A Conversion of oral cannabidiol to delta9-tetrahydrocannabinol seems not to occur in humans
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Abstract 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.
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Acute and chronic administration of CBD by various routes to healthy volunteers and patients with different clinical conditions did not induce significant adverse effects.
“According to comprehensive reviews, acute and chronic administration of CBD by various routes (oral, inhaled, intravenous) to healthy volunteers and patients with different clinical conditions did not induce significant adverse effects (50, 51), especially because a conversion of oral cannabidiol to THC seems not to occur in humans (52).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [52]
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- Authors
- Nahler, G., Grotenhermen, F., Zuardi, A. W., & Crippa, J. A. S.
- Affiliations
- Clinical Investigation Support (Austria) (AT)
- Nova Institut (DE)
- University of São Paulo Ribeirão Preto
- Universidade de São Paulo (BR)
- Corresponding author
- Nahler, Gerhard
- Venue
- Cannabis & Cannabinoid Research
- Publisher
- SAGE Publications
- Published
- 2017-01-01
- Volume
- 2
- Issue
- 1
- Pages
- 81-86
- ISSN
- 2378-8763 (ISSN-L)
- 2578-5125
- PMC
- PMC5510776
- OpenAlex
- W2613685814
- Cited by
- 61
- References
- 33
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 11 · 2022: 12 · 2021: 5 · 2020: 11 · 2019: 8 · 2018: 2
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cannabis and Cannabinoid Research (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (26/2014, 466805/2014‐4, 2014-4)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- cannabidiol, delta-9-tetrahydrocannabinol, delta-8-tetrahydrocannabinol, gastric juice, cannabinoid metabolism, nabilone, adverse effects, CB1 receptor
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