CB1 receptor: definition, functions and role in the effects of cannabis

CB1 receptors are a type of cannabinoid receptor found in the body. The cannabinoids like THC interact with these receptors to induce some of the subjective and therapeutic effects associated with cannabis. CB1 receptors, to which THC binds easily, are very abundant in the brain, which explains why you feel “high” when you use cannabis containing THC. Natural chemicals produced by the body, such as anandamide and 2-AG, also activate CB1 receptors.

What are CB1 receptors?

CB1 receptors are part of a biological system called endocannabinoid system, whose primary function is to maintain our body’s functional balance—or, more technically, to maintain homeostasis. These CB1 receptors, which are abundant in the brain, help regulate communication between cells to support homeostasis.

CB1 receptors and the compounds that bind to them can be visualized using the analogy of a lock and a key: The receptors are like a lock into which only certain keys fit; THC is an example of a key that fits this lock. When a THC molecule binds to a CB1 receptor, it activates the receptor, allowing the user to experience the effects of THC. Without cannabinoid receptors, cannabis would not be able to produce many of its characteristic effects in the body.

What do CB1 receptors do?

Cannabis compounds such as THC bind to CB1 receptors and activate them, allowing us to experience some of the characteristic effects of cannabis, such as euphoria. The activation or inhibition of CB1 receptors in neural signaling is also associated with a variety of other effects, including sensory perceptions, pain, memory, and mood, as well as the regulation of sleep and appetite.

The cannabinoids in cannabis are not the only compounds that interact with CB1 receptors; a natural chemical called anandamide also binds to CB1 receptors. If you’ve ever gone for a somewhat intense run, you’ll recognize the sensation of anandamide binding to CB1 receptors—a phenomenon known as the «runner’s high.» Another endocannabinoid produced in the body, 2-AG, also binds to CB1 receptors.

Repeated and frequent activation of CB1 receptors leads to a decrease in their expression, a phenomenon better known as the development of tolerance. This is why we tend to feel the effects of cannabis less intensely over time with frequent use.

What is the difference between CB2 receptors and other receptors?

CB1 and CB2 receptors are the two most abundant types of endocannabinoid receptors in the mammalian body. Activation of these two receptor types appears to have different regulatory functions. CB1 receptors appear to play a role in regulating a wide range of homeostatic functions that influence sleep, appetite, memory, mood, and sensory experience, among others. The CB2 receptors are thought to be involved in functions related to immunity and inflammation signaling.

How do CBD and THC affect CB1 receptors?

The THC, the most common cannabinoid in cannabis and the primary source of its euphoric effects, easily activates CB1 receptors. This interaction, which occurs in the brain and throughout the central nervous system, explains why cannabis with a high THC content so profoundly alters our state of mind and sensory experience.

The CBD does not directly activate CB1 receptors: it acts as a negative allosteric modulator, meaning it binds to a different site on the receptor and alters its conformation, reducing the effectiveness with which THC can activate it. This is why CBD-rich strains or the simultaneous use of CBD can mitigate the psychoactive effects of THC, without completely blocking them.

CB1 Antagonists: When to Block the Receptor

The development of drugs that target CB1 receptors has been the subject of intensive research. The rimonabant (Acomplia), a CB1 antagonist developed by Sanofi, was marketed in Europe between 2006 and 2008 as a treatment for obesity by blocking CB1 receptors in the hypothalamus to reduce appetite. It was withdrawn from the market in 2008 due to serious psychiatric side effects (depression, suicidal thoughts), a direct illustration of the importance of CB1 receptors in regulating mood and well-being.

Paradoxically, this setback has heightened interest in selective allosteric modulators (which modulate rather than completely block), an active area of research aimed at developing treatments without the adverse effects of complete blockade.