Worth Repeating: Cannabis May Help Combat Aging Of Brain


Graphic: BudFacts.com
Cannabis may help combat the effects of aging on the brain, and may even help ward off Alzheimer’s disease.

​​Welcome to Room 420, where your instructor is Mr. Ron Marczyk and your subjects are wellness, disease prevention, self actualization, and chillin’.

Worth Repeating
By Ron Marczyk, R.N.

Health Education Teacher (Retired)

Can THC along with whole family of other phytochemical cannabinoids found in marijuana prevent and treat Alzheimer’s disease and other neurodegenerative brain diseases, including the effects of aging?
Could cannabinoids be as important to neuro-brain health as we age as other foods, supplements such as omega-3 fatty acids, B vitamins, and aerobic exercise are?
In the near future will at-risk populations be encouraged to consume an RDA  for cannabinoids?
Will blood levels of cannabinoids correlate with protection against brain inflammation, similar to taking an aspirin a day to prevent cardiovascular disease?

Phytochemicals are plant chemicals, and cannabinoids are phytochemicals. It is of interest to note that other than being dried, cannabis is not refined in any way in a laboratory. It is consumed in its original organic natural state, like eating a fresh uncooked vegetable or piece of fruit.

Could regular THC ingestion, with the whole family of other cannabinoids found in the plant prevent neurodegenerative brain diseases as people age? 
Here I present 12 medical research abstracts as evidence to support this hypothesis, I urge you to discuss this information with your family doctor, especially if Alzheimer’s disease runs in your family genetics. 
Medical evidence is mounting that THC may not only prevent, but also treat neurodegeneration in general. The following abstract is an example of this.
“Endocannabinoids are bioactive lipids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the best studied endocannabinoids, and act as agonists (what turns the CB1 receptor on) of cannabinoid receptors.”
“Thus, AEA and 2-AG mimic several pharmacological effects of the exogenous cannabinoid delta9-tetrahydrocannabinol, the psychoactive principle of hashish and marijuana.”
“This new system will be briefly presented in this review, in order to put in a better perspective the role of the endocannabinoid pathway in neurodegenerative disorders, like Parkinson’s disease, Huntington’s disease, and multiple sclerosis as next-generation therapeutics will be discussed.”
Also see:
Current Molecular Med– 2006 Sep – Dept of Sciences, University of Connecticut, Storrs, CT 
The endogenous cannabinoid system has revealed potential avenues to treat many disease states. Medicinal indications of cannabinoid drugs including compounds that result in enhanced endocannabinoid responses (EER) have expanded markedly in recent years. 
The wide range of indications covers chemotherapy complications, tumor growth, addiction, pain, multiple sclerosis, glaucoma, inflammation, eating disorders, age-related neurodegenerative disorders, as well as epileptic seizures, traumatic brain injury, cerebral ischemia, and other excitotoxic insults.
Indeed, a great effort has led to the discovery of agents that selectively activate the cannabinoid system or that enhance the endogenous pathways of cannabinergic signaling.
The two known endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), are lipid molecules that are greatly elevated in response to a variety of pathological events.
This increase in endocannabinoid levels is suggested to be part of an on-demand compensatory response. Furthermore, activation of signaling pathways mediated by the endogenous cannabinoid system promotes repair and cell survival. 
The therapeutic potential of the endocannabinoid system has yet to be fully determined, and the number of medical maladies that may be treated will likely continue to grow. 
The decade of endocannbinoid therapeutics using cannabinergic medicines will be the new breakout medicine treatments of the near future.

Graphic: Marijuana and the Human Brain

Many next-generation drug treatments will come from this plant. Think of different strains of the cannabis plant as having different cannabinergic effects that are controlled and fine-tuned by the patients themselves. Standard for all new meds: titration through patient feedback.
Since 2000, research is starting to gather for yet another surprising possible THC/cannabinergic medical treatment, that being for neuro-inflammation of the brain.
The empirical research cited below suggests that THC offers neuroprotection to the aging brain by controlling neuroinflammation
As the science supporting the validity of endocannabinoid therapeutics progresses, the criminalization of marijuana and the repressive position of the U.S. government is becoming increasingly absurd. 
Big Pharma generally developed many new, very expensive drugs to treat conditions that, when studied over time, find that the original, inexpensive, generic older first-generation drugs many times outperform the new drugs, with fewer side effects, at a fraction of the cost. This is the case with cannabis: it’s hard to improve on evolutionary perfection. 
Remember: You can’t spell “healthcare” without “THC.”
Cannabis is the first and original medicine that has been the front line standard of care for more than 10,000 years!

Graphic: Discovery Fit & Health

​How’s that for a first generation medicine that has never caused a death due to its use? Safety and effective treatment for a wide spectrum for many illnesses, all in one plant! Since CB1 and CB2 receptors respond so perfectly to THC, and since humans and this plant have co-evolved for the past 10,000 years plus, cannabinoid molecules and receptors may both be woven into our DNA. They may run our biology as medicinal science is starting to discover. CB1 and CB2 receptors seem to located throughout our bodies, regulating our overall homeostasis.  

My 85-year-old mother has been living in a nursing home for the last seven years with dementia. It is always very emotional when I go to visit her. She no longer speaks coherently and does not know who I am, but she always reaches out to kiss my hand and face, as if her emotional memory is still working on some level. I talk to her but she doesn’t understand. I can only smile at her and comb her hair, and it always makes for a sad day.
As I learned of this current research I had a flashback that my mother is the same woman who found my first stash in my sock drawer when I was sixteen, and she and my father went ballistic on me. Now, more than four decades later, this is same substance that could possibly have prevented and treated her advanced, slow, fatal brain deterioration.
Both of my maternal grandmothers died from this disease, as will my mother. I have three genetic red flags in my immediate family. Shouldn’t we have an option to prevent this disease using THC? 
It’s time for an “exit strategy” for the failed War on Drugs.
So what goes wrong in the aging brain? And can marijuana prevent it?
There are three main breakdowns due to misspelled code in your family genetics that cause Alzheimers Disease:
1. Neuroinflammation caused by a brain autoimmune disease
The job of your immune system, which is made up of your white blood cells, is to destroy pathogens and malignant body cells–we all know this basic biology fact.
But did you know that you have a second, dedicated immune system that only patrols in and around the brain and spinal cord?    
Why is this? The brain protects itself against the environment, your brain and CNS are encased by a blood-brain barrier that doesn’t allow many to pass in or out of, including white blood cells. 
The brain is made up about 50 percent neurons and about 50 percent glial cells, with 20 percent of these cells being microglia attack cells.
These microglial cells have a different name, different shape, but same the job: distinguish self from non-self, then search and destroy.   
An autoimmune disease occurs when this system of self identification  breaks down, and the white blood cell now attacks its host. The same pathology happens in the brain, but now the microglial cells attack brain neurons, destroying them. As you lose brain cells your brain shrinks.
Evidence points to THC acting as an anti-inflammation medicine. Apparently this “stand down” signal is connected to THC activating CB1/2 receptors This down-regulation of the microglial seems to stop the neuroinflammation and loss of brain cells.  
2. Scar tissue develops in the brain, called beta amyloidal plaque  
Beta amyloidal plaque is a “protein misfolding disease.” As long strands of your brain cells uncoil to make copies of proteins they code for, the strand of DNA doesn’t fold open correctly, just like trying to open a broken umbrella. They assemble new proteins that are abnormal, unfunctioning, and that turn into the plaque. The wrong protein they make is the plaque.  Your DNA is now coding for scar tissue.
This is a micograph showing amyloid beta (brown) in senile plaques of the cerebral cortex.

Evidence points to the action of THC acting as an anti-inflammation medicine. Again apparently this “stand down signal” is connected to THC activating CB 1/2 receptors, but in this case seems to shut down this process. Apparently the neuroinflamation and the plaque development are connected.
3. The over-destruction of acetylcholine 
Acetylcholine is a neurotransmitter that encodes new memories into neurons, and also retrieves recent and old memories. After the signal is sent, acetylcholine is deactivated  by acetylcholinesterase, setting it open for the next signal.
In this genetic breakdown your brain makes way more acetylcholinesterase, which deactivates your short- and long-term memory. No acetylcholine–no memories.
What if there were a drug that would inhibit acetylcholinesterase?
This is how Aricept works.  However, THC is a superior medication in this regard.
In addition to acting as an inhibitor of acetylcholinesterase, it stops neuroinflammation and plaque formation. Three treatments
, one drug. Amazing.
Please note the dates of this current research: 2005-2009.
Here, then, is a “mini-meta” analysis of the most current research on this subject .     
Dept of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA. Mol Pharm. 2006 Nov.
Alzheimer’s disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer’s disease are expected to triple over the next 50 years.
Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients and reduce the health care costs attributable to Alzheimer’s disease.
Below is the chemical structure of Δ9-tetrahydrocannabinol (THC).

And here is that same THC molecule blocking the action of acetylcholinesterase. This enzyme breaks down acetylcholinesterase, the neurotransmitter needed to form new memories and retrieve old ones. 
Predicted binding mode of THC (gray) to AChE (orange ribbon). The catalytic triad residues of AChE (green) and water molecules included in the docking calculations (light blue spheres) are shown.

“Here, we demonstrate that the active component of marijuana, Delta9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE)……as well as prevents AChE-induced amyloid beta-peptide (Abeta) aggregation, the key pathological marker of Alzheimer’s disease.
“Compared to currently approved drugs prescribed for the treatment of Alzheimer’s disease, THC is a considerably superior inhibitor of Abeta aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.”
Cannabidiol: a promising drug for neurodegenerative disorders?
Neurodegenerative diseases represent, nowadays, one of the main causes of death in the industrialized country. They are characterized by a loss of neurons in particular regions of the nervous system. It is believed that this nerve cell loss underlies the subsequent decline in cognitive and motor function that patients experience in these diseases. A range of mutant genes and environmental toxins have been implicated in the cause of neurodegenerative disorders but the mechanism remains largely unknown.
At present, inflammation, a common denominator among the diverse list of neurodegenerative diseases, has been implicated as a critical mechanism that is responsible for the progressive nature of neurodegeneration. 
Since, at present, there are few therapies for the wide range of neurodegenerative diseases, scientists are still in search of new therapeutic approaches to the problem. An early contribution of neuroprotective and anti-inflammatory strategies for these disorders seems particularly desirable because isolated treatments cannot be effective.
In this contest, marijuana derivatives have attracted special interest, although these compounds have always raised several practical and ethical problems for their potential abuse. Nevertheless, among Cannabis compounds, cannabidiol (CBD), which lacks any unwanted psychotropic effect, may represent a very promising agent with the highest prospect for therapeutic use.
Cannabinoid receptors and their role in neuroprotection.
“Two G protein-coupled receptors for marijuana’s psychoactive component, Delta9-tetrahydrocannabinol, have been cloned to date, the cannabinoid CB1 and CB2 receptors.”
Evidence has accumulated over the last few years suggesting that endocannabinoid-based drugs may potentially be useful to reduce the effects of neurodegeneration. In fact, exogenous  (taken in from the outside) and endogenous cannabinoids were shown to exert neuroprotection in a variety of in vitro and in vivo models of neuronal injury via different mechanisms.
“The release of endocannabinoids during neuronal injury may constitute a protective response. If this neuroprotective function of cannabinoid receptor activation can be transferred to the clinic, it might represent an interesting target to develop neuroprotective agents.”
Alzheimer’s disease; taking the edge off with cannabinoids?

Alzheimer’s disease is an age-related neurodegenerative condition associated with cognitive decline. The pathological hallmarks of the disease are the deposition of beta-amyloid protein.
In recent years the proclivity of cannabinoids to exert a neuroprotective influence has received substantial interest as a means to mitigate the symptoms of neurodegenerative conditions.
In brains obtained from Alzheimer’s patients alterations in components of the cannabinoid system have been reported, suggesting that the cannabinoid system either contributes to, or is altered by, the pathophysiology of the disease.
Certain cannabinoids can protect neurons from the deleterious effects of beta
-amyloid and are capable of reducing tau phosphorylation.
The propensity of cannabinoids to reduce beta-amyloid-evoked oxidative stress and neurodegeneration, whilst stimulating neurotrophin expression neurogenesis, are interesting properties that may be beneficial in the treatment of Alzheimer’s disease.
Delta 9-tetrahydrocannabinol can also inhibit acetylcholinesterase activity and limit amyloidogenesis which may improve cholinergic transmission and delay disease progression.
Targeting cannabinoid receptors on microglia may reduce the neuroinflammation that is a feature of Alzheimer’s disease, without causing psychoactive effects. Thus, cannabinoids offer a multi-faceted approach for the treatment of Alzheimer’s disease by providing neuroprotection and reducing neuroinflammation, whilst simultaneously supporting the brain’s intrinsic repair mechanisms by augmenting neurotrophin expression and enhancing neurogenesis.
The evidence supporting a potential role for the cannabinoid system as a therapeutic target for the treatment of Alzheimer’s disease will be reviewed herewith.
Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation.
Alzheimer’s disease (AD) is characterized by enhanced beta-amyloid peptide (betaA) deposition along with glial activation in senile plaques, selective neuronal loss, and cognitive deficits. Cannabinoids are neuroprotective agents against excitotoxicity in vitro and acute brain damage in vivo.
This background prompted us to study the localization, expression, and function of cannabinoid receptors in AD and the possible protective role of cannabinoids after betaA treatment, both in vivo and in vitro.
Here, we show that senile plaques in AD patients express cannabinoid receptors CB1 and CB2, together with markers of microglial activation, and that CB1-positive neurons, present in high numbers in control cases, are greatly reduced in areas of microglial activation. 
Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.

Inflammation and Aging: Can endocannabinoids help?

Department of Psychology, Psychology Building, The Ohio State University,Columbus, OH 
March 2008
Aging often leads to cognitive decline due to neurodegenerative process in the brain. As people live longer, there exists a growing concern linked to long-term, slowly debilitating diseases, such as Alzheimer’s disease for which a cure has not yet been found.
Recently, the role of neuroinflammation has attracted attention due to its slow onset, chronic nature and its possible role in the development of many different neurodegenerative diseases.
In the future, treatment of chronic neuroinflammation may help counteract aspects of neurodegenerative disease.
Our recent studies have focused upon the endocannabinoid system for its unique effects on the expression of neuroinflammation.
The basis for the manipulation of the endocannabinoid system in the brain in combination with existing treatments for Alzheimer’s disease will be discussed in this review.
The Endocannabinoid System in Ageing:  A New Target for Drug Development
Department of Biomedical Sciences, University of Teramo, Teramo, Italy
Endocannabinoids are a new class of lipids, which include amides, esters and ethers of long chain polyunsaturated fatty acids.
Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol are the main endogenous agonists of cannabinoid receptorsable to mimic several pharmacological effects of Δ9-tetrahydrocannabinol, the active principle of Cannabis sativa preparations like hashish and marijuana.
AEA is released “on demand” from membrane lipids, and its activity at the receptors is limited by cellular uptake followed by intracellular hydrolysis. Together with AEA and congeners, the proteins which bind, synthesize, transport and hydrolyze AEA form the “endocannabinoid system”. Endogenous cannabinoids are present in the central nervous system and in peripheral tissues, suggesting a physiological role as broad spectrum modulators. 

This review summarizes the main features of the endocannabinoid system, and the latest advances on its involvement in ageing of central and peripheral cells.
In addition, the therapeutic potential of recently developed drugs able to modulate the endocannabinoid tone for the treatment of ageing and age-related human pathologies will be reviewed.
Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration.
The endocannabinoid system, including endogenous ligands (‘endocannabinoids’ ECs), their receptors, synthesizing and degrading enzymes, as well as transporter molecules, has been detected from the earliest stages of embryonic development and throughout pre- and postnatal development.
ECs are bioactive lipids, which comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the best studied ECs, and act as agonists of cannabinoid receptors.
Thus, AEA and 2-AG mimic several pharmacological effects of the exogenous cannabinoid delta9-tetrahydrocannabinol (Delta(9)-THC), the psychoactive principle of cannabis sativa preparations like hashish and marijuana.
Recently, however, several lines of evidence have suggested that the EC system may play an important role in early neuronal development as well as a widespread role in neurodegeneration disorders.
Many of the effects of cannabinoids and ECs are mediated by two G protein-coupled receptors (GPCRs), CB1 and CB2, although additional receptors may be implicated. Both CB1 and CB2 couple primarily to inhibitory G proteins and are subject to the same pharmacological influences as other GPCRs. This new system is briefly presented in this review, in order to put in a better perspective the role of the EC pathway from neurodevelopment to neurodegenerative disorders, like Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis.
Endocannabinoids and their involvement in the neurovascular system.
Current Neurovasc Res, Apr. 2004  Department of Biomedical Sciences, University of Teramo, Italy.
Endocannabinoids are a new class of lip
ids, Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol are the main endogenous agonists of cannabinoid receptors, able to mimic several pharmacological effects of Delta(9)-tetrahydrocannabinol, the active principle of Cannabis sativa preparations like hashish and marijuana.
It is known that the activity of AEA is limited by cellular uptake through a specific membrane transporter, followed by intracellular degradation by a fatty acid amide hydrolase. Together with AEA and congeners these proteins form the “endocannabinoid system”. The endogenous cannabinoids were identified in brain, and also in neuronal and endothelial cells, suggesting a potential role as modulators in the central nervous system and in the periphery. This review summarises the metabolic routes for the synthesis and degradation of AEA, and the latest advances in the involvement of this lipid in neurovascular biology. In addition, the therapeutic potential of the modulation of endocannabinoid metabolism for neuronal and vascular system will be also reviewed.
Mini Rev Med Chem. 2006 Mar;6(3):257-68.
New insights into endocannabinoid degradation and its therapeutic potential

Bari M, Battista N, Fezza F, Gasperi V, Maccarrone M.
Source: Department of Biomedical Sciences, University of Teramo, Teramo, Italy.
Endocannabinoids are amides, esters and ethers of long chain polyunsaturated fatty acids, which act as new lipidic mediators. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the main endogenous agonists of cannabinoid receptors, able to mimic several pharmacological effects of (-)-Delta9-tetrahydrocannabinol (THC), the active principle of Cannabis sativa preparations like hashish and marijuana.
The activity of AEA and 2-AG at their receptors is limited by cellular uptake through an anandamide membrane transporter (AMT), followed by intracellular degradation. A fatty acid amide hydrolase (FAAH) is the main AEA hydrolase, whereas a monoacylglycerol lipase (MAGL) is critical in degrading 2-AG. Here, we will review growing evidence that demonstrates that these hydrolases are pivotal regulators of the endogenous levels of AEA and 2-AG in vivo, overall suggesting that specific inhibitors of AMT, FAAH or MAGL may serve as attractive therapeutic targets for the treatment of human disorders.
Recently, the N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD), which synthesizes AEA from N-arachidonoylphosphatidylethanolamine (NArPE), and the diacylglycerol lipase (DAGL), which generates 2-AG from diacylglycerol (DAG) substrates, have been characterized. The role of these synthetic routes in maintaining the endocannabinoid tone in vivo will be discussed. Finally, the effects of inhibitors of endocannabinoid degradation in animal models of human disease will be reviewed, with an emphasis on their ongoing applications in anxiety, cancer and neurodegenerative disorders.

Photo: Ron Marczyk
Mr. Worth Repeating: former NYPD cop, former high school health teacher, the unstoppable Ron Marczyk, R.N., Toke of the Town columnist

​Editor’s note: Ron Marczyk is a retired high school health education teacher who taught Wellness and Disease Prevention, Drug and Sex Ed, and AIDS education to teens aged 13-17. He also taught a high school International Baccalaureate psychology course. He taught in a New York City public school as a Drug Prevention Specialist. He is a Registered Nurse with six years of ER/Critical Care experience in NYC hospitals, earned an M.S. in cardiac rehabilitation and exercise physiology, and worked as a New York City police officer for two years. Currently he is focused on how evolutionary psychology explains human behavior.