You’re about to discover how CBD went from a schedule 1 substance to the World Health Organization announcing they have found no evidence of negative side effects from taking CBD.
It all has to do with our CB1 and CB2 receptors…
Cannabinoid Receptors in the Body
Why We Have Cannabinoid Receptors
Our bodies regulate themselves like your thermostat sets the temperature of your home.
When we have a cold, our immune system protects us by getting as much of the virus out as possible.
Coughing clears out our lungs, mucous takes bacteria with it, and sneezing keeps our airways flushed.
But how do our bodies know when enough is enough? Why not just keep sneezing and coughing nonstop until we’re better?
Just like Goldilocks trying out every bed in the house before finding the right fit, our bodies wait for certain signals to know when to amp things up and when to tone it down.
Our endocannabinoid system plays an important role in keeping our bodies at comfortable homeostasis. Homeostasis is just a fancy way of describing how our bodies try to keep everything balanced.
Homeostasis is the reason your temperature almost always hovers around 98℉. You’ve experienced how uncomfortable slipping away from that norm can be the last time you had a fever.
But What Role Do Cannabinoids Play?
Our bodies actually produce their own cannabinoids called endocannabinoids (endo meaning within). But why do we have cannabinoid receptors?
These endocannbinoids feed into receptors that tell our bodies when to cool it on the inflammation, pain, and everything else they control.
If you or a loved one suffer from an autoimmune disease, this is a case where your immune system doesn’t know when to shut off.
Perfectly healthy organs and tissues are attacked by the immune system who thinks there is something wrong.
And even though we make our own cannabinoids, the ones found in plant sources like industrial hemp interact with our bodies in a different way.
Cannabinoids like CBD are like the exciting out of town visitor. Our endocannabinoid system breaks away from its usual routine to make accommodations.
And this is the exact same reason THC has psychoactive effects and why CBD will never get you high.
CBD can actually stop some THC and other cannabinoids from being absorbed because they block them from reaching the right receptor.
What are endocannabinoids?
Endocannabinoids are the type of cannabinoids our bodies naturally produce. Along with anandamide, 2-AG is the other main endocannabinoid scientists are aware of.
Endocannabinoids are only made when the body needs them. They are processed much faster than cannabinoids from foreign sources like THC.
THC can’t be broken down as fast as endocannabinoids which is why it effects last so much longer. You’re getting a huge dose of cannabinoids your body would never produce naturally.
This causes our endocannabinoid system to activated longer than nature intended.
Types of Endocannabinoids
Anandamide is named after the Sanskrit word for “divine joy” because it casts a blissful mood throughout our bodies.
Fatty acid amide hydrolase (FAAH) is the enzyme that helps process anandamide.But when we have too much FAAH it can deplete our natural levels of anandamide.
Low levels of anandamide are linked to higher rates of psychotic episodes in patients suffering from schizophrenia.
And in a double-blind study testing the effects of CBD against the common antipsychotic medication amisulpride, CBD came out the clear winner.
While both groups saw significant improvements in psychotic symptoms, the group taking CBD had no side effects and had higher levels of anandamide than the other group.
There is significant research documenting the link between anandamide and schizophrenia.
If CBD can increase anandamide levels without extra side effects it could be the perfect addition to a patients antipsychotic therapy.
But is it legal?
Yes, CBD is now a schedule 5 rather than schedule 1 substance. That puts it on par with cough syrup.
What is GPCR?
G-protein coupled receptors (GCPR) are the largest group of neurotransmitter receptors in the body.
They lie on the surface of cells and take in everything from light to the sugars and proteins from our last meal.
Researchers estimate that up to half of all medications work by binding to GPCRs.
CB1 and CB2 receptors are both GPCRs.
CB1 receptors are found in high concentrations in several parts of the brain while CB2 receptors are found on the outside of immune cells.
Both act as the cell’s mailbox. Before the cell can interact with a cannabinoid it needs to 1st pass through a CB1 or CB2 receptor.
CB1 receptors are also found in nerve endings where they may reduce painful sensations. CB2 receptors handle inflammation when tissue is hurt or damaged.
THC fits perfectly into either receptor. There are CB1 receptors in the hypothalamus which regulates moods and appetites. This is where THC’s psychoactive effects come from.
Not so with CBD. CBD doesn’t bind directly to either CB1 or CB2. It still interacts with them though…
Like we discussed earlier, CBD instead inhibits the breakdown of feel-good neurotransmitter anandamide.
History of Cannabinoid Discovery
It wasn’t long ago that scientists had no idea that we had a complex endocannabinoid system.
The Early Years
Cannabis research started as early as the 1940s. THC was the first cannabinoid to be isolated from the cannabis plant, followed by CBD that same year.
Researchers 1st saw CBD’s potential as a way to slow down the liver’s metabolism of certain compounds. They realized CBD could prolong the effects of sleep medication in mice.
When the mice were given the sleep medication, isolated CBD was able to extend the usual time the meds were active. THC did no such thing.
This makes sense since THC has no problem fitting into CB1 and CB2 receptors. It doesn’t have the same ability to slow down the metabolism of certain drugs and neurotransmitters the way CBD does.
But it wasn’t until the mid-80s researchers were sure we had at least 1 cannabinoid receptor. Until then we really didn’t know exactly why our bodies seemed to get such a kick out of cannabinoids.
A big part of this discovery was the advancements being made in our understanding of how GCPRs work.
The other big reason scientists were able to find cannabinoid receptors for the first time was the ability to detect receptor sites using radioactive material.
This radioactive material binds to the receptors and making them easy to locate.
This is what led researchers to find that THC directly interacts with endocannabinoid receptors.
What was most interesting to researchers was where they found most of the receptors.
They were in high concentrations around the parts of the brain responsible for everything from basic motor functions to emotional regulation.
In another 5 years, the 2nd receptor for these cannabinoids was found, giving us the CB1 and CB2 receptors we’re familiar with today.
These CB2 receptors weren’t just concentrated in the brain like the 1st receptor found a few years before. CB2 receptors seemed to be scattered throughout the body, their biggest attraction being to the surface of immune cells.
Researchers knew this was big news. If we have cannabinoid receptors throughout our bodies, the potential for activating them could be limitless.
Even though they weren’t sure what the potential for this knowledge was, for the 1st time the scientific community confirmed we have an entire internal system dedicated to interact with cannabinoids.
Wearing Out the System
Just like collagen production slows as we age and cause wrinkles, our endocannabinoid system can also lag when we need it most.
That’s where CBD comes in to save the day. CBD actually improves our endocannabinoid system by recalibrating our receptors.
When CBD interacts with CB1 and CB2 receptors, even though it’s not an exact fit like THC, it does improve their functionality.
So CBD can be used when our bodies own endocannabinoid system starts to run dry.
Since our bodies can only produce endocannabinoids when we need them and in limited amounts, it’s not uncommon for people to have cannabinoid deficiencies.
Research shows a cannabinoid deficiency can cause all sorts of negative symptoms, like headaches and irritability.
By taking supplemental cannabinoids like CBD we might restore homeostasis.
What is CECD?
Clinical endocannabinoid deficiency (CECD) is the official name for a lack of endocannabinoids.
In an interesting study looking at how endocannabinoids interact with GCPRs in mice, researchers found a connection between CECD and a diet low in polyunsaturated fatty acids.
Many Americans get plenty of saturated fats but not nearly enough polyunsaturated fats.
When researchers fed their lab mice a diet low in polyunsaturated fats, they found that a large number of the once active endocannabinoid receptors had detached from their GCPRs, rendering them useless.
These mice showed signs of emotional distress. By changing one component of their diet researchers were able to manipulate how the mice responded to stress.
This isn’t surprising given all the problems humans endure when they experience low endocannabinoid function.
Imbalanced Endocannabinoid System
In fact, CECD has been linked to several treatment-resistant conditions in humans. Migraines, fibromyalgia, and irritable bowel syndrome (IBS) create several problems for patients and their doctors.
What makes these conditions so frustrating is that they are based on subjective perceptions of pain, a migraine for 1 person may be debilitating whereas someone else might pop an aspirin and go throughout their day.
The same goes for other conditions. Even though they are caused by the same bodily functions, different people can experience the symptoms at very different intensities.
Patients often feel disillusioned by the ineffectiveness of the most common medications prescribed for these conditions as well. They might try treatment after treatment only to experience little relief.
Cannabinoids, especially CBD, have been shown to block many of the reactions that cause pain.
Endocannabinoids and Neurogenesis
Neurogenesis is the process of creating new neurons in the brain. Researchers used to believe this process only happened in the womb and for a few weeks or months after birth.
But this is no longer the case. Researchers now know certain parts of the brain are always replenishing themselves.
This came about in 1984 when stem cells were extracted from adult songbirds. Stem cells are the precursors for new developing neurons.
Further research confirmed this is also the case among mammals. For the most part neurogenesis in adults happens in 2 distinct parts of the brain.
Around the hippocampus is a layer of cells referred to as the subgranular zone (SGZ).
This area along with the olfactory bulb, the part of your brain responsible for your sense of smell, are where the majority of neurogenesis happens.
How CBD Affects Neurogenesis
Some of the mice were given THC to see how the effects differed from CBD. THC impaired learning while having no effect on neurogenesis.
CBD, on the other hand, didn’t impair learning at all and actually provided a boost to neurogenesis.
Why? Researchers think the most obvious reason is the high amount of CB1 receptors which are concentrated in the same parts of the brain neurogenesis occurs in.
They found that in the of CB1 receptors the mice didn’t experience the same rate of neurogenesis as before.
CB1 and the Marble Burying Test
Ever heard of the marble burying test? It’s a standard procedure researchers use to simulate anxiety or obsessive-compulsive behavior in mice and rats.
If 1 of these rodents is put in a cage with marbles scattered across the floor, the mice will bury the marbles, often within its own bedding area.
Rodents are known to do this with both harmful and harmless objects, the cause often attributed to anxiety.
So what happens when you give an anxious mouse CBD?
When given the largest dose in the experiement (60 mg) the mice only buried about half (48%) of the marbles in their cage.
But here’s where it gets interesting. Another group of mice were given diazepam, a popular anti-anxiety drug known under the brand name Valium.
The initial results were stellar. Diazepam lowered marble burying by 77%. Way more than what CBD was able to accomplish.
But something changed. The mice in both groups continued to receive their daily dose of either CBD or diazepam for a full 7 day week.
By day 7, the mice had built up a tolerance to diazepam, making the current dose ineffective for their anxiety. They went back to burying as many marbles as possible.
What about the mice taking CBD? Still, calm and collected little guys after 7 days of getting the same dose of CBD. CBD did not appear to lose it’s effectiveness as it became part of their daily routine.
CB2 and CBD Products
Some studies note a connection between the CB2 receptor and inflammation. This makes sense since most of our CB2 receptors live on immune cells.
In experiments where CB2 receptors are blocked or missing, the mice are prone to over inflammation.
This suggests to researchers that by targeting the CB2 receptors they can reduce the discomfort of conditions that cause excessive inflammation, like psoriasis.
It does this by acting as what biologists call an inverse agonism. A regular agonist binds to a receptor to cause some sort of outcome.
Instead of increasing inflammation, CBD causes the reverse effect.
CBD is able to relieve inflammation by slowing down the natural response of the CB2 receptors.
CB1 and CB2 and Cannabinoids
Endocannabinoids are the language of our immune system and mental stability.
You’ve seen how an imbalance in your endocannabinoid system can cause so many problems, many of which seem totally unrelated.
And while the research into the benefits of CBD may still be young, we know for a fact that our endocannabinoid system plays a huge role in our overall health.
We also know CBD can not make you high at all. It has no psychoactive properties whatsoever. It can’t directly interact with our CB1 and CB2 receptors
Experiment after experiment has found no notable adverse side effects to CBD either. Even the World Health Organization (WHO) officially recognizes the safety of CBD.
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