What the CB1 receptor is
The CB1 receptor is a protein on the surface of cells. It is coded by the CNR1 gene on chromosome 6. CB1 belongs to the G protein-coupled receptor family. The endocannabinoids anandamide and 2-AG bind CB1. THC, the main psychoactive compound in cannabis, binds CB1 as a partial agonist. CBD binds CB1 with low affinity and acts as a negative allosteric modulator in lab assays.
Where CB1 receptors are found
CB1 shows the highest density in the central nervous system. Regions with high levels include the cerebral cortex, hippocampus, basal ganglia, cerebellum, and amygdala. The hippocampus and basal ganglia rank among the densest sites in the brain.
Peripheral tissues with CB1 include liver, adipose tissue, skeletal muscle, pancreas, gut, skin, and peripheral nerve endings. Brainstem regions that control breathing hold few CB1 receptors. That low count is one reason THC does not stop respiration at doses that cause intoxication.
CB1 and CB2 Receptors: Locations, Ligands, and CBD Binding
How CB1 signaling works
CB1 couples to Gi/o proteins. Activation lowers cAMP by inhibiting adenylyl cyclase. It also closes voltage-gated calcium channels and opens GIRK potassium channels.
Most CB1 receptors sit on presynaptic terminals. The postsynaptic neuron releases endocannabinoids, which travel backward and bind CB1 on the terminal. This suppresses release of neurotransmitters such as GABA and glutamate. The process is called retrograde signaling.
CB1 and THC
THC affinity at human CB1 falls in the low nanomolar range, about 5 nM to 80 nM depending on the assay. Binding triggers the Gi/o cascade and produces the psychoactive effects linked to cannabis.
CB1 and CBD
CBD affinity at CB1 is much lower, in the low micromolar range. Reports place the Ki near 1 µM to 5 µM. That gap is about 100-fold or more compared with THC.
At low micromolar concentrations CBD behaves as a negative allosteric modulator at CB1. It changes the receptor response to THC and to endocannabinoids. CBD also inhibits the enzyme FAAH in vitro, which slows breakdown of anandamide. These results come from cell and animal studies. The human relevance is not settled.
Drugs that target CB1
Rimonabant (SR141716A) is a CB1 inverse agonist. The European Medicines Agency approved it in 2006 for obesity. It was withdrawn in 2008 after reports of psychiatric side effects, including depression and anxiety. Other CB1 inverse agonists, such as taranabant, stopped in trials for similar reasons.
What this means for CBD buyers
CBD does not activate CB1 in a way that causes intoxication. Full-spectrum hemp products may contain THC, which does. US law caps hemp at 0.3% THC by dry weight. A label lists total THC and the batch test result. Urine drug screens detect THC metabolites, and repeated use of full-spectrum products can lead to a positive result. Blood levels vary by dose, body weight, and product.