotsky et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Sleep disturbances are among the most prevalent and clinically significant co-occurring challenges in children with autism, with up to 80 percent experiencing chronic sleep difficulties (Courchesne, 2018, Esteban-Figuerola 2019). These commonly include sleep onset insomnia, sleep maintenance insomnia, and poor overall sleep quality (Hollway \u0026amp; Aman, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2011\u003c/span\u003e; Tchaconas \u0026amp; Adesman, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSleep difficulties in children with autism are multifactorial. Contributors include anxiety, sensory sensitivities, hyperactivity, circadian rhythm dysregulation, and neurobiological differences involving underdeveloped sleep regulatory circuitry (Sadeh et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2002\u003c/span\u003e; Malow et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). In addition, co-occurring but frequently underdiagnosed sleep disorders such as obstructive sleep apnea, periodic limb movement disorder, and restless sleep contribute to fragmented and insufficient sleep (Malow et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Persistent sleep disruption is associated with worsening daytime behavior, increased emotional dysregulation, impaired attention, and substantial negative effects on family quality of life (Sadeh et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2002\u003c/span\u003e; Tchaconas \u0026amp; Adesman, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePharmacologic treatment options for sleep disturbances in autism remain limited. The only U.S. Food and Drug Administration\u0026ndash;approved medications for children with autism spectrum disorder, risperidone and aripiprazole, are indicated for irritability rather than sleep and are associated with substantial metabolic, neurological, and behavioral adverse effects (Janssen Pharmaceuticals, Inc., 2020; Otsuka America Pharmaceutical, Inc., 2009; Hyman et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Other commonly used medications, including selective serotonin reuptake inhibitors, stimulants, and non-stimulants, demonstrate inconsistent effects on sleep and may exacerbate insomnia or behavioral symptoms (Hollway \u0026amp; Aman, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). Stimulants, while sometimes improving daytime attention, often worsen sleep onset and maintenance (Malow et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Melatonin is widely used and supported by evidence for improving sleep onset latency, yet its effects are frequently incomplete, particularly for sleep maintenance and long-term sleep quality (Gringras et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this context, families increasingly report the use of medicinal cannabis products to address sleep and behavioral challenges in children with autism. Caregivers commonly describe improvements in sleep duration, sleep continuity, and overall calmness (Aran et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Poleg et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Hemp-derived and cannabidiol-containing products are widely accessible through online and over-the-counter sources, and real-world use has rapidly outpaced the available clinical evidence, particularly regarding long-term efficacy and safety in pediatric populations (Volkow et al., \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn 2019, the legalization of medicinal cannabis for autism in Texas (Texas Department of Public Safety, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2019\u003c/span\u003e) created a unique opportunity to prospectively study real-world outcomes in a regulated clinical setting. Leveraging this policy change, the present study examines 18-month efficacy and safety outcomes of medicinal cannabis use in a prospective clinic registry of children with autism, with a focus on sleep duration and CGIC for sleep disturbance and quality of life.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003e\u003cstrong\u003e2.1\u0026nbsp;Study Design and Setting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis prospective observational study was conducted using a clinic-based registry of patients followed in a pediatric neurology and sleep medicine practice. The registry was established following the legalization of medicinal cannabis for autism in Texas in 2019 and was designed to capture real-world efficacy and safety outcomes associated with medicinal cannabis use. The study followed participants for a minimum of 18 months, with extended follow-up when available.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2\u0026nbsp;Participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants were children with autism receiving care in a specialty neurology and sleep clinic who elected to initiate medicinal cannabis as part of their clinical care. Inclusion criteria included a clinical diagnosis of autism spectrum disorder, the presence of severe sleep disturbance, and caregiver-reported concerns regarding sleep onset insomnia, sleep maintenance insomnia, or associated behavioral dysregulation. Participants included both medication-naïve patients and those who had previously failed multiple pharmacologic sleep interventions. Children with clinical features suggestive of obstructive sleep apnea (habitual snoring, witnessed apneas) or restless legs syndrome (caregiver-reported leg discomfort or urge to move) were excluded. These conditions were excluded a priori as they may independently disrupt sleep and act as mimickers or confounders of insomnia-related sleep disturbance.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA total of 68 patients elected to enroll in the registry and initiate medicinal cannabis treatment. Of these, 57 participants completed at least 18 months of follow-up and were included in the primary efficacy analyses. Eleven participants discontinued treatment prior to 18 months due to side effects (n = 7), cost-related barriers (n = 2), or travel or technical constraints (n = 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3\u0026nbsp;Ethics and Data Handling\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted using data collected as part of routine clinical care within a specialty clinic registry. Parents or legal guardians provided written informed consent for treatment and for inclusion of de-identified clinical data in research analyses. The study protocol was reviewed and determined to meet criteria for exempt research under applicable institutional policies, as it involved secondary analysis of de-identified clinical data. All data were stored within secure electronic medical records (eClinical Works v12.0.2) and the Texas Compassionate Use Registry (CURT), a state-maintained, HIPAA-compliant platform. No identifiable patient information was included in the analytic dataset.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4\u0026nbsp;Exposure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants initiated medicinal cannabis following shared decision-making between caregivers and clinicians. Cannabis products included tinctures and gummies containing cannabidiol (CBD) and tetrahydrocannabinol (THC) in varying ratios, including 1:1, 3:1, and 4:1 formulations. THC dosing was titrated gradually, beginning at 1.25 mg twice daily and increased in weekly increments of 1.25 mg as tolerated, to a maximum dose of 5 mg twice daily. Final dosing was individualized based on clinical response and tolerability. No new pharmacological sleep agents were initiated during the follow-up period. Participants continued previously prescribed medications, melatonin, or supplements at the discretion of their treating clinicians and caregivers, without protocol-mandated stabilization. Among participants who completed follow-up, the mean duration of treatment was 22 months, with a range of 18 to 30 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(INSERT TABLE 1 HERE)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.5\u0026nbsp;Outcome Measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSleep Outcomes:\u0026nbsp;\u003c/strong\u003eSleep duration was assessed using a combination of caregiver-maintained two-week sleep logs. Measurements were obtained prior to treatment initiation and repeated at the 18-month follow-up timepoint. Caregivers recorded bedtime, wake time, and nighttime awakenings during the logging period.\u003c/p\u003e\n\u003cp\u003eSleep onset insomnia and sleep maintenance insomnia were evaluated using the Caregiver Global Impression of Change (CGIC), a 7-point ordinal scale ranging from 1 (substantially improved) to 7 (substantially worsened). Caregivers completed CGIC at 18 months anchored to baseline status.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQuality of Life:\u0026nbsp;\u003c/strong\u003eCaregiver-perceived quality of life was assessed using the CGIC scale at 18 months, compared to the baseline. Caregivers were instructed to consider overall child functioning and family well-being when completing ratings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.6\u0026nbsp;Safety Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCaregivers prospectively recorded both initial and sustained adverse effects throughout the treatment period. Reasons for treatment discontinuation were documented.\u0026nbsp;\u003c/p\u003e"},{"header":"3. Statistical Analysis","content":"\u003cp\u003eDescriptive statistics were used to summarize participant characteristics, treatment exposure, and follow-up duration. Continuous variables are presented as means with standard deviations or medians with interquartile ranges, as appropriate, and categorical variables are presented as counts and percentages.\u003c/p\u003e \u003cp\u003eChanges in sleep duration from baseline to 18 months were analyzed using paired statistical tests. Normality of sleep duration differences was assessed visually and using standard distributional assessments. A paired t-test was used for normally distributed data, and the Wilcoxon signed-rank test was applied when distributional assumptions were not met.\u003c/p\u003e \u003cp\u003eCGIC outcomes were treated as ordinal variables and were summarized by distribution across all response categories. For interpretability, CGIC outcomes were additionally grouped into clinically meaningful categories: improved (scores 1\u0026ndash;3), no change (score 4), and worsened (scores 5\u0026ndash;7), with proportions reported for each group.\u003c/p\u003e \u003cp\u003eAnalyses were conducted among participants who completed at least 18 months of follow-up. Given the observational design and modest sample size, multivariable modeling was not performed. All statistical analyses were conducted using Microsoft Excel with embedded statistical functions.\u003c/p\u003e"},{"header":"4. Results","content":"\u003cp\u003e\u003cstrong\u003e4.1\u0026nbsp;Sleep Duration Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong participants completing at least 18 months of follow-up, mean caregiver-reported sleep duration increased from 6.8 to 8.1 hours (mean change +1.3 h, 95% CI 0.8–1.7; paired t-test p \u0026lt; 0.001), with 56% of participants achieving a ≥1-hour increase. Among children sleeping less than 6.5 hours at baseline (n = 22, 38%), mean sleep duration increased by 2.20 hours (95% CI 1.43–2.98), corresponding to a large within-subject effect (Cohen’s dz = 1.25).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(INSERT TABLE 2 HERE)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(INSERT FIGURE 1 HERE)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.2\u0026nbsp;Sleep Onset, Maintenance, and Quality Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCGIC ratings indicated improvement across multiple sleep domains. Improvements in sleep onset were reported by 41 of 57 caregivers (71.9%), while 16 (28.1%) reported no change and none reported worsening. For sleep maintenance, 43 caregivers (75.4%) reported improvement, 13 (22.8%) reported no change, and one (1.8%) reported worsening. Improvements in overall sleep quality were reported by 40 caregivers (70.2%), with the remaining 17 (29.8%) reporting no change.\u003c/p\u003e\n\u003cp\u003eIn descriptive analyses, improvements in sleep onset, maintenance, and duration were observed across formulation types, including balanced CBD:THC ratios and CBN-containing products, without a clear pattern favoring any single formulation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(INSERT TABLE 3 HERE)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.3\u0026nbsp;Quality of Life Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCGIC ratings demonstrated improvements in both child and caregiver quality of life. Improvement in child quality of life was reported by 52 of 57 caregivers (91.2%), while 4 (7.0%) reported no change and 1 (1.8%) reported worsening. Similarly, improvement in caregiver quality of life was reported by 51 caregivers (89.5%), with 3 (5.3%) reporting no change and 3 (5.3%) reporting worsening.\u003c/p\u003e\n\u003cp\u003eIn addition to sleep and quality of life measures, caregivers reported changes across several behavioral domains, including attention and focus, sensory sensitivities, anxiety and obsessive-compulsive features, and repetitive behaviors. Across these domains, most caregivers reported mild to moderate improvement, with fewer reporting no change and a small number reporting worsening. Improvements were most described as incremental rather than transformative, and behavioral responses varied across individuals. As these behavioral domains were assessed using caregiver impression ratings rather than validated behavioral instruments, they were not analyzed as primary outcomes and should be interpreted as descriptive, hypothesis-generating findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(INSERT TABLE 4 HERE)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(INSERT FIGURE 2 HERE)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.4\u0026nbsp;Safety Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCaregiver-reported adverse effects were common during the initial treatment period but declined over time. Approximately half of participants reported at least one adverse effect within the first two weeks of initiating medicinal cannabis, decreasing to approximately 20% by two months and to fewer than 10% by six months of treatment.\u003c/p\u003e\n\u003cp\u003eThe most frequently reported adverse effects included irritability, aggression, drowsiness, changes in appetite, weight gain, and rash. Most adverse effects were mild to moderate in severity and resolved with dose adjustment or continued treatment.\u003c/p\u003e\n\u003cp\u003eSeven participants discontinued medicinal cannabis between two and six months due to persistent adverse effects, including irritability (n = 3), changes in appetite (n = 2), lack of perceived benefit (n = 1), and rash (n = 1). Two additional participants discontinued due to unaffordability, as treatment costs were not covered by insurance, and two discontinued due to travel-related restrictions. No serious adverse events were reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(INSERT TABLE 5 HERE)\u003c/strong\u003e\u003c/p\u003e"},{"header":"5. Discussion","content":"\u003cp\u003eIn this prospective clinic registry, medicinal cannabis use was associated with sustained improvements in sleep duration over an 18-month period, with particularly pronounced gains among children with more severe baseline sleep restriction and deprivation. In addition, the majority of caregivers reported favorable global impressions of change across sleep onset, sleep maintenance, sleep quality, and both child and caregiver quality of life. Taken together, these findings suggest that medicinal cannabis may be associated with meaningful, durable improvements in sleep-related outcomes in children with autism when used in a real-world clinical setting.\u003c/p\u003e \u003cp\u003eSleep disturbances are among the most burdensome co-occurring challenges in autism, affecting not only daytime functioning and emotional regulation in children but also caregiver sleep, stress, and overall family well-being (Malow et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Tchaconas \u0026amp; Adesman, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Improvements in sleep duration and sleep continuity may therefore have downstream effects that extend beyond nighttime symptoms alone, including daytime behavior and family functioning (Sadeh et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2002\u003c/span\u003e). The high proportion of caregivers reporting improvements in both child and caregiver quality of life in this study underscores the clinical relevance of sleep as a treatment target in autism and highlights the potential family-level impact of interventions that meaningfully improve sleep (Malow et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2012\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe findings of this study are consistent with prior reports suggesting potential benefits of cannabinoid-based interventions on sleep and global functioning in autistic populations, while extending the literature by providing longer-term follow-up. Shorter-duration studies have reported caregiver-reported improvements in sleep and behavior, including open-label and observational cohorts from Israel demonstrating improvements in sleep and global functioning over periods ranging from eight weeks to six months (Aran et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Poleg et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Randomized controlled trials, including studies evaluating cannabidiol-dominant formulations, have reported modest improvements in behavior and related domains over short treatment intervals (Aran et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). The present study aligns with these reports while adding longitudinal data over 18 months, addressing an important gap in the literature regarding durability of effects in real-world clinical use.\u003c/p\u003e \u003cp\u003eSeveral limitations should be considered when interpreting these findings. As a specialty clinic\u0026ndash;based registry, the study population may overrepresent families with more severe sleep concerns and higher treatment engagement, which may limit generalizability to broader autistic populations. The observational design precludes causal inference, and outcomes were primarily caregiver-reported rather than derived from blinded or clinician-rated instruments (Hollway \u0026amp; Aman, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). The absence of a control group limits the ability to distinguish treatment effects from placebo response, regression to the mean, or natural developmental change. In addition, caregiver-reported outcomes are vulnerable to expectancy effects and heterogeneity in cannabis formulations and individualized dosing reflects real-world practice but limits conclusions regarding optimal product composition (Volkow et al., \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite these limitations, the prospective design, extended follow-up, and consistent pattern of findings across sleep and quality-of-life domains provide a clinically meaningful signal that warrants further investigation in controlled, long-term studies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eStatement of Ethics Approval: The study was reviewed and approved by the University of Texas at Dallas Office of Research Compliance, Institutional Review Board (IRB), with a waiver of informed consent due to the retrospective, de-identified nature of the registry data. All procedures were conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAmerican Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Publishing\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAran A, Cassuto H, Lubotzky A, Wattad N, Hazan E, Ben-Shalom E, Harel M (2021) Brief report: Cannabidiol-rich cannabis in children with autism spectrum disorder and severe behavioral problems - A retrospective feasibility study. J Autism Dev Disord 51(2):677\u0026ndash;684. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s10803-020-04500-5\u003c/span\u003e\u003cspan address=\"10.1007/s10803-020-04500-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCourchesne V, Bacon K, Courchesne E (2018) Sleep problems in autism spectrum disorder: Prevalence, nature, and possible biopsychosocial mechanisms. J Autism Dev Disord 48(6):1999\u0026ndash;2015. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s10803-017-3396-8\u003c/span\u003e\u003cspan address=\"10.1007/s10803-017-3396-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEsteban-Figuerola P, Canals J, Fern\u0026aacute;ndez-Cao JC, Val A, V (2019) Differences in sleep patterns between children with autism spectrum disorder and typically developing children: A meta-analysis. Autism Res 12(6):939\u0026ndash;947. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/aur.2105\u003c/span\u003e\u003cspan address=\"10.1002/aur.2105\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGringras P, Nir T, Breddy J, Frydman-Marom A, Findling RL (2017) Efficacy and safety of pediatric prolonged-release melatonin for insomnia in children with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry 56(11):948\u0026ndash;957e4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jaac.2017.09.414\u003c/span\u003e\u003cspan address=\"10.1016/j.jaac.2017.09.414\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHollway JA, Aman MG (2011) Sleep correlates of pervasive developmental disorders: A review of the literature. Res Dev Disabil 32(5):1399\u0026ndash;1421. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ridd.2011.02.001\u003c/span\u003e\u003cspan address=\"10.1016/j.ridd.2011.02.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHyman SL, Levy SE, Myers SM (2020) Identification, evaluation, and management of children with autism spectrum disorder. Pediatrics, 145(1), e20193447\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJanssen Pharmaceuticals, Inc (2020) Risperidone prescribing information. \u003cem\u003eU.S. Food and Drug Administration.\u003c/em\u003e \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020272s085,020588s072,021444s058lbl.pdf\u003c/span\u003e\u003cspan address=\"https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020272s085,020588s072,021444s058lbl.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalow BA, Byars K, Johnson K, Weiss SK, Bernal P, Goldman SE, Panzer R, Coury DL, Glaze DG (2012) A practice pathway for the identification, evaluation, and management of insomnia in children and adolescents with autism spectrum disorders. Pediatrics 130(Suppl 2):S106\u0026ndash;S124. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1542/peds.2012-0900I\u003c/span\u003e\u003cspan address=\"10.1542/peds.2012-0900I\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOtsuka America Pharmaceutical, Inc (2009) Aripiprazole prescribing information. U S Food Drug Adm \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021436Orig1s027.pdf\u003c/span\u003e\u003cspan address=\"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021436Orig1s027.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePoleg S, Golubchik P, Offen D, Weizman A (2019) Cannabidiol as a suggested candidate for treatment of autism spectrum disorder. Prog Neuropsychopharmacol Biol Psychiatry 89:90\u0026ndash;96. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.pnpbp.2018.08.030\u003c/span\u003e\u003cspan address=\"10.1016/j.pnpbp.2018.08.030\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSadeh A, Gruber R, Raviv A (2002) Sleep, neurobehavioral functioning, and behavior problems in school-age children. Child Dev 73(2):405\u0026ndash;417. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/1467-8624.00414\u003c/span\u003e\u003cspan address=\"10.1111/1467-8624.00414\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTchaconas A, Adesman A (2017) Sleep problems in children with autism spectrum disorders. Pediatr Clin North Am 64(3):563\u0026ndash;579. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.pcl.2017.01.014\u003c/span\u003e\u003cspan address=\"10.1016/j.pcl.2017.01.014\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTexas Department of Public Safety (2019) Compassionate Use Program. Retrieved March 2025, from \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.dps.texas.gov/section/compassionate-use-program\u003c/span\u003e\u003cspan address=\"https://www.dps.texas.gov/section/compassionate-use-program\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVolkow ND, Hampson AJ, Baler RD (2017) Don\u0026rsquo;t worry, be happy: Endocannabinoids and cannabis at the intersection of stress and reward. Annu Rev Pharmacol Toxicol 57:285\u0026ndash;308. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1146/annurev-pharmtox-010716-104615\u003c/span\u003e\u003cspan address=\"10.1146/annurev-pharmtox-010716-104615\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZablotsky B, Black LI, Maenner MJ, Schieve LA, Blumberg SJ (2019) Estimated prevalence of autism spectrum disorder among children aged 3\u0026ndash;17 years in the United States. Natl Health Stat Rep 65(142):1\u0026ndash;11\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003e\u003cem\u003eDemographics and Treatment Characteristics\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"492\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at enrollment (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e10.6 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e10.0 (1\u0026ndash;17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e44 (77.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e13 (22.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary formulation, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Tincture only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e26 (45.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Gummy only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e23 (40.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Combination (tincture + gummy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e8 (14.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCBD:THC ratio category\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39.0244%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Balanced (1:1 to 4:1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e41 (71.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;CBD-dominant (\u0026ge;10:1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e10 (17.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Mixed / variable ratios over time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e6 (10.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;CBN-containing products, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e12 (21.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDosing frequency, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Once daily\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e11 (19.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Twice daily\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e29 (50.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Three times daily\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e13 (22.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;As needed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e4 (7.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of treatment, (months)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 60.9756%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Mean (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39.0244%;\"\u003e\n \u003cp\u003e22 (18\u0026ndash;30)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u0026nbsp;\u003c/strong\u003e\u003cem\u003eSleep Duration Outcomes Before and After Medicinal Cannabis Exposure\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA. \u0026nbsp;Overall Cohort (n = 57)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"552\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76.8116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23.1884%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eValue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76.8116%;\"\u003e\n \u003cp\u003eSleep duration at baseline, mean (SD), hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23.1884%;\"\u003e\n \u003cp\u003e6.81 (SD: 1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76.8116%;\"\u003e\n \u003cp\u003eSleep duration at follow-up, mean (SD), hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23.1884%;\"\u003e\n \u003cp\u003e8.07 (SD: 1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76.8116%;\"\u003e\n \u003cp\u003eMean change in sleep duration (hours)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23.1884%;\"\u003e\n \u003cp\u003e+1.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76.8116%;\"\u003e\n \u003cp\u003e95% CI for mean change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23.1884%;\"\u003e\n \u003cp\u003e0.80 to 1.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76.8116%;\"\u003e\n \u003cp\u003ePaired t-test p-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23.1884%;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76.8116%;\"\u003e\n \u003cp\u003eParticipants with \u0026ge;1-hour increase in total sleep time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23.1884%;\"\u003e\n \u003cp\u003e32 / 57 (56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eB. \u0026nbsp;Children With Baseline Sleep Duration \u0026lt;6.5 Hours (n = 22, 38%)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"556\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 78.9946%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.0054%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eValue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 78.9946%;\"\u003e\n \u003cp\u003eSleep duration at baseline, mean (SD), hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.0054%;\"\u003e\n \u003cp\u003e4.84 (SD: 0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 78.9946%;\"\u003e\n \u003cp\u003eSleep duration at follow-up, mean (SD), hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.0054%;\"\u003e\n \u003cp\u003e7.05 (SD: 1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 78.9946%;\"\u003e\n \u003cp\u003eMean change in sleep duration (hours)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.0054%;\"\u003e\n \u003cp\u003e2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 78.9946%;\"\u003e\n \u003cp\u003e95% CI for mean change (hours)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.0054%;\"\u003e\n \u003cp\u003e1.43\u0026ndash;2.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 78.9946%;\"\u003e\n \u003cp\u003eWithin-subject effect size (Cohen\u0026rsquo;s dz)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.0054%;\"\u003e\n \u003cp\u003e1.25 (large)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003e\u003cem\u003eCaregiver-Reported Sleep Outcomes (CGIC) After Medicinal Cannabis Exposure (n = 57)\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"621\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5161%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSleep Domain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.1935%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImproved, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.6452%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo Change, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25.6452%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWorsened, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5161%;\"\u003e\n \u003cp\u003eSleep onset\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.1935%;\"\u003e\n \u003cp\u003e41 (71.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.6452%;\"\u003e\n \u003cp\u003e16 (28.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25.6452%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5161%;\"\u003e\n \u003cp\u003eSleep maintenance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.1935%;\"\u003e\n \u003cp\u003e43 (75.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.6452%;\"\u003e\n \u003cp\u003e13 (22.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25.6452%;\"\u003e\n \u003cp\u003e1 (1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5161%;\"\u003e\n \u003cp\u003eOverall sleep quality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.1935%;\"\u003e\n \u003cp\u003e40 (70.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.6452%;\"\u003e\n \u003cp\u003e17 (29.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25.6452%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u0026nbsp;\u003c/strong\u003e\u003cem\u003eCaregiver Global Impression of Change (CGIC): Quality of Life Outcomes (n = 57)\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"590\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 30.4569%;\"\u003e\n \u003cp\u003eOutcome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.335%;\"\u003e\n \u003cp\u003eImproved, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25.0423%;\"\u003e\n \u003cp\u003eNo Change, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.1658%;\"\u003e\n \u003cp\u003eWorsened, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 30.4569%;\"\u003e\n \u003cp\u003eChild quality of life\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.335%;\"\u003e\n \u003cp\u003e52 (91.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25.0423%;\"\u003e\n \u003cp\u003e4 (7.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.1658%;\"\u003e\n \u003cp\u003e1 (1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 30.4569%;\"\u003e\n \u003cp\u003eCaregiver quality of life\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.335%;\"\u003e\n \u003cp\u003e51 (89.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25.0423%;\"\u003e\n \u003cp\u003e3 (5.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22.1658%;\"\u003e\n \u003cp\u003e3 (5.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003c/strong\u003e\u003cstrong\u003eTable 5\u0026nbsp;\u003c/strong\u003e\u003cem\u003eSafety and Treatment Discontinuation Outcomes\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"616\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eA. Caregiver-Reported Adverse Effects Over Time\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003eOutcome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003ePercentage (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003eAny adverse effect within first 0-2 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003eApproximately 50%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003eAny adverse effect at 2 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003eApproximately 20%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003eAny adverse effect at 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003e\u0026lt;10%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eB. Treatment Discontinuation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003eReason for Discontinuation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003eTotal discontinued (of 68 enrolled)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003e11 (16.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Due to adverse effects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003e7 (10.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Irritability\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003e3 (4.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Changes in appetite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003e2 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Lack of perceived benefit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003e1 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Rash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003e1 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Due to unaffordability (insurance coverage)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003e2 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Due to travel-related restrictions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003e2 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eC. Serious Adverse Events\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003eOutcome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 73.0519%;\"\u003e\n \u003cp\u003eSerious adverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.9481%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Texas Child Neurology","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Autism spectrum disorder, Sleep disturbance, Pediatric insomnia, Medicinal cannabis, Cannabidiol (CBD), Tetrahydrocannabinol (THC)","lastPublishedDoi":"10.21203/rs.3.rs-8689930/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8689930/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePurpose\u003c/p\u003e\n\u003cp\u003eSleep disturbances are highly prevalent in children with autism and are associated with worsening daytime functioning and reduced family quality of life. Despite widespread real-world use of medicinal cannabis to address sleep difficulties, long-term prospective data on efficacy and safety in pediatric autism populations remain limited. This study evaluated 18-month efficacy and safety outcomes of medicinal cannabis use on sleep in children with autism using a prospective clinic registry.\u003c/p\u003e\n\u003cp\u003eMethods\u003c/p\u003e\n\u003cp\u003eThis prospective observational study enrolled 68 children with autism initiating medicinal cannabis treatment within a specialty clinic registry. Cannabis products included tinctures and gummies. Caregiver-reported sleep duration was assessed before treatment initiation and after sustained exposure. Caregiver Global Impression of Change (CGIC) was recorded using a 7-point ordinal scale ranging from substantially improved to substantially worsened. Of the initial\u003c/p\u003e\n\u003cp\u003ecohort of 68, 57 participants completed 18 months of follow-up: 11 discontinued treatment due to side effects (n = 7), cost (n = 2), or travel barriers (n = 2). Descriptive and paired analyses were conducted to evaluate sleep outcomes and caregiver-reported change.\u003c/p\u003e\n\u003cp\u003eResults\u003c/p\u003e\n\u003cp\u003eAmong participants completing at least 18 months of follow-up, mean caregiver-reported sleep duration increased from 6.8 to 8.1 hours, corresponding to a mean increase of 1.3 hours (95% CI 0.8–1.7). Improvements were most pronounced among children with more severe baseline sleep deprivation, with those sleeping less than six hours per night demonstrating a mean increase of 2.2 hours. Across caregiver-reported sleep domains, approximately 70-75% of caregivers reported improvement in sleep onset, sleep maintenance, and overall sleep quality, with minimal reports of worsening. CGIC ratings also indicated improvement in both child and caregiver quality of life in the majority of participants. Caregivers additionally reported modest, variable improvements across several behavioral domains, including attention, sensory sensitivities, anxiety, and repetitive behaviors, which were assessed descriptively. Adverse effects were most commonly reported early in treatment and declined over time, with treatment discontinuation due to persistent adverse effects occurring in a minority of participants and no serious adverse events observed.\u003c/p\u003e","manuscriptTitle":"Autism, Sleep, and Medicinal Cannabis: 18-Month Prospective Registry Outcomes on Efficacy and Safety","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-29 00:51:09","doi":"10.21203/rs.3.rs-8689930/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cfffbdf6-4f5f-4d99-9629-d9b5808fa253","owner":[],"postedDate":"January 29th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":61705049,"name":"Developmental Neuroscience"},{"id":61705050,"name":"Neurology"}],"tags":[],"updatedAt":"2026-01-29T00:51:09+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-29 00:51:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8689930","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8689930","identity":"rs-8689930","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}