Find the key
Game · the docking lab
▶ Play this chapter The script
Every line as it is spoken in the film, in order.
This is the lock. It's called CB1, and it sits in the wall of your brain cells. Drag THC into it.
Grab THC from the tray and drop it into the glowing pocket.
Click. That's cannabis. THC turns this lock part of the way, and the cell feels it.
Now the part that took scientists four years. Find the key your body makes.
Caffeine? Wrong lock. It works on a different receptor entirely.
Serotonin has its own locks. Not this one.
CBD, the other famous cannabis molecule. Surprise. It barely touches this lock.
That's THC again. Find the one your body makes.
Try the names you don't recognize.
That's yours. Anandamide. Your cells make it on demand. Its name comes from the Sanskrit word for bliss.
There's a second key of yours in that tray. Find it.
2-AG. Your brain makes far more of it than anandamide, and it turns the lock all the way.
Those are the keys your body was using long before anyone ever smoked anything. Now play. Try the blocker. Try the enzymes.
Rimonabant. A blocker. It jams the lock and turns it down below idle. Remember that name.
FAAH. It cuts anandamide in two. That's why your own keys only last moments.
MAGL. It takes 2-AG apart.
Your enzymes can't cut THC. Your liver has to clear it. That's one reason a high lasts hours, not moments.
Sources
Every claim in this chapter with its grade: E established · M emerging (one or two studies, or animals only) · F framework.
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- ECravatt BF et al. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 1996;384:83–7. (FAAH) link
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- EStructures: CB1–Gi from PDB 6N4B (Krishna Kumar et al. 2019); FAAH from PDB 1MT5 (Bracey et al. 2002); MAGL from PDB 3HJU (Labar et al. 2010). Ligand placement in CB1 is schematic (shape-matched to the co-crystallised agonist), not a computed binding pose. link
- EPertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-THC, cannabidiol and Δ9-THCV. Br J Pharmacol 2008;153:199–215. (THC is a CB1 partial agonist) link
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- ESugiura T et al. Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. J Biol Chem 1999;274:2794–801. (2-AG gives the largest response; anandamide acts as a partial agonist) link
- EThomas A et al. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol 2007;150:613–23. (CBD has low affinity for CB1) link
- MLeweke FM et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry 2012;2:e94. (double-blind trial against amisulpride in acute schizophrenia: CBD raised serum anandamide, and the rise was associated with clinical improvement; CBD moderately inhibits anandamide breakdown) link
- EUniProt P21554 · CNR1_HUMAN, cannabinoid receptor 1: a canonical sequence of 472 amino acids, with seven transmembrane helices. link