This article was scientifically reviewed by Daniel Hanna, PharmD
Since the earliest days of cannabis research, scientists have been stunned by the chemical complexity of the Cannabis sativa plant. The components of cannabis impact your body in different ways, but most cannabis compounds are thought to be relatively safe.
The pharmacokinetics (the way a chemical moves through the body) of cannabis are complex, but they’re important to know if you’re concerned about drug interactions or simply want to deepen your knowledge of this fascinating plant. In this guide, we’ll explain how cannabis is metabolized in the human body—cannabinoids, terpenes, and all.
Different cannabinoids, different pathways
The moment a dose of inhaled cannabis enters your lungs, dozens of different molecules start competing for space as they move into your bloodstream. Some of these chemicals, like delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD), may be relatively familiar, but less well-known compounds like terpinolene and apigenin are also present.
To date, even the most advanced cannabis scientists aren’t able to map exactly how all these different compounds affect the human body. For the purposes of this guide, we’ll mainly focus on THC and CBD here.
Terpenes also play a role
The majority of contemporary scientific research indicates that terpenes significantly impact the metabolism of cannabinoids in your body. This phenomenon is widely known as the entourage effect, and it’s believed to explain the unique experiences users have with various cannabis strains.
Given the complexity of compounds present in natural cannabis flower, it may never be possible to exactly pinpoint how terpenes and cannabinoids interact when cannabis is smoked. By isolating and combining certain terpenes and cannabinoids, however, we may be able to alter the metabolism of cannabis enough to achieve a specific pharmacokinetic profile.
Full-spectrum, holistic benefits
When kept in its whole, natural state, cannabis provides broad, holistic benefits. Beyond cannabis flower, certain types of vaporizer cartridges and edibles also keep the full entourage of the terpenes intact, allowing you to experience the benefits of cannabis in a variety of different ways.
Cannabinoid pharmacokinetics: the details
Now that you’ve had a basic overview of how cannabis works in your body, let’s get into the finer details:
What do the cannabinoid receptors do?
The cannabinoid THC and its variants (delta 8, THCV, etc.) primarily act on the CB1 and CB2 receptors, concentrated in the central and peripheral nervous systems respectively. Activation of CB2 receptors provides a non-intoxicating anti-inflammatory effect, but intense euphoria follows any significant activation of the brain’s CB1 receptors.
Notably, CBD does not activate either the CB1 or CB2 receptors. It acts on a separate biochemical pathway in the human body.
Why do we have cannabinoid receptors?
The human body has a natural endocannabinoid system that involves endogenous cannabinoid-like compounds such as anandamide. Cannabinoid receptors exist to accommodate these body-generated cannabinoids, which are usually called “endocannabinoids” to distinguish them from plant-originated “phytocannabinoids.”
Cannabis scientists have long thought that the human body has an “endocannabinoid system” and that using cannabinoids can stimulate this natural system in a variety of ways. Based on THC’s observable activity at the CB1 and CB2 receptors, this does appear to be the case.
What is the molecular target of CBD?
Scientists believe that the two primary molecular targets of CBD are the 5-HT and TRP neuroreceptors. Compared to THC, which mainly only acts at two neuroreceptors, CBD has been demonstrated to perform functions in many different ways throughout the body. Primarily, though, CBD has been observed to have high affinity for neuroreceptors in the 5-HT family, which govern serotonin and neuropathic pain, and neuroreceptors in the TRP family, which regulate inflammation and inflammatory pain.
This unique pharmacokinetic profile is what has made CBD such an object of fascination within the scientific community over the last decade. Epilepsy and countless other conditions are thought to be treated with CBD, but it still requires more research to understand the extent of its effectiveness.
Cannabis metabolism FAQ
Let’s finish things off with answers to commonly asked cannabis metabolism questions:
1. Can edibles damage the liver?
It’s unlikely that cannabinoids cause liver damage when ingested in normal doses. Limited studies on animals have been performed, and it appears certain cannabinoids may be hepatotoxic if ingested in extremely high concentrations.
Even if you use cannabis edibles regularly, however, you’re unlikely to damage your liver due to the cannabinoids you’re consuming. That doesn’t say anything, though, about the other ingredients in the cannabis edibles you eat. Make sure to use clean, simple ingredients to avoid ingesting something toxic that isn’t in your cannabis.
2. How much is 150 ng/ml of cannabinoids?
In the world of lab analytics, the measurement “ng/ml,” or nanograms per milliliter, is used to determine the concentration of a substance in a biological sample. For cannabis users, nanograms per milliliter is the measurement used for drug testing.
When it comes to cannabinoids like THC, 150 ng/ml is a relatively high concentration to be present in urine. A urinalysis reading that high would indicate significantly frequent cannabis use, which is why most drug tests set their THC threshold significantly lower.
3. How long does it take to get below 50 ng/ml for a urine test?
Depending on where you started, it can take anywhere from a few hours to a few weeks to reduce the nanograms of THC per milliliter of urine in your body down to 50. For light or occasional cannabis users, THC levels may never exceed 50 ng/ml in the first place. Otherwise, it’s simply a matter of how fast your body can excrete THC.
Hydrating properly, getting plenty of exercise, and sleeping well can all help your body expel contaminants like used-up cannabinoid molecules. Detox drinks, however, usually aren’t much more effective than lemon water and might contain dangerous artificial ingredients.
4. How do you “upregulate” cannabinoid receptors?
In biochemical parlance, “upregulation” is when you increase the number of desired neuroreceptors on a target cell, increasing its affinity for certain substances. In this case, the substances we want to upregulate our cells to become more sensitive toward are cannabinoids.
Research has identified a few different ways you might be able to upregulate your cannabinoid receptors without using cannabis. Certain foods, including chocolate and turmeric, may boost the expression of endocannabinoids in the body, and getting exercise may also provide the cannabinoid upregulation you’re looking for.
5. How do I reset my endocannabinoid system?
If you’re concerned you may have disrupted your endocannabinoid system by overusing cannabis, what you need is a “tolerance break:” a short break from cannabis use that allows your body to recover back to its original state. Afterward, you can take a close look at the way you’re using cannabis to determine if any changes need to be made.