By January 20, 2018Blog, CBD Clinical Trials
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For the last few years, there has been a lot of developments in science related to cannabis which has helped in understanding health and diseases.

The endocannabinoid system in which a signaling system in the body was discovered after lots of research involving the effects of marijuana. The system helps in regulating processes such as metabolism, energy levels, mood and much more.

Cannabis has been there for more than a thousand years. Investigations around the plant have led to great discoveries.

Marijuana has active compounds known as cannabinoids. They are more than 100 in number. They include THC and CBD. The two are known for their therapeutic effects. THC makes people high while CBD does not.

Medical researchers are using synthetic drugs for experimenting with helping improve endocannabinoid tone without having to bind to cannabinoid receptors directly.

Below are strategies scientists are using to harness the potential of the endocannabinoid system in healing.

Cannabinoid plants with a single molecule.

Dronabinol, which is found in pill form is marketed as Marinol. It is a single molecule THC extracted component that has been combined with sesame oil. FDA started its journey to approval in 1985 when there was an increase in demand for medical marijuana.

Others include Syndros which is liquid in form. THC is highly psychoactive but it is still accessible in more than 50 states as prescription medicine

CBD has not been legalized in those states but might soon be as FDA may be approving Epidiolex soon which is an anti-seizure medicine. Epidiolex happens to be pure CBD with a neglected amount of cannabidivarin with antiepileptic properties.

With the many possibilities of pharmaceutical CBD production, R&D firms are currently extracting single-molecule cannabinoids from yeast substrate to get CBDV. As this biotechnology improves, drug developers and pharmacists will have access to numerous single-molecule cannabis compounds.

Synthetic cannabinoid analogs

Researchers have created synthetic analogs of plant cannabinoids for both research and commercial use. Eli Lilly and Co came up with a synthetic THC known as Nabilone. It has been used to treat chemotherapy-induced nausea and vomiting.

Cesamet, which is the name it has been given while marketing it, has been used to help relieve chronic pain in Canada and a couple of other countries. Results from clinical trials indicate that it has shown to help improve PTSD, Parkinson’s, and multiple sclerosis, among others.

Scientists are using different synthetic analogs to investigate molecular mechanisms and biochemical pathways to investigate the endocannabinoid system. Such include WIN55, 212-2 and CP55, 940 which both bind to receptors CB1 and CB2. Most experimental drugs only bind to one receptor.

Cells bind to an agonist cannabinoid which then initiates a signaling series that regulates different processes thus protecting neurons from toxic insults. An antagonist, on the other hand, after binding to receptors, it inhibits them from signaling.

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Synthetic cannabinoid antagonists

CB1 receptors moderate THC’s psychoactive effects are crowded in the central nervous system and brain. When CB1 and THC bind, a person easily feels high and starving. Cravings are linked to the receptor CB1. If activation happens, there is induced appetite and if blocked there is a reduction

“SR141716,” was developed by Sanofi-Aventis initially as a tool for research. They blocked CB1 and observed the functions that were altered which helped understand the endocannabinoid system better.

Strategists from Sanofi thought they had the perfect pill for diets which saw them promote it in the market. Before long, it was pulled out due to the side effects that were experienced. This included depression, mood swings, seizures, insomnia, and nausea amongst others.

This helped prove that a great endocannabinoid system was essential for overall health.

Peripherally restricted CB1 agonists

The CB1 receptors which are the most common in the brain do influence neurological functions at large; which include the effects of marijuana in mood alteration. The receptors are also found in the liver, heart, kidneys and other organs.

Activating the CB1 receptors can bring about therapeutic effects, THC is what limits its use due to its psych activity shortcomings according to Big Pharma catechism.

Pharmaceutical researchers have developed CB1 agonists that can only activate the receptors away from the nervous system without crossing to the brain.

Selective CB2 agonists

Researchers have been pursuing this. It is supposed to bypass the brain and act on the peripheral system where there is more concentration of the CB2. These help in regulating pain perception, inflammation, and immune function

Working with compounds such as   HU 308 and JWH 133 that help in simulating CB2 receptors raises the chances of healing as the receptors are not in the brain and therefore no psychoactivity experienced.

However, there has not been much progress in synthesizing CB2 selective compounds after many trails. An Italian scientist says that the issue is surrounded by many hurdles.

Water-soluble cannabinoids

Naturally, cannabinoids and endocannabinoids are oil and do not dissolve in water. But their structure can be altered and they then dissolve without losing their therapeutic nature

There are ways of synthesizing water derivatives of THC that have been developed making it more bio viable than others

The initial water-soluble THC was developed in 1972. More research shows that cannabinoids can lower pressure in rabbits.

Online retailers claim to sell water-soluble CBD as a Nano emulsion. This pure CBD from nanotechnology is better in providing high bioavailability compared to what a CBD is extracted in a hydrophobic manner.

CBD isolates require on to take high doses which then reduces their efficiency than having a whole plant concentration. This then cancels out the effectiveness of the Nano emulsified CBD

Allosteric cannabinoid receptor modulators

Due to Psychoactive effects on the brain from a simulation of the cannabinoid receptors, researchers have developed compounds that change the shape of the CB1 receptor thus influencing how it signals without bringing about the THC effects. The allosteric either heighten or reduce the ability of a signal to be transmitted.

An affirmed modulator increases the potency of the receptor through anandamide and 2AG, thus increasing the effectiveness of the endocannabinoid system to protect.

Researchers in Scotland University have developed a positive allosteric modulator to help with pain and neurological disorders. This was tested on mice and it helped reduce inflammatory pain through a magnification of CB1 receptors responses to anandamide. Though allosteric effects are mostly not consistent across different species and thus this inhibits the development of a drug.

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Inhibitors of endocannabinoid metabolizing enzymes

Scientists have been researching a way to use synthetic designer drugs to enhance the endocannabinoid system without directly linking it to cannabinoid receptors.

Pharmacological processes of endocannabinoid signaling can be ascertained through inhibition of fatty acid amide hydrolase (FAAH) and Monoglycerol lipase., enzymes that break down cannabis molecules, anandamide and 2AG in that order.

A reduced amount of FAAH and MAGL results in more anandamide and 2AG thus increased activity of the cannabinoid receptors in the body. Drugs that reduce the endocannabinoid metabolic enzymes in an indirect way helps in boosting cannabinoid receptors signaling, thus one gets a natural high without even psychoactive effects of CB1 agonists.

FAAH and MAGL if inhibited could ease anxiety, hypertension, pain, colitis, and arthritis in animals.

As drug developers do their investigation on synthetic inhibitors, our very own kitchens exhibit the very signs of products that regulate the endocannabinoid an example being Nutmeg which prevents the breakdown of 2AG and anandamide?

Endocannabinoid reuptake inhibitors

Delay on the reuptake of 2AG and anandamide helps in augmenting the endocannabinoid tone. Researchers have developed inhibitors such as AM404 that inhibit the reuptake by targeting fatty acid-binding proteins. These aid in intracellular transportation and reuptake of cannabinoids.

Endocannabinoid levels are increased in the brain synapses due to block in access by these transport molecules. The results are increased cannabinoid receptor signaling and induced protective effects of the endocannabinoid.

Endocannabinoid reuptake is also inhibited by CBD and THC. Intensifying endocannabinoid tone through reuptake inhibition could a great mechanism for plants to offer protective effects from neurodegeneration as well as seizures among other great health benefits

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