How much THC gets into our brain? How fast does it reach the brain? Can the blood-brain barrier stop THC? How can you increase THC levels in the brain?
By Professor of Pot
THC needs to get into your brain to do just about everything it does. Even peripheral effects like increased heart rate may be caused by THC acting within the CNS. So how much do we actually know about THC (and other cannabinoids) getting into the brain? It turns out quite a lot.
How Much THC Gets Into Your Brain?
The truth is that we don’t know exactly what percent of blood THC makes it into our brain. Not many people will sign up for a study to biopsy their brain after smoking weed. However, we do have some other information to make a good estimate.
The first piece of evidence comes from animals. The brain-to-blood ratio of THC levels was generally consistent in mice (ratio=1.6), rats (ratio=2), and pigs (ratio=2.6).
So what data do we have in humans? Cannabinoids have been measured in the tissues of cadavers. The average brain-to-blood ratio was 3. So based on all available data, it appears that THC levels are several times higher in your brain than in your blood.
Why are THC levels even higher in the brain than the blood? The reason for this is likely because your brain is a very fatty tissue. THC is highly lipophilic and has a preference for settling into fat more than other tissues.
What about the psychoactive metabolite 11-OH-THC? This metabolite is formed in high quantities after taking edibles. Rumor has it that 11-OH-THC can more easily get into the brain. A study in rats supports this…the brain-to-blood ratio was twice as high for 11-OH-THC as for THC.
Do Other Cannabinoids Get Into Your Brain?
Because all cannabinoids have a generally similar structure, we can expect that most other cannabinoids can get into the brain as well. In the cadaver study above, they were also able to detect cannabinol (CBN) and cannabidiol (CBD) in human brain tissue. They were even able to detect the carboxy metabolite of THC (THC-COOH), indicating that other acid forms of cannabinoids, like tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), may be able to enter the brain.
Further information comes from mice, where one study looked at brain penetration of tetrahydrocannabivarin (THCV), CBD, cannabivarin (CBDV), and cannabigerol (CBG). You can see that there is a wide range of brain-to-blood ratios for each of these cannabinoids.
This study showed that THCV and CBDV were much better at getting into the brain than CBD and CBG. However, other studies in rodents have measured the brain-to-blood ratio of CBD to be around 2.
How Fast Does THC Reach Your Brain?
This depends on how you are consuming THC. If you start smoking, you may feel effects within minutes. But is this because of the time it takes THC to absorb from your lungs? Or the time it takes the THC to reach your brain?
A 1980 study answered this question by using intravenous administration, infusing THC directly into the bloodstream.
“Intravenous infusion of 5 mg THC over 2 min caused an instant and pronounced high in all subjects.”
This proves that THC can enter the brain extremely quickly. Nonetheless, the psychoactive effects continued to rise up to a peak at 15 minutes, even while plasma THC concentrations were falling at the same time. This indicates that there is a delay in THC reaching your brain relative to the levels already in the blood.
This same effect was observed with smoked cannabis. Peak blood concentrations are achieved within minutes after smoking, and yet there is a further delay until peak psychoactive effects. This effect is not observed with edibles, which makes sense since the slow THC absorption from the GI tract gives plenty of time for the blood and brain levels to equilibrate.
Why does this delay exist? Read the next section to find out…
Does the Blood-Brain Barrier Prevent THC From Reaching the Brain?
There are several reasons why THC entry to the brain is slow.
The first is that blood THC is highly bound to plasma proteins, such as albumin. This leaves only 3% of THC in its unbound state that is free to diffuse into the brain.
The second factor is the blood-brain barrier, a system which separates the blood from brain tissue. In the capillaries of most tissues, there are gaps between the endothelial cells that allow drugs to easily pass through. The specialized endothelial cells of the brain capillaries bind tightly together and block many substances from reaching the brain.
The blood-brain barrier will block any molecule which is not lipophilic enough to cross the cell membrane, unless there is a specialized transporter to bring that substance into the brain. However, THC is a highly lipophilic molecule that can diffuse across cell membranes. So the blood-brain barrier may slow down entry into the brain (since it will still take some time for THC to cross it), but it does not stop it.
There is one other part of the blood-brain barrier still to be discussed, and this may be the most important factor yet….
Drug Transporters – The Gatekeepers of THC Access to Your Brain
Drug transporters are proteins that pump molecules from one side of a membrane to the other. In the blood-brain barrier, they can pump drugs from inside the endothelial cells back out into the blood. Drug transporters can recognize a wide range of molecules and can reduce brain penetration of those drugs which they recognize.
THC is a substrate for two common drug transporters, called P-gp and BCRP. Scientists have generated two strains of mice, each lacking one of these transporters. These mice were used to evaluate whether they are limiting brain penetration of THC.
The study showed that both of the transporter-null mouse strains had higher brain THC levels. This indicates that these transporters are an important factor in limiting the amount of THC that gets into your brain. The difference in THC brain levels was especially large at 2-3 hours after dosing, indicating that the transporters may control how long you stay high for.
Do drug transporters really have an effect in humans though? Based on genetic evidence, the answer appears to be yes. There are different genetic variants of the P-gp transporter in humans that have low or high activity. Which one you have affects your risk of cannabis dependence.
How Does THC Get Out of Your Brain?
There are several ways that THC can exit from your brain. The first is the opposite of how it got in: as your blood THC levels drop, a concentration gradient will form that causes THC molecules to move from your brain across the blood-brain barrier and back into your blood. This is assisted by drug transporters that pump THC in this direction.
The other possible exit route is through the cerebrospinal fluid (CSF). The CSF is a clear fluid that circulates throughout the ventricles of your brain and your spine. THC could diffuse into the CSF, which eventually drains into your bloodstream.
Are There Ways to Increase THC Levels In Your Brain?
There are some myths on the topic of the blood-brain barrier that have been circulating a while. One of these myths is that eating a mango before smoking will get you higher because the myrcene in mango increases blood-brain barrier permeability. I researched this extensively and found absolutely no evidence that there is any effect on the blood-brain barrier.
However, it is possible to increase THC levels in your brain – just smoke more weed!
Besides this, the best (and probably only) strategy to increase THC brain penetration is to inhibit the drug transporters that pump THC out of your brain. You may be doing this without even realizing it – because CBD can inhibit these transporters.
However, timing matters – it may be better to take CBD before THC instead of at the same time. One study has shown that CBD does a better job of increasing brain THC levels when it is taken earlier. When given concurrently, CBD increased brain THC levels by 52%, but the same amount of CBD given 60 minutes prior increase brain THC by a whopping 160%.
There are also herbal supplements which inhibit these transporters and may increase the access of THC to your brain. I am still compiling the list, but will put them here soon. You can try them for yourself and see if they work!
Original article appeared here.
© 2017 Professor of Pot and www.profofpot.com. All rights reserved. Syndicated by special permission.