HU-210

HU-210
Clinical data
Other names1,1-Dimethylheptyl- 11-hydroxy- tetrahydrocannabinol
Legal status
Legal status
Identifiers
IUPAC name
  • (6aR,10aR)-9-(hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6H,6aH,7H,10H,10aH-benzo[c]isochromen-1-ol
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC25H38O3
Molar mass386.576 g·mol−1
3D model (JSmol)
SMILES
  • CCCCCCC(C)(C)C1=CC2=C([C@@H]3CC(=CC[C@H]3C(O2)(C)C)CO)C(=C1)O
InChI
  • InChI=1S/C25H38O3/c1-6-7-8-9-12-24(2,3)18-14-21(27)23-19-13-17(16-26)10-11-20(19)25(4,5)28-22(23)15-18/h10,14-15,19-20,26-27H,6-9,11-13,16H2,1-5H3/t19-,20-/m1/s1 ☒N
  • Key:SSQJFGMEZBFMNV-WOJBJXKFSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

HU-210 is a synthetic cannabinoid that was first synthesized in 1988 from (1R,5S)-myrtenol[1] by a group led by Raphael Mechoulam at the Hebrew University.[2][3][4] HU-210 is 100 to 800 times more potent than natural THC from cannabis and has an extended duration of action.[5] HU-210 has a binding affinity of 0.061nM at CB1 and 0.52nM at CB2 in cloned human cannabinoid receptors.[6] Compared to Delta-9-THC of 40.7nM at CB1. [7] HU-210 is the (–)-1,1-dimethylheptyl analog of 11-hydroxy- Δ8- tetrahydrocannabinol; in some references it is called 1,1-dimethylheptyl- 11-hydroxytetrahydrocannabinol. The abbreviation "HU" stands for Hebrew University.

Effects and research

HU-210, the (–) enantiomer of 11-OH-D8-THC-DMH, has almost all of the cannabinoid activity, while the (+) enantiomer, known as HU-211, is inactive as a cannabinoid and instead acts as an NMDA antagonist having neuroprotective effects.[8][9]

HU-210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal neural stem and progenitor cells likely via a sequential activation of CB1 receptors, Gi/o proteins, and ERK signaling. It was also indicated by this increased neural growth to entail antianxiety and antidepressant effects.[10]

HU-210, alongside other synthetic cannabinoids like WIN 55,212-2 and JWH-133, is implicated in preventing the inflammation caused by amyloid beta proteins involved in Alzheimer's disease, in addition to preventing cognitive impairment and loss of neuronal markers. This anti-inflammatory action is induced through the activation of cannabinoid receptors, which prevents microglial activation that elicits the inflammation. In addition, cannabinoids completely abolish neurotoxicity related to microglia activation in rat models.[11]

HU-210 is a potent analgesic with many of the same effects as natural THC.

HU-210 has an oral LD50 of 5,000mg/kg in rats and 14,200mg/kg in rabbits.[12] HU-210 has an LDLO (Lowest Lethal Dose amount) of 143mg/kg in humans.[12] Caffeine has an LD50 estimated to be 150–200 milligrams per kilogram. [13] Delta-8-THC LD50 has not been confirmed. In a 1973 study monkeys and dogs given 9,000mg/kg of Delta-8-THC was nonlethal.[14][15]

Chemistry

HU-210 is the enantiomer of HU-211 (Dexanabinol). The original synthesis of HU-210 is based on an acid-catalyzed condensation of (–)-Myrtenol and 1,1-Dimethylheptylresorcinol (3,5-Dihydroxy-1-(1,1-dimethylheptyl)benzol).[1]

HU-210 synthesis

HU-210 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,[16] so the signatory countries to these international drug control treaties are not required by said treaties to control HU-210.

New Zealand

HU-210 is banned in New Zealand as of 8 May 2014.[17]

United States

HU-210 is not listed in the list of scheduled controlled substances in the USA.[18] It is therefore not scheduled at the federal level in the United States, but it is possible that HU-210 could legally be considered an analog of Delta-8-THC (which is one of the substances controlled in Schedule I as "tetrahydrocannabinols"), and therefore sales or possession could potentially be prosecuted under the Federal Analogue Act.[19] A brief profile of HU-210 written and published by the Drug Enforcement Administration (DEA) in 2009 (but subsequently removed from the DEA's website several years later) stated that HU-210 is a Schedule I controlled substance under the Controlled Substances Act due to being similar to THC.[20] This indicates that the DEA might legally consider HU-210 to be an analogue of Delta-8-THC for the purposes of applying the Federal Analog Act to those that handle HU-210. An elucidation of the rationale for the DEA's claim was not presented, no references were cited, and the claim was eventually removed from the DEA's website. A version of the document (updated in 2013), now in PDF form, exists on the DEA Office of Diversion Control's website.[21] Claimed in this possibly misleading though definitive sounding document, with the same lack of detailed explanation or citation, is:

HU-210 is a schedule I controlled substance under the CSA.

Alabama

HU-210 is a Schedule I controlled substance in Alabama.[22]

(4)a. A synthetic controlled substance that is any material, mixture, or preparation that contains any quantity of the following chemical compounds, their salts, isomers and salts of isomers, unless specifically excepted, whenever the existence of these salts, isomers and salts of isomers is possible within the specific chemical designation or compound:

...

9. (6aR, 10aR)-9-(hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol, some trade or other names: HU-210.

Florida

HU-210 is a Schedule I controlled substance, categorized as a hallucinogen, making it illegal to buy, sell, or possess in the state of Florida without a license.[23]

(c) Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation that contains any quantity of the following hallucinogenic substances or that contains any of their salts, isomers, including optical, positional, or geometric isomers, homologues, nitrogen-heterocyclic analogs, esters, ethers, and salts of isomers, homologues, nitrogen-heterocyclic analogs, esters, or ethers, if the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation or class description: ... 47. HU-210 [(6aR,10aR)-9-(Hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol].

Vermont

Effective January 1, 2016, HU-210 is a regulated drug in Vermont designated as a "Hallucinogenic Drug."[24]

“Hallucinogenic Drug” means those specified in Section 7 of this rule including stramonium, mescaline or peyote, lysergic acid diethylamide, and psilocybin, and all synthetic equivalents of chemicals contained in resinous extractives of Cannabis sativa, or any salts or derivatives or compounds of any preparations or mixtures thereof, and any other substance having a hallucinogenic effect in the regulations adopted by the Board of Health under 18 V.S.A.§ 4202.

...

• Cannabimimetic Agents means, collectively, any chemical that is a cannabinoid receptor type 1 (CB1) or cannabinoid receptor type 2 (CB2) agonist, or any salts, isomers, derivatives, or analogs of these chemicals. Structural classes include but are not limited to:

(a) 2-(3-hydroxycyclohexyl)phenol with substitution at the 5-position of the phenolic ring by alkyl or alkenyl, whether or not substituted on the cyclohexyl ring to any extent.

(b) 3-(1-naphthoyl)indole or 3-(1-naphthyl)indole with substitution at the nitrogen atom of the indole ring, whether or not further substituted on the indole ring to any extent, whether or not substituted on the naphthoyl or naphthyl ring to any extent.

(c) 3-(1-naphthoyl)pyrrole with substitution at the nitrogen atom of the pyrrole ring, whether or not further substituted in the pyrrole ring to any extent, whether or not substituted on the naphthoyl ring to any extent.

(d) 1-(1-naphthylmethyl)indene with substitution of the 3-position of the indene ring, whether or not further substituted in the indene ring to any extent, whether or not substituted on the naphthyl ring to any extent.

(e) 3-phenylacetylindole or 3-benzoylindole with substitution at the nitrogen atom of the indole ring, whether or not further substituted in the indole ring to any extent, whether or not substituted on the phenyl ring to any extent.

(f) indole- (2,2,3,3-tetramethylcyclopropyl)methanone, with substitution at the nitrogen atom of the indole ring, whether or not further substituted in the indole ring to any extent, whether or not substituted on the phenyl ring to any extent.

(g) N- adamantyl-indole-3-carboxamide, with substitution at the nitrogen atom of the indole ring, whether or not further substituted in the indole ring to any extent, whether or not substituted on the phenyl ring to any extent.

(h) (1,3-thiazol-2- ylidine)-2,2,3,3- tetramethylcyclopropane-1-carboxamide, with substitution to any extent at any position of the thiazolylidine ring.

...

• HU-210; (6aR,10aR)-9-(hydroxymethyl)-6,6-dimethyl-3- (2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c] chromen-1-ol; OR [(6aR,10aR)-9-(hy droxymethyl)- 6,6-dimethyl-3-(2-methyl octan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol; OR 1,1-Dimethylheptyl-11-hydroxytetrahydrocannabinol

Other HU Cannabinoids

See also

References

  1. 1 2 Mechoulam R, Lander N, Zahalka J (January 1990). "Synthesis of the individual, pharmacologically distinct, enantiomers of a tetrahydrocannabinol derivative". Tetrahedron: Asymmetry. 1 (5): 315–318. doi:10.1016/S0957-4166(00)86322-3.
  2. ↑ Mechoulam R, Feigenbaum JJ, Lander N, Segal M, Järbe TU, Hiltunen AJ, Consroe P (September 1988). "Enantiomeric cannabinoids: stereospecificity of psychotropic activity". Experientia. 44 (9): 762–4. doi:10.1007/BF01959156. PMID 3416993. S2CID 19589995.
  3. ↑ Little PJ, Compton DR, Mechoulam R, Martin BR (March 1989). "Stereochemical effects of 11-OH-delta 8-THC-dimethylheptyl in mice and dogs". Pharmacology, Biochemistry, and Behavior. 32 (3): 661–6. doi:10.1016/0091-3057(89)90014-2. PMID 2544901. S2CID 140209484.
  4. ↑ Järbe TU, Hiltunen AJ, Mechoulam R (September 1989). "Stereospecificity of the discriminative stimulus functions of the dimethylheptyl homologs of 11-hydroxy-delta 8-tetrahydrocannabinol in rats and pigeons". The Journal of Pharmacology and Experimental Therapeutics. 250 (3): 1000–5. PMID 2550611.
  5. ↑ Devane WA, Breuer A, Sheskin T, Järbe TU, Eisen MS, Mechoulam R (May 1992). "A novel probe for the cannabinoid receptor". Journal of Medicinal Chemistry. 35 (11): 2065–9. doi:10.1021/jm00089a018. PMID 1317925.
  6. ↑ Stern, E.; Lambert, D. M. (2007). "Medicinal chemistry endeavors around the phytocannabinoids". Chemistry & Biodiversity. 4 (8): 1707–1728. doi:10.1002/cbdv.200790149. PMID 17712816. S2CID 24920412.
  7. ↑ Bow, E. W.; Rimoldi, J. M. (2016). "The Structure–Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation". Perspectives in Medicinal Chemistry. 8: 17–39. doi:10.4137/PMC.S32171. PMC 4927043. PMID 27398024.
  8. ↑ Howlett AC, Champion TM, Wilken GH, Mechoulam R (February 1990). "Stereochemical effects of 11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl to inhibit adenylate cyclase and bind to the cannabinoid receptor". Neuropharmacology. 29 (2): 161–5. doi:10.1016/0028-3908(90)90056-w. PMID 2158635. S2CID 28602221.
  9. ↑ Darlington CL (October 2003). "Dexanabinol: a novel cannabinoid with neuroprotective properties". IDrugs. 6 (10): 976–9. OCLC 112453448. PMID 14534855.
  10. ↑ Jiang W, Zhang Y, Xiao L, Van Cleemput J, Ji SP, Bai G, Zhang X (November 2005). "Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects". The Journal of Clinical Investigation. 115 (11): 3104–16. doi:10.1172/JCI25509. PMC 1253627. PMID 16224541.
  11. ↑ Ramírez BG, Blázquez C, Gómez del Pulgar T, Guzmán M, de Ceballos ML (February 2005). "Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation". The Journal of Neuroscience. 25 (8): 1904–13. doi:10.1523/JNEUROSCI.4540-04.2005. PMC 6726060. PMID 15728830.
  12. 1 2 "HU-210" (PDF). Material Safety Data Sheet. Cayman Chemical.
  13. ↑ Peters JM (6 May 1967). "Factors Affecting Caffeine Toxicity: A Review of the Literature". The Journal of Clinical Pharmacology and the Journal of New Drugs. 7 (3): 131–141. doi:10.1002/j.1552-4604.1967.tb00034.x.
  14. ↑ Thompson GR, Rosenkrantz H, Schaeppi UH, Braude MC (July 1973). "Comparison of acute oral toxicity of cannabinoids in rats, dogs and monkeys". Toxicology and Applied Pharmacology. 25 (3): 363–72. doi:10.1016/0041-008X(73)90310-4. PMID 4199474.
  15. ↑ "delta-8-Tetrahydrocannabinol". ChemIDplus. U.S. National Library of Medicine.
  16. ↑ "International Drug Control Conventions". United Nations Office on Drugs and Crime. Archived from the original on 12 January 2018. Retrieved 3 May 2018.
  17. ↑ "Synthetic cannabinoids: What they are". New Zealand Drug Foundation. Archived from the original on 2015-09-21. Retrieved 2015-07-18.
  18. ↑ "PART 1308 - Section 1308.11 Schedule I". Office of Diversion Control. Drug Enforcement Administration, U.S. Department of Justice. Archived from the original on 27 August 2009. Retrieved 3 May 2018.
  19. ↑ "Federal Controlled Substance Analogue Act Summary". Erowid Analog Law Vault. Archived from the original on 17 April 2018. Retrieved 3 May 2018.
  20. ↑ "Spice Cannabinoid - HU-210". Office of Diversion Control. Drug Enforcement Administration, U.S. Department of Justice. Archived from the original on 2012-01-17.
  21. ↑ "HU-210" (PDF). Office of Diversion Control. Drug Enforcement Administration, U.S. Department of Justice. January 2013. Archived from the original (PDF) on 2016-12-28. 6aR,10aR)-9-(hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c] chromen-1-ol)] [Purported Ingredient of “Spice”
  22. ↑ "Controlled substances, Schedule I, additional synthetic controlled substances and analogue substances included in, trafficking in controlled substance analogues, requisite weight increased, Secs. 13A-12-231, 20-2-23 am'd". Alabama Senate Bill 333. March 2014. Archived from the original on 4 March 2016. Retrieved 2 February 2017.
  23. ↑ "Chapter 893: Drug Abuse Prevention and Control". The 2020 Florida Statutes. The Florida Legislature. Archived from the original on 14 March 2018. Retrieved 3 May 2018.
  24. ↑ "Chapter 8 – Alcohol and Drug Abuse Subchapter 9: Regulated Drug Rule" (PDF). Code of Vermont Rules. Vermont Department of Health. 15 July 2017. Archived (PDF) from the original on 27 January 2017. Retrieved 3 May 2018.

Further reading

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