JWH-018 is a full agonist synthetic cannabinoid with a high binding affinity to CB1 and CB2 cannabinoid receptors. JWH-018 has not been used in therapy. Many of the risks linked to cannabis use are also present in the case of JWH-018, among them complications in patients suffering from cardiovascular diseases and triggering of acute psychosis. JWH-018 has not been used in therapy. Studies in mice showed anti-inflammatory and cancer chemopreventive properties of JWH-018.

PB-22, a recreational “designer drugs”, is a cannabimimetic agent, it is a full agonist of cannabinoid receptors. PB-22 has an EC50 of 5.1 nM for human CB1 receptors, and 37 nM for human CB2 receptors. PB-22 produces bradycardia and hypothermia in rats at doses of 0.3–3 mg/kg, suggesting potent cannabinoid-like activity. PB-22 was designated as a Schedule I controlled substance in the United States.

Tribufos is an organophosphate defoliant used for cotton crops. It is specifically used to defoliate cotton in preparation for machine harvesting. Tribufos inhibits CB1 in vivo, without cholinergic poisoning signs, by 50% at 50 mg/kg intraperitoneally with a recovery half-time of 3-4 days, indicating covalent derivatization.

Yangonin is a natural kavalactone found in the kava plant. Yangonin has been shown to possess binding affinity for the cannabinoid receptor CB1, where it behaves as an agonist. Yangonin also inhibits anchorage-dependent and independent growth of bladder cancer cell lines through induction of autophagic cell death. Yangonin displays marked in vitro toxicity on human hepatocytes with approximately 40% reduction in viability based on an ethidium bromide assay and FDA advises against the use of kava in food due to the potential risk of severe liver damage.

CE-178,253 benzenesulfonate is a CB1 antagonist discovered by Pfizer medicinal chemists. In vitro, CE-178,253 exhibits sub-nanomolar potency at human CB1 receptors in both binding (Ki = 0.33 nM) and functional assays (Ki = 0.07 nM). CE-178,253 has low affinity (Ki > 10,000 nM) for human CB2 receptors. In vivo, CE-178,253 exhibits concentration-dependent anorectic activity in both fast-induced re-feeding and spontaneous nocturnal feeding FI models. In two preclinical models of obesity, CE-178,253 dose-dependently promotes weight loss in diet-induced obese rats and mice.