REGISTRO DOI: 10.69849/revistaft/ar10202411160946
Felipe Santos Teixeira Martiniano¹; Jackeline Barbosa²; Leandro Cardozo-Batista³; Telma Florio⁴; Brenda Julia Cardoso Felix⁵; Ana Clara Pavaneli R. De Souza⁵; Carolina Carvalho de Freitas⁵; Giulia Bortoloni Agria⁵; Maria Vitória Franco Alves de Oliveira⁵; Pietra Kananovicz Fernandes⁵; Bianca Proença Bittar⁵; Fabrício Oliveira Santos⁵; Bruna Felix de Lima Souza Ramos⁵; Luiza Ramos⁶; Vanessa Andrade Belém⁷.
Abstract
Introduction: Autism Spectrum Disorder (ASD) encompasses a range of neurodevelopmental disorders characterized by persistent deficits in communication and social interaction, along with restrictive and repetitive behaviors. Conventional interventions often face limitations, prompting interest in alternative treatments, particularly those involving the endocannabinoid system (ECS) and cannabidiol (CBD). Objectives: This study aims to evaluate the role of the ECS and the efficacy of CBD as therapeutic interventions for ASD and its comorbidities. Methods: A literature review was conducted, focusing on articles published in Portuguese, Spanish, and English from 2019 to 2024. Databases such as the Virtual Health Library, LILACS Plus, and Medline were searched using descriptors: “Cannabidiol,” “Autism,” and “Endocannabinoid System”. Boolean terms “AND” and “OR” refined the results. A total of 7 articles from Medline and 3 from LILACS were initially identified. Results: The review identified 10 relevant articles that provided comprehensive insights into the effects of CBD on core ASD symptoms, including social interaction and anxiety. Most studies reported significant improvements in patients, with minimal adverse effects, emphasizing the safety of CBD compared to traditional treatments. Conclusion: The findings suggest that CBD may offer a promising alternative for treating ASD and its comorbidities, with a favorable safety profile. Continued research is essential to establish effective guidelines for clinical application.
Key words: Cannabidiol; Autism; Treatment; Endocannabinoid System; Comorbidities.
Introduction
Autism Spectrum Disorder (ASD) comprises a complex set of neurodevelopmental disorders characterized by persistent deficits in communication and social interaction, alongside restricted and repetitive patterns of behavior (Duque-Cartagena et al., 2024). Its prevalence has risen over the past few decades, reflecting both increased awareness of the disorder and broader diagnostic criteria (Espinosa-Díaz et al., 2024).
Conventional interventions, which include behavioral and pharmacological therapies, often face limitations in their efficacy and may lead to undesirable side effects, prompting the search for therapeutic alternatives (Qin et al., 2024).
In recent years, the endocannabinoid system (ECS) has emerged as an area of growing interest in ASD research due to its role in regulating neurological and behavioral functions (Jana et al., 2024). Cannabidiol (CBD), one of the key non-psychoactive compounds from the Cannabis sativa plant, has demonstrated potential in both preclinical and clinical studies to improve symptoms related to ASD, such as anxiety, socialization difficulties, and repetitive behaviors (Pedrazzi et al., 2024). The safety and tolerability of CBD, compared to conventional antipsychotic medications, make it an attractive option, especially in pediatric populations (Silva et al., 2023).
This work aims to explore the current literature on the use of cannabinoids, with a focus on CBD, as a promising therapeutic intervention for ASD and its comorbidities. It analyzes clinical evidence, mechanisms of action, and implications for clinical practice. Building on this goal, the primary aim of this study is to evaluate the role of the endocannabinoid system (ECS) and the efficacy of cannabidiol (CBD) as therapeutic interventions in the treatment of Autism Spectrum Disorder (ASD) and its comorbidities.
Method
This study conducts a literature review on the role of cannabidiol in the treatment of Autism Spectrum Disorder and its comorbidities.
The research was carried out in databases such as the Virtual Health Library, LILACS Plus, and Medline, using the following descriptors: “Cannabidiol”, (433 articles) “Autism” (1677) and ” Endocannabinoid System” (275 articles). Boolean terms “AND” and “OR” were employed to refine the results. Initially, we found a total of 2,385 articles in the data bases.
The search process involved applying these descriptors in the selected databases, filtering the results to ensure that only articles meeting the inclusion criteria were considered. To achieve this objective, we established inclusion criteria that encompass articles published in Portuguese, Spanish, and English, which are freely accessible online, and published in the last five years, from 2019 to 2024. A total of 26 articles responded the criteria considering autism a associated to cannabidiol and endocannabinoid System.
We read the abstracts of the selected articles to ensure their relevance to the proposed topic. After this screening, we chose 15 articles and read them in full, as they provided a comprehensive review of the topic. Finally, we selected the 10 articles that best supported the discussion of this research.
For data analysis, we compiled the 10 selected articles in a table (Table 1) and synthesized the main results of each, identifying common themes and divergences in the authors’ approaches and recommendations, thereby enriching the discussion of this study.
Results
Table 1 – Summary of the reviewed results
| Year | Authors | Objective | Conclusion |
| 2024 | Mazza JAS, Ferreira LS, Martins-Vieira AF, Beserra DDL e tal. | To observe the range of neurodevelopmental conditions characterized by deficits in social interaction, communication and behavior. | The observed improvements included increased communicative skills, attention, learning, eye contact, diminished aggression and irritability, and an overall increase in both the patient’s and family’s quality of life. |
| 2024 | Dallabrida KG, de Oliveira Bender JM, Chade ES, Rodrigues N, Sampaio TB. | To understand the impact of cannabinoids in the therapeutic treatment of patients with ASD, ADHD, and Alzheimer’s disease (AD). | cannabis products rich in CBD displayed a higher therapeutic potential for ASD children, while cannabis products rich in THC have been tested more for AD therapy. |
| 2024 | Junior, S., Medeiros, João, S., Sousa, Costa, Pontes, K. M., Borges et al. | To evaluate the efficacy and safety of a cannabis extract rich in cannabidiol (CBD) in children with ASD. | CBD-rich cannabis extract was found to improve one of the diagnostic criteria for ASD (social interaction), as well as features that often co-exist with ASD, and to have few serious adverse effects. |
| 2023 | Silva, Medeiros, W., Leandro, S., Borges, C. N., Brasil-Neto et al. | To conduct a retrospective analysis of 20 patients with autistic symptoms who were treated with full-spectrum cannabis extracts (FCEs) in a response-based, individually-tailored dosage regimen. | After FCE treatment, 18 out of 20 patients showed improvement in most core and comorbid symptoms of autism, and in quality of life for patients and their families. |
| 2023 | Mimura, P. M. P., Ferreira, L. S., & Pereira, C. L. | To present a brief review of the literature on the use of cannabinoids (CNB) in the management of ASD and epilepsy. | The use of CNB, both for epilepsy and for ASD, has been shown to be safe, however actual effectiveness has yet to be proven. |
| 2022 | Pedrazzi, J. F. C., Ferreira, F. R., Silva-Amaral, D., Lima, D. A et al. | Review the preclinical and clinical data supporting CBD’s potential as a treatment for the symptoms and comorbidities associated with ASD. | Cannabidiol (CBD) emerges as a possible strategy for treating ASD symptoms since it has relevant pharmacological actions on the endocannabinoid system and shows promising results in studies related to disorders in the central nervous system. |
| 2022 | Silva, E. A. da, Medeiros, W. M. B., Santos, J. P. M. D., Sousa et al. | CBD-rich cannabis extract was found to improve one of the diagnostic criteria for ASD (social interaction), as well as features that often co-exist with ASD, and to have few serious adverse effects. | Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and social interaction and by restricted and repetitive patterns of behavior. |
| 2021 | Augusto, R., Isaac, A. R., Freitas, H. R., Macedo, M., Schuck et al. | to discuss the fundamental role of the endocannabinoid system (ECS) in regulating various brain and bodily functions, including neurological development, appetite control, mood regulationincluding autism spectrum disorder (ASD). | Cannabidiol (CBD) is identified as a promising dietary supplement with beneficial properties for treating various health conditions. |
| 2020 | Loss CM, Teodoro L, Rodrigues GD, Moreira LR et al. | To discuss clinical and preclinical studies on schizophrenia and ASD investigating the behavioral, molecular, and functional. | The results point to CBD’s beneficial potential for the progression of these disorders supporting further investigations to strengthen its use. |
| 2019 | Fleury-Teixeira, P., Viegas, C. F., Leandro, S., Pereira et al. | to evaluate the effectiveness of standardized CBD-enriched Cannabis sativa extract (with a CBD to THC ratio of 75/1) in treating symptoms of Autism Spectrum Disorders (ASD). | The findings suggest that CBD-enriched Cannabis extract can significantly improve various ASD symptoms, particularly in non-epileptic patients, with most participants experiencing enhancements in multiple symptom categories and only mild adverse effects. |
Discussion
Research on the endocannabinoid system (ECS) and its role in Autism Spectrum Disorder (ASD) is rapidly evolving, with numerous studies highlighting the importance of this system in modulating behaviors and mental health. Augusto et al. (2021) emphasize that a loss of ECS control can significantly impact not only mental health but also the regulation of social behaviors. The ECS serves as a crucial modulator of brain homeostasis, and its dysregulation may contribute to neurodevelopmental conditions like ASD. This suggests that interventions targeting the ECS could be vital for treating these disorders. Furthermore, the interaction of the ECS with neurotransmitters may influence both cognitive and emotional functions, indicating its essential role in managing symptoms associated with ASD.
Dallabrida et al. (2024) provide robust evidence that cannabis-based products, particularly those rich in cannabidiol (CBD), improve fundamental ASD symptoms such as social interaction and anxiety. In their study, 80% of patients reported significant improvements after treatment with cannabis extracts. This finding aligns with Junior et al. (2024), who conducted rigorous clinical trials demonstrating that CBD is associated with improvements in attention deficit symptoms, a common comorbidity in individuals with ASD. The link between CBD and the reduction of ADHD symptoms is particularly relevant, as it shows that treatment may alleviate not only autistic symptoms but also adjacent areas that often complicate the clinical picture.
Regarding treatment safety, Silva et al. (2023) discuss that the use of cannabis extracts may be beneficial and safe for children with ASD. They observed that only 9.7% of participants reported mild adverse effects, such as insomnia and weight gain, which is crucial given concerns about side effects from traditional treatments. Frequently prescribed medications, such as risperidone and aripiprazole, can induce significant undesirable effects, compromising treatment adherence. This consideration is particularly relevant, as the search for alternatives with fewer side effects is a central goal in managing ASD. Moreover, the ability of CBD to provide relief without the severe side effects associated with traditional medications underscores its potential as a viable treatment option.
Additionally, the study by Silva et al. (2022) investigates the efficacy and safety of a CBD-rich cannabis extract in treating children with ASD. The results indicate significant improvements in various aspects related to ASD, including social interaction, anxiety, and psychomotor agitation. Notably, the robust study design—a randomized, double-blind, placebo-controlled trial—provides strong evidence supporting the effectiveness of CBD in addressing core symptoms of ASD. The low percentage of participants experiencing adverse effects reinforces the idea that CBD-rich extracts can serve as a safe alternative to traditional therapies, which often come with substantial side effects.
Mimura et al. (2023) explore the connection between ASD and epilepsy, noting that epilepsy prevalence is higher in ASD patients compared to the general population. This has led to a growing interest in using cannabinoids as a therapeutic alternative, especially for those who do not respond to conventional treatments. Loss et al. (2020) support this idea by discussing the potential of CBD to improve not only ASD symptoms but also those associated with epilepsy. Preclinical and clinical evidence suggests that CBD may positively affect the neurobiological pathways regulating both ASD and epilepsy, indicating that cannabinoid use may address comorbidities in an integrated manner. This holistic approach may be crucial for treatment, as many patients present multiple interrelated conditions that impact their quality of life.
Furthermore, Silva et al. (2023) highlights the personalized treatment approach involving full-spectrum cannabis extracts (FCEs) for 20 patients with autism symptoms. This retrospective analysis demonstrated significant improvements in core and comorbid autism symptoms, along with enhanced quality of life. The individualized dosing regimen allowed for adjustments based on observed effects, showcasing the flexibility of cannabinoid therapies. Notably, the study revealed the potential of FCEs to address symptoms like allotriophagia (Pica), which often do not respond well to conventional treatments.
However, Pedrazzi et al. (2022) caution about the heterogeneity of ASD, which can complicate treatment and the effectiveness of interventions. They emphasize that responses to cannabinoid treatment can vary widely among individuals, highlighting the need for personalized therapeutic approaches. Exploring the ECS should be accompanied by a deep understanding of individual characteristics, and continuous monitoring of patients is essential for optimizing outcomes. This personalization may involve adjustments in dosage and the choice of cannabinoid type, recognizing that there is no one-size-fits-all approach that works for all patients.
The convergence of findings reveals that while the use of cannabinoids shows significant promise, there are still gaps that need to be addressed in research. Loss et al. (2020) highlights the need for more robust clinical studies to validate the efficacy of CBD and other cannabinoids in a broader population, especially considering the diversity of symptoms and comorbidities present in ASD. Integrating clinical and preclinical evidence is crucial for building a more comprehensive understanding of the benefits of cannabinoids. Additionally, future research should focus on analyzing how different genetic and environmental profiles may influence the effectiveness of cannabinoid treatment.
In summary, the current literature suggests that the ECS and the use of cannabinoids, especially CBD, may offer valuable therapeutic alternatives for treating ASD and its comorbidities. However, it is imperative for the scientific community to continue investigating best practices and guidelines for the safe and effective use of cannabinoids in pediatric contexts. The pursuit of interventions that not only address ASD symptoms but also improve the quality of life for patients and their families should remain a central focus in future investigations.
Conclusion
The growing evidence regarding the role of the endocannabinoid system (ECS) in treating Autism Spectrum Disorder (ASD) suggests that the use of cannabinoids, particularly cannabidiol (CBD), may represent a promising therapeutic alternative. The reviewed studies indicate significant improvements in core ASD symptoms, including social interaction, anxiety, and comorbidities such as ADHD and behavioral disorders. The safety of treatment, with few reported adverse effects, reinforces the need to explore CBD as a viable option, especially in a pediatric context.
However, the heterogeneity of ASD requires personalized approaches, considering that the response to treatment can vary widely among individuals. Additionally, the interconnection between ASD and other conditions, such as epilepsy, highlights the importance of an integrated perspective that addresses multiple comorbidities. Despite the promising results, it is crucial that future research is conducted with scientific rigor to validate and expand these findings, ensuring that interventions are based on solid evidence.
The ongoing exploration of the endocannabinoid system (ECS) and the development of well-defined treatment protocols may provide new hope for individuals with ASD and their families, improving not only clinical symptoms but also overall quality of life. Therefore, investigating the use of cannabinoids should be a priority in mental health research, aiming for a deeper understanding of the mechanisms involved and the best practices for their clinical application.
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¹Medical resident in Internal Medicine at Beneficência Portuguesa Hospital in Santos.
²PhD in Medical Sciences – Federal University of Rio de Janeiro (UFRJ).
³PhD student in Health Sciences – Federal University of São Paulo – UNIFESP, medical student at the University of Ribeirão Preto – UNAERP, Guarujá campus.
⁴Master’s degree in Neuroscience and Behavior of the Interdisciplinary Postgraduate Program in Health Sciences at the Federal University of São Paulo – UNIFESP.
⁵Medical student at the University of Ribeirão Preto – UNAERP, Guarujá campus.
⁶Physician, Resident in Anesthesiology (HSERJ), Researcher at Canapse – National Academic Consortium of Cannabinology and Research.
⁷Nurse, Faculty of the South Coast of São Paulo – FALS.