Conversion of CBD to THC

Phytocannabinoids exist like precursors to their pharmacologically active counterparts.{{cite journal | vauthors = Huang S, Claassen FW, van Beek TA, Chen B, Zeng J, Zuilhof H, Salentijn GI | title = Rapid Distinction and Semiquantitative Analysis of THC and CBD by Silver-Impregnated Paper Spray Mass Spectrometry | journal = Analytical Chemistry | volume = 93 | issue = 8 | pages = 3794–3802 | date = March 2021 | pmid = 33576613 | pmc = 8023514 | doi = 10.1021/acs.analchem.0c04270 }}{{cite journal | vauthors = Caprari C, Ferri E, Vandelli MA, Citti C, Cannazza G | title = An emerging trend in Novel Psychoactive Substances (NPSs): designer THC | journal = Journal of Cannabis Research | volume = 6 | issue = 1 | pages = 21 | date = May 2024 | pmid = 38702834 | pmc = 11067227 | doi = 10.1186/s42238-024-00226-y | doi-access = free }} At least three independent methods have successfully converted CBD to THC.

• Despite the CBD and THC having the same molecular weight, multiple analytical methods are able to differentiate them.
• "on the recovery of both THC (86.7−90.0%) and CBD (92.3−95.6%). The slightly lower recovery of THC can be explained by the fact that THC is less polar than CBD and more likely to remain in the nonpolar sunflower oil."

CBD heated to 175,{{cite journal | vauthors = Daniels R, Yassin OA, Toribio JM, Gascón JA, Sotzing G | title = Re-Examining Cannabidiol: Conversion to Tetrahydrocannabinol Using Only Heat | journal = Cannabis and Cannabinoid Research | volume = 9 | issue = 2 | pages = 486–494 | date = April 2024 | pmid = 36516105 | doi = 10.1089/can.2022.0235 }} or 250–300 °C may partially be converted into THC.{{cite journal | vauthors = Czégény Z, Nagy G, Babinszki B, Bajtel Á, Sebestyén Z, Kiss T, Csupor-Löffler B, Tóth B, Csupor D | title = CBD, a precursor of THC in e-cigarettes | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 8951 | date = April 2021 | pmid = 33903673 | pmc = 8076212 | doi = 10.1038/s41598-021-88389-z | bibcode = 2021NatSR..11.8951C }} Even at room temperature, trace amounts of THC can be formed as a contaminant in CBD stored for long periods in the presence of moisture and carbon dioxide in the air, with storage under inert gas required to maintain analytically pure CBD.{{cite journal | vauthors = Citti C, Russo F, Linciano P, Strallhofer SS, Tolomeo F, Forni F, Vandelli MA, Gigli G, Cannazza G | title = Origin of Δ9-Tetrahydrocannabinol Impurity in Synthetic Cannabidiol | journal = Cannabis and Cannabinoid Research | volume = 6 | issue = 1 | pages = 28–39 | date = 2021 | pmid = 33614950 | pmc = 7891213 | doi = 10.1089/can.2020.0021 }}

• Heat is required to decarboxylate the non-psychoactive phytocannabinoid THCA to its psychoactive form, THC. Likewise, CBDA turns into CBD.
• From hemp plant material in an oven, cannabinoid concentration plots (time/temp) show THC:{{cite journal | vauthors=((Moreno, T.)), ((Dyer, P.)), ((Tallon, S.)) | journal=Industrial & Engineering Chemistry Research | title=Cannabinoid Decarboxylation: A Comparative Kinetic Study | volume=59 | issue=46 | pages=20307–20315 | date=18 November 2020 | url=https://pubs.acs.org/doi/10.1021/acs.iecr.0c03791 | issn=0888-5885 | doi=10.1021/acs.iecr.0c03791 | access-date=17 May 2024| url-access=subscription }}
• STP 0 minutes 0.20 mg/g
• 140-160C 20 minutes 0.27 mg/g
• 140-160C 60 minutes 0.05-0.15 mg/g
• 120C 45 minutes 0.27 mg/g
• 120C 90 minutes 0.20 mg/g
• 100C 90 minutes 0.25 mg/g
• 80C 120 minutes 0.24 mg/g

Multiple oxidation products form during degradation in the presence of oxygen, a process known as thermolysis In contrast, the absence of oxygen leads to a process called pyrolysis which significantly reduces the loss.

• "...the boiling point for THC has been determined at 157 °C, and the boiling point range for CBD sits between 160 and 180 °C."

File:Intramolekulare cyklisierung von CBD zu Δ9-THC.png

CBD converts to various isomers of THC with catalysts in acidic environments.{{cite journal | vauthors = Mechoulam R, Hanus L | title = Cannabidiol: an overview of some chemical and pharmacological aspects. Part I: chemical aspects | journal = Chemistry and Physics of Lipids | volume = 121 | issue = 1–2 | pages = 35–43 | date = December 2002 | pmid = 12505688 | doi = 10.1016/s0009-3084(02)00144-5 }} A wide variety of acids can be used, though different conditions result in varying yield and formation of characteristic impurities.{{cite journal | vauthors = Gaoni Y, Mechoulam R | title = Hashish—VII: The isomerization of cannabidiol to tetrahydrocannabinols. | journal = Tetrahedron | date = January 1966 | volume = 22 | issue = 4 | pages = 1481–1488 | doi = 10.1016/S0040-4020(01)99446-3 }}{{cite journal | vauthors = Kiselak TD, Koerber R, Verbeck GF | title = Synthetic route sourcing of illicit at home cannabidiol (CBD) isomerization to psychoactive cannabinoids using ion mobility-coupled-LC-MS/MS | journal = Forensic Science International | volume = 308 | issue = | pages = 110173 | date = March 2020 | pmid = 32028121 | doi = 10.1016/j.forsciint.2020.110173 }}{{cite journal | vauthors = Nelson KM, Bisson J, Singh G, Graham JG, Chen SN, Friesen JB, Dahlin JL, Niemitz M, Walters MA, Pauli GF | title = The Essential Medicinal Chemistry of Cannabidiol (CBD) | journal = Journal of Medicinal Chemistry | volume = 63 | issue = 21 | pages = 12137–12155 | date = November 2020 | pmid = 32804502 | doi = 10.1021/acs.jmedchem.0c00724 | pmc = 7666069 }}{{cite journal | vauthors = Golombek P, Müller M, Barthlott I, Sproll C, Lachenmeier DW | title = Conversion of Cannabidiol (CBD) into Psychotropic Cannabinoids Including Tetrahydrocannabinol (THC): A Controversy in the Scientific Literature | journal = Toxics | volume = 8 | issue = 2 | page = 41 | date = June 2020 | pmid = 32503116 | pmc = 7357058 | doi = 10.3390/toxics8020041 | doi-access = free }}

• Catalytic acid solution in 5 minutes in a microwave oven with a 40% THC (Δ9-THC) and 35% Δ-8-Tetrahydrocannabinol yield.{{cite journal | vauthors = Ramirez GA, Tesfatsion TT, Docampo-Palacios ML, Cruces I, Hellmann AJ, Okhovat A, Pittiglio MK, Ray KP, Cruces W | title = Ultrasonic or Microwave Modified Continuous Flow Chemistry for the Synthesis of Tetrahydrocannabinol: Observing Effects of Various Solvents and Acids | journal = ACS Omega | volume = 9 | issue = 11 | pages = 13191–13199 | date = March 2024 | pmid = 38524441 | pmc = 10956408 | doi = 10.1021/acsomega.3c09794 }}
• Adding protons until the CBD sterically-hindered alcohol functional group cyclises to the pyran ring of THC.{{cite journal | vauthors = Peng H, Shahidi F | title = Cannabis and Cannabis Edibles: A Review | journal = Journal of Agricultural and Food Chemistry | volume = 69 | issue = 6 | pages = 1751–1774 | date = February 2021 | pmid = 33555188 | doi = 10.1021/acs.jafc.0c07472 }}
• Lewis acids.{{cite journal | vauthors = Marzullo P, Foschi F, Coppini DA, Fanchini F, Magnani L, Rusconi S, Luzzani M, Passarella D | title = Cannabidiol as the Substrate in Acid-Catalyzed Intramolecular Cyclization | journal = Journal of Natural Products | volume = 83 | issue = 10 | pages = 2894–2901 | date = October 2020 | pmid = 32991167 | pmc = 8011986 | doi = 10.1021/acs.jnatprod.0c00436 }} - a continuous rather than batch implementation with similar materials
• Gaoni and Mechoulam{{cite journal | vauthors = Gaoni Y, Mechoulam R | title = Isolation, structure, and partial synthesis of an active constituent of hashish. | journal = Journal of the American Chemical Society | date = April 1964 | volume = 86 | issue = 8 | pages = 1646–1647 | doi = 10.1021/ja01062a046 }} also described a method for converting CBD to Δ9-THC comprising refluxing a mixture of CBD in ethanol containing 0.05% hydrogen chloride for 2 hours. Percentage yield of Δ9-THC (Δ1-THC) was 2%.{{cite journal | vauthors = Mechoulam R, Gaoni Y | title = A total synthesis of dl-Δ1-tetrahydrocannabinol, the active constituent of hashish | journal = Journal of the American Chemical Society | volume = 87 | issue = 14| pages = 3273–5 | date = July 1965 | pmid = 14324315 | doi = 10.1021/ja01092a065 | url = }} Using boron trifluoride, the yield was 70%{{cite journal | vauthors = Gaoni Y, Mechoulam R | title = The isolation and structure of delta-1-tetrahydrocannabinol and other neutral cannabinoids from hashish | journal = Journal of the American Chemical Society | volume = 93 | issue = 1 | pages = 217–24 | date = January 1971 | pmid = 5538858 | doi = 10.1021/ja00730a036 }} although purity was not given.{{cite patent | title = Conversion of CBD to delta8-THC and delta9-THC | inventor = Webster GR, Sarna L, Mechoulam R | assign = Full Spectrum Laboratories Ltd. | gdate = 15 July 2008 | url = https://patents.google.com/patent/US20040143126A1/en | country = US | number = 20040143126 }}

Methods have been claimed for converting CBD to a mixture of Δ8-THC and Δ9-THC using "Zeolites selected from the group consisting of analcime, chabazite, clinoptilolite, erionite, mordenite, phillipsite, and ferrierite."{{cite patent | title = Zeolite catalyst and method for preparation of aromatic tricyclic pyrans |url=https://patents.google.com/patent/US11352337B1/en | country = US | number = 11352337B1 | assign = Acid Neutral Alkaline Laboratory. | inventor = Gindelberger D | gdate = 7 June 2022 }}

When CBD is treated with acid, Δ-8-Tetrahydrocannabinol may form as an impurity. Nevertheless, Δ-8-Tetrahydrocannabinol can be isolated and subsequently converted into THC.

• Δ-8-Tetrahydrocannabinol, which can be converted to THC by addition of HCl followed by dehydrochlorination.{{cite journal | vauthors = Mechoulam R, Braun P, Gaoni Y | title = A stereospecific synthesis of (-)-delta 1- and (-)-delta 1(6)-tetrahydrocannabinols | journal = Journal of the American Chemical Society | volume = 89 | issue = 17 | pages = 4552–4 | date = August 1967 | pmid = 6046550 | doi = 10.1021/ja00993a072 }}{{cite journal | vauthors = Mechoulam R, Braun P, Gaoni Y | title = Syntheses of 1 -tetrahydrocannabinol and related cannabinoids | journal = Journal of the American Chemical Society | volume = 94 | issue = 17 | pages = 6159–65 | date = August 1972 | pmid = 5054408 | doi = 10.1021/ja00772a038 }}{{cite patent | title = Methods for purifying trans-(-)-δ9-tetrahydrocannabinol and trans-(+)-δ9 tetrahydrocannabinol | inventor = Gutman AL, Etinger M, Fedotev I, Khanolkar R, Nisnevich G, Pertsikov B, Rukhman I, Tishin B | assign = SVC Pharma LP | pubdate = 14 July 2016 | status = Abandoned | url = https://patents.google.com/patent/US20160199344A1/en | country = US | number = 20160199344 }}
• Treatment of the purified Δ8 -THC under Lucas' reagent gives the chloro compound. Following treatment with potassium tert-amylate, the desired (-)-6a,10 a-trans-Δ9 -tetrahydrocannabinol is yielded. The Mechoulam and Petrzilka methods require three steps and involve at least two careful chromatographic separations to obtain (-)-6a,10 a-trans-Δ9 -tetrahydrocannabinol of high purity.{{cite patent | title = Process for the preparation of (-)-6a,10a-trans-6a,7,8,10a-tetrahydrodibenzo[b,d]-pyrans | inventor = Razdan RK, Dalzell HC | assign = Application filed by Sheehan John C Institute for Research Inc. | gdate = 24 May 1977 | url = https://patents.google.com/patent/US4025516A/en | country = US | number = 4025516 }}

There is a debated hypothesis that oral CBD could be metabolized into THC under acidic conditions in the stomach and then absorbed into the bloodstream. However, neither THC nor any of its active metabolites have been detected in blood in animals or humans after ingesting CBD. There is no direct evidence of the conversion of CBD to THC in the human gut; both CBD and THC are excreted unchanged within human feces.

== History ==

The conversion of CBD to THC by an acid based cyclization reaction was first patented by Roger Adams in the 1940s.https://patents.google.com/patent/US2419937A/en

• THC production by yeast

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{{Cannabis}}

Category:Cannabis culture