REGISTRO DOI: 10.69849/revistaft/ar10202411160928
Felipe Santos Teixeira Martiniano¹; Jackeline Barbosa²; Leandro Cardozo-Batista³; Telma Florio⁴; Luiza Ramos⁵; Matheus Novaes de Souza⁶; Renata Alves da Costa⁷; Natan dos Santos Oliveira⁸; Fernanda Firak Cuevas Rocha Pereira⁸; Matheus Martinez de Castro Rebola⁸; Julio Elias Calheiros⁸; Elton Ramos da Luz⁹; Danilo Coutinho Lins de Andrade¹⁰; Claudia de Brito Araújo¹¹; José Carlos Varella Junior¹².
Abstract
Introduction: This study investigates the therapeutic potential of cannabidiol (CBD) in treating Alzheimer’s disease (AD), which is characterized by progressive cognitive decline, memory impairment, and behavioral changes. As traditional treatment options are limited, the exploration of alternative therapies, including CBD, has gained prominence in recent years. Objective: The aim of this research is to evaluate the efficacy of CBD in modulating neuroinflammation and oxidative stress, as well as its potential impact on slowing the progression of Alzheimer’s disease. Method: A literature review was conducted using ten articles published between 2019 and 2024. Databases such as the Virtual Health Library, LILACS Plus, and Medline were utilized, applying descriptors related to CBD and Alzheimer’s disease. The articles were filtered based on specific inclusion criteria, focusing on studies published in Portuguese, Spanish, and English that are freely accessible online. Results: The reviewed literature indicates that CBD may inhibit the formation of beta-amyloid plaques, a hallmark of Alzheimer’s pathology, suggesting its potential for both symptom relief and slowing disease progression. Additionally, the interaction between CBD and the endocannabinoid system (ECS) highlights its role in managing cognitive decline and memory issues associated with AD. Conclusion: While the findings are promising, there is a pressing need for more rigorous clinical studies to validate the efficacy and safety of CBD in Alzheimer’s treatment. This research underscores the potential of cannabinoids as a therapeutic option in managing neurodegenerative diseases.
Keywords: Cannabidiol, Alzheimer’s Disease, Endocannabinoid System.
Introduction
The therapeutic potential of cannabinoids, particularly cannabidiol (CBD), has garnered increasing attention in recent years, especially in the context of neurodegenerative diseases such as Alzheimer’s disease (AD) (Machado et al., 2024). AD, characterized by progressive cognitive decline, memory impairment, and behavioral changes, presents a significant challenge for patients, caregivers, and healthcare systems worldwide (Livingston et al., 2024). In the quest for effective treatments, the exploration of alternative therapies, including CBD, emerges as a promising avenue for research (Renard et al., 2024).
CBD, a non-psychoactive compound extracted from the Cannabis sativa plant, has shown potential in modulating various neurobiological processes (Schouten et al., 2024). Studies indicate that CBD possesses anti-inflammatory and antioxidant properties, which may play a crucial role in combating neuroinflammation and oxidative stress often observed in the pathology of AD (Andres et al., 2024; Costanza Mazzantini et al., 2024). Preliminary investigations suggest that CBD may inhibit the formation of beta-amyloid plaques-hallmarks of AD indicating its potential not only for symptom relief but also for slowing the progression of the disease (Patil et al., 2023; Costa et al., 2022).
Furthermore, the endocannabinoid system (ECS), responsible for regulating various physiological processes, has been implicated in the pathophysiology of Alzheimer’s disease (Barker et al., 2024). Dysregulation of the ECS may contribute to the exacerbation of cognitive symptoms, making it an important target for therapeutic interventions (Tudorancea et al., 2022). The interaction between CBD and the ECS suggests that modulating this system could offer new strategies for managing the symptoms of AD, particularly cognitive decline and memory issues (Dallabrida et al., 2024). Thus, the exploration of CBD’s role in addressing neuroinflammation and oxidative stress associated with AD further highlights its potential therapeutic value in the context of this study and about this complex disease.
In light of these considerations, the primary aim of this study is to investigate the therapeutic potential of cannabidiol (CBD) in treating Alzheimer’s disease, with a particular focus on its effects on neuroinflammation, oxidative stress, and neural plasticity.
Method
This study performed a literature review on the application of cannabidiol in treating Alzheimer’s disease and its related symptoms. The investigation utilized databases such as the Virtual Health Library, LILACS Plus, and Medline, applying descriptors like “Cannabidiol (433 articles)”, “Alzheimer (2.814 articles)” and “Endocannabinoid System (275 articles).” Boolean operators “AND” and “OR” were used to refine the search results. The total of articles found were 3.522. Initially, the search yielded a comprehensive number of articles across these databases.
The process involved implementing these descriptors in the chosen databases and filtering the outcomes to include only articles that met specific inclusion criteria. These criteria focused on articles published in Portuguese, Spanish, and English that were freely accessible online and published within the last five years, from 2019 to 2024 and including CBD and DA in the context. The total of articles remained were 24.
The abstracts of the selected articles were reviewed to confirm their relevance to the topic at hand. Following this preliminary evaluation, a selection of articles was made for full reading, as they provided an in-depth examination of the subject. Ultimately, 09 articles that most effectively contributed to the research discussion were selected.
To analyze the data, we arranged the 09 selected articles into a table (Table 1), highlighting the main findings from each. This organization facilitated the identification of shared themes and varying viewpoints among the authors, thereby enriching the discussion within this study.
Results
Table 1 – Summary of the reviewed results
| Year | Authors | Objective | Conclusion |
| 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. |
| 2022 | Costa, A. C., Helena, Pedrazzi, João F C, Pain, Duque, G., & Aprahamian, I. | To explore of the CBD and tetrahydrocannabinol (THC), as potential treatments for neurodegenerative diseases like Parkinson’s and Alzheimer’s. | Cannabinoids may have an important therapeutic role as adjunct treatments for patients with Parkinson’s and Alzheimer’s who do not respond well to first-line therapies, strong evidence from clinical trials is still lacking. |
| 2022 | Stefane, B., Milanezi, D. S., Priscila, Detoni, F. R., & Soriano, R. N. | To highlight the importance of understanding the pathophysiology of Alzheimer’s disease (AD) to improve treatment efficacy. | The review suggests that targeting gut microbiota may be a promising therapeutic approach for CBD in the context of AD, as addressing intestinal dysbiosis could help mitigate neuroinflammation and neuronal damage associated with the disease. |
| 2022 | Viana, Everson, P., Estadella, D., Ribeiro, D. A., & Socorro. | To review the current state of cannabinoid, use in neurodegenerative diseases, particularly focusing on Parkinson’s and Alzheimer’s diseases. | While there is growing evidence supporting CBD’s neuroprotective and anti-inflammatory effects, particularly in preclinical studies, clinical data remains less convincing. |
| 2022 | Morales, D. E., Patricio, F., Rebolledo-Bustillo, M., Garcia-Gomez, D et al. | To understand the dual role of CBD as both an antagonist and potential agonist at these receptors using computational methods: GPR55 and CB1. | Identified specific interacting sites in both receptors that contribute to CBD’s differential functional effects, enhancing the understanding of CBD’s pharmacology and its potential therapeutic applications. |
| 2022 | Paes-Colli, Y., Aguiar, A. F. L., Isaac, A. R., Ferreira, B. K et al. | To discuss the historical use of Cannabis in medicine, particularly its recent rise in Cannabis-based products for treating neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and Multiple Sclerosis. | The review highlights the anti-inflammatory, immunosuppressive, antioxidant, and neuroprotective properties of Cannabis-based medicines, which are associated with positive clinical outcomes in neurodegenerative diseases. |
| 2021 | Bittes, Y. P., Ribeiro, L. B., Anselmo, G. S., Dantas, T. C. L et al. | To describe the experience of family members/caregivers of people with Alzheimer’s disease who use cannabidiol as a form of treatment through Instituto Acalme (Associação Canabis Luz Medicinal). | Relevant for health as it deepens our understanding of the therapeutic potential of Cannabis-based treatments, which are gaining traction year by year. |
| 2019 | Plancarte-Sánchez, R., Mansilla-Olivares, A., De, A., & Meneses-González, F. | To explore the historical development and research surrounding cannabinoids, particularly focusing on their therapeutic potential across various medical conditions, including epilepsy, multiple sclerosis, and neurodegenerative diseases like Alzheimer’s.Efficacy of Cannabidiol (CBD) in the Treatment of Alzheimer’s Disease A Critical Review of Evidence and Clinical Implications | The review highlights significant advancements in understanding cannabinoids and their health effects amid ongoing controversies. It emphasizes the necessity for further research and systematic reviews to clarify the complex relationship between marijuana and health outcomes. Ultimately, it aims to establish a clearer framework for the clinical use of cannabinoids in various medical conditions. |
| 2019 | Camargo Filho, M. F. de A., Romanini, A. P., Pyrich, B. C., Pedri, E et al. | To describe the therapeutic and adverse effects of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in the treatment of Parkinson’s and Alzheimer’s diseases, based on a literature search in the Medline database from 2007 to 2017. | The results indicate promising therapeutic effects of CBD and THC, including reductions in motor and cognitive symptoms and neuroprotective actions, largely attributed to their antioxidant and anti-inflammatory properties. |
Discussion
The research on the use of cannabinoids, particularly cannabidiol (CBD), in the treatment of Alzheimer’s disease (AD) is rapidly expanding, reflecting both therapeutic promises and significant challenges faced in clinical practice. Dallabrida et al. (2024) emphasize that CBD possesses properties that modulate neuroinflammation and oxidative stress, crucial factors in the progression of AD. Preclinical studies suggest that CBD may inhibit the formation of beta-amyloid plaques, one of the main markers of AD, indicating not only potential symptom relief but also a possible slowdown of the disease’s progression. This perspective is supported by Costa et al. (2022), who point out that while preliminary evidence is encouraging, the lack of randomized clinical trials validating these findings in humans represents a critical gap in knowledge.
Furthermore, the interaction between the endocannabinoid system and the pathophysiology of AD is a point deserving special attention. Stefane et al. (2022) discusses the growing evidence that intestinal dysbiosis, characterized by an imbalance in microbiota, may exacerbate the pathological processes of AD. They suggest that CBD, by acting as a modulator of intestinal inflammation, could potentially reduce the permeability of the blood-brain barrier, a factor that often contributes to neuroinflammation and neuronal death. This connection between gut health and neurodegeneration is an innovative aspect that, if explored more deeply, could open new therapeutic avenues. Bittes et al. (2021) also reinforce this idea by mentioning that the health of the microbiome may be closely related to the course of AD, highlighting the need for more research on the relationship between cannabinoids and gut health.
Viana et al. (2022) complement this discussion by examining the interactions of CBD with cannabinoid receptors, particularly CB1 and CB2. Although many preclinical studies show promising results, they warn of the variability in clinical data, which often depends on factors such as patient profile heterogeneity and the complexity of AD mechanisms. Morales et al. (2022) support this view by stating that the response to cannabinoid treatment can vary widely among individuals, suggesting the need for personalized treatment strategies. They stress that individualization of treatment is essential to maximize the efficacy of CBD, especially considering the diverse manifestations of AD.
D’Avila et al. (2022) provide a more detailed insight into the molecular action of CBD, exploring how it modulates different receptors in the endocannabinoid system. The authors discuss the functional duality of CBD, which can act as both an antagonist and an agonist in different contexts. This functional complexity of cannabidiol suggests that its therapeutic applications may be broader than initially presumed. However, the need for well-designed clinical trials to validate these mechanisms remains crucial. Camargo Filho et al. (2019) complement this view, highlighting that while the therapeutic effects of CBD and delta-9-tetrahydrocannabinol (THC) are promising, there is still a significant lack of clinical studies exploring efficacy at different doses and treatment durations. They emphasize that future research should focus on delineating these aspects to provide clear guidance for the clinical use of cannabinoids.
Paes-Colli et al. (2022) also deserve attention for discussing the role of the endocannabinoid system in the pathophysiology of AD. The authors argue that modulation of this system can result in anti-inflammatory and neuroprotective effects, making a strong case for the use of cannabis-based products in the treatment of neurodegenerative diseases. However, the lack of clear regulation and conclusive clinical studies still poses a significant obstacle to implementing these treatments in clinical practice. They emphasize the importance of establishing clear guidelines to ensure the safe and effective use of these therapies, so that patients can benefit without excessive risks.
The study by Bittes et al. (2021) reveals the experiences of family members and caregivers of AD patients using CBD, highlighting that while many report improvements in quality of life and symptom management, the lack of clear information about treatment remains a challenge. The authors note that perceptions of efficacy and safety are crucial for treatment adherence, and uncertainty regarding benefits and adverse effects may lead to hesitation in use. Therefore, education and awareness about cannabinoid use are essential to facilitate acceptance of these therapies, fostering greater confidence among patients and healthcare professionals.
Additionally, the discussion about the adverse effects of cannabinoid use, as addressed by Camargo Filho et al. (2019), is vital for a comprehensive understanding of treatment. The authors highlight that, despite few adverse effects being reported, such as dry mouth and drowsiness, the need for careful monitoring of patients during treatment is undeniable. The lack of robust data on the long-term safety of cannabinoid use remains a concern that cannot be overlooked.
In summary, the discussion surrounding the use of CBD in the treatment of Alzheimer’s disease reveals a complex and multifaceted landscape. There is a growing consensus among researchers about the therapeutic potential of cannabinoids, but clinical evidence is still insufficient for widespread and safe recommendations. Scientific validation of cannabinoid therapies is essential for their effective integration into the management of AD, aiming to significantly improve the quality of life for patients and their caregivers. Collaboration among researchers, clinicians, and policymakers is crucial to advance the understanding and application of CBD and other cannabinoids in clinical practice. The development of clear guidelines, along with rigorous clinical studies, will be critical to ensuring that the potential benefits of cannabinoids are realized while mitigating associated treatment risks.
Conclusion
The use of cannabinoids, particularly cannabidiol (CBD), in the treatment of Alzheimer’s disease (AD) represents an area of growing interest and therapeutic potential. Although the available evidence is encouraging, it is still in development and lacks robust clinical validation. Current research suggests that CBD may offer significant benefits by modulating neuroinflammation, reducing oxidative stress, and improving neural plasticity key factors in the pathology of AD.
However, it is essential to recognize that individual responses to cannabinoid treatment can vary considerably, necessitating a personalized approach that considers each patient’s specific characteristics. Additionally, the absence of clear guidelines and regulation regarding the use of cannabis-based products remains a challenge that must be addressed to ensure safety and efficacy in treatment.
The reviewed studies highlight the urgent need for more well-structured randomized clinical trials that not only confirm the beneficial effects of CBD but also explore its long-term safety. Collaborative efforts among researchers, clinicians, and policymakers will be vital for integrating CBD and other cannabinoids into clinical practice, allowing patients with AD to benefit from innovative treatments that can improve their quality of life. The pursuit of new therapeutic strategies is crucial, and cannabinoids may play a significant role in the multidisciplinary approach necessary for effective management of Alzheimer’s disease.
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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.
⁵Physician, Resident in Anesthesiology (HSERJ), Researcher at Canapse – National Academic Consortium of Cannabinology and Research.
⁶Master’s Program in Aging Sciences – São Judas Tadeu University – PGCE.
⁷Psychologist, Master in Health Sciences – Federal University of São Paulo – UNIFESP.
⁸Medical student at the University of Ribeirão Preto – UNAERP, Guarujá campus.
⁹Medical student at International University Center – UNINTER.
¹⁰Family and Community Physician under the More Doctors Program.
¹¹Bachelor’s degree in Social Work – UNISA, with a postgraduate degree in Mental Health with emphasis on Chemical Dependency.
¹²Bachelor’s degree in Social Work – UNIFESP, with a postgraduate degree in Public Health Management.