Delta-8-Tetrahydrocannabinol

Delta-8-Tetrahydrocannabinol (Delta-8-THC, Δ8-THC) is a psychoactive cannabinoid found in the cannabis plant.[1][2] It is an isomer of Delta-9-Tetrahydrocannabinol (Delta-9-THC, Δ9-THC), the compound commonly known as THC. Delta-8-THC has antiemetic, anxiolytic, orexigenic, analgesic, and neuroprotective properties.[3]

Delta-8-THC
Names
IUPAC name
6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol
Other names
  • Δ8-THC
  • Δ-8-THC
  • Δ8-THC
  • δ-8-THC
  • (−)-trans-Δ8-tetrahydrocannabinol
  • (−)-trans-Δ8-tetrahydrocannabinol
  • Δ6-THC
  • Δ-6-THC
  • Δ6-THC
  • Δ1(6)-THC
  • (−)-trans-Δ6-tetrahydrocannabinol
  • (−)-trans-Δ6-tetrahydrocannabinol
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.165.076
Properties
C21H30O2
Molar mass 314.5 g/mol
Density 1.0±0.1 g/cm3
Boiling point 383.5±42.0 °C
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Effects

Delta-8-THC is slightly less potent than Delta-9-THC, but its psychological and physiological effects are qualitatively similar.[4][5] Delta-8-THC may cause increased heart rate, reddening of the eyes, dizziness, dryness of the mouth and throat, paresthesia, tinnitus, increased body awareness, weakness, muscle tension or tremor, reduced motor coordination, fatigue, sleepiness, changes in visual perception, altered visual imagery, enhancement of colors or contrasts, time distortion, changes in auditory perception, euphoria, tranquility, relaxation, racing thoughts, dreamy introspective states, or difficulty in thinking, speaking, reading, or remembering.[5]

Pharmacology

Pharmacodynamics

The pharmacodynamic profile of Delta-8-THC is similar to that of Delta-9-THC.[4][5] It is an agonist of CB1 and CB2 cannabinoid receptors with about half the potency of Delta-9-THC in most but not all measures of biological activity.[6] Delta-8-THC has been reported to have a Ki value of 44 ± 12 nM at the CB1 receptor and 44 ± 17 nM at the CB2 receptor.[7] These values are higher than those typically reported for Delta-9-THC at the same receptors,[8] indicating that Delta-8-THC binds to cannabinoid receptors less efficiently than Delta-9-THC.

Pharmacokinetics

The pharmacokinetic profile of Delta-8-THC is also similar to that of Delta-9-THC.[4][5] Following ingestion in humans, hepatic cytochrome P450 enzymes including CYP2C9 and CYP3A4 first convert Delta-8-THC into 11-hydroxy-Δ8-tetrahydrocannabinol (11-OH-Δ8-THC).[9][10] Next, dehydrogenase enzymes convert 11-OH-Δ8-THC into 11-nor-Δ8-tetrahydrocannabinol-9-carboxylic acid (11-nor-Δ8-THC-9-COOH, also known as Δ8-THC-11-oic acid).[10][11] Finally, Δ8-THC-11-oic acid undergoes glucuronidation by glucuronidase enzymes to form 11-nor-Δ8-tetrahydrocannabinol-9-carboxylic acid glucuronide (Δ8-THC-COOH-glu).[10][11] This final product is then excreted in the urine.[12][13]

Physical and chemical properties

Delta-8-THC is a tricyclic terpenoid. Although it has the same chemical formula as Delta-9-THC, one of its carbon-carbon double bonds is located in a different position.[4] This difference in structure increases the chemical stability of Delta-8-THC relative to Delta-9-THC, lengthening shelf life and allowing the compound to resist undergoing oxidation to cannabinol over time.[6] Like other cannabinoids, Delta-8-THC is very lipophilic (log P = 7.4[14]). It is an extremely viscous, colorless oil at room temperature.[15]

Delta-8-THC has a double bond (a) between the carbon atoms labeled 8 and 9. Delta-9-THC has a double bond (a) between the carbon atoms labeled 9 and 10.

History

The partial synthesis of Delta-8-THC was published in 1941 by Roger Adams and colleagues at the University of Illinois.[16] In 1942, the same research group studied its physiological and psychoactive effects after oral dosing in human volunteers.[17] Total syntheses of Delta-8-THC were achieved by 1965.[18] In 1966, the chemical structure of Delta-8-THC isolated from cannabis was characterized using modern methods by Richard L. Hively, William A. Mosher, and Friedrich W. Hoffmann at the University of Delaware.[19] A stereospecific synthesis of Delta-8-THC from olivetol and verbenol was reported by Raphael Mechoulam and colleagues at the Weizmann Institute of Science in 1967.[20] Delta-8-THC was often referred to as Delta-6-THC (Δ6-THC) in early scientific literature, but this name is no longer conventional among most authors.[21]

Society and culture

Since the 2018 United States Farm Bill was signed into law in December 2018, Delta-8-THC products isomerized from compliant sources (including industrial hemp and derivative cannabidiol extracts) have been sold by a range of digital vendors and a more limited array of brick and mortar retailers, including head shops. Ranging from bulk quantities of unrefined distillate to prepared edibles and atomizer cartridges suffused with cannabis-derived terpenes, they are usually marketed as federally legal alternatives to their Delta-9-THC counterparts.[22][23] However, the legal status of Delta-8-THC at the federal level is disputed between the Drug Enforcement Administration and the Hemp Industries Association.[24][25]

Research

Delta-8-THC has been studied as a potential treatment for nausea and vomiting associated with chemotherapy.[6] A clinical trial in Israel involving 108 cancer patients treated with chemotherapy was registered with the NIH in 2005, but the study was never completed.[26] Delta-8-THC is also studied as a potential topical treatment for glaucoma.[27] Although Delta-8-THC is a minor constituent of medical cannabis, no large clinical studies have been published on Delta-8-THC alone for any medical condition as of 2020 according to the NIH database.

See also

References
  1. "NCI Drug Dictionary". National Cancer Institute. 2011-02-02. Retrieved 2020-11-10.
  2. "Δ8-Tetrahydrocannabinol". webbook.nist.gov. U.S. Secretary of Commerce. Retrieved 2020-11-10.
  3. PubChem. "delta8-THC". pubchem.ncbi.nlm.nih.gov. Retrieved 2020-11-09.
  4. Razdan, Raj K. (1984), "CHEMISTRY AND STRUCTURE-ACTIVITY RELATIONSHIPS OF CANNABINOIDS: AN OVERVIEW", The Cannabinoids: Chemical, Pharmacologic, and Therapeutic Aspects, Elsevier, pp. 63–78, ISBN 978-0-12-044620-9, retrieved 2020-11-09
  5. Hollister, Leo E.; Gillespie, H. K. (1973). "Delta-8- and delta-9-tetrahydrocannabinol; Comparison in man by oral and intravenous administration". Clinical Pharmacology & Therapeutics. 14 (3): 353–357. doi:10.1002/cpt1973143353. ISSN 1532-6535.
  6. Abrahamov, Aya; Abrahamov, Avraham; Mechoulam, R. (1995). "An efficient new cannabinoid antiemetic in pediatric oncology". Life Sciences. 56 (23–24): 2097–2102. doi:10.1016/0024-3205(95)00194-b. ISSN 0024-3205.
  7. Bow, Eric W.; Rimoldi, John M. (2016). "The Structure–Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation". Perspectives in Medicinal Chemistry. 8: 17–39. doi:10.4137/pmc.s32171. ISSN 1177-391X.
  8. Pertwee, R G (2008). "The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin". British Journal of Pharmacology. 153 (2): 199–215. doi:10.1038/sj.bjp.0707442. ISSN 0007-1188. PMC 2219532. PMID 17828291.
  9. Stout, Stephen M.; Cimino, Nina M. (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. ISSN 0360-2532.
  10. Villamor, J. L.; Bermejo, A. M.; Tabernero, M. J.; Fernández, P.; Sánchez, I. (1998). "GC/MS Determination of 11-Nor-9-Carboxy-Δ 8 -tetrahydrocannabinol in Urine from Cannabis Users". Analytical Letters. 31 (15): 2635–2643. doi:10.1080/00032719808005332. ISSN 0003-2719.
  11. Valiveti, Satyanarayana; Hammell, Dana C.; Earles, D. Caroline; Stinchcomb, Audra L. (2005). "LC–MS method for the estimation of Δ8-THC and 11-nor-Δ8-THC-9-COOH in plasma". Journal of Pharmaceutical and Biomedical Analysis. 38 (1): 112–118. doi:10.1016/j.jpba.2004.11.055.
  12. Harvey, D.J.; Brown, N.K. (1991). "Comparative in vitro metabolism of the cannabinoids". Pharmacology Biochemistry and Behavior. 40 (3): 533–540. doi:10.1016/0091-3057(91)90359-A.
  13. Mechoulam, R.; Zvi, Z. Ben; Agurell, S.; Nilsson, I. M.; Nilsson, J. L. G.; Edery, H.; Grunfeld, Y. (1973). "Δ6-Tetrahydrocannabinol-7-oic acid, a urinary Δ6-THC metabolite: Isolation and synthesis". Experientia. 29 (10): 1193–1195. doi:10.1007/BF01935065. ISSN 0014-4754.
  14. Thomas, B. F.; Compton, D. R.; Martin, B. R. (1990). "Characterization of the lipophilicity of natural and synthetic analogs of delta 9-tetrahydrocannabinol and its relationship to pharmacological potency". The Journal of Pharmacology and Experimental Therapeutics. 255 (2): 624–630. ISSN 0022-3565. PMID 2173751.
  15. Rosenkrantz, Harris; Thompson, George R.; Braude, Monique C. (1972). "Oral and Parenteral Formulations of Marijuana Constituents". Journal of Pharmaceutical Sciences. 61 (7): 1106–1112. doi:10.1002/jps.2600610715. ISSN 0022-3549.
  16. Adams, Roger; Cain, C. K.; McPhee, W. D.; Wearn, R. B. (1941). "Structure of Cannabidiol. XII. Isomerization to Tetrahydrocannabinols1". Journal of the American Chemical Society. 63 (8): 2209–2213. doi:10.1021/ja01853a052. ISSN 0002-7863.
  17. Adams, R. (1942). "Marihuana: Harvey Lecture, February 19, 1942". Bulletin of the New York Academy of Medicine. 18 (11): 705–730. ISSN 0028-7091. PMC 1933888. PMID 19312292.
  18. Mechoulam, R. (1970-06-05). "Marihuana Chemistry". Science. 168 (3936): 1159–1165. doi:10.1126/science.168.3936.1159. ISSN 0036-8075.
  19. Hively, Richard L.; Mosher, William A.; Hoffmann, Friedrich W. (1966). "Isolation of trans-Δ6-Tetrahydrocannabinol from Marijuana". Journal of the American Chemical Society. 88 (8): 1832–1833. doi:10.1021/ja00960a056. ISSN 0002-7863.
  20. Mechoulam, Raphael.; Braun, P.; Gaoni, Yehiel. (1967). "Stereospecific synthesis of (-)-.DELTA.1- and (-)-.DELTA.1(6)-tetrahydrocannabinols". Journal of the American Chemical Society. 89 (17): 4552–4554. doi:10.1021/ja00993a072. ISSN 0002-7863.
  21. Pertwee, Roger G (2006). "Cannabinoid pharmacology: the first 66 years: Cannabinoid pharmacology". British Journal of Pharmacology. 147 (S1): S163–S171. doi:10.1038/sj.bjp.0706406. PMC 1760722. PMID 16402100.
  22. Farah, Troy (September 23, 2020). "Delta-8-THC Promises to Get You High Without the Paranoia or Anxiety". Discover Magazine. Retrieved November 9, 2020.
  23. "Is it legal to vape Delta 8 THC oils?". delta8thc.market. Retrieved 2015-12-08.
  24. Levey, Louis (October 23, 2020). "DEA Tried Banning New Cannabis Product, Sellers Still Selling". Dope Magazine. Retrieved November 10, 2020.
  25. King, Seth (January 18, 2021). "How Some THC Is Legal — For Now". Rolling Stone.
  26. "Comparison of Delta-8-THC to Ondansetron in the Prevention of Acute Nausea From Moderately Emetogenic Chemotherapy - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2020-11-10.
  27. Punyamurthula, Nagendra S.; Adelli, Goutham R.; Gul, Waseem; Repka, Michael A.; ElSohly, Mahmoud A.; Majumdar, Soumyajit (2016-11-30). "Ocular Disposition of ∆8-Tetrahydrocannabinol from Various Topical Ophthalmic Formulations". AAPS PharmSciTech. 18 (6): 1936–1945. doi:10.1208/s12249-016-0672-2. ISSN 1530-9932. PMC 5629008.
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