Therapeutic Potential and Predictive Pharmaceutical Modeling of Stilbenes in Cannabis sativa
Open accessAbstract
Cannabis sativa is a plant used for recreational and therapeutic purposes; however, many of the secondary metabolites in the plant have not been thoroughly investigated. Stilbenes are a class of compounds with demonstrated anti-inflammatory and antioxidant properties and are present in cannabis. Many stilbenes present in cannabis have been investigated for their therapeutic effects. Fourteen stilbenes have been identified to be present in cannabis, all of which are structurally dihydrostilbenoids, with half possessing a prenylated moiety. The stilbenes summarized in this analysis show varying degrees of therapeutic benefits ranging from anti-inflammatory, antiviral, and anti-cancer to antioxidant effects. Many of the identified stilbenes have been researched to a limited extent for potential health benefits. In addition, predictive in silico modeling was performed on the fourteen identified cannabis-derived stilbenes. This modeling provides prospective activity, pharmacokinetic, metabolism, and permeability data, setting the groundwork for further investigation into these poorly characterized compounds.
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Cannabis stilbenes are numerous, and many are unique to Cannabis, namely canniprene, cannastilbenes (I, IIa, and IIb), and many spiroindans, including cannabispirone.
“Cannabis stilbenes are numerous, and many are, to date, unique to Cannabis, namely canniprene, cannastilbenes (I, IIa, and IIb), and many spiroindans, including cannabispirone.”
From Exploring the Lesser-Known Bioactive Natural Products of Plant Species of the Genus Cannabis L.: Alkaloids, Phenolic Compounds, and Their Therapeutic Potential (2025) · cites this paper as [18]
The Introduction and Conclusions report fourteen stilbenes identified in Cannabis sativa, and §§2–3 identify canniprene and cannabistilbene I, IIa, and IIb. The cited paper does not establish that these compounds are unique to Cannabis, and the passages found do not identify cannabispirone or substantiate the claim about many spiroindans. No page numbers are available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredStilbenes have been reported to be less abundant but contribute to the plant's antioxidative profile and may enhance pharmacological effects of cannabinoids through synergistic interactions.
“Although stilbenes have been reported to be less abundant, they contribute to the plant’s antioxidative profile and may enhance the pharmacological effects of cannabinoids through synergistic interactions [18,19].”
From Exploring the Lesser-Known Bioactive Natural Products of Plant Species of the Genus Cannabis L.: Alkaloids, Phenolic Compounds, and Their Therapeutic Potential (2025) · cites this paper as [18]
The Introduction identifies stilbenes in cannabis, and §6.2 reports antioxidant activity for one stilbene, supporting the antioxidant aspect. The paper does not establish that stilbenes are less abundant than other cannabis compounds or that they enhance cannabinoids’ effects through synergy (searched: abundance, synergy, entourage effect). (LLM, conf=0.86)
Experimental — accuracy not yet measuredDihydroresveratrol reduced expression of IL-6, IL-18, and IL-1β mRNA in RAW 264.7 cells at 50 μM.
“Dihydroresveratrol exhibited anti-inflammatory activity, reducing the expression of IL-6, IL-18, and IL-1β mRNA in RAW 264.7 cells, when treated with 50 μM of the compound [18,121].”
From Exploring the Lesser-Known Bioactive Natural Products of Plant Species of the Genus Cannabis L.: Alkaloids, Phenolic Compounds, and Their Therapeutic Potential (2025) · cites this paper as [18]
Section 7.1 (page unavailable) reports that dihydroresveratrol decreased IL-6 mRNA expression and downregulated IL-1β and IL-18 expression in vitro. It does not identify RAW 264.7 cells or specify a 50 μM treatment, so those details are not supported by this paper's text. (LLM, conf=0.88)
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- Authors
- O’Croinin, C., Garcia Guerra, A., Doschak, M. R., Löbenberg, R., & Davies, N. M.
- Affiliations
- University of Alberta (CA)
- Faculty of Pharmacy and Pharmaceutical Sciences, Katz Centre for Pharmacy and Health Research, University of Alberta, Edmonton, AB T6G 2E1, Canada
- Corresponding author
- Davies, Neal M.
- Venue
- Pharmaceutics
- Publisher
- MDPI AG
- Published
- 2023-07-12
- Volume
- 15
- Issue
- 7
- Pages
- 1941
- ISSN
- 1999-4923 (ISSN-L)
- PMC
- PMC10386382
- OpenAlex
- W4384264283
- Cited by
- 25
- References
- 81
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 6 · 2023: 1
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Pharmaceutics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Mitacs research (Mitacs MI MA IT34436 RES0061921)
- Canurta to Applied Pharmaceutical Innovation (Mitacs MI MA IT34436 RES0061921)
- Faculty of Pharmacy and Pharmaceutical Sciences (Mitacs MI MA IT34436 RES0061921)
- Mitacs interns (Mitacs MI MA IT34436 RES0061921)
- NSERC master scholarship (Mitacs MI MA IT34436 RES0061921)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioactive natural compounds
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry and Biological Activities
- Keywords
- stilbenes, Cannabis sativa, secondary metabolites, anti-inflammatory activity, antioxidant activity, antiviral activity, anticancer activity, pharmacokinetic prediction, permeability prediction, in silico modeling, therapeutic potential
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