Parkinson’s Disease and the THCV in cannabis.

New British and Spanish research on one of cannabis’ cannabinoids show its great potential for treating Parkinson’s disease. The cannabinoid is the lesser known but hugely interesting THCV, aka Delta-9-tetrahydrocannabivarin. The molecule is present to varying decrees in different strains of cannabis, from trace amounts to a hefty proportion.

Unlike your own body’s cannabinoid anandamide, or its phyto(plant based)-cannabinoid cousin, THC, THCV does not activate CB1 receptors in your endocannbinoid regulatory system. Activation of these CB1 receptors, found mainly on nerve cells, is responsible for most of THC’s psychoactive effects and medical benefits. THC also activates CB2 receptors, found more on immune cells and thought responsible for some of cannabis’ beneficial effects on some autoimmune disorders. Like THC, THCV also binds with and activates these CB2 receptors. Like THC, THCV is a powerful antioxidant, capable of sopping up cell-killing free radicals. Unlike THC, THCV does not activate CB1 receptors. Instead, it blocks (serves as an antagonist to) the activation of the CB1 system. It may play a major role in future treatments of cardiometabolic diseases and obesity.

The International Association of Cannabinoid Medicine reported the research as follows:

Parkinson’s disease
Spanish and British researchers investigated the effects of Delta-9-
tetrahydrocannabivarin (THCV) in an animal model of Parkinson’s
disease
. They concluded that “given its antioxidant properties and
its ability to activate CB2 but to block CB1 receptors, Delta-9-THCV
has a promising pharmacological profile for delaying disease
progression in PD and also for ameliorating parkinsonian symptoms.”
(Source: García C, et al. Br J Pharmacol. 2011 Feb 16. [in press]).

The fact that the research was British and Spanish, not American, is telling. Americans are not allowed to research cannabis and are denied access to marijuana for research. The pathetic paucity of medical cannabis research in the USA is a literal crime against humanity, a function of politics of prohibition. Americans by the millions suffer untreated pain, blinding glaucoma and immobilizing Parkinson’s disease while all research is denied, decade after decade. Instead of following a science-based assessment (which would demand a rush to research medical cannabis), American science has been held hostage to authoritarian bureaucrats.

Your brain on anti-matter. Positron/gamma ray images of cannabinoid receptors in the human brain.

Those interested in medical cannabis will remember that the CB1 receptors, discovered less than 20 years ago, are activated by THC and other cannabinoids in cannabis. This activation provides the psychoactive effects of cannabis and also some of its other health enhancing properties. CB receptors also respond to endocannabinoids produced by own bodies, primarily in our nerve cells. The receptors are part of the endocannabinoid receptor (or regulatory) system, now seen as a major physiological system, with important roles in pain relief, neuroprotection and anti-inflammation, even digestion and vision.

Such CB1 activation by THC from the plant world or anandamide from our own cells, along with other cannabinoids produced by the cannabis plant or our own bodies, can provide profound health benefits. Cannabinoids also work by activating CB2 receptors (primarily found on immune cells). Independent of their actions on receptors, cannabinoids are anti-oxidants, protecting nerve cells and other tissue from oxidation stress.

In the photo below, the CB1 receptors are being marked by the inverse agonist, 18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Inverse agonists tend to cause receptors to respond in ways opposite their response to agonists such as THC and anandamide. In the case of cannabinoid receptors, hope that inverse agonists might serve as obesity control agents has faded with problems from nausea and mood disturbances.

The physics of what goes on during such as PET scan it astounding. The process would appear to be highly hazardous to health, yet the procedure is commonplace and apparently without risk. Markers with affinities for certain cell types, such as the compounds used above, MK-9470, emit anti-matter. A positron is the anti-matter equivalent of an electron. When it is emitted from the source, in this case on a CB1 receptor in the brain, it travels only a short distance, a millimeter or so, before encountering its matter equivalent, an electron.

When matter electron and antimatter positron meet, the result is annihilation. Such an encounter releases a short burst of highly energetic photons in the form of gamma rays. Why matter/antimatter annihilation with accompanying gamma ray burst inside the brain is not fatal is not exactly clear. Perhaps a high-energy physicist could comment. Or even a low-energy physicist after coffee.

During this positron emission tomography, sensors detect where the gamma rays are coming from and map these in a 3D representation of brain anatomy and activity.  In the images above the patterns of gamma rays being emitted from this matter/antimatter annihilation show the relative distributions of CB1 receptors in various parts of the human brain. See the original research for more detail. Although they are most highly concentrated in the brain, CB1 receptors are also found throughout the entire human body, mainly on nerve cell membranes.

Bliss out (and pump up) your brain with exercise.

Just as doing push-ups pumps up the size of your triceps, so does aerobic exercise appear to increase the volume of your brain! American researchers reporting in the British Journal of Sports Medicine show that physical exercise, especially aerobic activity, improves the functioning and structure of the brains of older people.

Improvements in brain size, with increased volumes of grey and white matter, and better brain function were found in both those with and without dementia. The so called functions of “executive control,” that help us carry on our lives planning, remembering and changing tasks are those first attacked by dementia. But study co-author Art Kramer of the University of Illinois notes that these functions are those most helped with exercise. Dementia is not only forestalled, but in some ways actually reversed with 6 months of aerobic activity. Brains benefiting from the exercise exertions of their owners maintained plasticity, essentially the capabilities to continue growing, developing and learning.

Although huge rewards accrue to both brain and body from simply walking, these researchers point out the increased benefit from more rigorous aerobic activities, such as jogging, that cause increases in heart rate and rate of breathing. So by all means walk your 10,000 steps a day, at least 5 miles, but also pick up the pace for some of those steps.  Jogging one of those five miles and moving your heart rate up into your age-appropriate training zone will yield great benefits, toning your body and growing your brain. Professor Kramer summarized, “We can safely argue that an active lifestyle with moderate amounts of aerobic activity will likely improve cognitive and brain function, and reverse the neural decay frequently observed in older adults.”

If you bliss out your brain with exercise, there is now good evidence your brain will return the favor. “Runner’s high,” is a flowing, blissful, pain-free experience associated with aerobic exercise. Formerly, the enjoyable mental and physical state was associated solely with endorphins, the body’s natural opiates. With the discovery of the endocannabinoid receptor system and endogenous cannabinoids produced by our own bodies, such as anandamide and 2-AG, this explanation is taking a new turn. After you begin exercising, your level of natural bliss cannabinoid anandamide elevates, and more of these bliss molecules float in your bloodstream, ready to jump the blood-brain barrier and activate CB1receptors on your nerve cells. The result is pain reduction and mood elevation.  So, in addition to endorphins, endocannabinoids such as anandamide reward you for your exercise efforts.

Better adaptive functioning and increased brain volumes are, at least in part, due to neurogenesis, the birth of new brain cells. Both exercise and cannabinoids promote neurogenesis. So, to gain huge health rewards, second-by-second, year-by-year, for your entire life, bliss out your brain with exercise. Walk every day, run some too, lift some weights, and every cell in your brain and body benefits.

Obama, Cigarettes and Cannabis

President-Elect Barack Obama has promised not to smoke cigarettes in the White House. Does not smoking in the house mean smoking in the entryways of the White House? Out in the Rose Garden?

Cigarettes are not just the most lethal drug confronting America, they are also the most addictive. The power of cigarette’s grip on human behavior its remarkably demonstrated by our next president. Barack Obama is literally the alpha male of human competence and self control. Master campaigner, victorious debater, now triumphantly poised to assume the most important job on the planet!

Yet still, of all people, the President-elect is not able to summon the will to not smoke tobacco cigarettes. As much as he would like to quit, as much as Michelle and the girls want him to quit, he will presumably duck out of the White House, furtively avoiding his family and to the chagrin of his Secret Service detail, light up a cigarette. Statistically, the smoke will cost him 11 1/2 minutes of his life, and each pack of 20 cigarettes will cost him 3 1/2 hours from his life.

Like most people who become addicted to cigarettes, Obama began as a teenager. Recent evidence shows that just a few cigarettes smoked by an adolescent can set up a lifelong addiction. Tobacco cigarettes were not the only drug smoked (and inhaled), “That was the point” by young Barack Obama:

  • One drug, cannabis with cannabinoids, he used and inhaled. Later, Obama stopped using cannabis when he chose to do so.
  • The other drug, tobacco cigarettes with nicotine, he also used and inhaled. Later, Obama could not totally stop using when he chose to do so.

Receptor discrimination?

When the young Obama smoked a tobacco cigarette, the main drug he inhaled was nicotine. Nicotine activates trans membrane receptors in cells, specifically the nicotinic acetylcholine receptor (AChR ). In less 10 seconds after taking a puff of tobacco smoke, nicotine molecules crossed his blood-brain barrier and fit like tiny keys into a locks normally activated by the neurotransmitter, acetylcholine. Nictoine causes the receptors to activate, change shape and initiate a chemical cascade. Young Barack would have felt modest elevation of energy and mood from AChR receptor activation.

When the young Obama smoked a cannabis “joint,” the main drug he inhaled was THC, short for Δ9-tetrahydrocannabinol. THC activates trans membrane receptors in cells, specifically the cannabinoid receptors, CB1 and CB2. In less than 10 seconds after taking a puff of cannabis smoke, THC molecules crossed his blood-brain barrier and fit like tiny keys into a locks normally activated by the neurotransmitter, anandamide. THC causes the CB1 (and CB2) receptors to activate, change shape and initiate a chemical cascade. Young Barack would have felt mild euphoria from CB1 receptor activation.

Nicotine is a powerful insecticide. THC is a powerful neuroprotective antioxidant, anti inflammatory and analgesic. Tobacco smoking is highly carcinogenic. No smoke inhalation is a good thing (nor is it necessary with the advent of vaporizers, but cannabis smoking is apparently not carcinogenic. Indeed, THC exhibits several capabilities for preventing, even shrinking tumors.

Tobacco use kills over 1,200 Americans each day. Cannabis use kills 0 Americans each day.

Legal Sanctions

The contrast in legal sanctions for young Barack’s smoking activities are the most startling. If Barack had been caught underage with cigarettes, the punishment, if any, would have been minor. Certainly nothing that would jeopardize his career and future presidential run.

Had Barack been caught and arrested for possesstion of cannabis, though, his future would have immediately dimmed. If given a felony conviction and jailed, as would be possible because of cannabis’  misguided, draconian Schedule 1 listing, Barack would likely now be unemployed. Luckily, because Barack avoided arrest, the “justice” system missed its opportunity to crush the life and career of our next president.

Tragically, Obama’s choice for Attorney General, Eric Holder, holds neocon, authoritarian views on exactly this issue. When part of the Clinton Administration, serving as US Attorney for Washington D.C., he pushed for mandatory jail time for young people caught with cannabis in that city.

Hopefully, as Barack Obama puffs on his occasional cigarette outside the White House, he will think of the vast 2,000,000+ prisoner gulag stretched out across America before him. Far too many of these prisoners languish in jail because they were snared by the dishonest, cruel and self-serving laws against a plant. More Americans are arrested for cannabis possession than all violent crimes combined.

As you take your smoke, please think, Mr. President, of all these American lives being crushed and crippled by such torments as mandatory minimums.  Eric Holder gleefully fed young cannabis prisoners to this incarceration industry and as AG may force many more American lives and families down into the grinder.  All for contact with a substance with true medical value, as opposed to the tobacco cigarettes from which Mr. President, huddled outside the White House, draws another nicotine puff.

Anandamide Why did they call it bliss?

In Jerusalem in the year 1992, Ananda, the Sanskrit word for bliss, named a newly identified molecule. Anandamide was given as name to the cannabinoid molecule first discovered being produced in the human body, that is, the first endocannabinoid. This revelation solved a decade’s old mystery. The discovery of anandamide and the receptor system it stimulates has greatly changed and grown our knowledge of the structure and functioning of our human bodies. What has been learned already offers to better our health and well-being.

A mystery and a great discovery.

The great discovery begins wrapped in a mystery: In the mid 1960’s researchers in Israel identified the active component of the plant Cannabis Sativa. Then, over a quarter century later, in 1990, researchers indentified natural receptors activated by this plant cannabinoid. The discovery of these receptors found them first in the brain, then throughout the human body.

The mystery: Why should human beings have a natural receptor system triggered by molecules from the flowers of a plant?

The discovery of the human cannabinoid receptor system and the natural substances that activate this system extends our knowledge of human body and its workings. The beneficial properties associated with the activation and modulation of this newly found system are profound: They offer a whole host of beneficial physiological functions including preventative and curative effects for many commonly afflicting diseases. Medicine in the 21st century will be fundamentally altered by the discovery of this system and the natural molecules we produce to manage it.

Jerusalem Journey

Jerusalem is sacred ground in many ways. It is central to three of the world’s most influential religions, and home to many of their key relics, both present and long past. The Wailing Wall, The Dome of the Rock and the Garden Tomb keep uneasy company with each other and with the ghosts of ancient structures, such as the Second Temple, twenty centuries ago burned to ash by the legions of Rome.

During all these thousands of years of Jerusalem history, back 1,000 years to the Crusades, back 2.000 years to the time Christ walked the city’s streets, and much further back, thousands of more years back, something else was constant in the land. Down these long centuries, humans were cultivating, trading and using a weedy plant across the Middle East of which Jerusalem is the center. The fast growing cannabis sativa provided its cultivators with useful fiber, nutritious seeds, potent medications and perhaps even helped stoke their spirituality.

Dr. Raphael  Mechoulam’s discoveries began when he undertook the investigation of the active components of cannabis sativa, the plant so long used in the Middle East for relieving aches and pains, inflammation and a score of other ails, and for enjoying its bliss-giving properties. He began by securing a chunk of hashish, concentrated products of the flowering female plant. In 1964 at the Weissmann Institute of Science at the Rehovoth campus of Hebrew University, he and his team discovered the major active ingredient in cannabis, THC.[i]
But that is the story of a later post.


[i] Gaoni, Y.; Mechoulam, R. Isolation, structure, and partial synthesis of an active constituent of hashish. J. Am. Chem. Soc. 1964, 86, 1646-1650.