Travel the human body on a weed puff: Cannabis Pharmacokinetics Pt. I

cannabis pharmakokinetics

Author’s Note: This article is the first installment in a two-part-series on Cannabis Pharmacokinetics — the science of how cannabis interacts with your body immediately following ingestion. In this case, we cover what happens after inhaling cannabis.

Albert Einstein probably didn’t smoke weed, despite the fervid hopes of countless stoned internet forum conversations. But he did work out his theory of relativity with a thought experiment that would blow the minds of any rec-room group of tokers discussing the universe late into the night: 

“What would I see if I could hitch a ride on a beam of light?”

In the same spirit, we here at WoahStork are taking a cue from the “Magic School Bus” and sending you on a journey through the human body. Our ride? A puff of pot smoke that leaves the station at 4:20.

And there’s certainly a lot to see out the windows. Burning pot produces more than 2,000 different compounds.

“Eighteen different classes of chemicals, including nitrogenous compounds, amino acids, hydrocarbons, carbohydrates, terpenes, and simple and fatty acids, contribute to the known pharmacological and toxicological properties of cannabis,” according to Chemistry and Biodiversity.

These are the chemical symbols of some important cannabinoids and their metabolites. Image courtesy of Chemistry and Biodiversity.

On our bus ride, we’re going to take a tour of your organs to watch them absorb, react to and get rid of the fun stuff that comes out when you burn cannabis flowers; a process called cannabis pharmacokinetics.

Make sure you sign up for the WeeklyWoah, WoahStork’s newsletter, so you don’t miss our second installment on cannabis pharmacokinetics. In it, we’ll trace the path of a pot brownie to show you how the body assimilates edibles.

Cannabis Pharmacokinetics: Membrane Absorption

The mucous membranes in the mouth, nasal cavities and throat all have millions of tiny capillaries near the surface of the tissue. This means all sorts of substances can enter your bloodstream through the mucous membranes; things like alcohol, nicotine and Delta-9 tetrahydrocannabinol (THC) and cannabidiol, (CDB). These two most potent cannabinoids in marijuana are joined by various other trace cannabinoids of different molecular configurations, as well as terpenes, which give pot its flavor and aroma, and other components.

cannabis pharmacokinetics mucous membrane
A diagram of a standard mucous membrane.

This ability of the mucous membranes to absorb cannabinoids is why some cannabis-based pharmaceuticals and concentrates are available as sublingual (under the tongue) sprays.

Epidiolex, for example, the first CBD-based drug FDA-approved for use in the U.S., comes as a sublingual spray.

Cannabis Pharmacokinetics: Lungs

If the mucous membranes are permeable to pharmaceuticals, then lung tissue is basically a sieve. The purpose of your lungs is to absorb gaseous chemicals, namely oxygen and nitrogen. This means the tiny organs that make up your lungs’ inner surfaces are uniquely designed by evolution to suck up whatever molecules you breathe in and incorporate them into your bloodstream, a process called “pulmonary assimilation.”

In fact, studies have shown that vaping or smoking is the most direct and efficient way of administering cannabinoids, similar in effect to intravenous injection of cannabis distillates.

“Pulmonary assimilation of inhaled THC causes a maximum plasma concentration within minutes, while psychotropic effects start within seconds to a few minutes, reach a maximum after 15 to 30 minutes, and taper off within 2 to 3 hours,” according to a study in the Journal of Cannabis Therapeutics. “Following oral ingestion, psychotropic effects set in with a delay of 30 to 90 minutes, reach their maximum after 2 to 3 hours, and last for about 4 to 12 hours, depending on dose and specific effect.”

Cannabis pharmacokinetics: A zoom in of the lungs, showing the alveoli, where gaseous molecules can be absorbed into the blood.
A zoom in of the lungs, showing the alveoli, where gaseous molecules can be absorbed into the blood.

Your lungs are the first site at which your body starts dividing up the components of weed smoke in a major way, so we’re gonna aim our Magic School Bus into the bloodstream to follow the good stuff. 

All that tar and ash you breathe in as you burn your bud? Most of that gets deposited on the walls of your lungs, gumming up the alveoli, the little berry-like clusters of capillaries bound up by a permeable membrane. 

Your lungs can break down a lot of tar, but not right away. Little by little, those big complex carbonized molecules get shuffled into the bloodstream and filtered out through the kidneys. But if you smoke every day, your lungs are gonna be black inside — they can’t keep up with daily deposits of new tar, whether from pot smoke, cigarettes or smoke from wood fires.

(Read our article on whether marijuana smoking causes lung cancer for more info.)

Vaping makes tar a non-issue, but that comes with its own problems — like toxic heavy metals released by the heating element. Vaping is still likely better for your lungs, but people haven’t been vaping long enough to get a solid conclusion about the long-term consequences.

Cannabis Pharmacokinetics: Bloodstream

Once the cannabinoids and their terpene pals enter the bloodstream, they begin interacting with the body’s internal endocannabinoid system. This is a sub-system of the central nervous system that helps regulate mood, appetite, perception, pain, stress response, sleep and a host of other crucial functions in the body.

The endocannabinoid system is a series of chemical locks and keys comprise this signaling system, which includes the CB1 and CB2 classes of receptor openings on brain and nerve cells. They’re built to receive anandamide (ADA) and 2-arachidonoylglycerol (2-AD), which are neurotransmitters the body produces naturally. 

Cannabis Pharmacokinetics: travel through the blood stream
Cannabinoids and terpenes will enter your bloodstream, where they travel throughout the body and brain alongside the other components commonly found in the bloodstream (like red and white blood cells).

These two chemicals are similar to THC and CBD, so much so that the phytocannabinoids (plant-derived ones, as opposed to your own endocannabinoids) hijack and partially activate the CB1 and CB2 receptors to produce the marijuana high and its therapeutic benefits.

(Read our full article on the endocannabinoid system here.)

Cannabis Pharmacokinetics: The Brain

The bloodstream carries all the cannabis components to the CB1 and CB2 receptors, which are concentrated in the brain and gut, but also throughout the body, to a lesser degree.

THC is the main psychoactive chemical in marijuana and the first one isolated in 1964 as an active component in cannabis. As a result, the metabolism of THC, or how your body breaks it down, is well studied.

Once your body uses the THC in its endocannabinoid receptors, it has to dispose of the chemical. This means your body’s enzymes have to pull apart the atoms of the THC molecule in a series of steps that form different chemicals in preparation for elimination through the liver and kidneys.

Cannabis Pharmacokinetics: CB1 and CB2 receptors
Once in the brain, cannabinoids interact with receptors, causing neurons to “fire” and signal to other neurons that cannabis has joined the electrical party.

And the endocannabinoid system also includes its own janitor in the form of an enzyme called fatty acid amide hydrolase (FAAH), which breaks down endocannabinoids immediately after use. This is important, because unlike other neurotransmitters, cannabinoids are fat soluble. Because all your cell walls are made of fat and cannabinoids are fat soluble, cannabinoids could theoretically float in and out of cell membranes and wreak havoc on the electrochemical function of other brain systems.

Instead, the FAAH chemical latches onto the cannabinoid — in this case, THC — to shuffle it into the circulatory system for removal. 

(Read our full article on the role of FAAH in the breakdown of cannabinoids in the body.)

Metabolism: Liver and Kidneys

The liver breaks down the pure THC in your bloodstream into THC-COOH and 11-OH-THC. The latter metabolite is the focus of drug tests you have to take for work, court or state supervision. Test results from subjects smoking for the first time showed metabolites were still measurable in the bloodstream after 50 hours, much longer than metabolites for other drugs of abuse like cocaine or alcohol, according to the Journal of Analytical Toxicology.

The liver is responsible for breaking down THC into the two metabolites mentioned above, via an enzyme called cytochrome P450. The enzyme sticks a group of oxygen and hydrogen molecules to the THC, which makes the fat-soluble THC molecule more water-soluble, meaning its possible for the kidneys to process and release in urine.

One of several reasons smoking marijuana gets you much higher faster with less pot than in edibles is because the cannabinoids bypass the liver as they enter the bloodstream.

About Adam Townsend 50 Articles
Adam Maxwell Townsend has been a journalist for 15 years. His reporting has covered science, technology and medicine. Currently, he edits and writes medical and pharmaceutical articles for consumer websites, including WoahStork.

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