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Cited by 97Cannabis and Cannabinoid ResearchPhytochemistry and Biological ActivitiesMedicinal Plant Research

Non-Cannabinoid Metabolites of Cannabis sativa L. with Therapeutic Potential

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Lowe, Henry, Steele, Blair, Bryant, Joseph, Toyang, Ngeh, Ngwa, Wilfred·2021·Plants
DOI 10.3390/plants10020400PMC PMC7923270
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Abstract

The cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most-prominent and most-studied secondary metabolites—Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Both Δ9-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids—of which approximately over 104 exist. This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus OC43 (HCov-OC43) that is responsible for COVID-19, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials. As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed.

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  • Cannabis contains nitrogen-containing specialized metabolites including alkaloids cannabisativine and anhydrocannabisativine, which are exclusive as of yet to Cannabis.

    “The nitrogen-containing (NC) specialized metabolites in Cannabis, which include alkaloids cannabisativine and anhydrocannabisativine, exclusive as of yet to Cannabis, simple amines with valuable activity like hordenine, produced notably by barley, and amides commonly found in medicinal plants, namely coumaroyltyramine and derivatives, as well as cannabisins.”

    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 [30]

    Section 2.5, “Alkaloids in Cannabis” (page not provided), identifies cannabisativine and anhydrocannabisativine as alkaloids produced by Cannabis sativa and defines alkaloids as nitrogen-containing compounds. It does not say that either alkaloid is exclusive to Cannabis; the paper's statement of uniqueness in section 2.6 concerns cannabisins instead. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Fifteen phenolic amides and lignanamides have been identified in Cannabis.

    “Additionally, fifteen phenolic amides and lignanamides have been identified in Cannabis (Figure 1 and Figure 2).”

    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 [30]

    Section 2.6 (page unavailable) identifies lignanamides produced in cannabis and mentions phenolic amides. It lists Cannabisin A–G, Grossamide, and four additional lignanamides, but does not state that fifteen phenolic amides and lignanamides have been identified. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • These metabolites are primarily found in the leaves and flowers of Cannabis.

    “These metabolites are primarily found in the leaves and flowers of Cannabis.”

    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 [30]

    Section 2.1 describes non-cannabinoid metabolites profiled in cannabis inflorescences and leaves. However, the Conclusions (section 3; page unavailable) say these phytochemicals occur throughout the plant, including roots and stems, and identify trichomes—not leaves and flowers—as the primary site of production. The copy does not establish that the metabolites are primarily found in leaves and flowers. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Other Cannabis metabolites include cannabisins A to G, cannabisins M, N and O, 3,3′-demethylheliotropamide, and grossamide, with cannabisins B and G present in roots.

    “Other metabolites include cannabisins A to G, as well as cannabisins M, N and O, 3,3′-demethylheliotropamide, and grossamide, with cannabisins B and G present in the roots [12,14,29,30,41].”

    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 [30]

    Section 2.6, “Lignanamides and Phenolic Acids” (page unavailable), lists cannabisins A–G, M, N and O, 3,3′-demethyl-heliotropamide, and grossamide as cannabis metabolites. It does not say that cannabisins B and G are present in roots; its specific location statement concerns M, N and O and 3,3′-demethyl-heliotropamide in hemp seed. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Flavonoids and stilbenes lack nitrogen, are derived from the phenylpropanoid pathway, and exhibit biological activities of medical interest.

    “While flavonoids and stilbenes lack a nitrogen atom in their structures, they are derived from the phenylpropanoid pathway and exhibit biological activities of medical interest.”

    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 [30]

    The Introduction identifies the phenylpropanoid pathway for flavonoids, and §§2.3 and 2.8 describe medically relevant biological activities of flavonoids and stilbenes. The copy does not identify that pathway for stilbenes or explicitly state that either class lacks nitrogen. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Lowe, H., Steele, B., Bryant, J., Toyang, N., & Ngwa, W.
Affiliations
  • University of Maryland, Baltimore (US)
  • University of the West Indies (JM)
  • Vilotos Pharmaceuticals Inc., Baltimore, MD 21202, USA
  • Brigham and Women's Hospital (US)
Corresponding author
  • Steele, Blair
  • Ngwa, Wilfred
ORCID
Venue
Plants
Publisher
MDPI AG
Published
2021-02-20
Volume
10
Issue
2
Pages
400
ISSN
2223-7747 (ISSN-L)
DOI
10.3390/plants10020400
PMC
PMC7923270
OpenAlex
W3131151527
Cited by
97
References
6
Citations by year
2026: 13 · 2025: 12 · 2024: 23 · 2023: 19 · 2022: 22 · 2021: 8
FWCI
2.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Plants (publishedVersion, cc-by)
  • Preprints.org (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry and Biological Activities
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Medicinal Plant Research
Keywords
Cannabis sativa, phytochemicals, flavonoids, terpenes, HCoV-OC43, COVID-19 pandemic, anticancer activity, medical cannabis, therapeutic potential

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