Category Archives: Amyotrophic lateral sclerosis (ALS) -Lou Gehrig’s disease

Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1G93 A) mouse model of amyotrophic lateral sclerosis

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“Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting voluntary muscle movement as well as cognitive and other behavioural domains at later disease stages. No effective treatment for ALS is currently available. Elevated neuroinflammation, oxidative stress and alterations to the endocannabinoid system are evident in ALS. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory and anti-oxidant properties. Thus, we evaluated the remedial effects of chronic oral cannabidiol (CBD) treatment on ALS-relevant behavioural domains in the copper-zinc superoxide dismutase 1 (SOD1) mouse model of ALS that carries a G93A mutation (SOD1G93A).

Methods: Male and female SOD1G93A and wild type-like (WT) littermates were fed either a control (CHOW) or CBD-enriched chow diet (equivalent to a dose of 36 mg/kg per day) beginning from 10 weeks of age. Bodyweight and motor performance were recorded weekly from 11 to 19 weeks and open field behaviours at 12 and 18 weeks. Mice were also tested for prepulse inhibition (PPI), social behaviours, as well as fear-associated memory.

Results: CBD treatment ameliorated the bodyweight loss in female SOD1G93A mice, tended to reinstate sociability in SOD1G93A males, strengthened social recognition memory in SOD1G93A females, and improved the PPI response in younger SOD1G93A females at higher prepulse intensities. CBD had no effect on motor impairments but instead reversed the anxiolytic-like phenotype of 12-week-old male SOD1G93A mice and decreased the acoustic startle response and strengthened cue freezing in male mice.

Conclusion: Thus, the current remedial oral dose of CBD delayed disease progression (inferred by bodyweight) in both male and female mice and improve specific cognitive deficits of SOD1G93A mice in a sex specific manner without altering the motor phenotype.”

https://pubmed.ncbi.nlm.nih.gov/40229540/

“In conclusion, the study discovered beneficial effects of oral CBD on the bodyweight deficit in both male and female SOD1G93 A mice as well as improving social recognition memory and the PPI response in female SOD1G93 A mice. CBD also reduced the ASR and increased the freezing response to a conditioned cue in both SOD1G93 A transgenic and WT male mice. However, CBD treatment did not reverse motor impairments or sensorimotor gating deficits. Thus, chronic oral CBD treatment at the dose administered here may be therapeutically useful for only particular ALS symptoms including bodyweight decline, which is an indicator of disease progression and declining survival rate (Dharmadasa et al. 2017). Further investigations should consider additional CBD dosing and beginning treatment at an earlier age prior to the onset of motor deficits. This could be followed by combination treatments of CBD and e.g. cannabinoid receptor antagonists to explore potential mechanisms behind observed CBD effects.”

https://link.springer.com/article/10.1007/s00213-025-06785-z

Amyotrophic Lateral Sclerosis, the Endocannabinoid System, and Exogenous Cannabinoids: Current State and Clinical Implications

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“A unifying mechanistic cause for amyotrophic lateral sclerosis (ALS) remains uncertain. Multiple pathophysiological processes appear to occur simultaneously.

Cannabinoids, including delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), and others found in cannabis, and cannabis extracts (CEs), appear to have activity in these pathogenic pathways, which have led to increasing interest in cannabinoids as therapeutic agents for ALS.

The use of cannabinoids as a treatment strategy is substantiated by preclinical evidence suggesting a role for the endocannabinoid system (ECS) in ALS and other neurodegenerative disorders.

Preclinical data indicate that cannabis and CEs have powerful antioxidative, anti-inflammatory, and neuroprotective effects in the SOD1G93A mouse model of ALS. The use of CEs in SOD1G93A murine models has been shown to prolong neuronal cell survival, which leads to delayed onset of the disease state, and slows progression of the disease.

Although research in humans remains limited, a few studies suggest that cannabis and CBD, in humans, provide benefits for both motor symptoms, including rigidity, cramps, and fasciculations, and non-motor symptoms including sleep quality, pain, emotional state, quality of life, and depression. There remains a need for further, well-designed clinical trials to validate further the use of an individual cannabinoid, or a combination of cannabinoids, as a disease-modifying therapy for ALS.”

https://pubmed.ncbi.nlm.nih.gov/39936266/

https://onlinelibrary.wiley.com/doi/10.1002/mus.28359

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

Cannabinol Regulates the Expression of Cell Cycle-Associated Genes in Motor Neuron-like NSC-34: A Transcriptomic Analysis

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“Cannabinoids are reported to have neuroprotective properties and play a role in neurogenesis and neuroplasticity in in vitro and in vivo models. Cannabinol (CBN) is a minor cannabinoid produced by the degradation of Δ9-tetrahydrocannabinol in Cannabis sativa L. and exhibits anti-oxidant, analgesic, anti-bacterial, and anti-inflammatory effects.

In this study, we explored the biological effects of 20 µM CBN (6.20 µg/mL) on differentiated NSC-34 cells by MTT assay and next-generation sequencing analysis on the transcriptome. KEGG and Gene Ontology enrichment analyses have been performed to evaluate potential CBN-associated processes.

Our results highlighted the absence of any cytotoxic effect of CBN. The comparative transcriptomic analysis pointed out the downregulation of Cdkn2a, Cdkn2c and Cdkn2d genes, which are known to suppress the cell cycle. Ccne2, Cdk2, Cdk7, Anapc11, Anapc10, Cdc23, Cdc16, Anapc4, Cdc27, Stag1, Smc3, Smc1a, Nipbl, Pds5a, Pds5b, and Wapl genes, renowned for their role as cell cycle progression activators, were instead upregulated. Our work suggests that CBN regulates the expression of many genes related to the cell cycle, which are required for axonal maturation, migration, and synaptic plasticity, while not affecting the expression of genes involved in cell death or tumorigenesis.”

https://pubmed.ncbi.nlm.nih.gov/38927547/

“The results obtained could be a starting point for testing CBN on models of motor neuron diseases characterized by synaptic dysfunctions and aberrant reactivation of the cell cycle leading to cell death.”

https://www.mdpi.com/2227-9059/12/6/1340

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/

The Therapeutic Potential and Molecular Mechanisms Underlying the Neuroprotective Effects of Sativex® – A Cannabis-derived Spray

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“Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants.

Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders.

The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.”

https://pubmed.ncbi.nlm.nih.gov/38318827/

https://www.eurekaselect.com/article/138318

Cannabis for the treatment of amyotrophic lateral sclerosis: What is the patients’ view?

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“Cannabis may have therapeutic benefits to relieve symptoms of amyotrophic lateral sclerosis (ALS) thanks to its pleiotropic pharmacological activity. This study is the first to present a large questionnaire-based survey about the “real-life” situation regarding cannabis use in the medical context in ALS patients in France. There were 129 respondents and 28 reported the use of cannabis (21.7%) to relieve symptoms of ALS. Participants mostly reported the use of cannabidiol (CBD) oil and cannabis weed and declared benefits both on motor (rigidity, cramps, fasciculations) and non-motor (sleep quality, pain, emotional state, quality of life, depression) symptoms and only eight reported minor adverse reactions (drowsiness, euphoria and dry mouth). Even if cannabis is mostly used outside medical pathways and could expose patients to complications (street and uncontrolled drugs, drug-drug interactions, adverse effects…), most of the participants reported “rational” consumption (legal cannabinoids, with only few combustion and adverse reactions). Despite some limitations, this study highlights the need for further research on the potential benefits of cannabis use for the management of ALS motor and non-motor symptoms. Indeed, there is an urgent need and call for and from patients to know more about cannabis and secure its use in a medical context.”

https://pubmed.ncbi.nlm.nih.gov/37460332/

https://www.sciencedirect.com/science/article/abs/pii/S0035378723009712?via%3Dihub