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Oral Cannabidiol Does Not Convert to Δ8-THC or Δ9-THC in Humans: A Pharmacokinetic Study in Healthy Subjects

Introduction: Recent studies have suggested that cannabidiol (CBD) could interconvert into Delta-8- and Delta-9- tetrahydrocannabinol. Materials and Methods: Thus, we tested the plasma samples of 120 healthy human subjects (60 male and 60 female), 60 in fasting and the other 60 under normal feeding conditions after acute administration of an oral solution containing CBD 300 mg. To do this, we developed a bioanalytical method to determine CBD and the presence of THC in plasma samples by…

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. 2020 Feb 27;5(1):89-98.

doi: 10.1089/can.2019.0024. eCollection 2020 Mar 1.

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José Alexandre S Crippa et al. Cannabis Cannabinoid Res. .

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Abstract

Introduction: Recent studies have suggested that cannabidiol (CBD) could interconvert into Delta-8- and Delta-9- tetrahydrocannabinol. Materials and Methods: Thus, we tested the plasma samples of 120 healthy human subjects (60 male and 60 female), 60 in fasting and the other 60 under normal feeding conditions after acute administration of an oral solution containing CBD 300 mg. To do this, we developed a bioanalytical method to determine CBD and the presence of THC in plasma samples by Ultra-High Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry. Results: The results showed that THC was not detected in plasma after the administration of CBD, and those study participants did not present psychotomimetic effects. Conclusions: The findings presented here are consistent with previous evidence suggesting that the oral administration of CBD in a corn oil formulation is a safe route for the administration of the active substance without bioconversion to THC in humans.

Keywords: UHPLC-ESI-MS/MS; cannabidiol; delta-8-tetrahydrocannabinol; delta-9-tetrahydrocannabinol; interconversion; pharmacokinetics; protein precipitation.

Conflict of interest statement

J.A.S.C., A.W.Z., and J.E.C.H. are coinventors of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023,” Def. US number Reg. 62193296; July 29, 2015; INPI on August 19, 2015 (BR1120150164927; Mechoulam R, Zuardi A.W., Kapczinski F, Hallak J.E.C, Guimarâes F.S., Crippa J.A.S., Breuer A). The University of São Paulo has licensed the patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1). The University of São Paulo has an agreement with PratiDonaduzzi Pharm to “develop a pharmaceutical product containing synthetic CBD and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson’s disease, and anxiety disorders.” J.A.S.C. is a member of the International Advisory Board of the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE – National Health and Medical Research Council, NHMRC).

Figures

FIG. 1.

FIG. 1.

Nomenclature, molecular formulas, and molar masses of the compounds analyzed.

FIG. 2.

FIG. 2.

Gradient conditions applied to the chromatographic method.

FIG. 3.

FIG. 3.

Selectivity of the LC-MS/MS method. (A) Blank plasma sample, (B) blank plasma sample spiked with IS, (C) blank plasma spiked with LLOQ: 1.5 ng/mL, (D) blank plasma spiked with ULQ: 500 ng/mL, (E) blank plasma spiked with Δ-THC, and (F) blank plasma spiked with Δ-THC. IS, Internal Standard; LC-MS/MS, chromatography triple quadrupole mass spectrometry; LLOQ, lower limit of quantification; THC, tetrahydrocannabinol.

FIG. 4.

FIG. 4.

MS/MS spectrums (precursor → product) of the (a) CBD, (b) Δ-THC, and (c) Δ-THC compounds, respectively. CBD, cannabidiol.

FIG. 5.

FIG. 5.

Chromatograms of Cmax of a volunteer at collection time 04:30 h in normal and approximate scale for the fed-pharmacokinetic study.

FIG. 6.

FIG. 6.

Chromatograms of Cmax of a volunteer at collection time 04:30 h on the average and approximate scale for the fasting pharmacokinetic study.

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