Neuroprotection and the Blood-Brain Barrier

What Is a Neuroprotective Agent?

Neuroprotective agents are an exciting new field of study in pharmacology studying interventive agents that help protect the brain and its neural networks from the damage other things can create or cause. Neuroprotective agents are sought out to help prevent or counteract damage created by a medical treatment, usually a medication, which has the potential to cause problems when used as part of a treatment to “fix” something else. A common example of this is the damage chemotherapy causes to the body while fighting cancer cells. Often viewed as necessary, chemo carries its own complications.

Generally a topic held sacred to the world of ischemia stroke and brain tumor treatment, researchers now believe other compounds beyond the known drugs may provide protective barriers within the brain from potential damage, an important boost to treatment for patients whose bodies are already working hard to heal. To date many of the chemical intervention agents have included calcium blockers, free-radical scavengers, and narcotic antagonists, all with their own issues and to date, little success. Of more promising value are compounds already found to provide benefit elsewhere in the body, such as tocopherol (Vitamin E) and ascorbic acid (Vitamin C). Active, aggressive research is being conducted for aides that are more compatible with the body and have higher rates of tolerance and use by the various bodily systems.

Along with vitamins already known to have protective effects on cardiovascular health, other peptides and proteins are being investigated. The challenge is the blood-brain barrier, or how the compound crosses between the vascular system and the blood into and then affects the neurological systems of the body residing within the brain. Think of it as translating to another language, but on a physical level. Many of the challenges for understanding the way the brain works, utilizes nutrients, responds to chemicals, and other transfer actions rests on trying to bridge the difficulty of doing so across the blood-brain barrier. The blood-brain barrier is how the brain is protected by the body, and it does a terrific job, sometimes too terrific, because life saving medications or compounds have just as much difficulty transiting this “wall” as the bad guys, and the whole system is one that we truly do not understand very well as yet.

Why is Cannabidiol so Promising to Blood-Brain Barrier Research?

So far the research around cannabidiol in both animals and humans is promising. A number of brain function and brain protection mechanisms appear to be happening when CBD is present, due to how it affects the endocannabinoid system and the interaction with other cannabinoids through the entourage effect. In particular are the neuroprotective anti-inflammatory effects being seen, since CBD appears to decrease the production of cytokines, the messenger compounds that send signals to the brain and body about inflammation, immunity, and blood cell production. While cytokines should work in a healthy manner, they often do not and they go rogue. CBD appears to decelerate their signal mechanisms when they are out of balance. CBD also appears to help maintain blood flow through channels during ischemic events, or stroke, helping preserve vital brain functions, and may help reduce vascular and neural inflammation.

CBD research in animal models and humans has shown numerous therapeutic properties for brain function and protection, both by its effect on the ECS (endocannabinoid system) directly and by influencing endogenous (those produced by the body) endocannabinoids. Broadly, cannabidiol has demonstrated anxiolytic (reduces anxiety), antidepressant, neuroprotective anti-inflammatory, and immunomodulatory (a chemical that influences or benefits the immune system response) benefits. CBD decreases the production of inflammatory cytokines; influences microglial cells (specialized cells that remove damaged neurons and infections from the body) to return to a ramified (spread out) state, preserves cerebral circulation during ischemic events (your brain does not get as much damage), and reduces vascular changes and neuroinflammation (swelling of nerve tissue, a common issue with traumatic brain injuries).

What is the blood-brain barrier and why is it so important?

The BBB as it is referred is a barrier system the human body utilizes to block chemicals, pathogens, and other things from entering brain tissue. The barrier consists of tightly packed cells that line the capillaries of the brain, and are highly effective at stopping most things that try and get through. Some things pass with no problem, though, such as neurotransmitters (the chemicals that give messages to your brain), glucose, and certain amino acids. Since the brain uses a tremendous amount of energy to function, it has to be “fed” and glucose provides a good portion of the fuel by combining with the oxygen you breath. Amino acids are both building blocks and some, neurotransmitters. The BBB protects the brain cells from invasion by many chemicals that do not belong taking up residence, but is unable to protect from some other molecules such as alcohol. This is why you may hear someone say alcohol “kills” brain cells, because it literally can and does.

CBD appears not to have a problem getting through the blood-brain barrier

Cannabidiol is just one of the 200 identified cannabinoids in Cannabis. All cannabinoids are what are called 21-carbon molecules, and are very similar to endocannabinoids made by the human body. While CBD is not psychotropic, it does not cause a euphoric feeling or altered mind state when consumed; it is from a purely biological perspective psychoactive, meaning it is able to cross the blood-brain barrier. Not every compound in Cannabis has the ability to pass through the blood-brain barrier, such as THCa, the precursor to THC. THCa is very unstable and has to be deoxylated, meaning heated or exposed to sunlight to convert carbon atoms (think bread to toast) to break down into components that can then pass through the barrier. THCa, while not able to pass, is thought to be one of the compounds that is effective for treating forms of epilepsy.

How does CBD work as a carrier?

Because cannabinoids are so similar to the endocannabinoids produced by the human body, some interesting and potentially life saving research prospects for delivery of life saving medications and treatment for brain injuries, tumors, and potentially controlling post ischemic stroke damage have come to light. CBD passes with relative ease through the blood-brain barrier without changing chemically, and in particular is outstanding to act as a facilitator of neural messaging. This makes it a good potential vehicle to carry other materials or messages into the affected regions of the brain, or structures affecting the brain such as an aneurysm caused by a stroke, or a tumor. This ability to pass through, even with another particle attached, is referred to by scientists as a “Trojan horse”.

Lipid nanocapsules have been in use for some time to deliver medications to various parts of the body for treatment of certain forms of cancer, but they have been pretty unsuccessful in getting past the well-engineered blood-brain barrier. This has made treatment of brain cancer and multiple sclerosis frustrating, to say the least. Promising research is being done in Europe where cannabidiol molecules are acting as carriers for nanoparticles of medications, allowing much easier transition of the blood-brain barrier and delivery where scientists want the medications to go while being able to control the delivery. Other similar delivery methods of engineered nanoparticles (artificial particles created from synthetic organics, usually non-toxic plastic or resin, that encapsulate the medicine) are under trials, but so far none is as effective as those recently done utilizing CBD molecules as the carrier agents.

Scientists are not sure why the CBD works so much better, but they think it has to do with the cannabinoid-endocannabinoid similarities. CBD is unique in that it does not bind to the receptors that take the particles into the brain, but attaches to them, facilitating the receptors to take things into the brain themselves. They are also studying the fact that CBD acts as an immune modulator in the human body, the effects of which are just now being researched. Since the body readily allows the passage of the endocannabinoids it makes, it is thought the very similar and non-antagonistic cannabidiol molecules are recognized in the same fashion. What is known is that cannabinoids help endocannabinoids bind with proteins in the blood-brain barrier and attach to neurotransmitter receptors more easily.

Much research is left to be done, but a method of treating brain tumors that is faster, more sure, and far less invasive than methods currently available, as well as helping with the challenges presented by multiple sclerosis, could prove to be a big win all the way around. Scientists are hoping that what they learn may be of use in helping patients with Parkinson’s, Alzheimer’s, and neuropathic pain as well.

You have our word on that.

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