The human endocannabinoid system does not live in one place. It is spread across nearly every organ and tissue in the body, which is why its influence shows up in mood, appetite, sleep, pain signaling, and immune response all at once. The system is a signaling network, not a gland or a single organ. Its parts are made where they are needed, used fast, and broken down on site.
what are cb1 and cb2 receptors
Four pieces make up the network: endocannabinoids (mostly anandamide and 2-AG), the receptors they bind to (CB1 and CB2), the enzymes that build and clear them (FAAH and MAGL), and the cells that host all of the above. Here is where each piece tends to concentrate.
The short answer
Receptors, enzymes, and endocannabinoids are found in the brain, spinal cord, peripheral nerves, immune organs, gut, skin, liver, fat tissue, bone, muscle, reproductive organs, and the cardiovascular and endocrine systems. If a tissue has cells, it very likely has some part of the endocannabinoid system running inside it.
CB1 receptors: heaviest in the nervous system
CB1 is one of the most abundant G protein-coupled receptors in the brain. Density is highest in the cerebral cortex, hippocampus, basal ganglia, cerebellum, and amygdala. Those regions map onto memory, movement, reward, fear, and coordination, which is a large part of why cannabis feels the way it does.
what is anandamide in the endocannabinoid system
- Brainstem: sparse CB1, one reason cannabis does not shut down breathing the way opioids can.
- Spinal cord: present in the dorsal horn, where pain signals arrive.
- Peripheral nerves: CB1 sits on sensory nerve endings, including those in the skin.
CB1 is not brain-only. You will also find it in the liver, fat cells, skeletal muscle, the gut lining, and the reproductive tract.
CB2 receptors: the immune side
CB2 shows up mostly on immune cells: microglia in the brain, macrophages, B cells, T cells, and natural killer cells. Tissue concentration is high in the spleen, tonsils, thymus, and lymph nodes. It also appears in the gut, bone, skin, liver, kidneys, and pancreas. In healthy brain tissue CB2 levels are low, but they climb during injury or inflammation.
Peripheral tissues where both show up
- Skin: keratinocytes, sebaceous glands, hair follicles, and sensory nerve endings.
- Gut: enteric neurons and the myenteric plexus, which help control motility.
- Bone: osteoblasts and osteoclasts, the cells that balance bone building and breakdown.
- Reproductive system: testes, sperm, uterus, and ovaries.
- Metabolic tissue: liver, pancreas, and adipose.
- Eye and heart: retina, myocardium, and blood vessels.
The enzymes travel with the receptors
FAAH and MAGL work inside cells, not on the surface. FAAH breaks down anandamide. MAGL breaks down 2-AG. They sit in the same tissues as CB1 and CB2, often in the postsynaptic cell right beside the receptor. That placement keeps endocannabinoid signals short and local, which is a big part of why researchers describe the system as working "on demand."
Why location matters if you use cannabis
THC binds CB1 and CB2 directly. CBD interacts more loosely with those receptors and also touches other targets such as TRPV1, GPR55, and PPARs. Because the endocannabinoid system is everywhere, cannabis can nudge many systems at once. That is also why side effects can show up far from wherever you feel the main effect. Location is not destiny, but it explains a lot.