Marijuana fights Alzheimer’s disease, Salk Institute scientists discover

Cannabinoids remove plaque-forming Alzheimer's proteins from brain cells

“Salk Institute scientists have discovered that a main compound found in marijuana can fight a toxic protein associated with Alzheimer’s disease. According to the scientists, at this time, there are no drugs that significantly inhibit cell death associated with Alzheimer’s disease (AD), Parkinson’s or Huntington’s diseases. However, the most recent data about Alzheimer’s and marijuana suggests that there is a therapeutic potential of cannabinoids (the chemical compounds secreted by cannabis flowers) for the treatment of AD. Cannabinoids are able to remove plaque-forming Alzheimer’s proteins from brain cells, reports the Medical Express on June 29.”  http://www.examiner.com/article/marijuana-fights-alzheimer-s-disease-salk-institute-scientists-discover

“Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells”  http://medicalxpress.com/news/2016-06-cannabinoids-plaque-forming-alzheimer-proteins-brain.html

“Cannabinoids remove toxic proteins associated with Alzheimer’s disease from the brain” http://www.irishexaminer.com/examviral/science-world/cannabinoids-remove-toxic-proteins-associated-with-alzheimers-disease-from-the-brain-407788.html

“Marijuana Compound Helps Remove Alzheimer’s Disease Protein From Brain” -brain.” http://www.scienceworldreport.com/articles/42990/20160630/marijuana-compound-helps-remove-alzheimers-disease-protein-from-brain.htm

“Marijuana compound removes toxic Alzheimer’s protein from the brain”  http://www.sciencealert.com/marijuana-compound-removes-toxic-alzheimer-s-protein-from-the-brain

“Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells”  https://www.sciencedaily.com/releases/2016/06/160629095609.htm

“Cannabinoids Remove Plaque-forming Alzheimer’s Proteins from Brain Cells”  https://www.laboratoryequipment.com/news/2016/06/cannabinoids-remove-plaque-forming-alzheimers-proteins-brain-cells

“MARIJUANA COMPOUND REMOVES ALZHEIMER’S PLAQUE FROM BRAIN CELLS, STUDY FINDS” http://www.popsci.com/marijuana-compound-removes-alzheimers-plaque-from-brain-cells-study

“Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells. Preliminary lab studies at the Salk Institute find THC reduces beta amyloid proteins in human neurons.” http://www.salk.edu/news-release/cannabinoids-remove-plaque-forming-alzheimers-proteins-from-brain-cells/

 

Fatty Acid Amide Hydrolase Binding in Brain of Cannabis Users: Imaging With the Novel Radiotracer [11C]CURB.

“One of the major mechanisms for terminating the actions of the endocannabinoid anandamide is hydrolysis by fatty acid amide hydrolase (FAAH), and inhibitors of the enzyme were suggested as potential treatment for human cannabis dependence.

In cannabis users, FAAH binding was significantly lower by 14%-20% across the brain regions examined than in matched control subjects.

Lower FAAH binding levels in the brain may be a consequence of chronic and recent cannabis exposure and could contribute to cannabis withdrawal. This effect should be considered in the development of novel treatment strategies for cannabis use disorder that target FAAH and endocannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/27345297

Cannabimimetic Drugs: Recent Patents in Central Nervous System Disorders.

“Agents acting via cannabinoid receptors have been widely developed; starting from the chemical structure of phytocannabinoids isolated from cannabis sativa plant, specific and selective compounds of these receptors have been produced ranging from partial to full agonists and /or antagonists endowed with different potency.

The enhanced interest on developing such classes of drugs is due to the beneficial properties widely reported by both anecdotal reports and scientific studies describing the potential medicinal use of cannabinoids and their derivatives in numerous pathological conditions in both in vitro and in vivo models.

The use of these drugs has been found to be of benefit in a wide number of neurological and neuropsychiatric disorders, and in many other diseases ranging from cancer, atherosclerosis, stroke, hypertension, inflammatory related disorders, and autoimmune diseases, just to mention some.

In particular, being the cannabinoid CB1 receptor a central receptor expressed by neurons of the central nervous system, the attention for the treatment of neurological diseases has been mainly focused on compounds acting via this receptor, however some of these compounds has been showed to act by alternative pathways in some cases unrelated to CB1 receptors.

Nonetheless, endocannabinoids are potent regulators of the synaptic function in the central nervous system and their levels are modulated in neurological diseases.

In this study, we focused on endocannabinoid mechanism of action in neuronal signaling and on cannabimimetic drug potential application in neurological disorders.

Finally, novel patents on cannabis-based drugs with applicability in central nervous system disorders are highlighted, to suggest future potential therapeutic utility of derivatives of this ancient plant.”

http://www.ncbi.nlm.nih.gov/pubmed/27334611

Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid

“The flowering plants of the genus Cannabis, which mainly comprises the sativa and indica species, have been recognized for medical treatment for millennia.

Although Cannabis contains nearly 500 compounds from 18 chemical classes, its physiological effects derive mainly from a family of naturally occurring compounds known as plant cannabinoids or phytocannabinoids. Of the more than 100 phytocannabinoids that have been identified in Cannabis, among the most important and widely studied are its main psychoactive constituent, Δ9-tetrahydrocannabinol (Δ9-THC), and the most important nonpsychoactive component, cannabidiol (CBD). Other biologically active phytocannabinoids that have been isolated in Cannabis include Δ8-THC, cannabinol, Δ9-tetrahydrocannabivarin, and cannabidivarin.

In recent research, orally administered cannabidiol (CBD) showed a relatively high incidence of somnolence in a pediatric population. Previous work has suggested that when CBD is exposed to an acidic environment, it degrades to Δ9-tetrahydrocannabinol (THC) and other psychoactive cannabinoids. To gain a better understanding of quantitative exposure, we completed an in vitro study by evaluating the formation of psychoactive cannabinoids when CBD is exposed to simulated gastric fluid (SGF).

SGF converts CBD into the psychoactive components Δ9-THC and Δ8-THC. The first-order kinetics observed in this study allowed estimated levels to be calculated and indicated that the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a physiological response. Delivery methods that decrease the potential for formation of psychoactive cannabinoids should be explored.

Despite persistent challenges with dosing and administration, CBD-based therapies have a good safety profile and a potential for efficacy in the treatment of a variety of medical conditions. The rapidly evolving sciences of drug delivery and cannabinoid pharmacology may soon lead to breakthroughs that will improve access to the benefits of this pharmacological class of agents. In addition, current technologies, such as transdermal-based therapy, may be able to eliminate the potential for psychotropic effects due to this acid-catalyzed cyclization by delivering CBD through the skin and into the neutral, nonreactive environment of the systemic circulation.”

http://online.liebertpub.com/doi/10.1089/can.2015.0004

Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy

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“Severe childhood epilepsies are characterized by frequent seizures, neurodevelopmental delays and impaired quality of life. In these treatment-resistant epilepsies, families often seek alternative treatments.

This survey explored the use of cannabidiol-enriched cannabis in children with treatment-resistant epilepsy. The survey was presented to parents belonging to a Facebook group dedicated to sharing information about the use of cannabidiol-enriched cannabis to treat their child’s seizures.

Nineteen responses met the inclusion criteria for the study: a diagnosis of epilepsy and current use of cannabidiol-enriched cannabis. Thirteen children had Dravet syndrome, four had Doose syndrome, and one each had Lennox-Gastaut syndrome and idiopathic epilepsy.

The average number of anti-epileptic drugs (AEDs) tried before using cannabidiol-enriched cannabis was 12. Sixteen (84%) of the 19 parents reported a reduction in their child’s seizure frequency while taking cannabidiol-enriched cannabis. Of these, two (11%) reported complete seizure freedom, eight (42%) reported a greater than 80% reduction in seizure frequency, and six (32%) reported a 25-60% seizure reduction.

Other beneficial effects included increased alertness, better mood and improved sleep. Side effects included drowsiness and fatigue.

Our survey shows that parents are using cannabidiol-enriched cannabis as a treatment for children with treatment-resistant epilepsy. Because of the increasing number of states that allow access to medical cannabis, its use will likely be a growing concern for the epilepsy community. Safety and tolerability data for cannabidiol-enriched cannabis use among children is not available. Objective measurements of a standardized preparation of pure cannabidiol are needed to determine whether it is safe, well tolerated and efficacious at controlling seizures in this difficult-to-treat pediatric population.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157067/

Hypothermia induced by delta9-tetrahydrocannabinol in rats with electrolytic lesions of preoptic region.

“The preoptic region (POR) is a primary central site for thermoregulation. Bilateral lesions of POR disrupt thermoregulation, and in rats, produce a characteristic syndrome including hyperthermia.

delta9-Tetrahydrocannabinol (delta9-THC), a potent hypothermic agent, appears to mediate this effect via some central mechanism. The studies reported here suggest that delta9-THC induces hypothermia at a site other than POR.

These data demonstrate that delta9-THC is able to induce a hypothermic response in rats whose body temperatures were elevated by POR ablation. Although delta9-THC does not appear to act primarily at POR to induce hypothermia, it is evident than an intact POR plays a role in modifying the duration and magnitude of delta9-THC induced hypothermia.”

http://www.ncbi.nlm.nih.gov/pubmed/996043

Pot a Common Remedy to Ease Back Pain

“Use of marijuana to ease back pain was common among patients at a university spine clinic in Colorado where pot has been legal for medical purposes since 2000, but most of the users did not have a prescription, according to research presented here.

Among 184 patients at a Colorado spine center, 19% said they used marijuana for pain relief, but less than half, 46%, actually had a prescription for the drug, according to study co-author Michael Finn, MD, an assistant professor of neurosurgery at the University of Colorado in Denver.

The most common way to use the drug was smoking it, 90%, followed by oral ingestion, 45%, and vaporization, 29%.

According to the users, marijuana worked. A total of 89% said it greatly or moderately relived their pain, and 81% said it worked as well as or better than narcotic painkillers.”

http://www.medpagetoday.com/MeetingCoverage/AdditionalMeetings/42228

Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood.

“Early life stress (ES) significantly increases predisposition to psychopathologies. Cannabinoids may cause cognitive deficits and exacerbate the effects of ES.

Nevertheless, the endocannabinoid system has been suggested as a therapeutic target for the treatment of stress- and anxiety-related disorders.

Here we examined whether cannabinoids administered during “late adolescence” (extensive cannabis use in humans at the ages 18-25) could reverse the long-term adverse effects of ES on neurocognitive function in adulthood.

WIN administered during late adolescence prevented these stress-induced impairments and reduced anxiety levels.

There is a crucial role of the endocannabinoid system in the effects of early life stress on behavior at adulthood.”

http://www.ncbi.nlm.nih.gov/pubmed/27317195

Exercise as an adjunctive treatment for cannabis use disorder.

“Despite cannabis being the most widely used illicit substance in the United States, individuals diagnosed with cannabis use disorder (CUD) have few well-researched, affordable treatment options available to them.

Although found to be effective for improving treatment outcomes in other drug populations, exercise is an affordable and highly accessible treatment approach that has not been routinely investigated in cannabis users. The aim of this paper is to inform the topic regarding exercise’s potential as an adjunctive treatment for individuals with CUD.

Given that exercise is a potent activator of the eCB system, it is mechanistically plausible that exercise could be an optimal method to supplement cessation efforts by reducing psychophysical withdrawal, managing stress, and attenuating drug cravings.”

http://www.ncbi.nlm.nih.gov/pubmed/27314543

“Exercise activates the endocannabinoid system.”  http://www.ncbi.nlm.nih.gov/pubmed/14625449

Cannabinoids in the Brain: New Vistas on an Old Dilemma

“The use of cannabis as a therapeutic and recreational substance goes back to thousands of years throughout Asia, Middle East, Southern Africa, and South America.

The discovery of Δ-9-tetrahydrocannabinol (Δ9-THC) by Mechoulam and Gaoni in the midsixties as the major psychoactive constituent of cannabis sativa led to another important discovery, namely, its specific binding site that was isolated and cloned in 1990. This first cannabinoid receptor was coined CB1R and triggered a number of investigations on its expression, localization, and function within the body tissue including the brain, in various species. This was followed by the discovery in 1992 of the first endocannabinoid (eCB), anandamide, followed by another cannabinoid receptor CB2R and a second endocannabinoid called 2-arachidonoylglycerol (2-AG). Later on, some of the enzymes responsible for their synthesis (N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD); diacylglycerol lipase (DAGL)) and degradation (fatty acid amide hydrolase (FAAH); monoacylglycerol lipase (MAGL)) were identified.

Studies on the expression and localization of the cannabinoid receptors in the brain have burgeoned in the last decade and have furnished valuable data on their putative involvement in various sensory-motor and cognitive functions in diverse animal species, including Man. These studies have recently received substantial attention from pharmaceutical companies as a potential source for novel treatments. Additionally, the dilemma of legalizing the use of cannabis in some countries makes the investigation on cannabinoid systems more momentous. This special issue is therefore timely and brings historical and groundbreaking novel research on the role of these cannabinoid receptors in the mammalian central nervous system (CNS).

We hope that the collected papers in this special issue will contribute to the understanding of the various mechanisms involved in the functions of the endocannabinoid system and the development of new pharmaceutical tools to treat visual disorders.”

http://www.hindawi.com/journals/np/2016/9146713/