Tag Archives: Cannabinoids

The endocannabinoid system in the inflammatory and neurodegenerative processes of multiple sclerosis and of amyotrophic lateral sclerosis.

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Abstract

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/20353778

The (endo)cannabinoid system in multiple sclerosis and amyotrophic lateral sclerosis.

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“Alterations of the endocannabinoid system (ECS) have been recently implicated in a number of neuroinflammatory and neurodegenerative conditions so that the pharmacological modulation of cannabinoid (CB) receptors and/or of the enzymes controlling synthesis, transport, and degradation of these substances has emerged as a valuable option to treat neurological diseases.

Here, we describe the current knowledge concerning the rearrangement of ECS in a primarily inflammatory disorder of the central nervous system such as multiple sclerosis (MS), and in a primarily degenerative condition such as amyotrophic lateral sclerosis (ALS).

 Furthermore, the data supporting a therapeutic role of agents modulating CB receptors or endocannabinoid tone in these disorders will also be reviewed. Complex changes of ECS take place in both diseases, influencing crucial aspects of their pathophysiology and clinical manifestations. Neuroinflammation, microglial activation, oxidative stress, and excitotoxicity are variably combined in MS and in ALS and can be modulated by endocannabinoids or by drugs targeting the ECS.”

http://www.ncbi.nlm.nih.gov/pubmed/17678961

Medical Marijuana For Multiple Sclerosis and Amyotrophic Lateral Sclerosis

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“Marijuana has been classified as a Schedule 1 narcotic since the 1960’s, which means it is deemed by the federal government to have no medicinal value and heavy risk. However, there is an increasing body of research to show that marijuana can be helpful for certain debilitating conditions and 15 states have now legalized it for medicinal usage. One of those conditions research is showing marijuana’s medicinal value is multiple sclerosis (MS) and another is Amyotrophic Lateral Sclerosis (ALS). They are both diseases involving neurologic deterioration.

Approximately 200 individuals per week are diagnosed with MS, with the usual onset between 20 and 40 years of age. The disease has no known cure and involves a neuro-degeneration in which the brain and spinal cord nerves undergo a gradual destruction of its protective tissue called myelin.

Myelin covers these regions in what’s called a Myelin sheath, and as the sheath degenerates symptoms include painful muscle spasms, numbness, impaired vision, loss of coordination, tremors, weakness, and imbalance (ataxia). The disease is progressive and can become incapacitating and lead to death.

MS patients may find that marijuana relieves symptoms of spasticity, tremors, imbalance, depression, and fatigue. Numerous studies have looked at Sativex, which is an oral cannabis spray developed in the UK. It has been shown to relieve pain, spasticity, depression, fatigue, and incontinence.

THC appears to have some immunosuppressive or immunomodulatory effects. This may be beneficial to MS patients. Long term studies need to be completed to see if this is for real and a disease modifying effect is real.

Lou Gehrig’s disease, also called Amyotrophic Lateral Sclerosis, involves the ongoing loss of the brain’s motor neurons. It is rapidly progressive, and usually fatal. There is no known cause. The usual age of onset is 40 to 60 years, and men are more commonly affected.

The most well known person with ALS is Stephen Hawking, a physicist who has lived for over 40 years after being diagnosed. He is the exception, the unfortunate usual prognosis is grim, with about half of patients dying with 2.5 years of onset.

The cannabinoids in medical marijuana may protect against glutamate toxicity. This may be very helpful because ALS involves excessive glutamate in the brain tissue, spinal fluid, and serum of those suffering.

By lowering the chance of glutamate toxicity, there is a chance that marijuana may have a neuroprotective effect. In addition, patients describe alleviation of pain and spasms, improvement of appetite, and less drooling issues which is a common problem with ALS.”

By David L. Greene

 

Δ⁹-tetrahydrocannabinol (Δ⁹-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson’s disease.

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Neuropathology and Applied Neurobiology

“Δ⁹-tetrahydrocannabinol (Δ⁹-THC) is neuroprotective in models of Parkinson’s disease (PD).

Although CB1 receptors are increased within the basal ganglia of PD patients and animal models, current evidence suggests a role for CB1 receptor-independent mechanisms.

Here, we utilized a human neuronal cell culture PD model to further investigate the protective properties of Δ⁹-THC.

We found CB1 receptor up-regulation in response to MPP+, lactacystin and paraquat and a protective effect of Δ⁹-THC against all three toxins. This neuroprotective effect was not reproduced by the CB1 receptor agonist WIN55,212-2 or blocked by the CB1 antagonist AM251. Furthermore, the antioxidants α-tocopherol and butylhydroxytoluene as well as the antioxidant cannabinoids, nabilone and cannabidiol were unable to elicit the same neuroprotection as Δ⁹-THC.

 

We have demonstrated up-regulation of the CB1 receptor in direct response to neuronal injury in a human PD cell culture model, and a direct neuronal protective effect of Δ⁹-THC that may be mediated through PPARγ activation.”

https://www.ncbi.nlm.nih.gov/pubmed/22236282

“In conclusion, we have demonstrated up-regulation of the CB1 receptor in a human cell culture model of PD, as well as a direct neuroprotective effect of the phytocannabinoid, Δ9-THC, not mediated by the CB2 receptor. Although a CB1 receptor-mediated effect cannot totally be excluded, we propose that activation of PPARγ leading to antioxidant effects is highly relevant in mediating the neuroprotection afforded by Δ9-THC in our model.”

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2990.2011.01248.x/full

Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson’s disease: importance of antioxidant and cannabinoid receptor-independent properties.

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Abstract

“We have recently demonstrated that two plant-derived cannabinoids, Delta9-tetrahydrocannabinol and cannabidiol (CBD), are neuroprotective in an animal model of Parkinson’s disease (PD), presumably because of their antioxidant properties. To further explore this issue, we examined the neuroprotective effects of a series of cannabinoid-based compounds, with more selectivity for different elements of the cannabinoid signalling system, in rats with unilateral lesions of nigrostriatal dopaminergic neurons caused by local application of 6-hydroxydopamine. We used the CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA), the CB2 receptor agonist HU-308, the non-selective agonist WIN55,212-2, and the inhibitors of the endocannabinoid inactivation AM404 and UCM707, all of them administered i.p. Daily administration of ACEA or WIN55,212-2 did not reverse 6-hydroxydopamine-induced dopamine (DA) depletion in the lesioned side, whereas HU-308 produced a small recovery that supports a possible involvement of CB2 but not CB1 receptors. AM404 produced a marked recovery of 6-hydroxydopamine-induced DA depletion and tyrosine hydroxylase deficit in the lesioned side. Possibly, this is caused by the antioxidant properties of AM404, which are derived from the presence of a phenolic group in its structure, rather than by the capability of AM404 to block the endocannabinoid transporter, because UCM707, another transporter inhibitor devoid of antioxidant properties, did not produce the same effect. None of these effects were observed in non-lesioned contralateral structures. We also examined the timing for the effect of CBD to provide neuroprotection in this rat model of PD. We found that CBD, as expected, was able to recover 6-hydroxydopamine-induced DA depletion when it was administered immediately after the lesion, but it failed to do that when the treatment started 1 week later. In addition, the effect of CBD implied an upregulation of mRNA levels for Cu,Zn-superoxide dismutase, a key enzyme in endogenous defenses against oxidative stress. In summary, our results indicate that those cannabinoids having antioxidant cannabinoid receptor-independent properties provide neuroprotection against the progressive degeneration of nigrostriatal dopaminergic neurons occurring in PD. In addition, the activation of CB2 (but not CB1) receptors, or other additional mechanisms, might also contribute to some extent to the potential of cannabinoids in this disease.”

http://www.ncbi.nlm.nih.gov/pubmed/17196181

Cannabinoids and Parkinson’s disease.

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Abstract

“Cannabinoid-based medicines have been proposed as clinically promising therapies in Parkinson’s disease (PD), given the prominent modulatory function played by the cannabinoid signaling system in the basal ganglia. Supporting this pharmacological potential, the cannabinoid signaling system experiences a biphasic pattern of changes during the progression of PD. Thus, early and presymptomatic stages, characterized by neuronal malfunctioning but little evidence of neuronal death, are associated with desensitization/downregulation of CB(1) receptors. It was proposed that these losses may be part of the pathogenesis itself, since they can aggravate different cytotoxic insults which are controlled in part by cannabinoid signals, mainly excitotoxicity but also oxidative stress and glial activation. By contrast, intermediate and, in particular, advanced stages of parkinsonism characterized by a profound nigral degeneration and occurrence of major parkinsonian symptoms (e.g. bradykinesia), are associated with upregulatory responses of CB(1) receptors, possibly CB(2) receptors too, and the endocannabinoid ligands for both receptor types. This would explain the motor inhibition typical of this disease and the potential proposed for CB(1) receptor antagonists in attenuating the bradykinesia typical of PD. In addition, certain cannabinoid agonists have been proposed to serve as neuroprotective molecules in PD, given their well-demonstrated capability to reduce excitotoxicity, calcium influx, glial activation and, in particular, oxidative injury that cooperatively contribute to the degeneration of nigral neurons. However, the potential of cannabinoid-based medicines in PD have been still scarcely studied at the clinical level despite the existence of solid and promising preclinical evidence. Considering the relevance of these preclinical data, the need for finding treatments for motor symptoms that may be alternative to classic dopaminergic replacement therapy, and the lack of efficient neuroprotective strategies in PD, we believe it is of major interest to develop further studies that allow the promising expectations generated for these molecules to progress from the present preclinical evidence towards a real clinical application.”

http://www.ncbi.nlm.nih.gov/pubmed/19839934

An overview of Parkinson’s disease and the cannabinoid system and possible benefits of cannabinoid-based treatments.

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Abstract

“Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder with a heterogeneous clinical picture and a variable rate of progression. PD is characterized by degeneration of the pigmented neuromelanin bearing cells of the pars compacta of the substantia nigra that leads to a severe dopaminergic denervation of the striatum. Current treatments for PD rely on dopamine replacement therapy, most commonly with the dopamine precursor levodopa. Despite the many recent advances in the symptomatic treatment of PD, there is still no realistic prospect for a cure. In recent years, new data support the idea of a relevant role for the cannabinoid system in PD. As cannabinoids have neuroprotective properties, they have been proposed as potentially useful neuroprotective substances in PD, as well as to alleviate some symptoms in specific circumstances (i.e. parkinsonian tremor associated with overactivity to the subthalamic nucleus; levodopa-induced dyskinesia). By contrast, CB(1) receptor antagonists might be useful to reduce bradykinesia in patients refractory to classic levodopa treatment. The present article will review all data about the relationship between PD and the cannabinoid system including: i) the usefulness of cannabinoid-related compounds to alleviate some PD symptoms; ii) that cannabinoid-based compounds might provide protection against the progression of neuronal injury characteristic of this disease; iii) the influence of cannabinoids on local inflammatory events associated with the pathogenesis in PD. Collectively, all these evidence support that the management of the cannabinoid system might represent a new approach to the treatment of PD.”

http://www.ncbi.nlm.nih.gov/pubmed/17168732

The endocannabinoid system in Parkinson’s disease.

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Abstract

“Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder of largely unknown etiology caused by a pathological cascade resulting in the degeneration of midbrain dopaminergic neurons of the substantia nigra pars compacta (SNpc) projecting to the nucleus striatum, the main input station of the basal ganglia neuronal circuit. The components of the endocannabinoid (ECB) system are highly expressed at different levels in the basal ganglia neural circuit where they bidirectionally interact with dopaminergic, glutamatergic and GABAergic signaling systems. In particular, at synapses linking cortical and striatal neurons, endocannabinoids (ECBs) are known to critically modulate synaptic transmission and to mediate the induction of a particular form of synaptic plasticity, the long-term depression. The evidence that ECBs play a central role in regulating basal ganglia physiology and motor function and the profound modifications occurring in ECB signaling after dopamine depletion in both experimental models of PD and patients suffering from the disease, provide support for the development of pharmacological compounds targeting the ECB system as symptomatic and neuroprotective therapeutic strategies for PD.”

http://www.ncbi.nlm.nih.gov/pubmed/18781984

Natural brain substance linked to Parkinson’s symptoms

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“Neuroscientists have found that a substance similar to the active ingredient in marijuana but produced naturally in the brain helps to control mobility — and may offer a novel target for treating Parkinson’s disease.

The findings by Stanford University researchers, reported in the latest issue of the journal Nature, show how marijuana-like “endocannabinoids” — one of the many chemicals used in the brain to transmit signals — form part of the neural machinery that directs normal physical movement.

A shortage of the endocannabinoids, the scientists found, can knock the system out of balance to produce the characteristic tremor, rigidity and other mobility problems of Parkinson’s disease patients…”

Read more; http://www.sfgate.com/health/article/Natural-brain-substance-linked-to-Parkinson-s-2650879.php

Parkinsons’ Helped By Marijuana-Lke Chemicals In Brain

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(February 11, 2007) “Marijuana-like chemicals in the brain may point to a treatment for the debilitating condition of Parkinson’s disease. In a study published in Nature, researchers from the Stanford University School of Medicine report that endocannabinoids, naturally occurring chemicals found in the brain that are similar to the active compounds in marijuana and hashish, helped trigger a dramatic improvement in mice with a condition similar to Parkinson’s.

“This study points to a potentially new kind of therapy for Parkinson’s disease,” said senior author Robert Malenka, MD, PhD, the Nancy Friend Pritzker Professor in Psychiatry and Behavioral Sciences. “Of course, it is a long, long way to go before this will be tested in humans, but nonetheless, we have identified a new way of potentially manipulating the circuits that are malfunctioning in this disease.””

Read More: http://www.medicalnewstoday.com/releases/62616.php