The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset.

“Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron loss, paralysis and death within 2-5 years of diagnosis. Currently, no effective pharmacological agents exist for the treatment of this devastating disease. Neuroinflammation may accelerate the progression of ALS. Cannabinoids produce anti-inflammatory actions via cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), and delay the progression of neuroinflammatory diseases…

 …treatment with non-selective cannabinoid partial agonists prior to, or upon, symptom appearance minimally delays disease onset and prolongs survival through undefined mechanisms…

…Δ9-Tetrahydrocannabinol (Δ9-THC) is the main psychoactive constituent in the plant Cannabis sativa (marijuana) and produces its effects by activation of cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) cannabinoid receptors. CB1 receptors are expressed throughout the CNS, while CB2 receptors are expressed predominantly in immune cells and non-neuronal tissues. Therapeutic agents which modulate the cann-abinoid system are effective in treating a wide variety of disorders characterized by inflammation. More specifically, drugs which activate CB2 receptors successfully improve the symptoms of several inflammatory diseases…

More importantly, daily injections of the selective CB2 agonist AM-1241, initiated at symptom onset, increase the survival interval after disease onset by 56%. Therefore, CB2 agonists may slow motor neuron degeneration and preserve motor function, and represent a novel therapeutic modality for treatment of ALS.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819701/

 

Medical Marijuana For Multiple Sclerosis and Amyotrophic Lateral Sclerosis

“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.

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

Therapeutic effects of Delta9-THC and modafinil in a marmoset Parkinson model.

Abstract

“Current therapies for Parkinson’s disease (PD) like l-dopa and dopamine (DA) agonists have declined efficacy after long term use. Therefore, research towards supplementary or alternative medication is needed. The implementation in PD can be expedited by application of compounds already used in the clinic. In this study the therapeutic effects of the psychoactive compounds Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and modafinil were tested in the 1-methyl-1,2,3,6-tetrahydropyridine (MPTP)-marmoset model for PD. The anti-parkinson effects of Delta(9)-THC (4 mg/kg) and modafinil (100 mg/kg) in parkinsonian marmosets were assessed with two behavioral rating scales covering parkinsonian symptoms and involuntary movements and two test systems assessing the locomotor activity and hand-eye coordination. Delta(9)-THC improved activity and hand-eye coordination, but induced compound-related side-effects. Modafinil improved activity and observed parkinsonian symptoms but not hand-eye coordination. It can be concluded that both compounds have therapeutic values and could supplement existing therapies for PD.”

http://www.ncbi.nlm.nih.gov/pubmed/18222654

Marijuana is helping to treat parkinson’s

“My sister, who lives in Holland, is a Parkinson’s patient who is treating her condition with marijuana – or derivatives of it. In the last couple of months, Dutch doctors have been allowed to prescribe marijuana-based medication for Parkinson’s, and my sister has taken advantage of this change in the law.

Several products are available, including Marinol, a synthetic form of THC (tetrahydrocannabiol), the active ingredient of marijuana. This US-made product is expensive – 10 capsules cost 86 euros (£60) – and is not yet approved for Parkinson’s. It has so far been tested only on AIDS and MS patients.

Nonetheless, my sister has started to show spectacular results. She now has clarity of mind, she can turn around in bed by herself and doesn’t have to wake her husband to help her get out of bed. Her stiffness has gone and she is no longer an invalid…”

http://www.wddty.com/marijuana-is-helping-to-treat-parkinson-s.html

Marijuana-Like Compounds May Aid Array Of Debiliatiing Conditions Ranging From Parkinson’s Disease To Pain

“Oct. 27, 2004 — No longer a pipe dream, new animal research now indicates that marijuana-like compounds can aid a bevy of debilitating conditions, ranging from brain disorders such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease, to pain and obesity.

Research from California Pacific Medical Center in San Francisco points to the promise of marijuana-like treatments for those with the fatal brain disorder ALS, also known as Lou Gehrig’s disease.

“Our research indicates that select marijuana compounds, including THC, significantly slow the disease process and extend the life of mice with ALS,” says study author Mary Abood, PhD.

The study extends earlier work from Abood’s group that found that THC also can alleviate some ALS symptoms, like muscle spasms, in patients.

ALS wreaks its havoc by harming nerve cells that control muscles. As a consequence of the damage, an estimated 5,000 Americans afflicted annually experience progressive muscle weakness that can hinder movement, speech, even swallowing and breathing. New treatments for ALS are desperately needed…

“For the first time, our research shows the neuroprotective value of marijuana-like compounds in a well-established animal model of Parkinson’s disease,” says study author Andrea Giuffrida, PhD, of the University of Texas Health Science Center in San Antonio.

Parkinson’s afflicts some 1 million Americans. Symptoms include slowness of movement, muscle stiffness, and shaky tremors, which can harm a person’s ability to walk, talk, write, and eat. This havoc results from the death or injury of brain cells that produce the chemical dopamine.

“There are therapies that can help replenish depleted levels of dopamine and provide symptomatic relief, but none can reverse, prevent, or delay the progression of Parkinson’s disease,” says Giuffrida. “Our research shows that marijuana-like compounds may be able to answer this need.””

Read more: http://www.sciencedaily.com/releases/2004/10/041027102621.htm

 

Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures.

Abstract

“Cannabinoids derived from Cannabis sativa demonstrate neuroprotective properties in various cellular and animal models. Mitochondrial impairment and consecutive oxidative stress appear to be major molecular mechanisms of neurodegeneration. Therefore we studied some major cannabinoids, i.e. delta-9-tetrahydrocannabinolic acid (THCA), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in mice mesencephalic cultures for their protective capacities against 1-methyl-4-phenyl pyridinium (MPP(+)) toxicity. MPP(+) is an established model compound in the research of parkinsonism that acts as a complex I inhibitor of the mitochondrial respiratory chain, resulting in excessive radical formation and cell degeneration. MPP(+) (10 μM) was administered for 48 h at the 9th DIV with or without concomitant cannabinoid treatment at concentrations ranging from 0.01 to 10 μM. All cannabinoids exhibited in vitro antioxidative action ranging from 669 ± 11.1 (THC), 16 ± 3.2 (THCA) to 356 ± 29.5 (CBD) μg Trolox (a vitamin E derivative)/mg substance in the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay. Cannabinoids were without effect on the morphology of dopaminergic cells stained by tyrosine hydroxylase (TH) immunoreaction. THC caused a dose-dependent increase of cell count up to 17.3% at 10 μM, whereas CBD only had an effect at highest concentrations (decrease of cell count by 10.1-20% at concentrations of 0.01-10 μM). It influenced the viability of the TH immunoreactive neurons significantly, whereas THCA exerts no influence on dopaminergic cell count. Exposure of cultures to 10 μM of MPP(+) for 48 h significantly decreased the number of TH immunoreactive neurons by 44.7%, and shrunken cell bodies and reduced neurite lengths could be observed. Concomitant treatment of cultures with cannabinoids rescued dopaminergic cells. Compared to MPP(+) treated cultures, THC counteracted toxic effects in a dose-dependent manner. THCA and CBD treatment at a concentration of 10 μM lead to significantly increased cell counts to 123% and 117%, respectively. Even though no significant preservation or recovery of neurite outgrowth to control values could be observed, our data show that cannabinoids THC and THCA protect dopaminergic neurons against MPP(+) induced cell death.”

http://www.ncbi.nlm.nih.gov/pubmed/22571976

Cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by the proteasomal dysfunction.

“Cannabinoids (CBs) from the Cannabis sativa L. plant, including tetrahydrocannabinol, the principal psychoactive component of marijuana, produce euphoria and relaxation and also impair motor coordination, perception of time, and short-term memory. The principal actions of CBs are mediated by activation of their cognate receptors on presynaptic nerve ends. Various types of cannabinoid receptors, including the orphan G-protein coupled receptors CB1 and CB2, are found in blood vessels, the central nervous system, and immune cells. While CB1 is expressed abundantly in several areas in the brain as well as in peripheral tissues, CB2 is primarily expressed in the immune system, although it was recently detected at low levels in peripheral nerve endings, microglial cells, and astrocytes, as well as in the cerebellum and brain stem. CB1 receptor activation is involved in the control of neural cell fate and mediates neuroprotectivity in different in vivo models of brain injury, including excitotoxicity and ischemia.

In recent years, the capacity of CBs to effect neuroprotection and neurotoxicity has received increasing attention. Evidence of possible neuroprotective effects has accumulated in vitro from models of neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases and multiple sclerosis, as well as from in vivo clinical trial data. These compounds are also able to decrease inflammation by acting on glial cells that influence neuronal survival. The molecular mechanisms underlying cannabinoid-mediated neuroprotection are still poorly understood, but may include the direct activation of neuronal survival signaling pathways through cannabinoid receptors or indirect effects mediated by microglial CB2-receptor stimulation.

Here, we investigated the neuroprotective function of a synthetic cannabinoid-receptor agonist (WIN55.212.2)… These results indicate that WIN55.212.2 may be a candidate for treatment of neurodegenerative diseases, including Parkinson’s disease.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145842/

Cannabinoids reduce levodopa-induced dyskinesia in Parkinson’s disease: a pilot study.

Abstract

“The lateral segment of the globus pallidus (GPl) is thought to be overactive in levodopa-induced dyskinesia in PD. Stimulation of cannabinoid receptors in the GPl reduces gamma-aminobutyric acid (GABA) reuptake and enhances GABA transmission and may thus alleviate dyskinesia. In a randomized, double-blind, placebo-controlled, crossover trial (n = 7), the authors demonstrate that the cannabinoid receptor agonist nabilone significantly reduces levodopa-induced dyskinesia in PD.”

http://www.ncbi.nlm.nih.gov/pubmed/11739835

Smoked cannabis proven effective in treating neuropathic pain.

UC San Diego Health

“Smoked cannabis eased pain induced in healthy volunteers, according to a study by researchers at the University of California, San Diego (UCSD) Center for Medical Cannabis Research (CMCR.) However, the researchers found that less may be more.”

“The results, showing a medium-dose (4% THC by weight) of cannabis to be an effective analgesic, converged with results from the CMCR’s first published study, a paper by UCSF researcher Donald Abrams, M.D. published in the journal Neurology in February 2007. In that randomized placebo-controlled trial, patients smoking the same dose of cannabis experienced a 34% reduction in HIV-associated sensory neuropathy pain—twice the rate experienced by patients receiving a placebo.”

““This study helps to build a case that cannabis does have therapeutic value at a medium-dose level,” said Grant. “It also suggests that higher doses aren’t necessarily better in certain situations – something also observed with other medications, such as antidepressants.””

Read more: http://phys.org/news112456382.html

“Smoked Cannabis Proven Effective In Treating Neuropathic Pain”  https://www.sciencedaily.com/releases/2007/10/071024141745.htm

“Smoked cannabis proven effective in treating neuropathic pain”  https://medicalxpress.com/news/2007-10-cannabis-proven-effective-neuropathic-pain.html

“Smoked Cannabis Proven Effective in Treating Neuropathic Pain”  https://health.ucsd.edu/news/2007/pages/10-24-medical-cannabis.aspx