{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:10:42Z","timestamp":1787008242435,"version":"build-2736575974"},"reference-count":75,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cannabis &amp; Cannabinoid Research"],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Over the last decade, there has been a significant increase in the production of multiple tetrahydrocannabidiol (THC) related products\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      the acid catalysis of cannabidiol (CBD). The widespread availability of CBD and the unregulated or poorly regulated nature of its use have flooded the market with THC-containing products of unverifiable provenance and frequently contaminated by trace metals and residual solvents. Under non-optimized, poorly controlled, or harsh reaction conditions, these acid-catalyzed transformations yield multiple cannabinoids including \u0394\n                      <jats:sup>9<\/jats:sup>\n                      -THC and \u0394\n                      <jats:sup>8<\/jats:sup>\n                      -THC, along with numerous side products. These side products are rarely identified or quantified accurately, and their safety and pharmacology remain largely unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>This review aims to present an up-to-date understanding of one of the fundamental transformations in cannabinoid chemistry: the cyclization of CBD to THC. This knowledge will facilitate the development of safer, cleaner, more affordable, and accessible cannabinoid products while guiding medical practitioners and regulators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>We conducted a literature review of studies published over the last 5\u20136 years on the interconversion of CBD to THC. Our review focused on the following key aspects: (1) advances in understanding reaction mechanisms and optimizing desirable reaction outcomes; (2) development of new catalysts, including \u201cgreen chemistry\u201d approaches such as solid-supported acids; and (3) implementation of fit-for-purpose analytical methods to better characterize reaction outcomes and reassess the accuracy of cannabis and hemp product labeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Provided strict quality controls of materials, reaction conditions, and related isolation techniques, the latest research of the acid-catalyzed CBD cyclization shows that it is feasible to access products with elevated and consistently high quality, enriched with either CBD or THC fractions, in a cost-effective manner. Among a spectrum of possible products, easy access to low-potency THC compositions may be particularly relevant for serving the needs of medical patients consuming cannabis and hemp-derived cannabinoids including dose titration as well as to supporting safe and responsible use in recreational markets now saturated with overly potent products.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/can.2025.0015","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T21:17:51Z","timestamp":1745011071000},"page":"377-388","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Acid-Catalyzed Conversion of Cannabidiol to Tetrahydrocannabinols: En Route to Demystifying Manufacturing Processes and Controlling the Reaction Outcomes"],"prefix":"10.1177","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2707-6701","authenticated-orcid":false,"given":"Alex","family":"Nivorozhkin","sequence":"first","affiliation":[{"name":"C-Click Life Sciences, Inc., San Diego, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Palfreyman","sequence":"additional","affiliation":[{"name":"C-Click Life Sciences, Inc., San Diego, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01865a508"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)99446-3"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00993a072"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29061249"},{"key":"e_1_3_4_6_2","unstructured":"H.R.2-Agriculture Improvement Act of 2018. 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