How doctors treat ALS with cannabis in humans and animals

Medical data and clinical reports, what doctors learned about ALS and cannabis - its powerful antioxidant, anti-inflammatory, and neuro-protective properties

"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. There is an overwhelming amount of preclinical and clinical evidence to warrant initiating a multi-center randomized, double-blind, placebo-controlled trial of cannabis as a disease-modifying compound in ALS." - Researchers, American Journal of Hospice & Palliative Medicine


We present here, some of the overwhelming preclinical and clinical evidence about cannabis and ALS, that should warrant the undivided attention of both doctor and patient alike.  Cannabis and its active ingredients; THC, and CBD are disease-modifying compounds in ALS. Preclinical medical data indicate that cannabis has powerful antioxidative, anti-inflammatory, and neuroprotective effects.


1 Amyotrophic Lateral Sclerosis - ALS: delayed disease progression in rodents by treatment with a cannabinoid. Raman the year of 2004.  Amyotrophic Lateral Sclerosis - ALS & Other Motor Neuron Disorders 5: 33-39.

*Competent and effective treatment for amyotrophic lateral sclerosis - ALS-   remains elusive. Two of the primary hypotheses underlying motor neuron vulnerability are susceptible 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 d9THC  was effective if administered either before or after onset of signs in the Amyotrophic Lateral Sclerosis - ALS mouse model  -  hSOD G93A transgenic rodents.


*Dosing at the onset of tremors delayed motor impairment and prolonged survival in d9THC treated rodents 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 fifty percent with much greater accuracy than could be attained for any other measure of decline.In vitro, d9THC was extremely effective at reducing oxidative damage in spinal cord cultures. Additionally, d9THC is anti-excitotoxic in vitro.


These cellular workings may underlie the presumed neuroprotective effect in ALS. Because d9THC is well accepted, it and other cannabinoids may prove to be entirely new medicinal targets for the treatment of Amyotrophic Lateral Sclerosis - ALS



2 Cannabinol delays symptom and condition onset in SOD1 transgenic rodents without affecting survival.Weydt the year of 2005.  Amyotrophic Lateral Sclerosis - ALS & Other Motor Neuron Disorders 6: 182-184.

*Medicinal options for Amyotrophic Lateral Sclerosis - ALS  -  ALS, the most common adult-onset motor neuron disorder, remain limited. Emerging evidence from clinical medical medical studies and transgenic mouse models of Amyotrophic Lateral Sclerosis - ALS suggests that phytocannabinoids, the bioactive ingredients of marijuana  -  Cannabis sativa might have some medicinal benefit in this disease. However, d9THC, the main cannabinoid in marijuana, causes mind-altering effects and is partially addictive, compromising its clinical usefulness.


*We therefore tested whether cannabinol  -  CBN, a nonpsychotropic cannabinoid, influences disease progression and survival in the SOD1  -  G93A mouse model of ALS. CBN was delivered via subcutaneously implanted osmotic mini-pumps  -  5 milligram/kilograms/day over a period of up to 12 wks.. We found that this treatment significantly delays disease onset by more than two wks. while survival was not affected. Further research is needed to determine whether non-psychotropic phytocannabinoids might be useful in treating symptoms of ALS."



3 Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in SOD1 rodents. Bilsland the year of 2006.  The FASEB Journal 20: 1003-1005.Ibid.

*Amyotrophic lateral sclerosis  -  ALS is a fatal neurodegenerative disorder described by the selective loss of motoneurons in the spinal cord, brainstem, and motor cortex. However, despite intensive research, an effective treatment for this disease remains elusive. In this medical study, we show that treatment of post symptomatic, 90-day-old SOD1G93A rodents with a synthetic-chemical cannabinoid, WIN55,212–2, significantly delays disease progression.

Lou Gehrig Dies of Lou Gehrig's Disease


*Furthermore, genetic ablation of the Faah enzyme, Data and Results indicate raised levels of the endocannabinoid (body's own) anandamide, which prevented the appearance of disease signs in 90-day-old SOD1G93A rodents. Surprisingly, elevation of cannabinoid levels with either WIN55,212–2 or Faah ablation had no effect on lifespan. Ablation of the CB1 receptor, in contrast, had no effect on disease onset in SOD1G93A rodents but significantly extended lifespan. Together, these Data and Results show that phytocannabinoids have significant neuroprotective effects in this model of Amyotrophic Lateral Sclerosis - ALS and suggest that these beneficial effects may be mediated by non-CB1 receptor workings.



4 Cannabis and amyotrophic lateral sclerosis: hypothetical and practical applications, and a call for clinical trials. Carter the year of 2010. American Journal of Hospice & Palliative Medicine 27: 347-356.

*Significant advances have increased our understanding of the molecular workings 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 multi medication regimen, including glutamate antagonists, antioxidants, a centrally acting anti-inflammatory agent, microglial cell modulators -including tumor necrosis factor alpha [TNF-alpha] 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 medical data indicate that cannabis has powerful antioxidative, anti-inflammatory, and neuroprotective effects. In the G93A-SOD1 Amyotrophic Lateral Sclerosis - 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 and condition 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 symptom and condition management viewpoint, clinical trials with cannabis are the next logical step. Based on the currently available scientific & medical 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.



5 Survey of cannabis use in subjects with amyotrophic lateral sclerosis. Amtmann the year of 2004. The American Journal of Hospice and Palliative Care 21: 95-104.

*Cannabis or 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 medical study is the first, anonymous survey of persons with Amyotrophic Lateral Sclerosis - 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 Amyotrophic Lateral Sclerosis - ALS that reported using cannabis limits the interpretation of the survey findings, the Data and 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 hrs..

*The endocannabinoid (body's own) system in the inflammatory and neurodegenerative processes of multiple sclerosis and of amyotrophic lateral sclerosis.

*Multiple sclerosis -MS and amyotrophic lateral sclerosis -ALS are chronic conditions of the central nervous system -CNS, featured by a complex interplay between inflammation and neurodegeneration. Increasing evidence supports the action of the endocannabinoid (body's own) 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 part as modulator of disease processes, but it may also be disrupted by the same conditions. Agents modulating cannabinoid receptors or endocannabinoid (body's own) tone provides promising medicinal opportunities in the treatment of inflammatory neurodegenerative disorders of the CNS



6 Abnormal sensitivity of cannabinoid CB1 receptors in the striatum of rodents with experimental amyotrophic lateral sclerosis: .

*Amyotrophic lateral sclerosis -ALS is a fatal neurodegenerative disease that primarily affects motor neurons. However, other neuronal systems are also involved, and the aim of this medical study was to investigate the action of the nucleus striatum. By means of neurophysiological recordings in slices, we have investigated both excitatory and inhibitory synaptic transmission in the striatum of G93A-SOD1 Amyotrophic Lateral Sclerosis - ALS rodents, along with the sensitivity of these synapses to cannabinoid CB1 receptor stimulation.

*We saw a reduced incidence of glutamate-mediated spontaneous excitatory postsynaptic currents  -  EPSCs and increased incidence of GABA-mediated spontaneous inhibitory postsynaptic currents  -  IPSCs recorded from striatal neurons of Amyotrophic Lateral Sclerosis - ALS in rodents, possibly due to presynaptic defects in transmitter release. The sensitivity of cannabinoid CB1 receptors controlling both glutamate and GABA transmission was remarkably potentiated in Amyotrophic Lateral Sclerosis - ALS rodents, indicating that adaptations of the endocannabinoid (body's own) system might be involved in the pathophysiology of ALS.

*In conclusion, our medical data identifies some potential physiological causes of striatal dysfunction in Amyotrophic Lateral Sclerosis - ALS rodents, and suggest that cannabinoid CB1 receptors might be potential medicinal targets for this dramatic disease.


7 The endocannabinoid (body's own) system in gp120-mediated insults and HIV-associated dementia.

*Endocannabinoids  -  eCBs include a group of lipid mediators that work as endogenous agonists at cannabinoid  -  CB-1, CB-2 and vanilloid  -  TRPV1 receptors. In the last two decades a number of eCBs-metabolizing enzymes have been discovered that, together with eCBs and congeners, target receptors and proteins responsible for their transport and intracellular trafficking form the so-called "endocannabinoid (body's own) system"  -  ECS. Within the central nervous system ECS elements participate in neuroprotection against neuroinflammatory/neurodegenerative conditions like Alzheimer's disease,

*Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. More recently, a part for eCBs has been documented also in human immunodeficiency virus-1  -  HIV-1 envelope glycoprotein gp120-mediated insults, and in HIV-associated dementia  -  HAD. The modulation of ECS in the latter disease conditions is the subject of this review, that will also address the molecular workings underlying the neuroprotective effects of eCBs.

*In particular, the interactions between neurons and glia during neuroinflammation, and the alterations of ECS in these cells upon gp120 insults and HAD will be discussed, along with the potential medicinal exploitation of ECS-oriented medications for the treatment of HAD and related disorders.



8 d9THC for cramps in amyotrophic lateral sclerosis: a randomised, double-blind crossover trial.

*Motivation: Animal and human medical studies suggest that the two main constituents of
cannabis sativa, d9THC and cannabidiol  -  CBD have quite different significant effects. However, to date the two compounds have largely been studied separately. Objective: To evaluate and compare the significant pharmacological effects of both d9THC and Cannabidiol-CBD in the same human volunteers.

*Protocol: A randomised, double-blind, crossover, placebo controlled trial was conducted in 16 normally healthy male patients. Oral d9THC ten milligram or Cannabidiol-CBD 600 milligrams or placebo was administered in three consecutive sessions, at one-month intervals.

*Physiological measures and symptom and condition ratings were assessed before, and at 1, 2 and
3 hrs. post medication dosing. The area under the curve  -  AUC between baseline and 3 hrs., and the maximum absolute change from baseline at 2 hrs. were analyzed by one-way repeated measures analysis of variance, with medication condition d9THC or Cannabidiol-CBD or placebo as the factor. Data and Results: Relative to both placebo and CBD, dosing of d9THC was associated with anxiety, dysphoria, positive psychotic  symptoms, physical and mental sedation, subjective intoxication  -  AUC and effect at 2 hrs.: p<0.01, an increase in heart rate. There were no differences between Cannabidiol-CBD and placebo on any symptomatic, physiological variable.


*Findings: In normally healthy volunteers, d9THC has marked acute behavioural and physiological effects, whereas Cannabidiol-CBD has proven to be safe and well accepted.



9 Single-dose Pharmacokinetics and Tolerability of Oral d9THC in Subjects with Amyotrophic Lateral Sclerosis.

*History: Phytocannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis  -  ALS. We assessed the pharmacokinetics  -  PK and tolerability of d9THC in Amyotrophic Lateral Sclerosis - ALS subjects.

*Protocol: Nine subjects received d9THC single oral doses of 5 milligrams and 10mg, separated by a wash-out period of two wks.. Blood samples for the determination of d9THC, 11-nor-9-carboxy-THC  -  THC-COOH and hydroxy-THC  -  THC-OH were taken up to 8 hrs. after intake. Adverse events were assessed by visual analogue scales  -  VAS. Plasma amounts of the active metabolite d9THC-OH were submitted to sequential pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a proxy for d'9 THC's cardiovascular effects.

*Data and Results: Drowsiness, euphoria, orthostasis, sleepiness, vertigo and weakness were significantly more frequent in subjects receiving 10 milligrams compared to 5 milligrams d9THC. A marked interindividual variability was found for the absorption of oral d9THC  -  84 percent and elimination of d9THC-COOH  -  45 percent. PK medical data did not support any clinically relevant deviation from linear PK in the investigated range of amounts. Plasma amounts of d9THC-OH were positively correlated with the individual heart rate. An Emax-model was successfully fitted to individual heart rate, with a d9THC-OH plasma amount of 3.2 x ten -  -4 μmol/L for EC -  fifty and an Emax of 93 bpm for heart rate.

*Findings: The higher ten milligram dose of d9THC was dose-limiting in subjects with ALS. High interindividual PK varying needs individuell titration of d9THC for potential medicinal use in subjects with ALS.



10 Interplay of cannabinoid 2  -  CB2 receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration (death of nerve cells)

*Remote neuronal degeneration and death/insult, which often occur in regions remote, but functionally connected to the primary lesion site, may play a pivotal part in extending neuronal damage/dysfunction following traumatic brain insult, stroke, or peripheral nerve insult, as well as in chronic neurodegenerative conditions such as multiple sclerosis and Amyotrophic Lateral Sclerosis - ALS.

*Even though the exact workings of remote neuronal insult are poorly understood and no efficacious treatment options are available, it involves glial activation, inflammation, oxidative/nitrative stress, and apoptotic cell death. The newly discovered endocannabinoid (body's own) signaling system consisting of endocannabinoids (body's own)   -  endogenous bioactive lipid mediators, their synthetic-chemical and metabolizing enzymes, and their primary G protein-coupled cannabinoid 1 and 2  -  CB -  1 and CB2 receptors has been implicated in the regulation of numerous physiological and pathological processes/functions, including those associated with neurodegeneration (death of nerve cells). Using a well-described rodent model of remote neuronal degeneration.

*Oddi et al.have demonstrated that targeting CB2 cannabinoid receptors may represent a promising entirely new approach to attenuate this pathological process. This editorial discusses the clinical significance of these interesting observations and the workings of the potential interplay of CB -  2 receptors with nitric oxide synthases, oxidative and nitrative stress, and cell fatality during remote neurodegeneration (death of nerve cells).



11 Medicinal Potential of Phytocannabinoids in Neurodegenerative Disorders: A Selective Review

*The endocannabinoid (body's own) system  -  ECS is now recognised as an important modulator of various central nervous system processes. More recently, an increasing body of evidence has accumulated to suggest antioxidant, anti-inflammatory and neuroprotective roles of ECS. In this review, we discuss the part and medicinal potential of ECS in neurodegenerative disorders such as Alzheimer's disease  -  AD, Parkinson's disease, multiple sclerosis, Huntington's disease, Tourette's syndrome, brain ischemia and amyotrophic lateral sclerosis  -  ALS. Elements of the ECS, such as fatty acid amide hydrolase or the cannabinoid receptors are now considered as promising pharmacological targets for some conditions.

*Although still preliminary, recent reports suggest that modulation of the ECS may constitute a entirely new approach for the treatment of AD. There are windows of opportunity in conditions mitigated by significant events such as trauma and ischemia as well in conditions that may involve altered functionality of the target receptors of the ECS, such as in AD.

*The ECS changes in Parkinson's disease could be compensatory as well as pathogenic of the illness process and needs further understanding and clinical medical studies are still in the preliminary stage. There is not enough evidence to support the use of phytocannabinoids in treating Huntington's disease, tics and obsessive compulsive behaviour in Tourette's syndrome.

*Evidence on medicinal use of phytocannabinoids in multiple sclerosis and Amyotrophic Lateral Sclerosis - ALS is currently limited. A major challenge for future research is the development of entirely new compounds with more selectivity for various components of the ECS which could target different neurotoxic pathways and be used in combination therapy.



12 How Does Cannabis Impact the Progression of ALS?

 *Bob Strider began experiencing the symptoms of Amyotrophic Lateral Sclerosis - ALS in 1998, specifically the loss of function in his right arm and problems swallowing. An avid cannabis enthusiast, he had used cannabis heavily for decades, and he believes has kept the progression of his disease slow but steady. In the year of 2012, Strider began manufacturing his own cannabis oils, dosing himself with approximately a gram a day for sixty days. Within ten days of his regimen, he regained control of his right arm and was able to stop using opiates to manage his pain.

*Another remarkable case comes from Cathy Jordan, who was diagnosed with Amyotrophic Lateral Sclerosis - ALS in 1986 and given less than five years to live. In the winter of 1989, Jordan spent the holiday in Florida, preparing for the end of her life, when she made a crucial discovery. While walking on the beach one night, she smoked a joint of Myakka Gold and felt her symptoms cease, essentially experiencing the neuroprotective effects of cannabis before they’d been proven.


MMJDOCTORONLINE Notes:  We provide Medical Marijuana Recommendations, Cannabis ID Cards and Grower's Permits in California.  The process is 100% online and patients don't pay until they are approved.  Documents are used in State at cannabis clubs, dispensaries, cooperatives, delivery services and other points of cannabis based medicine access.




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