四氫大麻酚

四氫大麻酚 (THC)
臨床資料
懷孕分級	C;
依賴性	生理：無 ; 心理：不確定
成癮性	不確定
ATC碼	A04AD10 (WHO) ;
法律規範狀態
法律規範	Schedule I and III (US);
藥物動力學數據
生物利用度	10-35% (吸入)，6-20% (口服)
血漿蛋白結合率	95-99%
藥物代謝	主要在肝臟中為CYP2C代謝
生物半衰期	1.6-59小時
排泄途徑	65-80% (糞便)，20-35% (尿液)，以酸型代謝物的形式
識別資訊
	IUPAC命名法 (−)-(6aR,10aR)-6,6,9-trimethyl-; 3-pentyl-6a,7,8,10a-tetrahydro-; 6H-benzo[c]chromen-1-ol; (−)-(6aR,10aR)-6,6,9-三甲基-3-戊基-6a,7,8,10a-四氫-6H-苯並[c]色烯-1-酚; ;
CAS號	1972-08-3
PubChem CID	16078;
IUPHAR/BPS	2424;
DrugBank	DB00470 ;
ChemSpider	15266 ;
UNII	7J8897W37S;
ChEBI	CHEBI:66964 ;
ChEMBL	ChEMBL465 ;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID6021327 ;
ECHA InfoCard	100.153.676
化學資訊
化學式	C21H30O2
摩爾質量	314.45
3D模型（JSmol（英語：JSmol））	交互式圖像;
比旋度（英語：Specific rotation）	−152° (乙醇)
沸點	157 °C（315 °F）
	SMILES C1=C(CC[C@@H]3[C@@H]1C2=C(C=C(C=C2OC3(C)C)CCCCC)O[H])C;

四氫大麻酚（Tetrahydrocannabinol，簡稱THC），又稱Δ⁹-四氫大麻酚（Δ⁹-THC）、Δ¹-THC（根據舊命名法），為大麻素之一，是大麻中的主要精神活性物質。

Quick Facts 臨床資料, 懷孕分級 ...

Close

四氫大麻酚最早由以色列雷霍沃特魏茨曼科學研究所的三名研究人員在1964年分離出來。^[4]^[5]^[6] 純品四氫大麻酚在低溫下為玻璃狀固體，溫度升高時其粘度逐漸增加。

與植物中的其他多數藥理活性次級代謝產物類似，四氫大麻酚是在大麻中發現的一種脂類^[7]，四氫大麻酚的存在被認為是植物（對於草食性動物）的自我防禦機制。^[8] 而且，四氫大麻酚在UV-B段（280～315納米）的強吸收，可能對植物具保護作用，使其免受紫外線的傷害。^[9]^[10]^[11]

THC及其雙鍵異構體及其立體異構體是聯合國「精神藥物公約」中規定的三種大麻素之一（另外兩種是Dimethylheptylpyran和Parahexyl）。它在1971年被列在附表一，但是在世界衛生組織（WHO）的建議之後，在1991年被重新分類到附表二。根據隨後的研究，世界衛生組織建議將這一重新分類列入不那麼嚴格的附表三^[12]。「麻醉品單一公約」（附表一和附表四）安排大麻作為植物。根據1970年美國國會通過的「受控物質法案（英語：Controlled Substances Act）」，美國聯邦法律^[13]明確地將其列入附表一。

作用機制

四氫大麻酚是一種經典大麻素受體激動劑，通過中樞型受體大麻素Ⅰ型受體（英語：Cannabinoid receptor type 1）CB₁(K_i=10nM^[14])，和末梢型受體CB₂ (K_i=24nM^[14])發揮作用^[15]。

物理和化學特性

發現和結構識別

早期發現：羅傑·亞當斯從大麻中分離和鑑定出大麻二酚，顯示它與大麻酚和四氫大麻酚的關係^[16]。THC後來由希伯來大學藥學院的一個研究小組研究，他們在1964年報告了他們的工作成果^[4]，和1970年6月，拉斐爾·梅喬勒姆（英語：Raphael Mechoulam）報告了大量的工作成果^[17]。

可溶性

四氫大麻酚是一種芳香類萜，因此難溶於水，但易溶於多數有機溶劑中，特別是脂類和醇^[18]。

生物合成

四氫大麻酚羧酸的生物合成

大麻植物內四氫大麻酚主要是以四氫大麻酚羧酸(THCA)的形式存在，後者是由香葉基焦磷酸與2,4-二羥基-6-戊基苯甲酸酶促縮合產生的大麻萜酚酸^[19] 在THC酸合成酶催化下環化而得。經過一段時間後，或者被加熱時，四氫大麻酚羧酸被脫羧，得到THC。THCA生物合成的途徑類似於在蛇麻花朵中產生苦味酸hum草酮的途徑^[20]^[21]。

藥代動力學

人體內的四氫大麻酚主要被代謝為11-羥基-THC，該代謝物仍有精神活性，繼續被代謝則產生11-正-9-羧基-THC。從人類和動物體內可鑑定出超過100種四氫大麻酚的代謝物，但其中以11-羥基-THC和11-正-9-羧基-THC含量最高^[22]。四氫大麻酚的代謝過程主要在肝臟中進行，為細胞色素P450酶類CYP2C9、CYP2C19和CYP3A4所催化^[23]。有超過＞55％的THC從糞便中排泄，約20％的THC從尿液排泄。糞便中主要檢測到11-羥基-THC。通過尿液排泄的主要代謝物則為11-正-9-羧基-THC的葡糖醛酸酯及游離的11-正-9-羧基-THC。^[24]

參看

花生四烯乙醇胺

參考文獻

[1]
Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003, 42 (4): 327–60. PMID 12648025. doi:10.2165/00003088-200342040-00003.
[2]
Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts? (PDF). www.haworthpress.com. [2009-10-22]. （原始內容 (PDF)存檔於2010-09-02）.
↑
Tetrahydrocannabinol （頁面存檔備份，存於網際網路檔案館） bei ChemIDplus
[4]
Gaoni, Yechiel; Raphael Mechoulam. Isolation, structure and partial synthesis of an active constituent of hashish (PDF). Journal of the American Chemical Society. 1964, 86 (8): 1646–1647 [2008-05-31]. doi:10.1021/ja01062a046.
[5]
Interview with the winner of the first ECNP Lifetime Achievement Award: Raphael Mechoulam, Israel （頁面存檔備份，存於網際網路檔案館） February 2007
[6]
Geller, Tom. (2007)."Cannabinoids: A Secret History （頁面存檔備份，存於網際網路檔案館）", Chemical Heritage Newsmagazine, 25 (2)
[7]
Firn, Richard (2010). Nature's Chemicals. Oxford: Biology.
[8]
Pate, D.W. Chemical ecology of Cannabis. J. Int. Hemp Assoc. 1994, 1 (29): 32–37 [2009-12-08]. （原始內容存檔於2020-03-27）.
[9]
Pate, D.W. Possible role of ultraviolet radiation in evolution of Cannabis chemotypes. Economic Botany. 1983, 37: 396–405. doi:10.1007/BF02904200 (不活躍 2009-12-04).
[10]
Lydon, J; A.H. Teramura. Photochemical decomposition of cannabidiol in its resin base. Phytochemistry. 1987, 26: 1216. doi:10.1016/S0031-9422(00)82388-2.
[11]
Lydon, J; A.H. Teramura, C.B. Coffman. UV-B radiation effects on photosynthesis, growth and cannabinoid production of two Cannabis sativa chemotypes. Photochem. Photobiol. A. 1987, 46: 201. doi:10.1111/j.1751-1097.1987.tb04757.x.
[12]
A Primer on the UN Drug Control Conventions. Transnational Institute. [2017-11-25]. （原始內容存檔於2018-02-03）.
[13]
存档副本. [2017-11-25]. （原始內容存檔於2017-08-09）.
[14]
PDSP Database – UNC. NIMH Psychoactive Drug Screening Program. [11 June 2013]. （原始內容存檔於2013-11-08）.
[15]
Pertwee RG. The pharmacology of cannabinoid receptors and their ligands: An overview. International Journal of Obesity. 2006, 30: S13–S18. PMID 16570099. doi:10.1038/sj.ijo.0803272.
[16]
Roger Adams, Madison Hunt, J. H. Clark. Structure of Cannabidiol, a Product Isolated from the Marihuana Extract of Minnesota Wild Hemp.. Journal of the American Chemical Society. 1940, 62: 196–200 [2017-11-25]. doi:10.1021/ja01858a058. （原始內容存檔於2018-04-11）.
[17]
Mechoulam R. Marihuana chemistry. Science. 1970, 168 (3936): 1159–66. Bibcode:1970Sci...168.1159M. PMID 4910003. doi:10.1126/science.168.3936.1159.
[18]
Garrett ER, Hunt CA. Physicochemical properties, solubility, and protein binding of Δ⁹-tetrahydrocannabinol. J. Pharm. Sci. July 1974, 63 (7): 1056–64. PMID 4853640. doi:10.1002/jps.2600630705.
[19]
Fellermeier M, Zenk MH. Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol. FEBS Lett. May 1998, 427 (2): 283–5. PMID 9607329.
[20]
Marks MD, Tian L, Wenger JP, Omburo SN, Soto-Fuentes W, He J, Gang DR, Weiblen GD, Dixon RA. Identification of candidate genes affecting Δ9-tetrahydrocannabinol biosynthesis in Cannabis sativa. Journal of Experimental Botany. 2009, 60 (13): 3715–26. PMC 2736886 . PMID 19581347. doi:10.1093/jxb/erp210.
[21]
Baker PB, Taylor BJ, Gough TA. The tetrahydrocannabinol and tetrahydrocannabinolic acid content of cannabis products. J Pharm Pharmacol. June 1981, 33 (6): 369–72. PMID 6115009. doi:10.1111/j.2042-7158.1981.tb13806.x.
[22]
Aizpurua-Olaizola, Oier; Zarandona, Iratxe; Ortiz, Laura; Navarro, Patricia; Etxebarria, Nestor; Usobiaga, Aresatz. Simultaneous quantification of major cannabinoids and metabolites in human urine and plasma by HPLC-MS/MS and enzyme-alkaline hydrolysis. Drug Testing and Analysis. 2016-01-01: n/a–n/a [2017-11-25]. ISSN 1942-7611. doi:10.1002/dta.1998. （原始內容存檔於2017-12-01）（英語）.
[23]
Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Science. March 2007, 80 (15): 1415–9. PMID 17303175. doi:10.1016/j.lfs.2006.12.032.
[24]
Huestis MA. Pharmacokinetics and metabolism of the plant cannabinoids, Δ⁹-tetrahydrocannabinol, cannabidiol and cannabinol. Handb Exp Pharmacol. 2005, 168 (168): 657–90. PMID 16596792. doi:10.1007/3-540-26573-2_23.

外部連續

[pmid12648025-1] [1]
Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003, 42 (4): 327–60. PMID 12648025. doi:10.2165/00003088-200342040-00003.

[2] [2]
Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts? (PDF). www.haworthpress.com. [2009-10-22]. （原始內容 (PDF)存檔於2010-09-02）.

[3] 
Tetrahydrocannabinol （頁面存檔備份，存於網際網路檔案館） bei ChemIDplus

[doi10.1021/ja01062a046-4] [4]
Gaoni, Yechiel; Raphael Mechoulam. Isolation, structure and partial synthesis of an active constituent of hashish (PDF). Journal of the American Chemical Society. 1964, 86 (8): 1646–1647 [2008-05-31]. doi:10.1021/ja01062a046.

[5] [5]
Interview with the winner of the first ECNP Lifetime Achievement Award: Raphael Mechoulam, Israel （頁面存檔備份，存於網際網路檔案館） February 2007

[6] [6]
Geller, Tom. (2007)."Cannabinoids: A Secret History （頁面存檔備份，存於網際網路檔案館）", Chemical Heritage Newsmagazine, 25 (2)

[7] [7]
Firn, Richard (2010). Nature's Chemicals. Oxford: Biology.

[Pate1994-8] [8]
Pate, D.W. Chemical ecology of Cannabis. J. Int. Hemp Assoc. 1994, 1 (29): 32–37 [2009-12-08]. （原始內容存檔於2020-03-27）.

[Pate1983-9] [9]
Pate, D.W. Possible role of ultraviolet radiation in evolution of Cannabis chemotypes. Economic Botany. 1983, 37: 396–405. doi:10.1007/BF02904200 (不活躍 2009-12-04).

[Lydon1987a-10] [10]
Lydon, J; A.H. Teramura. Photochemical decomposition of cannabidiol in its resin base. Phytochemistry. 1987, 26: 1216. doi:10.1016/S0031-9422(00)82388-2.

[Lydon1987b-11] [11]
Lydon, J; A.H. Teramura, C.B. Coffman. UV-B radiation effects on photosynthesis, growth and cannabinoid production of two Cannabis sativa chemotypes. Photochem. Photobiol. A. 1987, 46: 201. doi:10.1111/j.1751-1097.1987.tb04757.x.

[12] [12]
A Primer on the UN Drug Control Conventions. Transnational Institute. [2017-11-25]. （原始內容存檔於2018-02-03）.

[13] [13]
存档副本. [2017-11-25]. （原始內容存檔於2017-08-09）.

[PDSP_Database-14] [14]
PDSP Database – UNC. NIMH Psychoactive Drug Screening Program. [11 June 2013]. （原始內容存檔於2013-11-08）.

[pmid16570099-15] [15]
Pertwee RG. The pharmacology of cannabinoid receptors and their ligands: An overview. International Journal of Obesity. 2006, 30: S13–S18. PMID 16570099. doi:10.1038/sj.ijo.0803272.

[16] [16]
Roger Adams, Madison Hunt, J. H. Clark. Structure of Cannabidiol, a Product Isolated from the Marihuana Extract of Minnesota Wild Hemp.. Journal of the American Chemical Society. 1940, 62: 196–200 [2017-11-25]. doi:10.1021/ja01858a058. （原始內容存檔於2018-04-11）.

[pmid4910003-17] [17]
Mechoulam R. Marihuana chemistry. Science. 1970, 168 (3936): 1159–66. Bibcode:1970Sci...168.1159M. PMID 4910003. doi:10.1126/science.168.3936.1159.

[Garrett1974-18] [18]
Garrett ER, Hunt CA. Physicochemical properties, solubility, and protein binding of Δ⁹-tetrahydrocannabinol. J. Pharm. Sci. July 1974, 63 (7): 1056–64. PMID 4853640. doi:10.1002/jps.2600630705.

[pmid9607329-19] [19]
Fellermeier M, Zenk MH. Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol. FEBS Lett. May 1998, 427 (2): 283–5. PMID 9607329.

[20] [20]
Marks MD, Tian L, Wenger JP, Omburo SN, Soto-Fuentes W, He J, Gang DR, Weiblen GD, Dixon RA. Identification of candidate genes affecting Δ9-tetrahydrocannabinol biosynthesis in Cannabis sativa. Journal of Experimental Botany. 2009, 60 (13): 3715–26. PMC 2736886 . PMID 19581347. doi:10.1093/jxb/erp210.

[21] [21]
Baker PB, Taylor BJ, Gough TA. The tetrahydrocannabinol and tetrahydrocannabinolic acid content of cannabis products. J Pharm Pharmacol. June 1981, 33 (6): 369–72. PMID 6115009. doi:10.1111/j.2042-7158.1981.tb13806.x.

[22] [22]
Aizpurua-Olaizola, Oier; Zarandona, Iratxe; Ortiz, Laura; Navarro, Patricia; Etxebarria, Nestor; Usobiaga, Aresatz. Simultaneous quantification of major cannabinoids and metabolites in human urine and plasma by HPLC-MS/MS and enzyme-alkaline hydrolysis. Drug Testing and Analysis. 2016-01-01: n/a–n/a [2017-11-25]. ISSN 1942-7611. doi:10.1002/dta.1998. （原始內容存檔於2017-12-01）（英語）.

[23] [23]
Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Science. March 2007, 80 (15): 1415–9. PMID 17303175. doi:10.1016/j.lfs.2006.12.032.

[pmid16596792-24] [24]
Huestis MA. Pharmacokinetics and metabolism of the plant cannabinoids, Δ⁹-tetrahydrocannabinol, cannabidiol and cannabinol. Handb Exp Pharmacol. 2005, 168 (168): 657–90. PMID 16596792. doi:10.1007/3-540-26573-2_23.

[1]

[2]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]