The endocannabinoid system in one paragraph
The endocannabinoid system (ECS) is a signaling network. It has three parts: endocannabinoids, receptors, and enzymes. Endocannabinoids are lipid molecules the body makes. They bind two receptors, CB1 and CB2. Enzymes break them down after use. The system runs in the brain, spinal cord, organs, and immune tissue. It adjusts appetite, pain, mood, memory, sleep, and immune response.
how does thc affect the endocannabinoid system
Receptors: CB1 and CB2
CB1 was cloned in 1990 by Lisa Matsuda and coworkers at the National Institute of Mental Health. It ranks among the most abundant receptors in the brain. Density is high in the cortex, hippocampus, cerebellum, and basal ganglia. CB2 was cloned in 1993. It sits in large part on immune cells, including microglia. THC, the main psychoactive compound in cannabis, binds both receptors. THC acts as a partial agonist at CB1.
Human Endocannabinoid System Location: A Comprehensive Guide
Endocannabinoids: anandamide and 2-AG
Anandamide, or AEA, was found in 1992 by Raphael Mechoulam, William Devane, and colleagues. The name comes from the Sanskrit word ananda. 2-Arachidonoylglycerol, or 2-AG, was identified in the mid-1990s. Levels of 2-AG in the brain are higher than levels of anandamide. Anandamide is a partial agonist at CB1. 2-AG is a full agonist.
Endocannabinoids differ from most neurotransmitters. They are not stored in vesicles. Neurons make them on demand. They travel backward from the postsynaptic cell to the presynaptic cell and bind CB1 there. That backward signal is called retrograde transmission.
Enzymes: FAAH and MAGL
FAAH breaks down anandamide. MAGL breaks down 2-AG. These enzymes keep endocannabinoid signals short. A signal lasts seconds to minutes in most cases.
What it does in the body
- Appetite and energy balance
- Pain signaling
- Mood and stress response
- Memory and learning
- Sleep
- Immune and inflammatory response
Where cannabis fits
Plant compounds called phytocannabinoids interact with the ECS at different points. THC binds CB1 and CB2. CBD binds CB1 with low affinity. CBD works through other targets, including serotonin 5-HT1A receptors and the enzyme FAAH. The FDA has approved three cannabis-related drugs: Epidiolex (cannabidiol) for two seizure types, dronabinol (Marinol) for chemotherapy-induced nausea and AIDS-related weight loss, and nabilone (Cesamet) for chemotherapy-induced nausea.
What is not settled
Researchers do not know the full role of the ECS in several conditions. Clinical evidence for most cannabis uses is limited. Dosing, long-term effects, and interactions with other drugs remain under study.