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Cannabis Cannabinoid Res. 2017 May 1;2(1):81-86. doi: 10.1089/can.2017.0009. eCollection 2017.

A Conversion of Oral Cannabidiol to Delta9-Tetrahydrocannabinol Seems Not to Occur in Humans.

Author information

CIS Clinical Investigation Support GmbH, Wien, Austria.
Nova-Institut GmbH, Chemiepark Knapsack, Hürth, Germany.
Department of Neuroscience and Behavior, University of São Paulo Ribeirão Preto, Brazil and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM).


Cannabidiol (CBD), a major cannabinoid of hemp, does not bind to CB1 receptors and is therefore devoid of psychotomimetic properties. Under acidic conditions, CBD can be transformed to delta9-tetrahydrocannabinol (THC) and other cannabinoids. It has been argued that this may occur also after oral administration in humans. However, the experimental conversion of CBD to THC and delta8-THC in simulated gastric fluid (SGF) is a highly artificial approach that deviates significantly from physiological conditions in the stomach; therefore, SGF does not allow an extrapolation to in vivo conditions. Unsurprisingly, the conversion of oral CBD to THC and its metabolites has not been observed to occur in vivo, even after high doses of oral CBD. In addition, the typical spectrum of side effects of THC, or of the very similar synthetic cannabinoid nabilone, as listed in the official Summary of Product Characteristics (e.g., dizziness, euphoria/high, thinking abnormal/concentration difficulties, nausea, tachycardia) has not been observed after treatment with CBD in double-blind, randomized, controlled clinical trials. In conclusion, the conversion of CBD to THC in SGF seems to be an in vitro artifact.


acid-catalyzed cyclization; cannabidiol; degradation; delta9-tetrahydrocannabinol; gastric fluid; isomerization

Conflict of interest statement

G.N. is manager of an independent consultancy firm and medical advisor of Trigal Pharma GmbH. F.G. is Executive Director of IACM,, and medical advisor of MedCann, A.W.Z. and J.A.C. are coinventors (Mechoulam R, JC, Guimaraes FS, AZ, JH, Breuer A) of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023”; Def. US No. Reg. 62193296; 29/07/2015; INPI em 19/08/2015 (BR1120150164927). University of São Paulo licensed it to Phytecs Pharm (Resolução USP No. 15.1.130002.1.1). University of São Paulo has an agreement with Prati-Donaduzzi (Toledo, Brazil): “Desenvolvimento de um produto farmacêutico contendo canabidiol sintético e comprovação de sua segurança e eficácia terapêutica na epilepsia, esquizofrenia, doença de Parkinson e transtornos de ansiedade.” J.A.C. received a travel support from BSPG-Pharm.

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