JWH-081 is an analgesic chemical from the naphthoylindole family, which acts as a cannabinoid agonist at both the CB1 and CB2 receptors. With a Ki of 1.2nM it is fairly selective for the CB1 subtype, its affinity at this subtype is measured at approximately 10x the affinity at CB2(12.4nM). It was discovered by and named after John W. Huffman.
JWH-203 (1-pentyl-3-(2-chlorophenylacetyl)indole) is an analgesic chemical from the phenylacetylindole family that acts as a cannabinoid agonist with approximately equal affinity at both the CB1 and CB2 receptors, having a Ki of 8.0 nM at CB1 and 7.0 nM at CB2. It was originally discovered by, and named after, John W. Huffman, but has subsequently been sold without his permission as an ingredient of synthetic cannabis smoking blends. Similar to the related 2'-methoxy compound JWH-250, the 2'-bromo compound JWH-249, and the 2'-methyl compound JWH-251, JWH-203 has a phenylacetyl group in place of the naphthoyl ring used in most aminoalkylindole cannabinoid compounds, and has the strongest in vitro binding affinity for the cannabinoid receptors of any compound in the phenylacetyl group.
JWH-210 is an analgesic chemical from the naphthoylindole family, which acts as a potent cannabinoid agonist at both the CB1 and CB2 receptors, with Ki values of 0.46 nM at CB1 and 0.69 nM at CB2. It is one of the most potent 4-substituted naphthoyl derivatives in the naphthoylindole series, having a higher binding affinity (i.e. lower Ki) at CB1 than both its 4-methyl and 4-n-propyl homologues JWH-122 (CB1 Ki 0.69 nM) and JWH-182 (CB1 Ki 0.65 nM) respectively, and than the 4-methoxy compound JWH-081 (CB1 Ki 1.2 nM). It was discovered by and named after John W. Huffman.
JWH-122 is a synthetic cannabimimetic that was discovered by John W. Huffman. It is a methylated analogue of JWH-018. It has a Ki of 0.69 nM at CB1 and 1.2 nM at CB2.
JWH-019 is an analgesic chemical from the naphthoylindole family that acts as a cannabinoid agonist at both the CB1 and CB2 receptors. It is the N-hexyl homolog of the more common synthetic cannabinoid compound JWH-018. Unlike the butyl homolog JWH-073, which is several times weaker than JWH-018, the hexyl homolog is only slightly less potent, although extending the chain one carbon longer to the heptyl homolog JWH-020 results in dramatic loss of activity. These results show that the optimum side chain length for CB1 binding in the naphthoylindole series is the five-carbon pentyl chain, shorter than in the classical cannabinoids where a seven-carbon heptyl chain produces the most potent compounds. This difference is thought to reflect a slightly different binding conformation adopted by the naphthoylindole compounds as compared to the classical cannabinoids, and may be useful in characterizing the active site of the CB1 and CB2 receptors.
RCS-4, or 1-pentyl-3-(4-methoxybenzoyl)indole, is a synthetic cannabinoid drug sold under the names SR-19, BTM-4, or Eric-4, but originally, OBT-199.
MDA-19 (also known as BZO-HEXOXIZID) is a drug that acts as a potent and selective agonist for the cannabinoid receptor CB2, with reasonable selectivity over the psychoactive CB1 receptor, though with some variation between species. In animal studies it was effective for the treatment of neuropathic pain, but did not effect rat locomotor activity in that specific study. The pharmacology of MDA-19 in rat cannabinoid receptors have been demonstrated to function differently than human cannabinoid receptors with MDA-19 binding to human CB1 receptors 6.9× higher than rat CB1 receptors.
APINACA (AKB48, N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide) is a drug that acts as a reasonably potent agonist for the cannabinoid receptors. It is a full agonist at CB1 with an EC50 of 142 nM and Ki of 3.24 nM (compared to the Ki of Δ9-THC at 28.35 nM and JWH-018 at 9.62 nM), while at CB2 it acts as a partial agonist with an EC50 of 141 nM and Ki of 1.68 nM (compared to the Ki of Δ9-THC at 37.82 nM and JWH-018 at 8.55 nM). Its pharmacological characterization has also been reported in a discontinued patent application. It had never previously been reported in the scientific or patent literature, and was first identified by laboratories in Japan in March 2012 as an ingredient in synthetic cannabis smoking blends, along with a related compound APICA. Structurally, it closely resembles cannabinoid compounds from a University of Connecticut patent, but with a simple pentyl chain on the indazole 1-position, and APINACA falls within the claims of this patent despite not being disclosed as an example.
AB-FUBINACA (AMB-FUBINACA) is a psychoactive drug that acts as a potent agonist for the cannabinoid receptors, with Ki values of 0.9 nM at CB1 and 23.2 nM at CB2 and EC50 values of 1.8 nM at CB1 and 3.2 nM at CB2. It was originally developed by Pfizer in 2009 as an analgesic medication but was never pursued for human use. In 2012, it was discovered as an ingredient in synthetic cannabinoid blends in Japan, along with a related compound AB-PINACA, which had not previously been reported.
AB-PINACA is a compound that was first identified as a component of synthetic cannabis products in Japan in 2012.
5F-PB-22 is a designer drug which acts as a cannabinoid agonist. The structure of 5F-PB-22 appears to have been designed with an understanding of structure–activity relationships within the indole class of cannabinoids.
AB-CHMINACA is an indazole-based synthetic cannabinoid. It is a potent agonist of the CB1 receptor (Ki = 0.78 nM) and CB2 receptor (Ki = 0.45 nM) and fully substitutes for Δ9-THC in rat discrimination studies, while being 16x more potent. Continuing the trend seen in other cannabinoids of this generation, such as AB-FUBINACA and AB-PINACA, it contains a valine amino acid amide residue as part of its structure, where older cannabinoids contained a naphthyl or adamantane residue.
ADB-PINACA is a cannabinoid designer drug that is an ingredient in some synthetic cannabis products. It is a potent agonist of the CB1 receptor and CB2 receptor with EC50 values of 0.52 nM and 0.88 nM respectively. Like MDMB-FUBINACA, this compound incorporates the unnatural amino acid tert-leucine.
5F-APINACA is an indazole-based synthetic cannabinoid that has been sold online as a designer drug. Structurally it closely resembles cannabinoid compounds from patent WO 2003/035005 but with a 5-fluoropentyl chain on the indazole 1-position, and 5F-APINACA falls within the claims of this patent, as despite not being disclosed as an example, it is very similar to the corresponding pentanenitrile and 4-chlorobutyl compounds which are claimed as examples 3 and 4.
CUMYL-THPINACA (also known as SGT-42) is an indazole-3-carboxamide based synthetic cannabinoid. CUMYL-THPINACA acts as a potent agonist for the cannabinoid receptors, with approximately 6x selectivity for CB1, having an EC50 of 0.1nM for human CB1 receptors and 0.59nM for human CB2 receptors.
MDMB-FUBINACA (also known as MDMB(N)-Bz-F and FUB-MDMB) is an indazole-based synthetic cannabinoid that is a potent agonist for the cannabinoid receptors, with Ki values of 1.14 nM at CB1 and 0.1228 nM at CB2 and EC50 values of 0.2668 nM at CB1 and 0.1411 nM at CB2, and has been sold online as a designer drug. Its benzyl analogue (instead of 4-fluorobenzyl) has been reported to be a potent agonist for the CB1 receptor (Ki = 0.14 nM, EC50 = 2.42 nM). The structure of MDMB-FUBINACA contains the amino acid, 3-methylvaline or tert-leucine methyl ester.
PX-2 is an indazole-based synthetic cannabinoid that has been sold online as a designer drug. It contains a phenylalanine amino acid amide as part of its structure.
5F-ADBICA (also known as 5F-ADB-PICA) is an indole-based synthetic cannabinoid that is a potent agonist at CB1 receptors and CB2 receptors with EC50 values of 0.77 nM and 1.2 nM respectively.
FUB-PB-22 (QUFUBIC) is an indole-based synthetic cannabinoid that is a potent agonist of the CB1 receptor and has been sold online as a designer drug.
ADB-FUBIATA (AD-18, FUB-ACADB, ADB-FUBIACA) is a synthetic cannabinoid compound first identified in 2021. It is closely related in structure to the older compound ADB-FUBICA but with the amide linker group extended by the addition of a methylene bridge. It started to be sold as an ingedient in grey-market synthetic cannabis blends following the introduction of legislation in China which for the first time introduced general controls on various classes of synthetic cannabinoids, but did not encompass compounds where the linker group had been extended in this fashion. ADB-FUBIATA has many times lower affinity for cannabinoid receptors than ADB-FUBICA with an EC50 of only 635 nM at CB1, but retains full agonist activity at this target, while being practically inactive at CB2.
