CBD efficacy on nonmotor symptoms of Parkinson Disease anxiety & psychosis


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This is the last section of a review article Managing Psychosis in Parkinson Disease

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Results from preclinical and preliminary studies also suggest that cannabidiol (CBD) has therapeutic potential for nonmotor symptoms of PD.14 The multifaceted mechanism of action as an agonist of 5-HT1A, partial agonist of CB1 and CB2 receptors, and antagonist of the G-protein–coupled receptor GPR55 reverses the iron-induced epigenetic modification of mitochondrial DNA and the reduction of succinate dehydrogenase activity and decreases the levels of the pro-inflammatory cytokines IL-1β, TNF-α, IFN-β, IFN-γ, IL-17, and IL-6—all of which decrease pro-inflammatory mediators resulting in neuroprotective, anxiolytic, and antipsychotic effects.14

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“Several in vitro experiments have demonstrated promising neuro- protective effects of CBD in PD models. In one of these models, using PC12 and SH-SY5Y cells treated with MPP+ [1-methyl-4-phenylpyridinium], CBD increased cell viability, differentiation, and the expression of axonal [GAP-43] and synaptic [synaptophysin and synapsin I] proteins,” Ferreria-Junior and colleagues wrote,15 while acknowledging the paucity of studies that have addressed the biological bases for the purported effects of CBD on PD. “Double-blind, placebo-controlled, randomized trials with larger samples of patients with PD are needed to elucidate the possible effectiveness and mechanisms involved in the therapeutic potential of CBD in this movement disorder. This will also include the putative effects of CBD in preventing L-dopa–induced severe [adverse] effects and preventing PD progression.”

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The endocannabinoid system serves as an important filter of excitatory, inhibitory, and modulatory inputs that act at the midbrain and terminal regions to orchestrate DA neurotransmission by controlling DA cell body firing patterns, terminal release, and effects on postsynaptic sites in the striatum.16 Beneficial effects of CBD administration have been observed prior to or immediately after induction of PD-like symptoms in animal studies, which may suggest a preventive role rather than a therapeutic one.14 In an early open-label pilot study to evaluate the efficacy of CBD on nonmotor symptoms of PD in 6 patients with PDP, psychotic symptoms significantly decreased under CBD treatment, as evaluated by the brief psychiatric rating scale and the Parkinson psychosis questionnaire.17

 

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Psychiatric comorbidities prevalent in the majority of patients with PD are associated with more disease severity, impaired QOL, and increased use of healthcare resources, with longer hospital stays and re-hospitalizations adding to the total cost burden.

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Curcumin-like Drug Slows Aging, Reverses Memory Deficits


Drug Slows Aging, Reverses Memory Deficits

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Possible Alzheimer’s & Parkinsons Drug

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Roll over and click on BOLD links above and below to open article – unable to indicate color blue.

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“…potential Alzheimer’s drug works by reducing the rate of aging at the molecular level, according to a new study led by Salk Institute scientists.

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The study explains how the drug both improves cognition and reduces the rate of aging, when given to very old mice.

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Study authors say a drug that inhibits aging may succeed where drugs specifically aimed at Alzheimer’s have failed.

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Getting the drug into human clinical trials will require a little over $1 million.”

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 The study was published in the journal Aging Cell….

The mitochondrial ATP synthase is a shared drug target for aging and dementia

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 Salk Institute News

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….“This really glues together everything we know about J147 in terms of the link between aging and Alzheimer’s,” says Dave Schubert, head of Salk’s Cellular Neurobiology Laboratory and the senior author on the new paper. “Finding the target of J147 was also absolutely critical in terms of moving forward with clinical trials.”

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Schubert’s group developed J147 in 2011, after screening for compounds from plants with an ability to reverse the cellular and molecular signs of aging in the brain. J147 is a modified version of a molecule (curcumin) found in the curry spice turmeric. In the years since, the researchers have shown that the compound reverses memory deficits, potentiates the production of new brain cells, and slows or reverses Alzheimer’s progression in mice. However, they didn’t know how J147 worked at the molecular level.

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In the new work, led by Schubert and Salk Research Associate Josh Goldberg, the team used several approaches to home in on what J147 is doing. They identified the molecular target of J147 as a mitochondrial protein called ATP synthase that helps generate ATP—the cell’s energy currency—within mitochondria. They showed that by manipulating its activity, they could protect neuronal cells from multiple toxicities associated with the aging brain. Moreover, ATP synthase has already been shown to control aging in C. elegans worms and flies.

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“We know that age is the single greatest contributing factor to Alzheimer’s, so it is not surprising that we found a drug target that’s also been implicated in aging,” says Goldberg, the paper’s first author.

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Further experiments revealed that modulating activity of ATP synthase with J147 changes the levels of a number of other molecules—including levels of ATP itself—and leads to healthier, more stable mitochondria throughout aging and in disease.

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“I was very surprised when we started doing experiments with how big of an effect we saw,” says Schubert. “We can give this to old mice and it really elicits profound changes to make these mice look younger at a cellular and molecular level.”

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The results, the researchers say, are not only encouraging for moving the drug forward as an Alzheimer’s treatment, but also suggest that J147 may be useful in other age-associated diseases as well.

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“People have always thought that you need separate drugs for Alzheimer’s, Parkinson’s and stroke” says Schubert. “But it may be that by targeting aging we can treat or slow down many pathological conditions that are old-age-associated.”

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Metformin

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From WebMD, March 29, 2017:

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“Doctors have prescribed metformin, the most common drug to treat type 2 diabetes, for about 60 years. But it’s received new attention as a possible anti-aging drug after researchers in Britain found that people with diabetes who took it outlived some of their peers who did not have the disease by 15%.

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“They compared them to a whole bunch of people who were matched for weight and smoking and [other factors] but who didn’t have diabetes,” says Steven Austad, PhD, chairman of the biology department at the University of Alabama at Birmingham. “It turned out the diabetics on metformin were living longer than the non-diabetics who were not on metformin. … It was very, very intriguing.”

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Austad is a bio-gerontologist and scientific director of the American Federation for Aging Research….

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Scientists believe the drug works in the mitochondria, the powerhouses in the body’s cells that convert sugars like glucose into energy. Austad says metformin makes those powerhouses run more efficiently, reducing the release of substances known as free radicals. Free radicals can damage cells, hurting their ability to reproduce and causing defects.”

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….Resveratrol, a compound found in grapes and nuts, may reduce stress that leads to cell aging. Research shows it can extend life span in yeast, worms, and fish, but these effects haven’t been demonstrated in humans yet.”

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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