Cannabis Research for Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis (ALS) is a rare group of neurological diseases that mainly involve the nerve cells (neurons) responsible for controlling voluntary muscle movement. Voluntary muscles produce movements like chewing, walking, breathing and talking. The disease is progressive, meaning the symptoms get worse over time. Currently, there is no cure for ALS and no effective treatment to halt, or reverse, the progression of the disease.
Amyotrophic Lateral Sclerosis (ALS) belongs to a wider group of disorders known as motor neuron diseases, which are caused by gradual deterioration (degeneration) and death of motor neurons. Motor neurons are nerve cells that extend from the brain to the spinal cord and to muscles throughout the body. These motor neurons initiate and provide vital communication links between the brain and the voluntary muscles.
Messages from motor neurons in the brain (called upper motor neurons) are transmitted to motor neurons in the spinal cord and to motor nuclei of brain (called lower motor neurons) and from the spinal cord and motor nuclei of brain to a particular muscle or muscles.
In ALS, both the upper motor neurons and the lower motor neurons degenerate or die, and stop sending messages to the muscles. Unable to function, the muscles gradually weaken, start to twitch (called fasciculations), and waste away (atrophy). Eventually, the brain loses its ability to initiate and control voluntary movements. — National Institute of Neurological Disorders and Stroke
Below is a Library of Cannabis Research Studies for Amyotrophic Lateral Sclerosis (ALS). My Great-Uncle Duane passed from Lou Gehrig’s disease also know as Amyotrophic Lateral Sclerosis (ALS).
Targeting the Endocannabinoid System: a Predictive, Preventive, and Personalized Medicine-Directed Approach to the Management of Brain Pathologies
European Association for Predictive, Preventive and Personalised Medicine | March 2020Abstract: “Cannabis-inspired medical products are garnering increasing attention from the scientific community, general public, and health policy makers. A plethora of scientific literature demonstrates intricate engagement of the endocannabinoid system with human immunology, psychology, developmental processes, neuronal plasticity, signal transduction, and metabolic regulation. Despite the therapeutic potential, the adverse psychoactive effects and historical stigma, cannabinoids have limited widespread clinical application. Therefore, it is plausible to weigh carefully the beneficial effects of cannabinoids against the potential adverse impacts for every individual. This is where the concept of “personalized medicine” as a promising approach for disease prediction and prevention may take into the account. The goal of this review is to provide an outline of the endocannabinoid system, including endocannabinoid metabolizing pathways, and will progress to a more in-depth discussion of the therapeutic interventions by endocannabinoids in various neurological disorders.” — Study
Neuroprotection by Cannabinoids in Neurodegenerative Diseases
Alzheimer’s, Dementia & Cognitive Neurology | 2018Abstract: “The cannabinoids are found to have particular application as neuroprotectants for mental and motor dysfunction in neurodegenerative diseases. The neuroprotective properties of cannabinoids suggest their therapeutic use for limiting neurological damage. The cannabinoids treatments should not only aim to alleviate specific symptoms but also attempt to delay/arrest disease progression and to repair the damaged structures. The author conducted a review of studies published between 1974 and 2011. The search was performed using the following PubMed search terms: “Cannabinoids” and “Neurodegenerative Diseases” and 287 papers were detected. The articles were examined and the overlapping or insufficiently clear works were excluded. Finally we chose 117 articles regarding the latest international guidelines, the pathophysiology of neurodegenerative diseases and the various therapeutic choices. The studies reported in the present review support the view that the cannabinoid signalling system is a key modulatory element in the activity of the basal ganglia. This idea is supported by different anatomical, electrophysiological, pharmacological and biochemical data. Furthermore, these studies indicate that the cannabinoid system is impaired in different neurological disorders that directly or indirectly affect the basal ganglia, which supports the idea of developing novel pharmacotherapies with compounds that selectively target specific elements of the cannabinoid system. ” — Study
Evaluation of 4-Oxo-Quinoline-Based CB2 PET Radioligands in R6/2 Chorea Huntington Mouse Model and Human ALS Spinal Cord Tissue
European Journal of Medicinal Chemistry | January 2018Abstract: “The cannabinoid receptor 2 (CB2) has been implicated in a series of neurodegenerative disorders and has emerged as an interesting biological target for therapeutic as well as diagnostic purposes. In the present work, we describe an improved radiosynthetic approach to obtain the previously reported CB2-specific PET radioligand [18F]RS-126 in higher radiochemical yields and molar activities. Additionally, the study revealed that prolongation of the [18F]RS-126 fluoroalkyl side chain ultimately leads to an improved stability towards mouse liver enzymes but is accompanied by a reduction in selectivity over the cannabinoid receptor 1 (CB1). Huntington-related phenotypic changes as well as striatal D2R downregulation were confirmed for the transgenic R6/2 mouse model. CB2 upregulation in R6/2 Chorea Huntington mice was observed in hippocampus, cortex, striatum and cerebellum by qPCR, however, these results could not be confirmed at the protein level by PET imaging. Furthermore, we evaluated the utility of the newly developed [11C]RS-028, a potent [18F]RS-126 derivative with increased polarity and high selectivity over CB1 in post-mortem human ALS spinal cord and control tissue. Applying in vitro autoradiography, the translational relevance of CB2 imaging was demonstrated by the specific binding of [11C]RS-028 to post-mortem human ALS spinal cord tissue.” — Study
Cannabinoids Involvement in Neurodegenerative Diseases
Current Neurobiology | October 2017Abstract: “The cannabinoids are found to have particular application as neuroprotectants for mental and motor dysfuction in neurodegenerative diseases. The neuroprotective properties of cannabinoids suggest their therapeutic use for limiting neurological damage. The cannabinoids treatments should not only aim to alleviate specific symptoms but also attempt to delay/arrest disease progression and to repair the damaged structures. The author conducted a review of studies published between 1974 and 2011. The search was performed using the following PubMed search terms: “Cannabinoids” and “Neurodegenerative Diseases” and 287 papers were detected. The articles were examined, and the overlapping or insufficiently clear works were excluded. Finally, we chose 117 articles regarding the latest international guidelines, the pathophysiology of neurodegenerative diseases and the various therapeutic choices. The studies reported in the present review support the view that the cannabinoid signalling system is a key modulatory element in the activity of the basal ganglia. This idea is supported by different anatomical, electrophysiological, pharmacological and biochemical data. Furthermore, these studies indicate that the cannabinoid system is impaired in different neurological disorders that directly or indirectly affect the basal ganglia, which supports the idea of developing novel pharmacotherapies with compounds that selectively target specific elements of the cannabinoid system.” — Study
Modeling Neurodegenerative Disorders for Developing Cannabinoid-Based Neuroprotective Therapies
Methods in Enzymology | July 2017Abstract: “The increase in lifespan during the last 50 years, mainly in developed countries, has originated a progressive elevation in the incidence of chronic neurodegenerative disorders, for which aging is the key risk factor. This fact will definitively become the major biomedical challenge during the present century, in part because the expectation of a persisting elevation in the population older than 65 years over the whole population and, on the other hand, because the current lack of efficacious therapies to control these disorders despite years of intense research. This chapter will address this question and will stress the urgency of developing better neuroprotective and neurorepair strategies that may delay/arrest the progression of these disorders, reviewing the major needs to solve the causes proposed for the permanent failures experienced in recent years, e.g., to develop multitarget strategies, to use more predictive experimental models, and to identify early disease biomarkers. This chapter will propose the cannabinoids and their classic (e.g., endocannabinoid receptors and enzymes) and nonclassic (e.g., peroxisome proliferator-activated receptors, transcription factors) targets as a useful strategy for developing novel therapies for these disorders, based on their broad-spectrum neuroprotective profile, their activity as an endogenous protective system, the location of the endocannabinoid targets in cell substrates critical for neuronal survival, and their ability to serve for preservation and rescue, but also for repair and/or replacement, of neurons and glial cells against cytotoxic insults.” — Study
Neuroprotective Effect of Cannabinoids Nanoplatforms in Neurodegenerative Diseases
Journal of Drug Delivery Science and Technology | April 2017Abstract: “The cannabinoid substances contained in the Cannabis sativa plant have been shown to have great potential in a wide variety of therapeutic applications. However, its neuroprotective capacity has been the most widely studied in diseases such as Alzheimer’s, Parkinson’s, Huntington’s, multiple sclerosis and amyotrophic lateral sclerosis.
Knowing the problems of formulating these substances in different dosage forms and their side effects, the present paper addresses different alternatives offered by the use of nanotechnology to transport these drugs in suitable platforms, as well as the different methodologies and materials used for this purpose.” — Study
Cannabinoid Receptor 2 Signaling in Neurodegenerative Disorders: From Pathogenesis to a Promising Therapeutic Target
Frontiers in Neuroscience | February 2017Abstract: “As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically. Moreover, recent studies have shown that endogenous cannabinoid signaling plays a number of modulatory roles throughout the central nervous system (CNS), including the neuroinflammation and neurogenesis. In particular, the up-regulation of type-2 cannabinoid (CB2) receptors has been found in a number of neurodegenerative disorders. Thus, the modulation of CB2 receptor signaling may represent a promising therapeutic target with minimal psychotropic effects that can be used to modulate endocannabinoid-based therapeutic approaches and to reduce neuronal degeneration. For these reasons this review will focus on the CB2 receptor as a promising pharmacological target in a number of neurodegenerative diseases.” — Study
Up-Regulation of CB2 Receptors in Reactive Astrocytes in Canine Degenerative Myelopathy, a Disease Model of Amyotrophic Lateral Sclerosis.
Disease Models and Mechanisms | January 2017Abstract: “Targeting the CB2 receptor afforded neuroprotection in SOD1G93A mutant mice, a model of amyotrophic lateral sclerosis (ALS). The neuroprotective effects of CB2 receptors were facilitated by their up-regulation in the spinal cord in SOD1G93A mutant mice. Herein, we have investigated whether a similar CB2 receptor up-regulation, as well as parallel changes in other endocannabinoid elements, are evident in the spinal cord of dogs with degenerative myelopathy (DM), caused from mutations in the superoxide dismutase 1 gene (SOD1). We used well-characterized post-mortem spinal cords from unaffected and DM-affected dogs. Tissues were used first to confirm the loss of motor neurons using Nissl staining, which was accompanied by glial reactivity (elevated GFAP and Iba-1 immunoreactivity). Next, we investigated possible differences in the expression of endocannabinoid genes measured by qPCR between DM-affected and control dogs. We found no changes in the CB1 receptor (also found with CB1 receptor immunostaining) as well as in NAPE-PLD, DAGL, FAAH and MAGL enzymes. In contrast, CB2 receptor levels were significantly elevated in DM-affected dogs determined by qPCR and Western-blotting, results reconfirmed in the grey matter using CB2 receptor immunostaining. Using double-labelling immunofluorescence, CB2 receptor immuno-labelling co-localized with GFAP but not Iba-1, indicating up-regulation of CB2 receptors on astrocytes in DM-affected dogs. In summary, our results demonstrated a marked up-regulation of CB2 receptors occurring in the spinal cord in canine DM, which was concentrated in activated astrocytes. Such receptors may be used as a potential target to enhance the neuroprotective effects exerted by these glial cells.” — Study
Can Cannabinoids be a Potential Therapeutic Tool in Amyotrophic Lateral Sclerosis?
Neural Regeneration Research | December 2016Abstract: “Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motor neuron system. Over the last years, a growing interest was aimed to discovery new innovative and safer therapeutic approaches in the ALS treatment. In this context, the bioactive compounds of Cannabis sativa have shown antioxidant, anti-in ammatory and neuroprotective e ects in preclinical models of central nervous system disease. However, most of the studies proving the ability of cannabinoids in delay disease progression and prolong survival in ALS were performed in animal model, whereas the few clinical trials that investigated cannabinoids-based medicines were focused only on the alleviation of ALS-related symptoms, not on the control of disease progression. e aim of this report was to provide a short but important overview of evidences that are useful to better characterize the e cacy as well as the molecular pathways modulated by cannabinoids.”— Study
Endocannabinoid Metabolism in Neurodegenerative Diseases
Neuroimmunology and Neuroinflammation | December 2016Abstract: “Endocannabinoids are endogenous lipid mediators contributing to a variety of physiological, pharmacological, and pathological processes primarily through acting on cannabinoid receptors (CB1R and CB2R), which are targets of Δ9-tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient in marijuana.[1] Although N-arachidonoyl ethanolamide is the first identified endocannabinoid, 2-arachidonoylglycerol (2-AG), the second identified endocannabinoid, is the most abundant ligand produced in our body and a full agonist for CB1R and CB2R.[2] It has been well recognized that 2-AG is a retrograde messenger modulating synaptic transmission and plasticity at both inhibitory GABAergic and excitatory glutamatergic synapses in the brain.[2-4] In particular, augmentation of 2-AG signaling by inhibition of its metabolism has been attracted attention recently due to its profound anti-inflammatory and neuroprotective properties.” — Study
Gingival Stromal Cells As An In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis
Journal of Cellular Biochemistry | November 2016Abstract: “Research in recent years has extensively investigated the therapeutic efficacy of mesenchymal stromal cells in regenerative medicine for many neurodegenerative diseases at preclinical and clinical stages. However, the success rate of stem cell therapy remains less at translational phase. Lack of relevant animal models that potentially simulate the molecular etiology of human pathological symptoms might be a reason behind such poor clinical outcomes associated with stem cell therapy. Apparently, self-renewal and differentiation ability of mesenchymal stem cells may help to study the early developmental signaling pathways connected with the diseases, such as Alzheimer’s disease, Amyotrophic lateral sclerosis (ALS), etc., at in vitro level. Cannabidiol, a non-psychotrophic cannabinoid, has been demonstrated as a potent anti-inflammatory and neuroprotective agent in neurological preclinical models. In the present study, we investigated the modulatory role of cannabidiol on genes associated with ALS using human gingiva-derived mesenchymal stromal cells (hGMSCs) as an in vitro model system. Next generation transcriptomic sequencing analysis demonstrated considerable modifications in the expression of genes connected with ALS pathology, oxidative stress, mitochondrial dysfunction, and excitotoxicity in hGMSCs treated with cannabidiol. Our results suggest the efficacy of cannabidiol to delineate the unknown molecular pathways, which may underlie ALS pathology at an early stage using hGMSCs as a compelling in vitro system. ” — Study
Medical Cannabis: Pharmacy Focus on Treatment Options for Neurologic Conditions
US Pharmacists | January 2016Abstract: “Medical cannabis (marijuana) is re-emerging as a treatment option for many medical conditions in the United States. The cannabis plant contains chemicals that are both psychoactive (delta-9-tetrahydrocannabinol [THC]) as well as non-psychoactive (cannabidiol [CBD]). Its components are being successfully used to lessen seizure activity, treat pain and muscle spasticity, provide neuroprotection, reverse neuronal damage, and reduce symptoms of Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and several other neurologic conditions via important effects on the endocannabinoid system. Despite federal restrictions, twenty-four states and Washington, DC, have passed laws allowing the recommendation and use of medical cannabis in selected patients. Legislators, industry, and leaders in healthcare professions should be encouraged to increase efforts to remove barriers to research.
In opposition to and without the support of federal law, individual states have been passing laws through legislative action or citizen initiative that allow physicians to recommend medical cannabis to selected patients.1 The medical use and regulation of cannabis have a long and interesting history, both nationally and internationally. While the terms medical marijuana and cannabis are often used interchangeably, practitioners who recommend it prefer the scientific term cannabis, as it is used in historical documents. The Marihuana Tax Act of 1937 basically introduced the controversial word “marijuana” into federal policy, during a time of political and racial unrest.2 The law, in effect, made the cultivation, sale, and use of the plant an impossibility for prescribers and patients.” — Study
Cannabinoids In Neurodegenerative Disorders And Stroke/Brain Trauma: From Preclinical Models To Clinical Applications
Neurotherapeutics | October 2015Abstract: “Cannabinoids form a singular family of plant-derived compounds (phytocannabinoids), endogenous signaling lipids (endocannabinoids), and synthetic derivatives with multiple biological effects and therapeutic applications in the central and peripheral nervous systems. One of these properties is the regulation of neuronal homeostasis and survival, which is the result of the combination of a myriad of effects addressed to preserve, rescue, repair, and/or replace neurons, and also glial cells against multiple insults that may potentially damage these cells. These effects are facilitated by the location of specific targets for the action of these compounds (e.g., cannabinoid type 1 and 2 receptors, endocannabinoid inactivating enzymes, and non-endocannabinoid targets) in key cellular substrates (e.g., neurons, glial cells, and neural progenitor cells). This potential is promising for acute and chronic neurodegenerative pathological conditions. In this review, we will collect all experimental evidence, mainly obtained at the preclinical level, supporting that different cannabinoid compounds may be neuroprotective in adult and neonatal ischemia, brain trauma, Alzheimer’s disease, Parkinson’s disease, Huntington’s chorea, and amyotrophic lateral sclerosis. This increasing experimental evidence demands a prompt clinical validation of cannabinoid-based medicines for the treatment of all these disorders, which, at present, lack efficacious treatments for delaying/arresting disease progression, despite the fact that the few clinical trials conducted so far with these medicines have failed to demonstrate beneficial effects.” — Study
The Endocannabinoid System: A Putative Role in Neurodegenerative Diseases
International Journal of High Risk Behaviors and Addiction | May 2013Abstract: “Following the characterization of the chemical structure of D9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, researchers have moved on with scientific valuable explorations…The aim of this review is to highlight the role of endocannabinoid system in neurodegenerative diseases…The article is a critical analysis of the most recent data currently present in scientific literature on the subject; a qualitative synthesis of only the most significant articles has been performed…In central nervous system, endocannabinoids show a neuromodulatory function, often of retrograde type. This way, they play an important role in synaptic plasticity and in cognitive, motor, sensory and affective processes. In addition, in some acute or chronic pathologies of central nervous system, such as neurodegenerative and neuroinflammatory diseases, endocannabinoids can perform a pro-homeostatic and neuroprotective function, through the activation of CB1 and CB2 receptors. Scientific evidence shows that an hypofunction or a dysregulation of the endocannabinoid system may be responsible for some of the symptoms of diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases…The important role played by endocannabinoid system promises interesting developments, in particular to evaluate the effectiveness of new drugs in both psychiatry and neurology. ” — Study
Tetrahydrocannabinol (THC) For Cramps In Amyotrophic Lateral Sclerosis: A Randomised, Double-blind Crossover Trial
Journal of Neurology Neurosurgery Psychiatry | May 2010Abstract: “Many patients with amyotrophic lateral sclerosis (ALS) experience cramps during the course of the disease but so far, none of the medications used has been of proven benefit. The objective was to determine the effect of orally administered tetrahydrocannabinol (THC) on cramps in ALS patients…Complete data were available from 22 patients. THC was well tolerated. There was no evidence for a treatment effect on cramp intensity, number of cramps, fasciculation intensity or any of the other secondary outcome measures…This interventional study with orally administered THC 5 mg twice daily did not demonstrate subjective improvement of cramp intensity in ALS patients.” — Study
Cannabis And Amyotrophic Lateral Sclerosis: Hypothetical And Practical Applications, And A Call For Clinical Trials
American Journal of Hospice and Palliative Care | May 2010Abstract: “Significant advances have increased our understanding of the molecular mechanisms of amyotrophic lateral sclerosis (ALS), yet this has not translated into any greatly effective therapies. It appears that a number of abnormal physiological processes occur simultaneously in this devastating disease. Ideally, a multidrug regimen, including glutamate antagonists, antioxidants, a centrally acting anti-inflammatory agent, microglial cell modulators (including tumor necrosis factor alpha [TNF-α] inhibitors), an antiapoptotic agent, 1 or more neurotrophic growth factors, and a mitochondrial function-enhancing agent would be required to comprehensively address the known pathophysiology of ALS. Remarkably, cannabis appears to have activity in all of those areas. Preclinical data indicate that cannabis has powerful antioxidative, anti-inflammatory, and neuroprotective effects. In the G93A-SOD1 ALS mouse, this has translated to prolonged neuronal cell survival, delayed onset, and slower progression of the disease. Cannabis also has properties applicable to symptom management of ALS, including analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, and sleep induction. With respect to the treatment of ALS, from both a disease modifying and symptom management viewpoint, clinical trials with cannabis are the next logical step. Based on the currently available scientific data, it is reasonable to think that cannabis might significantly slow the progression of ALS, potentially extending life expectancy and substantially reducing the overall burden of the disease.” — Study
The Endocannabinoid System In The Inflammatory And Neurodegenerative Processes Of Multiple Sclerosis And Of Amyotrophic Lateral Sclerosis
Experimental Neurology | July 2010Abstract: “Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are chronic diseases of the central nervous system (CNS), featured by a complex interplay between inflammation and neurodegeneration. Increasing evidence supports the involvement of the endocannabinoid system (ECS) in both inflammatory and neurodegenerative processes typical of these pathological conditions. Exogenous or endogenous cannabinoids regulate the function of immune system by limiting immune response. On the other hand, by preventing excitotoxic damage, cannabinoids protect neuronal integrity and function. Of note, the ECS not only plays a role as modulator of disease processes, but it can also be disrupted by the same diseases…Agents modulating cannabinoid receptors or endocannabinoid tone provide promising therapeutic opportunities in the treatment of inflammatory neurodegenerative disorders of the CNS.” — Study
Cannabinoid Receptors And Endocannabinoids: Role In Neuroinflammatory And Neurodegenerative Disorders
CNS & Neurological Disorders drug Targets | November 2010Abstract: “he G-protein coupled receptors for Δ⁹-tetrahydrocannabinol, the major psychoactive principle of marijuana, are known as cannabinoid receptors of type 1 (CB₁) and 2 (CB₂) and play important functions in degenerative and inflammatory disorders of the central nervous system. Whilst CB₁ receptors are mostly expressed in neurons, where they regulate neurotransmitter release and synaptic strength, CB₂ receptors are found mostly in glial cells and microglia, which become activated and over-express these receptors during disorders such as Alzheimer’s disease, multiple sclerosis, amyotropic lateral sclerosis, Parkinson’s disease, and Huntington’s chorea. The neuromodulatory actions at CB₁ receptors by endogenous agonists (‘endocannabinoids’), of which anandamide and 2-arachidonoylglycerol are the two most studied representatives, allows them to counteract the neurochemical unbalances arising during these disorders. In contrast, the immunomodulatory effects of these lipophilic mediators at CB₂ receptors regulate the activity and function of glia and microglia. Indeed, the level of expression of CB₁ and CB₂ receptors or of enzymes controlling endocannabinoid levels, and hence the concentrations of endocannabinoids, undergo time- and brain region-specific changes during neurodegenerative and neuroinflammatory disorders, with the initial attempt to counteract excitotoxicity and inflammation. Here we discuss this plasticity of the endocannabinoid system during the aforementioned central nervous system disorders, as well as its dysregulation, both of which have opened the way to the use of either direct and indirect activators or blockers of CB₁ and CB₂ receptors for the treatment of the symptoms or progression of these diseases.” — Study
The Endocannabinoid System As A Target For The Treatment Of Neurodegenerative Disease
The British Journal of Pharmacology | March 2010Abstract: “The Cannabis sativa plant has been exploited for medicinal, agricultural and spiritual purposes in diverse cultures over thousands of years. Cannabis has been used recreationally for its psychotropic properties, while effects such as stimulation of appetite, analgesia and anti-emesis have lead to the medicinal application of cannabis. Indeed, reports of medicinal efficacy of cannabis can been traced back as far as 2700 BC, and even at that time reports also suggested a neuroprotective effect of the cultivar. The discovery of the psychoactive component of cannabis resin, Δ9-tetrahydrocannabinol (Δ9-THC) occurred long before the serendipitous identification of a G-protein coupled receptor at which Δ9-THC is active in the brain. The subsequent finding of endogenous cannabinoid compounds, the synthesis of which is directed by neuronal excitability and which in turn served to regulate that excitability, further widened the range of potential drug targets through which the endocannabinoid system can be manipulated. As a result of this, alterations in the endocannabinoid system have been extensively investigated in a range of neurodegenerative disorders. In this review we examine the evidence implicating the endocannabinoid system in the cause, symptomatology or treatment of neurodegenerative disease. We examine data from human patients and compare and contrast this with evidence from animal models of these diseases. On the basis of this evidence we discuss the likely efficacy of endocannabinoid-based therapies in each disease context.” — Study
Increasing Cannabinoid Levels By Pharmacological And Genetic Manipulation Delay Disease Progression In SOD1 Mice
The Official Journal of the Federation of American Societies of Experimental Biology | March 2006Abstract: “Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motoneurons in the spinal cord, brain stem, and motor cortex. However, despite intensive research, an effective treatment for this disease remains elusive. In this study we show that treatment of post-symptomatic, 90-day-old SOD1G93A mice with a synthetic cannabinoid, WIN55,212–2, significantly delays disease progression. Furthermore, genetic ablation of the Faah enzyme, which results in raised levels of the endocannabinoid anandamide, prevented the appearance of disease signs in 90-day-old SOD1G93A mice. Surprisingly, elevation of cannabinoid levels with either WIN55,212–2 or Faah ablation had no effect on life span. Ablation of the CB1 receptor, in contrast, had no effect on disease onset in SOD1G93A mice but significantly extended life span. Together these results show that cannabinoids have significant neuroprotective effects in this model of ALS and suggest that these beneficial effects may be mediated by non-CB1 receptor mechanisms.— Bilsland, L. G., Dick, J. R. T., Pryce, G., Petrosino, S., Di Marzo, V., Baker, D., Greensmith, L. Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in SOD1 mice.” — Study
Cannabinol Delays Symptom Onset In SOD1 (G93A) Transgenic Mice Without Affecting Survival
Amyotrophic Lateral Sclerosis | July 2009Abstract: “Therapeutic options for amyotrophic lateral sclerosis (ALS), the most common adult‐onset motor neuron disorder, remain limited. Emerging evidence from clinical studies and transgenic mouse models of ALS suggests that cannabinoids, the bioactive ingredients of marijuana (Cannabis sativa) might have some therapeutic benefit in this disease. However, Δ9‐tetrahydrocannabinol (Δ9‐THC), the predominant cannabinoid in marijuana, induces mind‐altering effects and is partially addictive, compromising its clinical usefulness…We found that this treatment significantly delays disease onset by more than two weeks while survival was not affected. Further research is necessary to determine whether non‐psychotropic cannabinoids might be useful in ameliorating symptoms in ALS.” — Study
Survey Of Cannabis Use In Patients With Amyotrophic Lateral Sclerosis
The American Journal of Hospice and Palliative Care | March 2004Abstract: “Cannabis (marijuana) has been proposed as treatment for a widening spectrum of medical conditions and has many properties that may be applicable to the management of amyotrophic lateral sclerosis (ALS). This study is the first, anonymous survey of persons with ALS regarding the use of cannabis. There were 131 respondents, 13 of whom reported using cannabis in the last 12 months. Although the small number of people with ALS that reported using cannabis limits the interpretation of the survey findings, the results indicate that cannabis may be moderately effective at reducing symptoms of appetite loss, depression, pain, spasticity, and drooling. Cannabis was reported ineffective in reducing difficulties with speech and swallowing, and sexual dysfunction. The longest relief was reported for depression (approximately two to three hours).” — Study
Amyotrophic Lateral Sclerosis: Delayed Disease Progression In Mice By Treatment With A Cannabinoid.
Journal of Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders | April 2003Abstract: “Effective treatment for amyotrophic lateral sclerosis (ALS) remains elusive. Two of the primary hypotheses underlying motor neuron vulnerability are susceptibility to excitotoxicity and oxidative damage. There is rapidly emerging evidence that the cannabinoid receptor system has the potential to reduce both excitotoxic and oxidative cell damage. Here we report that treatment with Δ9‐tetrahydrocannabinol (Δ9‐THC) was effective if administered either before or after onset of signs in the ALS mouse model (hSODG93A transgenic mice). Administration at the onset of tremors delayed motor impairment and prolonged survival in Δ9‐THC treated mice when compared to vehicle controls. In addition, we present an improved method for the analysis of disease progression in the ALS mouse model. This logistic model provides an estimate of the age at which muscle endurance has declined by 50% with much greater accuracy than could be attained for any other measure of decline. In vitro, Δ9‐THC was extremely effective at reducing oxidative damage in spinal cord cultures. Additionally, Δ9‐THC is anti‐excitotoxic in vitro. These cellular mechanisms may underlie the presumed neuroprotective effect in ALS. As Δ9‐THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS.” — Study
Marijuana In The Management Of Amyotrophic Lateral Sclerosis
American Journal of Hospice and Palliative Medicine | July 2001Abstract: “Marijuana has been proposed as treatment for a widening spectrum of medical conditions. Marijuana is a substance with many properties that may be applicable to the management of amyotrophic lateral sclerosis (ALS). These include analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, and sleep induction. In addition, marijuana has now been shown to have strong antioxidative and neuroprotective effects, which may prolong neuronal cell survival. In areas where it is legal to do so, marijuana should be considered in the pharmacological management of ALS. Further investigation into the usefulness of marijuana in this setting is warranted.” — Study
Cannabis Research Library
Over 1000 studies covering over 130 topics compiled for easy browsing.
