Category Archives: Huntington’s Disease

Cannabinol’s Modulation of Genes Involved in Oxidative Stress Response and Neuronal Plasticity: A Transcriptomic Analysis

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“Cannabis sativa is a remarkable source of bioactive compounds, with over 150 distinct phytocannabinoids identified to date. Among these, cannabinoids are gaining attention as potential therapeutic agents for neurodegenerative diseases.

Previous research showed that cannabinol (CBN), a minor cannabinoid derived from Δ9-tetrahydrocannabinol, exhibits antioxidant, anti-inflammatory, analgesic, and anti-bacterial effects.

The objective of this study was to assess the protective potential of 24 h CBN pre-treatment, applied at different concentrations (5 µM, 10 µM, 20 µM, 50 µM, and 100 µM), in differentiated neuroblastoma × spinal cord (NSC-34) cells. Transcriptomic analysis was performed using next-generation sequencing techniques.

Our results reveal that CBN had no negative impact on cell viability at the tested concentrations. Instead, it showed a significant effect on stress response and neuroplasticity-related processes. Specifically, based on the Reactome database, the biological pathways mainly perturbed by CBN pre-treatment were investigated.

This analysis highlighted a significant enrichment in the Reactome pathway’s cellular response to stress, cellular response to stimuli, and axon guidance.

Overall, our results suggest that CBN holds promise as an adjuvant agent for neurodegenerative diseases by modulating genes involved in neuronal cell survival and axon guidance.”

https://pubmed.ncbi.nlm.nih.gov/40563376/

“Aging and neurodegenerative diseases are characterized by a progressive decline in cellular functions, including genomic instability, epigenetic alterations, mitochondrial dysfunction, and chronic inflammation. Our study supports that CBN exerts pleiotropic effects by modulating key molecular pathways involved in oxidative stress response, DNA repair, and neuronal survival. These results suggest that CBN positively modulates the response to cellular damage, stimulating the antioxidant response through the Nrf2 pathway and reducing the sensitivity to programmed cell death, as demonstrated by the regulation of caspases and other genes related to neuronal survival. These effects indicate that CBN may be able to support neuronal health under conditions of chronic stress, a hallmark of neurodegenerative diseases. These findings pave the way for further research into CBN’s therapeutic potential, emphasizing the need for in vivo studies to validate its efficacy and safety profile in neurodegenerative disease models.”

https://www.mdpi.com/2076-3921/14/6/744

Emerging nano-derived therapy for the treatment of dementia: a comprehensive review

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“Dementia includes a variety of neurodegenerative diseases that affect and target the brain’s fundamental cognitive functions. It is undoubtedly one of the diseases that affects people globally. The ameliorating the disease is still not known; the symptoms, however, can be prevented to an extent. Dementia encompasses Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Lewy body dementia, mixed dementia, and various other diseases.

The aggregation of β-amyloid protein plaques and the formation of neurofibrillary tangles have been concluded as the foremost cause for the onset of the disease. As the cases climb, new neuroprotective methods are being developed in the form of new drug delivery systems that provide targeted delivery.

Herbal drugs like Ashwagandha, Brahmi, and Cannabis have shown satisfactory results by not only treating the symptoms but have also been shown to reduce and ameliorate the formation of amyloid plaque formation.

This article explores the intricate possibilities of drug delivery and the absolute use of herbal drugs to target neurodegenerative diseases. The various possibilities of nanotechnology currently available with new emerging techniques are also discussed.”

https://pubmed.ncbi.nlm.nih.gov/40268841/

https://link.springer.com/article/10.1007/s13346-025-01863-3

Cannabinoids: Role in Neurological Diseases and Psychiatric Disorders

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“An impact of legalization and decriminalization of marijuana is the gradual increase in the use of cannabis for recreational purposes, which poses a potential threat to society and healthcare systems worldwide. However, the discovery of receptor subtypes, endogenous endocannabinoids, and enzymes involved in synthesis and degradation, as well as pharmacological characterization of receptors, has led to exploration of the use of cannabis in multiple peripheral and central pathological conditions.

The role of cannabis in the modulation of crucial events involving perturbed physiological functions and disease progression, including apoptosis, inflammation, oxidative stress, perturbed mitochondrial function, and the impaired immune system, indicates medicinal values.

These events are involved in most neurological diseases and prompt the gradual progression of the disease. At present, several synthetic agonists and antagonists, in addition to more than 70 phytocannabinoids, are available with distinct efficacy as a therapeutic alternative in different pathological conditions. The present review aims to describe the use of cannabis in neurological diseases and psychiatric disorders.”

https://pubmed.ncbi.nlm.nih.gov/39796008/

“Cannabis sativa L. (marijuana), an ancient plant with medicinal values, has been used for medicinal, recreational, and spiritual purposes for a long time worldwide.”

“The discovery of the ECS has sparked the interest of many researchers worldwide due to its potential therapeutic contribution to some of the incurable neurodegenerative diseases such as AD, PD, HD, and psychological abnormalities. To date, studies have uncovered the expression, location, structures, and mechanism of cannabinoid receptors.

When the endocannabinoid system’s associations with other biochemical pathways are fully elucidated, many medical and political changes will be seen, such as the legalization of marijuana and new therapeutic approaches to neurodegenerative diseases.

Recent developments regarding crystal structure and cryoEM open the door to understanding the structural complexity and future therapeutic implication of cannabinoids in neurological and psychiatric disorders. Most genes associated with neurological diseases have been defined; however, the molecular details of other changes are largely elusive and are of immense interest to be explored. At this stage, it will be interesting to elucidate the role of CB2R as a neuroprotective strategy in addition to other proteins that are modulated following cannabis administration.

Neuroinflammation, oxidative stress, and disrupted cell organelles, specifically mitochondria, are intimately associated with compelling causative factors for disease progression and are potential therapeutic avenues to explore in neurodegeneration, along with psychological disturbances; therefore, they should be the prime objective for future studies on cannabinoids to develop novel therapeutic chimeric molecules with minimum side effects and maximum benefits.”

https://www.mdpi.com/1422-0067/26/1/152

Cannabidiol induces autophagy via CB1 receptor and reduces α-synuclein cytosolic levels

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“Numerous studies have explored the role of cannabinoids in neurological conditions, chronic pain and neurodegenerative diseases. Restoring autophagy has been proposed as a potential target for the treatment of neurodegenerative diseases.

In our study, we used a neuroblastoma cell line that overexpresses wild-type α-synuclein to investigate the effects of cannabidiol on autophagy modulation and reduction in the level of cytosolic α-synuclein.

Our results demonstrated that cannabidiol enhances the accumulation of LC3-II- and GFP-LC3-positive vesicles, which indicates an increase in autophagic flux. In addition, cannabidiol-treated cells showed a reduction in cytosolic α-synuclein levels. These effects were inhibited when the cells were treated with a CB1 receptor-selective antagonist, which indicates that the biological effects of cannabidiol are mediated via its interaction with CB1 receptor. Additionally, we also observed that cannabinoid compounds induce autophagy and α-synuclein degradation after they interact with the CB1 receptor.

In summary, our data suggest that cannabidiol induces autophagy and reduces cytosolic α-synuclein levels. These biological effects are mediated preferentially through the interaction of cannabidiol with CB1 receptors, and therefore, cannabinoid compounds that act selectively on this receptor could represent a new approach for autophagy modulation and degradation of protein aggregates.”

https://pubmed.ncbi.nlm.nih.gov/39710053/

https://www.sciencedirect.com/science/article/pii/S0006899324006693?via%3Dihub

Therapeutic potentials of cannabidiol: Focus on the Nrf2 signaling pathway

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“Cannabidiol (CBD), a cannabinoid that does not create psychoactive activities, has been identified as having a multitude of therapeutic benefits.

This study delves into the chemical properties, pharmacokinetics, safety and toxicity, pharmacological effects, and most importantly, the association between the therapeutic potential of CBD and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.

The relationship between Nrf2 and CBD is closely linked to certain proteins that are associated with cardiovascular dysfunctions, cancers, and neurodegenerative conditions. Specifically, Nrf2 is connected to the initiation and progression of diverse health issues, including nephrotoxicity, bladder-related diseases, oral mucositis, cancers, obesity, myocardial injury and angiogenesis, skin-related inflammations, psychotic disorders, neuropathic pain, Huntington’s disease, Alzheimer’s disease, Parkinson’s disease, neuroinflammation, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis.

The association between CBD and Nrf2 is a zone of great interest in the medical field, as it has the potential to significantly impact the treatment and prevention of wide-ranging health conditions. Additional investigation is necessary to entirely apprehend the mechanisms underlying this crucial interplay and to develop effective therapeutic interventions.”

https://pubmed.ncbi.nlm.nih.gov/39491419/

“CBD plays a protective role in cardiovascular dysfunctions, cancers, and neurodegenerative conditions by targeting the Nrf2 signaling pathway.”

https://www.sciencedirect.com/science/article/pii/S0753332223016037?via%3Dihub

Cannabidiol and Neurodegeneration: From Molecular Mechanisms to Clinical Benefits

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“Neurodegenerative disorders (NDs) such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce malfunction of psycho-motor functions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-β, huntingtin, and tau, and accumulation of its associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation.

Cannabidiol is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo.

Cannabidiol has gained attention as a promising therapeutic drug candidate for the management of neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as its clinical applications in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area.”

https://pubmed.ncbi.nlm.nih.gov/38969143/

https://www.sciencedirect.com/science/article/abs/pii/S1568163724002046?via%3Dihub

Cannabinoids’ Role in Modulating Central and Peripheral Immunity in Neurodegenerative Diseases

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“Cannabinoids (the endocannabinoids, the synthetic cannabinoids, and the phytocannabinoids) are well known for their various pharmacological properties, including neuroprotective and anti-inflammatory features, which are fundamentally important for the treatment of neurodegenerative diseases.

The aging of the global population is causing an increase in these diseases that require the development of effective drugs to be even more urgent. Taking into account the unavailability of effective drugs for neurodegenerative diseases, it seems appropriate to consider the role of cannabinoids in the treatment of these diseases.

To our knowledge, few reviews are devoted to cannabinoids’ impact on modulating central and peripheral immunity in neurodegenerative diseases. The objective of this review is to provide the best possible information about the cannabinoid receptors and immuno-modulation features, peripheral immune modulation by cannabinoids, cannabinoid-based therapies for the treatment of neurological disorders, and the future development prospects of making cannabinoids versatile tools in the pursuit of effective drugs.”

https://pubmed.ncbi.nlm.nih.gov/38928109/

“The increasing acceptance of cannabinoids caused novel preclinical research of neurodegenerative diseases, which was collected and analyzed in this review. These studies demonstrated the neuroprotective properties of many cannabinoids through various cellular and molecular pathways in neurodegenerative diseases. The strengthening connection between the periphery and the CNS in the context of neurodegenerative diseases, together with the extensive immune activities of cannabinoids in both arenas, shows the complexity of immune modulation and the enormous therapeutic potential of cannabinoids in neurodegenerative diseases, which are very difficult to manage.”

https://www.mdpi.com/1422-0067/25/12/6402

Cannabinoids: Potential for Modulation and Enhancement When Combined with Vitamin B12 in Case of Neurodegenerative Disorders

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“The enduring relationship between humanity and the cannabis plant has witnessed significant transformations, particularly with the widespread legalization of medical cannabis.

This has led to the recognition of diverse pharmacological formulations of medical cannabis, containing 545 identified natural compounds, including 144 phytocannabinoids like Δ9-THC and CBD. Cannabinoids exert distinct regulatory effects on physiological processes, prompting their investigation in neurodegenerative diseases. Recent research highlights their potential in modulating protein aggregation and mitochondrial dysfunction, crucial factors in conditions such as Alzheimer’s Disease, multiple sclerosis, or Parkinson’s disease.

The discussion emphasizes the importance of maintaining homeodynamics in neurodegenerative disorders and explores innovative therapeutic approaches such as nanoparticles and RNA aptamers. Moreover, cannabinoids, particularly CBD, demonstrate anti-inflammatory effects through the modulation of microglial activity, offering multifaceted neuroprotection including mitigating aggregation. Additionally, the potential integration of cannabinoids with vitamin B12 presents a holistic framework for addressing neurodegeneration, considering their roles in homeodynamics and nervous system functioning including the hippocampal neurogenesis.

The potential synergistic therapeutic benefits of combining CBD with vitamin B12 underscore a promising avenue for advancing treatment strategies in neurodegenerative diseases. However, further research is imperative to fully elucidate their effects and potential applications, emphasizing the dynamic nature of this field and its potential to reshape neurodegenerative disease treatment paradigms.”

https://pubmed.ncbi.nlm.nih.gov/38931480/

“Since neurodegenerative diseases like Alzheimer’s, Parkinson’s, multiple sclerosis, Huntington’s, and amyotrophic lateral sclerosis present significant healthcare and therapeutic challenges due to not only their complex etiology or pathophysiology but symptoms severity as well, it is important to keep the attention on improving constantly effective therapeutic methods devoted to neurodegenerative diseases treatment.

Recent studies indicate cannabinoids, particularly from Cannabis sativa, to hold promise in addressing key pathological processes associated with these disorders.

Cannabinoids, especially THC and CBD, demonstrate anti-aggregative effects, modulating the endocannabinoid system and interacting with cannabinoid receptors 1 and 2, offering potential in mitigating protein aggregation seen in disorders like multiple sclerosis. They also activate CBR1, protecting against mitochondrial dysfunction, crucial in diseases disrupting energy distribution, such as demyelination.

Emerging evidence suggests that vitamin B12, essential for cellular processes, could complement therapeutic strategies, potentially enhancing the effects of CBD. Additionally, CBD shows promise in reversing locomotor changes in Parkinson’s disease independently of NPR-19 receptors, while also protecting dopaminergic neurons and reducing reactive oxygen species accumulation. Thus, the integration of nanoparticles of β-caryophyllene, a CB2R binder, as explored by Alberti et al. (2020) [4], represents potential advancement in developing therapies that improve drug BBB crossing and enhance overall treatment efficacy, moreover, accordingly, the process aimed at combining RNA aptamers with cannabinoids and vitamin B12 may offer precise targeted therapies, but rigorous testing is necessary before clinical use.

This combined approach represents a promising frontier in neurodegenerative disease treatment, highlighting ongoing research into cannabinoids’ effects and applications across various disease contexts. Understanding their interaction with mitochondrial function and cellular communication holds potential for novel therapeutic strategies. Further investigation is needed to fully grasp cannabinoids’ effects and applications in diverse disease contexts.”

https://www.mdpi.com/1424-8247/17/6/813

Medicinal cannabis in neurodegenerative disorders: an open label, dose finding, safety and efficacy study

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“Aim: Currently, there exist no curative treatments for neurodegenerative disorders. Recently, there has been a resurgence of interest in the use of medicinal cannabis to improve neurological conditions. 

Methods: A 12-month, open label, dose-finding, safety and efficacy study was conducted including 48 subjects with a variety of neurodegenerative disorders. 

Results: In our participants, we observed a reduction in pain, improved sleep, enhanced well-being and less agitation. 

Conclusion: Our findings suggest that medicinal cannabis might be useful in patients with neurodegenerative disorders in controlling pain, enhancing sleep, reducing difficult behaviors, controlling unusual and complex symptoms when other treatments have failed – this offers medicinal cannabis a role in palliation.”

https://pubmed.ncbi.nlm.nih.gov/38639578/

Cannabinoids in Medicine: A Multifaceted Exploration of Types, Therapeutic Applications, and Emerging Opportunities in Neurodegenerative Diseases and Cancer Therapy

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“In this review article, we embark on a thorough exploration of cannabinoids, compounds that have garnered considerable attention for their potential therapeutic applications. Initially, this article delves into the fundamental background of cannabinoids, emphasizing the role of endogenous cannabinoids in the human body and outlining their significance in studying neurodegenerative diseases and cancer. Building on this foundation, this article categorizes cannabinoids into three main types: phytocannabinoids (plant-derived cannabinoids), endocannabinoids (naturally occurring in the body), and synthetic cannabinoids (laboratory-produced cannabinoids). The intricate mechanisms through which these compounds interact with cannabinoid receptors and signaling pathways are elucidated. A comprehensive overview of cannabinoid pharmacology follows, highlighting their absorption, distribution, metabolism, and excretion, as well as their pharmacokinetic and pharmacodynamic properties. Special emphasis is placed on the role of cannabinoids in neurodegenerative diseases, showcasing their potential benefits in conditions such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis. The potential antitumor properties of cannabinoids are also investigated, exploring their potential therapeutic applications in cancer treatment and the mechanisms underlying their anticancer effects. Clinical aspects are thoroughly discussed, from the viability of cannabinoids as therapeutic agents to current clinical trials, safety considerations, and the adverse effects observed. This review culminates in a discussion of promising future research avenues and the broader implications for cannabinoid-based therapies, concluding with a reflection on the immense potential of cannabinoids in modern medicine.”

https://pubmed.ncbi.nlm.nih.gov/37759788/

https://www.mdpi.com/2218-273X/13/9/1388