Cannabinol - Wikipedia

Naturally-occurring cannabinoid Not to be confused with cannabidiol or cannabinodiol. Cannabinol

Legal status
Legal status	CA: Unscheduled UK: Class B US: Unscheduled
Identifiers
IUPAC name 6,6,9-Trimethyl-3-pentyl-benzo[c]chromen-1-ol
CAS Number	521-35-7 N
PubChem CID	2543
IUPHAR/BPS	740
ChemSpider	2447 Y
UNII	7UYP6MC9GH
KEGG	C07580 Y
ChEMBL	ChEMBL74415 Y
CompTox Dashboard (EPA)	DTXSID3048996
ECHA InfoCard	100.216.772
Chemical and physical data
Formula	C21H26O2
Molar mass	310.437 g·mol−1
3D model (JSmol)	Interactive image
Melting point	76–77 °C (169–171 °F) [1]
Solubility in water	Insoluble in water,[2] soluble in methanol[3] and ethanol[4] mg/mL (20 °C)
SMILES Oc2cc(cc1OC(c3c(c12)cc(cc3)C)(C)C)CCCCC
InChI InChI=1S/C21H26O2/c1-5-6-7-8-15-12-18(22)20-16-11-14(2)9-10-17(16)21(3,4)23-19(20)13-15/h9-13,22H,5-8H2,1-4H3 Y Key:VBGLYOIFKLUMQG-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Cannabinol (CBN) is a mildly psychoactive phytocannabinoid that acts as a low affinity partial agonist at both CB1 and CB2 receptors. This activity at CB1 and CB2 receptors constitutes interaction of CBN with the endocannabinoid system (ECS).

Although CBN shares the same mechanism of action as other phytocannabinoids (e.g., Delta-9-tetrahydrocannabinol, Δ9-THC), it has a lower affinity for CB1 receptors, meaning that much higher doses of CBN are required in order to experience effects, such as mild sedation.

It was the first cannabinoid to be isolated from cannabis and was discovered in 1896.

Pharmacology

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Pharmacodynamics

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Both THC and CBN activate the CB1 (Ki = 211.2 nM) and CB2 (Ki = 126.4 nM) receptors.[5] Each compound acts as a low affinity partial agonist at CB1 receptors with THC demonstrating 5x–10× greater affinity to the CB1 receptor.[5][6][7][8][9][10] Like THC, CBN has a higher selectivity for CB2 receptors[5][8] which are located throughout the central and peripheral nervous system, but are primarily associated with immune function. CB2 receptors are known to be located on immune cells throughout the body, including macrophages, T cells, and B cells. These immune cells have been shown to decrease production of immune-related chemical signals (e.g., cytokines) or undergo apoptosis as a consequence of CB2 agonism by CBN.[11] In cell culture, CBN demonstrates antimicrobial effects, particularly in instances of antibiotic-resistant bacteria.[12] CBN has also been reported to act as an ANKTM1 channel agonist at high concentrations (>20nM).[6] While some phytocannabinoids have been shown to interact with nociceptive and immune-related signaling via transient receptor potential channels (e.g., TRPV1 and TRPM8), there is currently limited evidence to suggest that CBN acts in this way.[6][13] In preclinical rodent studies, CBN, anandamide and other CB1 agonists have demonstrated inhibitory effects on GI motility, reversible via CB1R blockade (i.e., antagonism).[6]

In considering the efficacy of cannabis-based products, there remains controversy surrounding a concept termed “the entourage effect”. This concept describes a widely reported but poorly-understood synergistic effect of certain cannabinoids when phytocannabinoids are coadministered with other naturally-occurring chemical compounds in the cannabis plant (e.g., flavonoids, terpenoids, alkaloids). This entourage effect is often cited to explain the superior efficacy observed in some studies of whole-plant-derived cannabis therapeutics as compared to isolated or synthesized individual cannabis constituents.[14]

Putative receptor targets

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The table highlights several common cannabinoids along with putative receptor targets and therapeutic properties. Exogenous (plant-derived) phytocannabinoids are identified with an asterisk while remaining chemicals represent well-known endocannabinoids (i.e., endogenously produced cannabinoid receptor ligands).

Full Name	Known Receptor Targets	Putative Therapeutic Properties
Cannabichromene (CBC)	Agonist at CB2,[15] TRPV3, and most potent phytocannabinoid at TRPA1[15][13] Very low efficacy at TRPV1 and TRPV4, but may reduce expression of TRPV4 in the presence of inflammation[13] High affinity for CB1 but no observed functional activity[15] Antagonist at TRPM8[13]	Antimicrobial and anti-inflammatory[15] Potential neuroprotective effects[15] Potential efficacy in treatment of inflammatory pain[15]
Cannabidiol (CBD)	Very weak affinity for CB1 and CB2[16] Conflicting reports but generally described as negative allosteric modulator at CB1 & CB2, altering THC activity when THC & CBD are coadministered[16] Agonist at TRPA1,[13] TRPV1 (high potency at this “capsaicin receptor” without ablative effects[13]), TRPV2, TRPV3, PPARγ, 5-HT1A, A2 and A1 adenosine receptors[16] Highest potency at TRPV1[13] Antagonist at GPR55, GPR18, 5-HT3A,[16] with highest potency as antagonist at TRPM8[13] Inverse agonist at GPR3, GPR6, and GPR12[16]	Anti-inflammatory[17][13] Anti-convulsant[17] Potential efficacy in treatment of inflammatory and chronic pain[13]
Cannabigerol (CBG)	Low affinity agonist and partial agonist at CB1 and CB2, respectively[15] Agonist at α2adrenoceptor[15] and TRP channels such as TRPA1, TRPV2, and TRPV3, with highest potency as agonist at TRPV1[13] Readily desensitizes but low affinity for TRPV4[13] Antagonist at 5-HT1A[15] and TRPM8[13]	Anti-microbial, anti-inflammatory, and anti-nociceptive effects[15] Neuroprotective properties via mitigation of oxidative stress[15] Potential anti-tumor agent[15] Potential efficacy in treatment of chemotherapy-induced muscle atrophy and weight loss[15]
Cannabinol (CBN)	Agonist at CB1 and CB2, with some evidence of slightly higher affinity at CB2[15] Low affinity agonist at TRPV1, TRPV2, TRPV3, TRPV4, and TRPA1,[13] but readily desensitizes TRPV4[13] Antagonist at TRPM8[13]	Antimicrobial and anti-inflammatory / immunosuppressive effects[15] Potential efficacy in treatment of ocular disease and epidermolysis bullosa[15] Reported neuroprotective effects (synergistic if coadministered with other cannabinoids)[15] Relevance to pain, itch, and inflammation via TRP channel activity[15]
Tetrahydrocannabinol (THC) / Delta-9-Tetrahydrocannabinol (Δ9-THC)	Agonist at CB1 and CB2, as well as GPR55, GPR18, PPARγ, and TRPA1[13][16] Antagonist at TRPM8[13][16] and 5-HT3A[16] Differing activity across TRP channels: highest potency phytocannabinoid at TRPV2; modest activity at TRPV3, TRPV4, TRPA1, and TRPM8; no activity observed at TRPV1[13] Importantly, 11-OH-THC, the active metabolite generated via first-pass-metabolism of THC, demonstrates different binding profile at TRP channels[13]	Potential relevance to sleep induction (e.g., increased adenosine levels[16]) and increased quality of sleep[13] Dose-dependent anxiolytic effects,[13] with anxiogenic effects at high doses Appetite stimulation[13][14] Anti-nausea[13][14] In combination with CBD, potential efficacy in treatment of spasticity, neuropathic pain and muscle spasticity (see Sativex: THC-containing therapeutic approved in Europe as treatment for Multiple Sclerosis)
2-Arachidonoylglycerol (2-AG)	Partial agonist at CB1 (e.g., on lysosomal surface, increasing lysosomal integrity) and CB2[16] Agonist at GPR55, GPR18, GPR119, PPAR, and robust activation at TRPV4[13][16]	Anti-oxidative properties[16] Increased lysosomal stability & integrity[16] Attenuation of mitochondrial damage during cell stress[16]
Anandamide (AEA)	Agonist at GPR18, GPR119, and PPAR, with robust activation at TRPV4, and very high efficacy at TRPA1[13][16] Potent partial agonist at GPR55[16][14] Low-affinity full agonist at TRPV1,[13][14] with similar but less potent affinity as compared to capsaicin[13] Antagonist at TRPM8[13]	Anti-oxidative properties[16]

Neurotransmitter interactions

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In the brain, the canonical mechanism of CB1 receptor activation is a form of short-term synaptic plasticity initiated via retrograde signaling of endogenous CB1 agonists such as 2AG or AEA (two primary endocannabinoids). This mechanism of action is called depolarization-induced suppression of inhibition (DSI) or depolarization-induced suppression of excitation (DSE),[18] depending on the classification of the presynaptic neuron acted upon by the retrograde messenger (see diagram at left). In the case of CB1R agonism on the presynaptic membrane of a GABAergic interneuron, activation leads to a net effect of increased activity, while the same activity on a glutamatergic neuron leads to the opposite net effect. The release of other neurotransmitters is also modulated in this way, particularly dopamine, dynorphin, oxytocin, and vasopressin.[18]

Pharmacokinetics

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When administered orally, CBN demonstrates a similar metabolism to Δ9-THC, with the primary active metabolite produced through the hydrolyzation of C9 as part of first-pass metabolism in the liver. The active metabolite generated via this process is called 11-OH-CBN, which is 2x as potent as CBN, and has demonstrated activity as a weak CB2 antagonist. This metabolism starkly contrasts that of Δ9-THC in terms of potency, given that 11-OH-THC has been reported to have 10× the potency of Δ9-THC.

Due to high lipophilicity and first-pass metabolism, there is low bioavailability of CBN and other cannabinoids following oral administration. CBN metabolism is mediated in part by CYP450 isoforms 2C9 and 3A4. The metabolism of CBN may be catalyzed by UGTs (UDP-glucuronosyltransferases), with a subset of UGT isoforms (1A7, 1A8, 1A9, 1A10, 2B7) identified as potential substrates associated with CBN glucuronidation. The bioavailability of CBN following administration via inhalation (e.g., smoking or vaporizing) is approximately 40% that of intravenous administration.

A small study of six cannabis users found a highly variable half life of 32 ±  17 hours upon intravenous administration.[19] Similar to CBD, CBN is metabolized by the CYP2C9 and CYP3A4 liver enzymes and thus the half-life is sensitive to genetic factors that effect the levels of these enzymes.[20]

Chemistry

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Chemical structure

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Cannabinoid receptor agonists are categorized into four groups based on chemical structure. CBN, as one of the many phytocannabinoids derived from Cannabis Sativa L, is considered a classical cannabinoid. Other examples of compounds in this group include dibenzopyran derivatives such as Δ9-THC, well-known for underlying the subjective "high" experienced by cannabis users, as well as Δ8-THC, and their synthetic analogs. In contrast, endogenously produced cannabinoids (i.e., endocannabinoids), which also exert effects through CB agonism, are considered eicosanoids, distinguished by notable differences in chemical structure.

Compared to Δ9-THC, one additional aromatic ring confers CBN with a slower and more limited metabolic profile (see § CBN Formation & Metabolism). In contrast to THC, CBN has no double bond isomers nor stereoisomers. CBN can degrade into HU-345 from oxidation. In the case of oral administration of CBN, first-pass metabolism in the liver involves the addition of a hydroxyl group at C9 or C11, increasing the affinity and specificity of CBN for both CB1 and CB2 receptors (see 11-OH-CBN).

History

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CBN was the first cannabinoid to be isolated from cannabis extract in the late 1800s. Specifically, it was discovered by Barlow Wood, Newton Spivey, and Easterfield in 1896.[21] In the early 1930s, CBN's structure was identified by Cahn,[22][23] marking the first development of a cannabis extract. Its structure and chemical synthesis were achieved by 1940, followed by some of the first preclinical research studies to determine the effects of individual cannabis-derived compounds in vivo.[8]

Society and culture

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Legal status

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CBN is not listed in the schedules set out by the United Nations' Single Convention on Narcotic Drugs from 1961 nor their Convention on Psychotropic Substances from 1971,[24] so the signatory countries to these international drug control treaties are not required by these treaties to control CBN.

United States

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According to the 2018 Farm Bill,[25] extracts from the Cannabis sativa L. plant, including CBN, are legal under US federal law as long as they have a delta-9 Tetrahydrocannabinol (THC) concentration of 0.3% or less.[26][27]

Biosynthesis

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This diagram represents the biosynthetic and metabolic pathways by which phytocannabinoids (e.g., CBD, THC, CBN) are created in the cannabis plant. Starting with CBG-A, the acidic forms of certain phytocannabinoids are generated via enzymatic conversion. From there, decarboxylation (i.e., catalyzed by combustion or heat) yields the most well-known metabolites present in the cannabis plant. CBN is unique in that it does not arise from a pre-existing acidic form, but rather is generated through the oxidation of THC.

CBN is unique among phytocannabinoids in that its biosynthetic pathway involves conversion directly from Δ9-THC, rather than from an acidic precursor form of CBN (e.g., Δ9-THC arises through decarboxylation of THC-A). CBN can be found in trace amounts in the Cannabis plant, found mostly in cannabis that is aged and stored, allowing for CBN formation through the oxidation of the cannabis plant's main psychoactive and intoxicating chemical, tetrahydrocannabinol (THC). This process of oxidation occurs via exposure to heat, oxygen, and/or light. Although reports are limited, CBN-A has also been measured at very low levels in the cannabis plant, thought to have formed via hydrolyzation of THC-A (see Phytocannabinoid Biosynthesis diagram, below).

References

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1. ^ Cannabinol from PubChem
2. ^ Lide DR (2012). CRC Handbook of Chemistry and Physics. CRC Press. pp. 3–90. ISBN 978-1-43988049-4.
3. ^ "Cannabinol solution, analytical standard, for drug analysis". Sigma-Aldrich. c046.
4. ^ "Cannabinol" (PDF). Biotrend. Archived from the original (PDF) on May 22, 2016.
5. ^ a b c Rhee MH, Vogel Z, Barg J, Bayewitch M, Levy R, Hanus L, et al. (September 1997). "Cannabinol derivatives: binding to cannabinoid receptors and inhibition of adenylylcyclase". Journal of Medicinal Chemistry. 40 (20): 3228–3233. doi:10.1021/jm970126f. PMID 9379442.
6. ^ a b c d Abood ME, Pertwee RG (2005). Cannabinoids. Berlin: Springer. ISBN 3-540-22565-X. OCLC 65169431.
7. ^ Corroon J (October 2021). "Cannabinol and Sleep: Separating Fact from Fiction". Cannabis and Cannabinoid Research. 6 (5): 366–371. doi:10.1089/can.2021.0006. PMC 8612407. PMID 34468204.
8. ^ a b c Pertwee RG (January 2006). "Cannabinoid pharmacology: the first 66 years". British Journal of Pharmacology. 147 (Suppl 1): S163–S171. doi:10.1038/sj.bjp.0706406. PMC 1760722. PMID 16402100.
9. ^ Andre CM, Hausman JF, Guerriero G (February 4, 2016). "Cannabis sativa: The Plant of the Thousand and One Molecules". Frontiers in Plant Science. 7: 19. doi:10.3389/fpls.2016.00019. PMC 4740396. PMID 26870049.
10. ^ Aizpurua-Olaizola O, Elezgarai I, Rico-Barrio I, Zarandona I, Etxebarria N, Usobiaga A (January 2017). "Targeting the endocannabinoid system: future therapeutic strategies". Drug Discovery Today. 22 (1): 105–110. doi:10.1016/j.drudis.2016.08.005. PMID 27554802. S2CID 3460960.
11. ^ "Cannabinol (Code C84510)". NCI Thesaurus. National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services.
12. ^ Pattnaik F, Nanda S, Mohanty S, Dalai AK, Kumar V, Ponnusamy SK, et al. (February 2022). "Cannabis: Chemistry, extraction and therapeutic applications". Chemosphere. 289: 133012. Bibcode:2022Chmsp.28933012P. doi:10.1016/j.chemosphere.2021.133012. PMID 34838836. S2CID 244679123.
13. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac Muller C, Morales P, Reggio PH (January 15, 2019). "Cannabinoid Ligands Targeting TRP Channels". Frontiers in Molecular Neuroscience. 11: 487. doi:10.3389/fnmol.2018.00487. PMC 6340993. PMID 30697147.
14. ^ a b c d e Legare CA, Raup-Konsavage WM, Vrana KE (2022). "Therapeutic Potential of Cannabis, Cannabidiol, and Cannabinoid-Based Pharmaceuticals". Pharmacology. 107 (3–4): 131–149. doi:10.1159/000521683. PMID 35093949.
15. ^ a b c d e f g h i j k l m n o p q r Sampson PB (January 2021). "Phytocannabinoid Pharmacology: Medicinal Properties of Cannabis sativa Constituents Aside from the "Big Two"". Journal of Natural Products. 84 (1): 142–160. doi:10.1021/acs.jnatprod.0c00965. PMID 33356248. S2CID 229694293.
16. ^ a b c d e f g h i j k l m n o p q Cherkasova V, Wang B, Gerasymchuk M, Fiselier A, Kovalchuk O, Kovalchuk I (October 2022). "Use of Cannabis and Cannabinoids for Treatment of Cancer". Cancers. 14 (20): 5142. doi:10.3390/cancers14205142. PMC 9600568. PMID 36291926.
17. ^ a b Mead A (June 14, 2019). "Legal and Regulatory Issues Governing Cannabis and Cannabis-Derived Products in the United States". Frontiers in Plant Science. 10: 697. doi:10.3389/fpls.2019.00697. PMC 6590107. PMID 31263468.
18. ^ a b Diana MA, Marty A (May 2004). "Endocannabinoid-mediated short-term synaptic plasticity: depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE)". British Journal of Pharmacology. 142 (1): 9–19. doi:10.1038/sj.bjp.0705726. PMC 1574919. PMID 15100161.
19. ^ Johansson E, Ohlsson A, Lindgren JE, Agurell S, Gillespie H, Hollister LE (September 1987). "Single-dose kinetics of deuterium-labelled cannabinol in man after intravenous administration and smoking". Biomedical & Environmental Mass Spectrometry. 14 (9): 495–499. doi:10.1002/bms.1200140904. PMID 2960395.
20. ^ Stout SM, Cimino NM (February 2014). "Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review". Drug Metabolism Reviews. 46 (1): 86–95. doi:10.3109/03602532.2013.849268. PMID 24160757. S2CID 29133059.
21. ^ Wood TB, Spivey WN, Easterfield III TH (1899). "III.—Cannabinol. Part I". Journal of the Chemical Society, Transactions. 75: 20–36. doi:10.1039/CT8997500020.
22. ^ Cahn RS (1932). "174. Cannabis indica resin. Part III. The constitution of cannabinol". Journal of the Chemical Society (Resumed): 1342–1353. doi:10.1039/JR9320001342.
23. ^ Pertwee RG (January 2006). "Cannabinoid pharmacology: the first 66 years". British Journal of Pharmacology. 147 (Suppl 1): S163–S171. doi:10.1038/sj.bjp.0706406. PMC 1760722. PMID 16402100.
24. ^ "UN International Drug Control Conventions". United Nations Office on Drugs and Crime. United Nations Commission on Narcotic Drugs. Archived from the original on March 17, 2014. Retrieved February 15, 2017.
25. ^ Office of the Commissioner (October 18, 2021). "FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD)". FDA.
26. ^ Mead A (May 2017). "The legal status of cannabis (marijuana) and cannabidiol (CBD) under U.S. law". Epilepsy & Behavior. 70 (Pt B): 288–291. doi:10.1016/j.yebeh.2016.11.021. PMID 28169144.
27. ^ "Section 1308.11 Schedule I". Code of Federal Regulations. Office of Diversion Control, Drug Enforcement Administration, U.S. Department of Justice. Archived from the original on February 9, 2012.

External links

[edit] Look up cannabinol in Wiktionary, the free dictionary.

• Erowid Compounds found in Cannabis sativa

v t e Cannabinoids
Phytocannabinoids(comparison)	Cannabibutols CBB Cannabichromenes CBC CBCA CBCA-A CBCB CBCBA CBCP CBCPA CBCV CBCVA CBCQ Cannabicyclols CBL CBLA CBLB CBLP CBLPA CBLV CBLVA Cannabidiols CBD CBDA CBD-C1 CBD-C5 CBDB CBDBA CBDD CBDH CBDP CBDPA CBDM CBDMA CBDV CBDVA CBDQ Cannabielsoins CBE CBEA CBEA-A CBEA-B CBEB CBEP CBEPA CBEV Cannabigerols CBG CBGA CBGB CBGBA CBGM CBGAM CBGP CBGPA CBNR CBNRA CBNRA-A CBGV CBGVA CBGVA-A CBGQ Cannabiphorols CBP Cannabinols CBN CBNA CBN-C1 CBN-C2 CBN-C4 CBNM CBND CBNDA CBNP CBNPA CBVD CBVDA Cannabitriols CBT CBTA CBTB CBTV CBTVA CBTP CBTPA Cannabivarins CBV CBVA Delta-8-tetrahydrocannabinols Delta-8-THC Delta-8-THCA Delta-8-THCA-A Delta-8-THCB Delta-8-THCP Delta-8-THCV Delta-9-tetrahydrocannabinols Delta-9-THC (THC) THCA THCMA THCA-A THCA-B THCBA THCA-C4 THCC THCA-C1 THCA-A-C1 THCA-B-C1 THCB THCH THCP THCPA THCV THCVA THCQ Delta-10-Tetrahydrocannabinols Delta-10-THC Miscellaneous cannabinoids Δ8-iso-THC Δ4(8)-iso-THC 7,8-Dihydrocannabinol 8,9-Dihydrocannabidiol CBCF Cannabicitran CBF Cannabiglendol CBM CBR CBRPA Caryophyllene DCBF Alkylamides Epigallocatechin gallate Gallocatechol Hexahydrocannabinol (HHC) Perrottetinene Serinolamide A Yangonin Active metabolites 3'-OH-THC 7-OH-CBD 8,11-DiOH-THC 11-COOH-THC 11-OH-CBN 11-OH-HHC 11-OH-Δ8-THC 11-OH-Δ9-THC
Endocannabinoids	Arachidonoyl ethanolamide (AEA; anandamide) 2-Arachidonoylglycerol (2-AG) 2-Arachidonyl glyceryl ether (2-AGE; noladin ether) 2-Oleoylglycerol (2-OG) N-Arachidonoyl dopamine (NADA) N-Arachidonylglycine (NAGly) 2-Arachidonoyl lysophosphatidylinositol (2-ALPI) N-Arachidonoyl serotonin (AA-5-HT) Docosatetraenoylethanolamide (DEA) Lysophosphatidylinositol (LPI) Oleamide Oleoylethanolamide (OEA) Palmitoylethanolamide (PEA) RVD-Hpα Stearoylethanolamide (SEA) O-Arachidonoyl ethanolamine (O-AEA; virodhamine)
Syntheticcannabinoidreceptoragonists /neocannabinoids	Classical cannabinoids(dibenzopyrans) 1,2-Didehydro-3-oxo-THCO 9-OH-HHC 9-Nor-9β-HHC A-40174 A-41988 A-42574 Ajulemic acid AM-087 AM-411 AM-855 AM-905 AM-906 AM-919 AM-926 AM-938 AM-2389 AM-4030 AM-7438 AM-11245 AMG-1 AMG-3 AMG-36 AMG-41 CP 42,096 Delta-3-THC Delta-4-THC Delta-7-THC Delta-10-THC Dexanabinol (HU-211) DMHP Dronabinol HU-210 HU-243 JWH-051 JWH-056 JWH-057 JWH-065 JWH-091 JWH-102 JWH-103 JWH-124 JWH-130 JWH-133 JWH-138 JWH-139 JWH-142 JWH-143 JWH-161 JWH-186 JWH-187 JWH-188 JWH-189 JWH-190 JWH-191 JWH-215 JWH-216 JWH-217 JWH-224 JWH-225 JWH-226 JWH-227 JWH-229 JWH-230 JWH-233 JWH-247 JWH-254 JWH-256 JWH-277 JWH-278 JWH-298 JWH-299 JWH-300 JWH-301 JWH-310 JWH-336 JWH-338 JWH-339 JWH-340 JWH-341 JWH-349 JWH-350 JWH-352 JWH-353 JWH-354 JWH-355 JWH-356 JWH-357 JWH-358 JWH-359 JWH-360 JWH-361 JWH-362 KM-233 L-759,633 L-759,656 Levonantradol (CP 50,5561) Menabitan Nabazenil Nabidrox (Canbisol) Nabilone Nabitan Naboctate O-224 O-581 O-774 O-806 O-823 O-1057 O-1125 O-1191 O-1238 O-2048 O-2113 O-2365 O-2372 O-2373 O-2383 O-2426 O-2484 O-2545 O-2694 O-2715 O-2716 O-3223 O-3226 Parahexyl Pirnabine SP-111 THC hemisuccinate THC-O-acetate THC-O-phosphate Non-classicalcannabinoids Cannabicyclohexanol Cannabinor CBD-DMH CP 47,497 (C6)-CP 47,497 (C9)-CP 47,497 CP 55,244 CP 55,940 Delta-6-Cannabidiol Etrinabdione HU-320 HU-331 HU-336 HU-345 HU-446 HU-465 HU-910 HUF-101 Nonabine O-1376 O-1422 O-1601 O-1656 O-1657 O-1660 O-1663 O-1871 Onternabez (HU-308) SPA-229 Tinabinol Adamantoylindoles 5F-AKB-48 APICA STS-135 Benzimidazoles AZ-11713908 AZD-1940 BIM-018 FUBIMINA MCHB-1 PF-03550096 RQ-00202730 Benzoylindoles 1-Butyl-3-(2-methoxybenzoyl)indole 1-Butyl-3-(4-methoxybenzoyl)indole 1-Pentyl-3-(2-methoxybenzoyl)indole AM-630 AM-679 AM-694 AM-1241 AM-2233 GW-405,833 (L-768,242) Pravadoline RCS-4 WIN 54,461 Cyclohexylphenols CP-47,947 CP-55,940 Eicosanoids AM-883 AM-1346 ACEA ACPA Methanandamide (AM-356) O-585 O-689 O-1812 O-1860 O-1861 Indazole-3-carboxamides 4F-MDMB-BINACA 4'Cl-CUMYL-PINACA 4'F-CUMYL-5F-PINACA 5Cl-APINACA 5F-ADB 5F-ADB-PINACA 5F-AMB 5F-APINACA 5F-CUMYL-PINACA 5F-EDMB-PINACA 5F-EMB-PINACA AB-CHMINACA AB-FUBINACA AB-FUBINACA 2-fluorobenzyl isomer AB-PINACA ADB-BINACA ADB-BUTINACA ADB-CHMINACA ADB-HEXINACA ADB-FUBINACA ADB-PINACA ADB-4en-PINACA ADB-5'Br-PINACA ADMB-3TMS-PRINACA Adamantyl-THPINACA ADSB-FUB-187 AMB-CHMINACA AMB-FUBINACA APINACA (AKB48) APP-FUBINACA CUMYL-3TMS-PRINACA CUMYL-4CN-BINACA CUMYL-CBMINACA CUMYL-CHSINACA CUMYL-FUBINACA CUMYL-NBMINACA CUMYL-PINACA CUMYL-THPINACA CUMYL-TSINACA EMB-FUBINACA FUB-APINACA MDMB-4en-PINACA MDMB-5Br-INACA MDMB-BINACA MDMB-CHMINACA MDMB-FUBINACA MN-18 PX-2 PX-3 THQ-PINACA Indole-3-carboxamides 4'F-CUMYL-5F-PICA 5F-ADBICA 5F-EDMB-PICA 5F-MDMB-PICA 5F-NNE1 5F-PCN 5F-SDB-006 AB-FUBICA AB-PICA ADBICA ADB-FUBICA APICA BMS-F CUMYL-BICA CUMYL-CBMICA CUMYL-CHMICA CUMYL-NBMICA CUMYL-PICA CUMYL-5F-PICA FDU-NNE1 MDMB-CHMICA MMB-CHMICA MMB-2201 MN-25 (UR-12) NNE1 PX-1 Org 28312 Org 28611 SDB-006 STS-135 Indole-3-carboxylates 5F-PB-22 FDU-PB-22 FUB-PB-22 QUCHIC (BB-22) QUPIC (PB-22) NM-2201 Naphthoylindazoles THJ-018 THJ-2201 Naphthoylindoles 5F-JWH-398 AM-1220 AM-1221 AM-1235 AM-2201 AM-2232 CHM-081 EAM-2201 FUB-JWH-018 JWH-004 JWH-007 JWH-009 JWH-011 JWH-015 JWH-016 JWH-018 JWH-019 JWH-020 JWH-042 JWH-043 JWH-046 JWH-047 JWH-048 JWH-049 JWH-050 JWH-070 JWH-072 JWH-073 JWH-076 JWH-077 JWH-079 JWH-080 JWH-081 JWH-082 JWH-083 JWH-093 JWH-094 JWH-095 JWH-096 JWH-097 JWH-098 JWH-099 JWH-100 JWH-116 JWH-120 JWH-122 JWH-148 JWH-149 JWH-151 JWH-153 JWH-159 JWH-160 JWH-163 JWH-164 JWH-165 JWH-166 JWH-180 JWH-181 JWH-182 JWH-189 JWH-193 JWH-198 JWH-200 JWH-210 JWH-211 JWH-212 JWH-213 JWH-234 JWH-235 JWH-236 JWH-239 JWH-240 JWH-241 JWH-242 JWH-258 JWH-259 JWH-260 JWH-261 JWH-262 JWH-265 JWH-266 JWH-267 JWH-268 JWH-387 JWH-398 JWH-416 JWH-417 JWH-422 JWH-423 JWH-424 JWH-425 MAM-1220 MAM-2201 NE-CHMIMO Naphthoylpyrroles JWH-030 JWH-031 JWH-032 JWH-033 JWH-036 JWH-044 JWH-045 JWH-145 JWH-146 JWH-147 JWH-150 JWH-156 JWH-243 JWH-244 JWH-245 JWH-246 JWH-292 JWH-293 JWH-307 JWH-308 JWH-309 JWH-346 JWH-347 JWH-348 JWH-363 JWH-364 JWH-365 JWH-366 JWH-367 JWH-368 JWH-369 JWH-370 JWH-371 JWH-372 JWH-373 Naphthylmethylindenes JWH-171 JWH-176 JWH-220 Naphthylmethylindoles JWH-175 JWH-184 JWH-185 JWH-192 JWH-194 JWH-195 JWH-196 JWH-197 JWH-199 Phenylacetylindoles Cannabipiperidiethanone JWH-167 JWH-201 JWH-202 JWH-203 JWH-204 JWH-205 JWH-206 JWH-207 JWH-208 JWH-209 JWH-237 JWH-248 JWH-249 JWH-250 JWH-251 JWH-252 JWH-253 JWH-302 JWH-303 JWH-304 JWH-305 JWH-306 JWH-311 JWH-312 JWH-313 JWH-314 JWH-315 JWH-316 RCS-8 Pyrazolecarboxamides 5F-AB-FUPPYCA 5F-AMPPPCA AB-CHFUPYCA Tetramethylcyclo-propanoylindazoles FAB-144 Tetramethylcyclo-propanoylindoles 5Br-UR-144 5Cl-UR-144 A-796,260 A-834,735 FUB-144 UR-144 XLR-11 XLR-12 Others 2F-QMPSB 4-HTMPIPO 4CN-CUMYL-BUT7AICA 5F-PY-PICA 5F-PY-PINACA 5F-3-pyridinoylindole 5F-ADB-P7AICA 5F-CUMYL-P7AICA 5F-CUMYL-PEGACLONE A-836,339 A-955,840 A-PBITMO A-PONASA Abnormal cannabidiol AB-001 ADB-FUBHQUCA ADB-FUBIATA ADB-P7AICA AM-1248 AM-1714 BAY 38-7271 BAY 59-3074 BzODZ-EPyr CB-13 CB-86 CBS-0550 CUMYL-4CN-B7AICA CUMYL-CB-MEGACLONE CUMYL-CH-MEGACLONE CUMYL-PEGACLONE EG-018 GSK-554,418A GW-842,166X JTE 7-31 LASSBio-881 LBP-1 Leelamine MDA-7 MDA-19 MEPIRAPIM NESS-040C5 NMDMSB NMP-7 O-889 O-1269 O-1270 O-1399 O-1602 O-2220 Olorinab PF-03550096 PSB-SB-1202 PTI-1 PTI-2 PTI-3 QMPSB S-444,823 S-777,469 SER-601 Tedalinab URB-447 VSN-16 WIN 55,212-2 WIN 56,098
Allosteric CBRTooltip Cannabinoid receptor ligands	AEF0117 GAT100 Org 27569 Org 27759 Org 29647 PSNCBAM-1 Pregnenolone RTI-371 ZCZ-011
Endocannabinoidenhancers(inactivation inhibitors)	4-Nonylphenylboronic acid AM-404 Arachidonoyl serotonin Arvanil BIA 10-2474 Biochanin A CAY-10401 CAY-10429 Genistein Guineesine IDFP JNJ 1661010 JNJ-42165279 JZL184 JZL195 Kaempferol LY-2183240 MK-4409 O-1624 O-2093 Oleoylethanolamide (OEA) Olvanil Palmitoylethanolamide (PEA) PF-04457845 PF-622 PF-750 PF-3845 PHOP URB-447 URB-597 URB-602 URB-754 VDM-11
Anticannabinoids(antagonists/inverseagonists/antibodies)	AM-251 AM-281 AM-630 AM-1387 AM-4113 AM-6527 AM-6545 BML-190 Brizantin (Бризантин) CAY-10508 CB-25 CB-52 CB-86 Dietressa (Диетресса) Drinabant (AVE1625) Hemopressin Ibipinabant (SLV319) JTE-907 LH-21 LY-320,135 MDA-77 MJ-15 MK-9470 NESS-0327 NIDA-41020 O-606 O-1184 O-1248 O-1918 O-2050 O-2654 Otenabant (CP-945,598) PF-514273 PipISB PSB-SB-487 Rimonabant (SR141716) Rosonabant (E-6776) SR-144,528 Surinabant (SR147778) Taranabant (MK-0364) TM-38837 VCHSR
See also: Cannabinoid receptor modulators (cannabinoids by pharmacology) List of: AM cannabinoids JWH cannabinoids Designer drugs § Synthetic cannabimimetics

v t e Cannabinoid receptor modulators
Receptor(ligands)	CB1Tooltip Cannabinoid receptor type 1 Agonists(abridged,full list) 2-AG 2-AGE (noladin ether) 11-Hydroxy-THC α-Amyrin · β-Amyrin AB-CHMINACA AM-1172 AM-1220 AM-1221 AM-1235 AM-2201 AM-2232 Anandamide Arvanil AZ-11713908 Cannabinol CB-13 CP 47,497 CP 55,940 Dimethylheptylpyran DEA ECG EGCG Epicatechin Gallocatechol (gallocatechin) Honokiol HU-210 JWH-007 JWH-015 JWH-018 JWH-073 Kavain L-759,633 Levonantradol Menabitan Nabilone Nabitan NADA O-1812 Oleamide Pravadoline Serinolamide A THC (dronabinol) UR-144 WIN 55,212-2 Yangonin Inverse agonists AM-251 INV-202 Monlunabant Rimonabant Surinabant Taranabant TM-38837 Zevaquenabant Antagonists AM-6545 Cannabidiol Cannabigerol Drinabant Falcarinol (carotatoxin) Hemopressin Ibipinabant LY-320,135 MK-9470 NESS-0327 O-2050 Otenabant PF-514273 PipISB Rosonabant Selonabant THCV VCHSR Virodhamine CB2Tooltip Cannabinoid receptor type 2 Agonists 2-AG 2-AGE (noladin ether) 3,3'-Diindolylmethane 4-O-Methylhonokiol α-Amyrin · β-Amyrin A-796,260 A-834,735 A-836,339 AM-1172 AM-1221 AM-1235 AM-1241 AM-2232 Anandamide AZ-11713908 Cannabinol Caryophyllene CB-13 CBS-0550 CP 55,940 GW-405,833 (L-768,242) GW-842,166X HU-308 JTE 7-31 JWH-007 JWH-015 JWH-018 JWH-73 JWH-133 L-759,633 L-759,656 Lenabasum (anabasum) Magnolol MDA-19 Nabitan NADA Olorinab (APD-371) PF-03550096 S-444,823 SER-601 Serinolamide A UR-144 Tedalinab THC (dronabinol) THCV Tetrahydromagnolol Virodhamine Antagonists 4-O-Methylhonokiol AM-630 BML-190 Cannabidiol Honokiol JTE-907 SR-144,528 WIN 54,461 WIN 56,098 NAGly(GPR18) Agonists Abnormal cannabidiol ACPA AM251 Anandamide Cannabidiol NADGly THC (dronabinol) O-1602 Antagonists PSB-CB5 O-1918 GPR55 Agonists 2-AGE (noladin ether) 2-ALPI Abnormal cannabidiol AM-251 CID1011163 CID1252842 CID1792579 CP 55,940 GSK-494581A Lysophosphatidylinositol ML-184 ML-185 ML-186 O-1602 Oleoylethanolamide Palmitoylethanolamide THC (dronabinol) Antagonists Cannabidiol CID-16020046 ML-191 ML-192 ML-193 O-1918 PSB-SB-487 PSB-SB-1202 PSB-SB-1203 Tetrahydromagnolol GPR119 Agonists 2-Oleoylglycerol Anandamide APD668 AR-231,453 AS-1269574 MBX-2982 N-Oleoyldopamine Oleoylethanolamide Olvanil PSN-375,963 PSN-632,408
Transporter(modulators)	eCBTsTooltip Endocannabinoid transporter Inhibitors: 5'-DMH-CBD AM-404 AM-1172 Arachidonoyl serotonin Arvanil Cannabidiol Guineensine LY-2183240 O-2093 OMDM-2 Paracetamol (acetaminophen) SB-FI-26 UCM-707 URB-597 VDM-11 WOBE490 WOBE491 WOBE492
Enzyme(modulators)	FAAHTooltip Fatty acid amide hydrolase Inhibitors: 4-Nonylphenylboronic acid AACOCF3 AM-404 Arachidonoyl serotonin BIA 10-2474 Biochanin A Genistein IDFP JNJ-1661010 JNJ-42165279 JZL-195 Kaempferol LY-2183240 MAFP Palmitoylisopropylamide Paracetamol (acetaminophen) PF-3845 PF-750 Redafamdastat (JZP-150, PF-04457845) SA-47 SA-57 TAK 21d TC-F 2 UCM710 URB-597 Activators: PDP-EA MAGL Inhibitors: ABX-1431 IDFP JJKK 048 JW 642 JZL-184 JZL-195 JZP-361 KML 29 MAFP MJN110 NAM Pristimerin URB-602 ABHD6 Inhibitors: JZP-169 JZP-430 KT182 KT185 KT195 KT203 LEI-106 ML294 ML295 ML296 UCM710 WWL-70 ABHD12 Inhibitors: Betulinic acid Maslinic acid MAFP Oleanolic acid Orlistat (tetrahydrolipstatin) Ursolic acid
Others	Precursors: Phosphatidylethanolamine NAPE Diacylglycerol Others: 2-PG (directly potentiates activity of 2-AG at CB1 receptor) ARN-272 (FAAH-like anandamide transporter inhibitor)
See also Receptor/signaling modulators Cannabinoids (cannabinoids by structure)