What Happens to Our CB1 and CB2 Receptors with Chronic Use of Phytocannabinoids?
Our body has a special system called the endocannabinoid system (ECS), which helps control things like mood, sleep, appetite, pain, and even the immune system. This system has two main types of receptors called CB1 and CB2.
Receptors are like tiny locks, and cannabinoids are the keys that fit into them.
CB1 receptors are mostly found in the brain and help control things like mood, memory, and pain.
CB2 receptors are found in the immune system and help manage things like inflammation and immune response.
Phytocannabinoids are cannabinoids that come from plants, like THC and CBD in cannabis. When we consume cannabis, these phytocannabinoids attach to the CB1 and CB2 receptors in our bodies, causing various effects like feeling high (from THC) or relaxed (from CBD).
However, if someone uses cannabis a lot over time (called chronic use), the receptors start to change. The CB1 receptors in particular can become less sensitive or responsive. This means that over time, you might need more cannabis to feel the same effects as before. This is what we call tolerance.
Why Do We Build Up a Resistance to Phytocannabinoids?
When the CB1 receptors in your brain are constantly activated by THC from cannabis, your body tries to balance things out. To do this, it can either reduce the number of receptors available or make them less sensitive to THC. This process is called downregulation. It’s the body’s way of protecting itself from being overstimulated.
Think of it like drinking coffee. If you drink it every day, your body gets used to it, and you might need more and more coffee to feel energized. The same thing happens with cannabinoids—your body adjusts, and you build up a resistance.
Chronic cannabis use can also reduce the natural cannabinoids (called endocannabinoids) that our body makes. This means that the endocannabinoid system itself becomes less active, which contributes to the need for higher doses of cannabis to feel the same effects.
Does Our Body Prioritize Endocannabinoids Over Phytocannabinoids (messengers)?
Yes, our body does give priority to endocannabinoids, which are cannabinoids (messengers) produced naturally by the body. These endocannabinoids—like anandamide (often called the “bliss molecule”) and 2-AG—are made only when the body needs them. Once they’ve done their job, they are quickly broken down by enzymes (special proteins that help break things down).
Enzymes in the ECS are like tiny cleaners. After messengers in your body send signals to help you feel good or calm, enzymes like FAAH and MAGL clean them up so the signals don’t last too long, this helps the body maintain balance, a state called homeostasis.
On the other hand, phytocannabinoids (cannabinoids from plants) are introduced into the body from outside sources, like cannabis. Because they’re not produced by the body, they often come in higher doses than the body’s natural cannabinoids. When this happens, the body has to work harder to balance the system. It does this by breaking down excess cannabinoids and making the receptors less responsive.
How to "Reset" Your Cannabinoid Receptors
If someone has built up a tolerance to cannabis, there are ways to help “reset” the CB1 and CB2 receptors to make them more responsive again:
Take a Break (Tolerance Break or "T-Break"): The most effective way to lower your tolerance is to stop using cannabis for a while. This gives the receptors time to return to their normal sensitivity. Even a break of two to four weeks can significantly reduce tolerance and make cannabis more effective again.
Microdosing: Instead of consuming large amounts of cannabis, some people choose to microdose—taking very small amounts of cannabis at a time. This helps activate the receptors gently, without overwhelming them. This can help prevent the development of tolerance over time.
Exercise and Healthy Eating: Activities like exercise can naturally boost the body’s production of endocannabinoids, especially anandamide (which gives you that “runner’s high”). Eating a diet rich in omega-3 fatty acids (found in foods like fish, walnuts, and flaxseeds) also supports the endocannabinoid system and helps keep the receptors healthy.
Use More CBD: While taking a break from THC, some people switch to using CBD products. Unlike THC, CBD doesn’t cause the same tolerance issues and can actually help balance the endocannabinoid system. CBD is known for its anti-inflammatory and relaxing effects and can be a good option during a tolerance break.
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