THC and CBD act on different targets. THC binds CB1 and CB2 receptors as a partial agonist. CBD binds those two receptors with weak affinity and does most of its work at other proteins.
what makes cb2 receptors an anti inflammatory target
Short answer
Different receptors, and a different mechanism at the shared ones. THC is a partial agonist at CB1 and CB2. CBD shows Ki values near 3 to 5 micromolar at both receptors, versus 5 to 40 nanomolar for THC at CB1 in binding assays. At CB1, CBD acts as a negative allosteric modulator: it binds a site apart from the THC site and lowers the response THC produces.
THC: CB1 and CB2, plus other targets
CB1 sits in the brain and central nervous system, with smaller pools in liver, fat tissue, and peripheral nerves. CB2 sits on immune cells. THC activates both. CB1 activation produces the high, the change in time perception, the appetite increase, and the rise in heart rate. THC also acts as an antagonist at GPR55 and shows activity at PPAR-gamma and TRPV1 at higher concentrations.
CBD: weak at CB1 and CB2
CBD binds CB1 and CB2 with Ki values near 3 to 5 micromolar in standard radioligand assays. That number sits about 100 to 1,000 times above the THC affinity. At common product doses CBD does not outcompete THC at the receptor. Cell studies show negative allosteric modulation at CB1 at low micromolar concentrations. At 10 micromolar and above, CBD can act as an antagonist at CB1 and CB2. Human data on CBD blunting the THC high is mixed.
cannabinoid receptor agonists and antagonists
Other targets for CBD
- 5-HT1A: agonist. Animal models link this to reduced anxiety and reduced nausea.
- TRPV1: agonist. This vanilloid receptor also responds to capsaicin and heat.
- GPR55: antagonist. GPR55 is called a third cannabinoid receptor in some papers.
- PPAR-gamma: agonist. This nuclear receptor sits in inflammation and metabolism paths.
- Adenosine A2A: indirect effect. CBD blocks the ENT1 transporter, which raises adenosine in tissue.
- FAAH: weak inhibition. FAAH breaks down anandamide, so slower breakdown raises anandamide levels.
Enzymes and drug interactions
CBD inhibits CYP3A4, CYP2C19, and CYP2D6. THC inhibits the same enzymes with less potency. These enzymes clear clobazam, warfarin, and tacrolimus. The FDA label for Epidiolex, a purified CBD drug, lists these interactions. Receptor data from a dish does not set a human dose.
What this means for ratio labels
A 1:1 gummy states milligrams of THC and milligrams of CBD. It does not state receptor occupancy. Inhaled THC reaches the brain in seconds to minutes. Oral THC and oral CBD peak in blood at 1 to 3 hours. CBD oral bioavailability runs near 6 percent in most studies. Product form changes exposure, not receptor target.
Claims with no human data
No human study measures CBD blocking CB1 in the brain at store doses of 10 to 50 mg. The negative allosteric data comes from cell assays. Whether a 25 mg dose changes THC binding in a person is not established.