Description
Why BCP as a selective CB2 full agonist
- β-Caryophyllene (BCP) is a widely occuring terpene in nature
- BCP is a full agonist with good affinity at CB2 (Ki = 155 nM) [x]
- The CB2 full agonists, BCP and JWH-133, are significantly more efficacious than the partial agonist, GW-405833. For example, the full agonists are neuroprotective in ischemia, while the partial agonist is not, despite GW-405833 having very high affinity at CB2 (Ki = 3.6 nM); showing the importance of choosing a CB2 full agonist [x, x, x, x]
- BCP has negligible affinity at CB1 (Ki = 10 000 nM), avoiding undesirable effects associated with CB1 [x]
- For comparison, THC has good affinity at CB1 (Ki = 40.7 nM) [x]
- BCP has a 2.24 hr half-life in mice [x]
CB2 β-arrestin 2 pathway upregulates 5-HT2A, but not CB1
- The CB1/2 agonist, CP-55940, upregulates 5-HT2A and a CB2 antagonist (AM-630) blocks the upregulation, while a CB1 antagonist (PF-514273) doesn’t; showing that CB2 can upregulate 5-HT2A and CB1 cannot [x]
- The β-arrestin 2 > ERK1/2 > AP-1 + 5-HT2A promoter pathway upregulates 5-HT2A [x, x]
