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Journal of Cannabis Research logoLink to Journal of Cannabis Research
. 2026 Jul 21;8:108. doi: 10.1186/s42238-026-00470-4

Phytochemistry, bioactivity, and medicinal use of Cannabis sativa roots: a comprehensive review

Tiago Antônio Heringer 1,✉, Chana de Medeiros da Silva 1,#, Daniela Fernandes Ramos 2,#, Lia Gonçalves Possuelo 1,#
PMCID: PMC13670809  PMID: 42477783

Abstract

Background

Cannabis sativa is among the earliest domesticated plants and has been widely utilized for nutritional, industrial, and medicinal purposes. While its aerial parts, particularly the leaves and inflorescences, have been extensively studied due to their recreational and therapeutic applications, the roots remain comparatively neglected, despite their long-standing use in traditional medicine for treating wounds, burns, and inflammation.

Aim

This review aims to summarize the current knowledge on the phytochemical composition and biological activities of C. sativa roots, with emphasis on their pharmacological potential. 

Results

The roots of C. sativa contain a diverse spectrum of secondary metabolites, including phytosterols, alkaloids, terpenes, and phenolic compounds. These bioactive constituents have been reported to exert antioxidant, anti-inflammatory, and antimicrobial activities. In vivo studies further demonstrate nociceptive and antispasmodic effects, with no evidence of cytotoxicity.

Conclusion

C. sativa roots represent an underexplored pharmacognostic resource with significant potential for the discovery of novel bioactive compounds. Their chemical diversity and biological activities provide a strong rationale for renewed scientific attention, supporting future research into this underestimated part of a species of growing medical and economic relevance.

Keywords: Cannabis, Medical; Plants, Medicinal; Phytochemicals; Plant Roots

Introduction

Cannabis sativa was originally domesticated in Eurasia around 2737 BC and was one of the first cultivated plants. Its fibers are widely used to make fabrics, the leaves are used to feed animals, and the seeds are consumed by humans, in addition to the psychoactive use of its flowers (Araújo et al. 2024).

Although currently cultivated on a global scale, this plant exhibits distinct phenotypic variations that are directly influenced by the specific geographical environment in which it develops (Odieka et al. 2022). Despite ongoing taxonomic debates, the prevailing convention classifies the genus Cannabis as a single species, Cannabis sativa L. (Schilling et al. 2020). Since antiquity, this species has been recognized for its therapeutic properties, being extensively utilized in both traditional and modern medicine due to the rich diversity of phytochemicals biosynthesized across various parts of its botanical structure (Ryz et al. 2017).

More than 500 compounds have been identified and most of them are cannabinoids, which were first discovered in this species. Notably, cultivars of this plant also hold other classes of secondary metabolites, such as phenols, flavonoids, alkaloids, terpenes, steroids, and resins (Dalli et al. 2023).

As a medicinal plant, C. sativa roots were initially used to relieve pain, heal burns, and treat infected wounds. However, the leaves and inflorescences became the primary focus of scientific inquiry due to the extensive clinical research into the therapeutic properties and pharmacological activity of the cannabinoids concentrated in the plant’s aerial parts (Hurgobin et al. 2021). In this context, the roots have been the subject of several studies on their phytochemical composition, but few studies have addressed their medicinal potential (Kornpointner et al. 2021).

This study aimed to conduct a review to identify the bioactive compounds and biological activities described for C. sativa roots.

Methods

Searches were conducted in the following databases: Index Medicus Western Pacific (WPRO), Latin American and Caribbean Health Sciences Literature (LILACS), Spanish Bibliographic Index of Health Sciences (IBECS), and SCOPUS, as well as PubMed, Cochrane Library, Web of Science, and Scientific Electronic Library Online (SciELO). The keywords used were: “roots” AND “Cannabis sativa” AND (“extract” OR “medicinal use”).

Studies published up to December 2024 were included, with no limit on publishing date. Firstly, evaluators checked the titles and abstracts, looking for words that referred to tests for the medicinal use of the roots. Full papers in Portuguese and English were included if they had conducted in vitro and in vivo analyses using C. sativa roots extracts for medicinal use or compounds isolated from these extracts. Review articles, duplicate studies, and paid access papers were excluded.

Bioactive compounds

Plants produce various compounds to protect them from microorganisms and other environmental factors. When consumed, these compounds alleviate oxidative stress, inflammatory processes, and prevent various diseases (Moges et al. 2025). Table 1 shows the compounds identified in C. sativa roots, their isolated amounts, and their biological activities, which will be divided and discussed according to their classes.

Table 1.

Biological activities of compounds found in C. sativa roots

Class Compound Quantities(ref) Biological Activity Reference
Phenolic compounds
graphic file with name 42238_2026_470_Figa_HTML.gif Vanillin

0,0076 mg/g (Elhendawy et al. 2019)

0,0006 mg/g (Huang et al. 2023)

 Antitumor, neuroprotective, antimicrobial (Arya et al. 2021; Elhendawy et al. 2019; Huang et al. 2023)
graphic file with name 42238_2026_470_Figb_HTML.gif p-Coumaroyltyramine 0,01978 mg/g (Elhendawy et al. 2019) Antitumor, antibacterial, antiurease, antifungal, antiviral, neuroprotective and cardioprotective (Araújo et al. 2024; Bakrim et al. 2024; Elhendawy et al. 2019; Menezes et al. 2021)
graphic file with name 42238_2026_470_Figc_HTML.gif Serinic acid 0,0011 mg/g (Huang et al. 2023) Antioxidant and anti-inflammatory (Bartel et al. 2024; Huang et al. 2023)
graphic file with name 42238_2026_470_Figd_HTML.gif Cetopinoresinol 0,00335 mg/g (Huang et al. 2023) Antitumor, antioxidant and immunomodulatory (Chen et al. 2012; Huang et al. 2023)
graphic file with name 42238_2026_470_Fige_HTML.gif Feruloyltyramine 0,00445 mg/g (Huang et al. 2023) Anti-inflammatory, anti-asthmatic (Araújo et al. 2024; Menezes et al. 2021; Gagné et al. 2024)
graphic file with name 42238_2026_470_Figf_HTML.gif Dihydrobenzofuran 0,0006 mg/g (Huang et al. 2023) Antiparasitic (Judžentienė et al. 2023; Omar et al. 2016)
graphic file with name 42238_2026_470_Figg_HTML.gif Vanillic acid 0,00625 mg/g (Huang et al. 2023) Anti-inflammatory (Huang et al. 2023)
graphic file with name 42238_2026_470_Figh_HTML.gif Syringol  < LOQ (Huang et al. 2023) Anti-tumor (Huang et al. 2023; Intisar et al. 2012)
Alkaloids
graphic file with name 42238_2026_470_Figi_HTML.gif Cannabisativin  < LOQ (Araújo et al. 2024) Analgesic, antiparasitic, antipyretic, antiemetic, antitumor, diuretic and analgesic (Araújo et al. 2024; Lowe et al. 2021; Huang et al. 2023; Menezes et al. 2021; Gagné et al. 2024)
Cannabinoids
graphic file with name 42238_2026_470_Figj_HTML.gif Cannabichromene Anti-inflammatory and anti-tumor (Maiocchi et al. 2024; Whynot et al. 2023; Huang et al. 2023)
graphic file with name 42238_2026_470_Figk_HTML.gif Cannabinol 0,0002 mg/g (Huang et al. 2023) Antimicrobial, anti-inflammatory, sleep regulator (Huang et al. 2023; Saleska et al. 2024; Gu et al. 2019)
graphic file with name 42238_2026_470_Figl_HTML.gif Cannabivarin 0,00045 mg/g (Huang et al. 2023) Antitumor (Whynot et al. 2023; Huang et al. 2023)
graphic file with name 42238_2026_470_Figm_HTML.gif 0,0003 mg/g (Huang et al. 2023) Neurological effects, rheumatological pain, sleep regulator and anxiety disorders (Carvalho et al. 2024; Komatsu et al. 2024; Pathak et al. 2024; Wang et al. 2024; Huang et al. 2023; Saleska et al. 2024)
graphic file with name 42238_2026_470_Fign_HTML.gif Cannabidiolic acid  < LOQ (Gagné et al. 2024) Antimicrobial, antinausea and antitumor effects (Gagné et al. 2024; Pellati et al. 2018)
Terpenes
graphic file with name 42238_2026_470_Figo_HTML.gif Glutinol  < LOQ (Kornpointner et al. 2021) Antitumor and antidiabetic (Kornpointner et al. 2021; Fantoukh et al. 2023; Abdel-Sattar et al. 2015; Pamunuwa et al. 2016)
graphic file with name 42238_2026_470_Figp_HTML.gif Friedelanol

0,239 mg/g (Ferrini et al. 2022)

0,06–0,20 mg/g (Kornpointner et al. 2021)

 Antitumor, anti-inflammatory and antioxidant (Kornpointner et al. 2021; Oliveira et al. 2024; Waghole et al. 2022; Elhendawy et al. 2019; Huang et al. 2023; Ferrini et al. 2022)
graphic file with name 42238_2026_470_Figq_HTML.gif Friedelin

0,42—0,71 mg/g (Kornpointner et al. 2021)

0,288 mg/g (Ferrini et al. 2022)

0,065 mg/g (Huang et al. 2023)

 Antitumor, anti-inflammatory, antimicrobial and antifungal (Kornpointner et al. 2021; Singh et al. 2023; Elhendawy et al. 2019; Huang et al. 2023; Judžentienė et al. 2023; Ferrini et al. 2022)
graphic file with name 42238_2026_470_Figr_HTML.gif β-Amyrin  < LOQ (Kornpointner et al. 2021) Anti-inflammatory, analgesic, antihyperglycemic and nephroprotective (Judžentienė et al. 2023; Alam et al. 2024; Angsusing et al. 2024; Roohi et al. 2024)
graphic file with name 42238_2026_470_Figs_HTML.gif β-Amirone  < LOQ (Kornpointner et al. 2021) Analgesic, antidiarrheal and hypoglycemic (Kornpointner et al. 2021; Taher et al. 2024)
graphic file with name 42238_2026_470_Figt_HTML.gif Oleanolic acid 0,0014 mg/g (Huang et al. 2023) Antitumor, antimycobacterial (Zhou et al. 2024; Huang et al. 2023; Deng et al. 2024; Mazzarotti et al. 2024; Saini et al. 2024)
graphic file with name 42238_2026_470_Figu_HTML.gif Ursolic acid  < LOQ (Gagné et al. 2024) Antitumor, antimycobacterial (Gagné et al. 2024; Saini et al. 2024; Zeng et al. 2024)
Phytosterols
graphic file with name 42238_2026_470_Figv_HTML.gif Fucosterol  < LOQ (Kornpointner et al. 2021) Antiviral, antitumor, antiparasitic (Kornpointner et al. 2021; Li et al. 2021; Mo et al. 2018; Perumal et al. 2018)
graphic file with name 42238_2026_470_Figw_HTML.gif Oleamide  < LOQ (Kornpointner et al. 2021) Antibacterial and sleep regulation (Kornpointner et al. 2021; Purwantiningsih et al. 2024; Roy et al. 2021)
graphic file with name 42238_2026_470_Figx_HTML.gif Ethyl palmitate  < LOQ (Kornpointner et al. 2021) Antiviral and anti-inflammatory (Kornpointner et al. 2021; Sagna et al. 2023; Saeed et al. 2012)
graphic file with name 42238_2026_470_Figy_HTML.gif Ethyl linoleate  < LOQ (Kornpointner et al. 2021)

Healing, antimicrobial, antioxidant and anti-

inflammatory

 (Kornpointner et al. 2021; Alavi and Ashengroph 2023; Park et al. 2014; Jelenko et al. 1975)
graphic file with name 42238_2026_470_Figz_HTML.gif Ethyl stearate  < LOQ (Kornpointner et al. 2021) Anti-inflammatory and neuroprotective (Kornpointner et al. 2021; Huang et al. 2023; Miya et al. 2023)
graphic file with name 42238_2026_470_Figaa_HTML.gif β-Sitosterol 0,687 mg/g (Ferrini et al. 2022) Antiviral, antitumor, analgesic and antidiarrheal (Kornpointner et al. 2021; Khan et al. 2022; Elhendawy et al. 2019; Huang et al. 2023; Ferrini et al. 2022; Taher et al. 2024)
graphic file with name 42238_2026_470_Figab_HTML.gif Campesterol 0,172 mg/g (Ferrini et al. 2022) Antimicrobial (Freitas da Silva et al. 2023; Elhendawy et al. 2019; Judžentienė et al. 2023; Ferrini et al. 2022)
graphic file with name 42238_2026_470_Figac_HTML.gif Stigmasterol 0,202 mg/g (Ferrini et al. 2022) Anti-inflammatory (Yu et al. 2022; Judžentienė et al. 2023; Ferrini et al. 2022; Angsusing et al. 2024)
graphic file with name 42238_2026_470_Figad_HTML.gif Palmitic acid  < LOQ (Judžentienė et al. 2023) Anti-tumor (Xu et al. 2024; Judžentienė et al. 2023; Zhu et al. 2021)
graphic file with name 42238_2026_470_Figae_HTML.gif γ-Sitosterol  < LOQ63 Antiviral and antitumor (Shokry et al. 2023; Khan et al. 2022; Judžentienė et al. 2023)
graphic file with name 42238_2026_470_Figaf_HTML.gif Palmitoleic acid 0,03185 mg/g (Elhendawy et al. 2019) Antibacterial (Elhendawy et al. 2019; Han et al. 2024; Xu et al. 2025)
graphic file with name 42238_2026_470_Figag_HTML.gif Ergosterol peroxide 0,0007 mg/g (Huang et al. 2023) Antiviral and antimycobacterial (Zhou et al. 2019; Chiou et al. 2024; Duan et al. 2021; Duarte et al. 2007; Huang et al. 2023)
graphic file with name 42238_2026_470_Figah_HTML.gif α-linolenic acid 0,00255 mg/g (Huang et al. 2023) Antitumor, anti-inflammatory and antioxidant (Yuan et al. 2022; Huang et al. 2023)
graphic file with name 42238_2026_470_Figai_HTML.gif Linoleic acid 0,00125 mg/g (Huang et al. 2023) Antioxidant and anti-tumor (Huang et al. 2023; Gagné et al. 2024)
graphic file with name 42238_2026_470_Figaj_HTML.gif Dotriacontene 0,0007 mg/g (Huang et al. 2023) Anti-inflammatory (Huang et al. 2023)
graphic file with name 42238_2026_470_Figak_HTML.gif Pentadecanoic acid 0,00885 mg/g (Elhendawy et al. 2019) Antibiofilm, anti-inflammatory, antifibrotic and antitumor (Galdiero et al. 2021; Venn-Watson and Schork 2023; Huang et al. 2023)
graphic file with name 42238_2026_470_Figal_HTML.gif Palmitoleic acid 0,03185 mg/g (Elhendawy et al. 2019) Anti-inflammatory and antimicrobial (Huang et al. 2023; Tabashsum et al. 2025)
graphic file with name 42238_2026_470_Figam_HTML.gif Stearolic acid  < LOQ (Gagné et al. 2024) Anti-parasitic (Gagné et al. 2024; Alloatti et al. 2013; Londero et al. 2018)
Open in a new tab

Caption: < LOQ—Below Limit of Quantification; (ref)—Reporting study

Phenolic compounds

Phenolic compounds are a heterogeneous group of phytochemicals found in plants, divided into classes according to their chemical structure and biological function. These metabolites are crucial for the defense mechanisms of the plant and can contribute to human health with its anti-inflammatory, antioxidant, and antimicrobial properties (Baptista et al. 2024). Phenolic compounds can be divided into groups such as phenolic acids, flavonoids, tannins, and lignans, which have a basic structure containing an aromatic ring with one or more hydroxyls. Their antioxidant capacity can be closely related to the number of free hydroxyls; thus compounds that donate more electrons have a higher antioxidant activity (de Castro et al. 2022).

One of the phenolic compounds isolated from C. sativa roots was vanillin, a substance widely used in the industry as a food flavoring. A range of therapeutic properties have been associated to it, such as antitumor, neuroprotective, and antimicrobial activity, as well as being used to potentiate the action of antibiotics such as gentamicin, chloramphenicol, ciprofloxacin, and meropenen against resistant strains of P. aeruginosa, S. aureus, and E. coli (Arya et al. 2021).

P-coumaroyltyramine helps to prevent heart and vascular diseases and neurological disorders, and is also effective in antitumor, antibacterial, antiurease, antifungal, and antiviral activity tests (Bakrim et al. 2024). Serinic acid works as a nutraceutical, improving oxidative damage, anti-inflammatory action, thus reducing metabolic risks and dyslipidemia (Bartel et al. 2024). Cetopinoresinol has anti-tumor activity due to its immunomodulatory and antioxidant capacity (Chen et al. 2012).

Alkaloids

Alkaloids are nitrogen-based organic compounds that have various biological activities. Due to presenting different chemical structures, they can be divided into isoquinolines, pyridines, quinolines, among others. Such composition enables various actions and effects such as anticancer, anti-inflammatory, antibacterial, and antiviral activities (Chua et al. 2024; Yan et al. 2021). These organic compounds have at least one nitrogen atom in an amine-type structure, which is usually incorporated into a cyclic system. This characteristic allows them to react with acids to form salts (Eguchi et al. 2019).

Cannabisativine is an alkaloid that was first isolated from C. sativa roots in 1975. By investigating this compound, a study has found analgesic and antiparasitic activities, as well as antipyretic, antiemetic, antitumor, diuretic, and analgesic capabilities (Lowe et al. 2021). It is a macrolactam, which is a cyclic amide derived from carboxylic amino acids and characterized by a 1-azacycloalkan-2-one structure (or analogues) with unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Its chemical structure includes three fused rings: a pyridine ring, a piperidine ring, and a 13-membered lactam ring, and it has hydroxyl and amine functional groups (Radwan et al. 2021).

Cannabinoids

This class is not found in large quantities in roots. They have a carbocyclic structure with 21 carbon atoms, generally formed by three rings: cyclopentane, tetrahydropyran, and benzene. The main cannabinoids include Δ⁹-tetrahydrocannabinol (Δ⁹-THC), cannabidiol (CBD), and cannabinol (CBN) (Barrales-Cureño et al. 2020).

CBD is the main cannabinoid found in C. sativa and is the most studied one, known for its neurological effects, aid in pain alleviation, and treatment of rheumatological diseases and disorders such as anxiety (Carvalho et al. 2024; Komatsu et al. 2024; Pathak et al. 2024; Wang et al. 2024). Another cannabinoid found in the roots is tetrahydrocannabivarin, which is very similar in nomenclature to Δ⁹-THC. Notably, it has very different characteristics, having been tested as an appetite regulator for the treatment of obesity and diabetes (Haghdoost et al. 2024). Cannabichromene has anti-inflammatory activity (Maiocchi et al. 2024) and shows results in reducing the proliferation of bladder cancer cells, along with other cannabinoids such as cannabivarin (Whynot et al. 2023).

Terpenes

These are hydrocarbons derived from isoprene (C₅H₈) and can be classified according to the number of isoprene units they contain: monoterpenes (C₁₀H₁₆), sesquiterpenes (C₁₅H₂₄), diterpenes (C₂₀H₃₂), among others. Their basic structure is made of multiple isoprene units joined head-to-tail, forming linear chains or complex cyclic structures that have antioxidant, anti-tumor, and anti-inflammatory characteristics (Lukman et al. 2024).

Glutinol is one of the compounds found in C. sativa roots, which has shown antitumor action against MCF-7 breast tumor cell lines (Fantoukh et al. 2023). Some compounds derived from this terpene have shown antifungal activity against phytopathogenic fungi of the genus Fusarium (2024). Also, friedelanol has antitumor and anti-inflammatory properties (Oliveira et al. 2024; Waghole et al. 2022). Friedelin is another triterpene of the same class isolated from roots, presenting antitumor and anti-inflammatory properties, as well as antimicrobial activity against: Gram-positive bacteria, such as S. aureus, S. epidermidis, and Bacillus cereus; Gram-negative bacteria, such as Proteus mirabilis, E. coli, K. pneumoniae; and the fungi Aspergillus fumigates and Trichophyton rubrum (Singh et al. 2023).

Phytosterols

Phytosterols are plant sterols structurally similar to cholesterol, characterized by a tetracyclic cyclopentanoperhydrophenanthrene nucleus with a side chain on carbon 17. The most common phytosterols include β-sitosterol, campesterol, and stigmasterol, which have a double bond at position 5 and methyl or ethyl substituents on the side chain at carbon 24 (Barkas et al. 2023). Phytosterols were the most found class in the studies included in this review. They are nonpolar substances found in different plant species and studied for various purposes due to their high antioxidant capacity (Liu et al. 2024). β and γ-sitosterol are esters analogous to cholesterol, which have antiviral properties (Shokry et al. 2023) and antitumor activities (Khan et al. 2022), which are also found in fucosterol (Jiang et al. 2023; Li et al. 2021; Mo et al. 2018), and antiparasitic properties when tested against Plasmodium falciparum (Perumal et al. 2018).

Oleamide has demonstrated antibacterial properties against the bacterium P. aeruginosa (Purwantiningsih et al. 2024), and is an important endocannabinoid in sleep regulation (Roy et al. 2021). Ethyl palmitate has antiviral (Sagna et al. 2023) and anti-inflammatory properties (Saeed et al. 2012), whereas ethyl linoleate is effective as a wound healer, antimicrobial, antioxidant (Alavi and Ashengroph 2023), and anti-inflammatory (Park et al. 2014). Campesterol has emerged as an alternative source of new antimicrobial substances and has been tested against various bacteria with semi-synthesized compounds from campesterol (Freitas da Silva et al. 2023).

Studies have indicated antitumor activity of palmitic acid (Zhou et al. 2024; Xu et al. 2024), Ergosterol peroxide has promising antiviral properties against different viruses (Zhou et al. 2019; Chiou et al. 2024; Duan et al. 2021) and is active in tests against MTB (Duarte et al. 2007), while α-linolenic acid has antitumor, anti-inflammatory, and antioxidant activities (Yuan et al. 2022). Pentadecanoic acid has shown antibiofilm activity against C. albicans and K. pneumoniae (Galdiero et al. 2021), anti-inflammatory, antifibrotic, and anticancer activities via the activation of enzymes such as Adenosine Monophosphate-Activated Protein Kinase (AMPK), and inhibition of the JAK-STAT pathway, which signals cytokines that control the inflammatory process (Venn-Watson and Schork 2023).

Different extraction processes were conducted: cold maceration; hot and cold maceration; fermentation and cold maceration; hot maceration with fermentation, and cold maceration. By using these different processes, authors aimed to test the increased effectiveness in obtaining compounds and the antioxidant capacity of each one, proving the effectiveness of obtaining stigmasterol according to the increased complexity of the extraction process (Yu et al. 2022).

Biological activities

The use of C. sativa roots in traditional medicine has led to some research using extracts of this pharmacogen, and tests have been conducted on its antimicrobial, anti- inflammatory, and antioxidant activity in vitro, as well as evaluating other biological activities in vivo, such as antipyretic, antinociceptive, and antispasmodic action.

Antimicrobial activity

The antimicrobial activities of the isolated compounds of the extracts were tested focusing on their medicinal use (Table 2). Two compounds showed promising activity: campesterol and p-coumaroyltyramine; The first one was found to hold fungicidal activity against C. neoformans with an IC50 value of 13.7 μg/mL. The latter one showed activity against the Gram-negative bacterium E. coli with an IC50 value of 0.8 μg/mL (Elhendawy et al. 2019). Campesterol is a phytosteroid present in different plant species, some of which have anti-inflammatory activity (Wang et al. 2020), and p-coumaroyltyramine is known for its antiviral, antimicrobial, and anticoagulant activities (Masi et al. 2021). The extracts had inhibitory results when tested against S. aureus, E. coli, and C. albicans. Note that the concentration used to inhibit Gram-positive bacteria was high (> 800 µg/mL) (Gagné et al. 2024).

Table 2.

Antimicrobial results of studies with Cannabis sativa roots

Compound Microorganism MIC ref
Campesterol1 C. neoformans 13.7 μg/mL Elhendawy et al. 2019)
p-coumaroyltyramine1 E. coli 0.8 μg/mL
AgNPs S. aureus 65 μg/mL Suman et al. 2022)
E. coli 70 μg/mL
P. aeruginosa 75 μg/mL
K. pneumoniae 60 μg/mL

Aqueous extract2

Acid–base extract2

 C. albicans

180 μg/mL

120 μg/mL

 Gagné et al. 2024)
Open in a new tab

Caption: 1—Isolated compound; 2—Extract

AgNPs silver nanoparticles, MIC minimum inhibitory concentration

Another study tested the antimicrobial capacity of Cannabis roots by obtaining silver nanoparticles (AgNPs). The ethanolic extract was used to obtain the AgNPs, which were tested against Gram-positive and Gram-negative bacteria, obtaining the following minimum inhibitory concentrations: S. aureus (65 μg/mL), E. coli (70 μg/mL), P. aeruginosa (75 μg/mL), and K. pneumoniae (60 μg/mL)91. This same study tested the hemolytic capacity and cytotoxic effect of AgNPs, founding no effect. The extract was not characterized. Nevertheless, obtaining and analyzing the AgNPs was promising, because they have emerged as a new alternative treatment for resistant bacteria, acting mainly on the membranes of microorganisms, facilitating the permeability of other compounds or changing the physicochemical properties of this membrane by breaking it (Alavi and Ashengroph 2023).

Anti-inflammatory properties

The anti-inflammatory capacity of the Cannabis root extract and the isolated compounds, two triterpenes and one phytosterol, showed promising results in both the extract and the terpenic compounds, helping to prevent the expression of inflammation markers such as interleukin IL6 and Tnfα (Ferrini et al. 2022). When measuring the production of IL-6 by liposaccharide stimulation of differentiated human monocytic leukemia (THP-1) cells, a significant result was obtained from the aqueous extract of C. sativa roots (Gagné et al. 2024).

In another study, the anti-inflammatory properties of the isolated compounds were tested, in which the six isolated cannabinoids showed anti-inflammatory effects by reducing pro-inflammatory cytokines in an inflammasome model with THP-1 cells. Six of the other non-cannabinoid compounds reduced the expression of the IL1β and TNFα markers (Huang et al. 2023). In recent years, the anti-inflammatory and immunomodulatory capacity of terpenes has been widely studied. Notably, they are abundant in various plant species, so they have been increasingly highlighted as anti-inflammatory and immunomodulatory compounds (Miranda et al. 2022). Phytosterols are similar in structure to cholesterol and have antitumor, antioxidant, and anti-inflammatory properties (Liu et al. 2022). Phenols and polyphenols can chelate or annul oxidizing compounds, acting as natural anti-inflammatories (Fernandes et al. 2023).

A study evaluated the anti-inflammatory effect of the cannabis roots extracts using RAW264.7 murine macrophage cells, which were treated with liposaccharides. Besides evaluating the anti-inflammatory effect, the authors also investigated the expression of the Nitric Oxide Synthesis Inducing Protein (iNOS), an inflammatory marker. The authors identified that the anti-inflammatory effect was proportional to the complexity of the extraction and the amount of stigmasterol in the sample (Yu et al. 2024).

Antioxidant properties

The antioxidant activity of the root extract (Table 3) and of the isolated compounds in which the extract performed best (80%), with most compounds being slightly less efficient (65%), was in the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) test. There was a difference in the chelating capacity between the isolated compounds showing the extract was the most efficient (80%), followed by β-sitosterol (75%), in the Fe + chelating test. The same results were obtained when tested in cell culture to see if the antioxidant capacity was maintained. Note that when the cytotoxicity and DNA damage capacity of C. sativa root extracts were tested, no damage to DNA structures was ideintified (Ferrini et al. 2022).

Table 3.

Antioxidant analysis of studies on Cannabis sativa roots

Extract/compound Test performed Results Ref
Friedelin1

DPPH

Fe chelator

832.4 ± 1.7 μg/mL

883.5 ± 7.2 μg/mL

 Ferrini et al. 2022)
β-Sitosterol1

DPPH

Fe chelator

920.2 ± 3.4 μg/mL

858.8 ± 6.2 μg/mL
Friedelanol1

DPPH

Fe chelator

875.1 ± 1.7 μg/mL

547.6 ± 6.3 μg/mL
Ethanolic2

DPPH

Fe chelator

420.1 ± 2.1 μg/mL

385.5 ± 3.0 μg/mL
Ethanolic2

FRAP ABTS

Intracellular oxidation

97.1 ± 3.8

89.1 ± 2.5

0.809 ± 0.013

 Kornpointner et al. 2021)
Methanolic2 DPPH 1.556 ± 0.004 mmol/L Judžentienė et al. 2023)
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Caption: 1—Isolated compound; 2—Extract

DPPH 2,2-diphenyl-1-picrylhydrazyl radical, FRAP Iron Antioxidant Power, ABTS antioxidant capacity of 2,2'- azinobis-3-ethylbenzothiazoline-6-sulfonic acid

Another study tested antioxidant capacity using the Iron Antioxidant Power (FRAP) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) techniques. The researcher also employed an in vivo technique, using the fungus Saccharomyces cerevisiae to assess the intracellular antioxidant power, obtaining a promising result. However, this capacity cannot be attributed to the triterpenes, since another sample with more triterpenes showed the lowest antioxidant action value, which may be due to the phytosterols (Kornpointner et al. 2021). When the antioxidant capacity was tested using the ABTS test, the aqueous extract showed greater antioxidant capacity when compared to the ethanolic and basic acid extracts (Gagné et al. 2024). An analysis of the antioxidant potential by hydrogen peroxide inhibition (H2O2) was conducted, in which the roots showed antioxidant capacity (Judžentienė et al. 2023). Secondary metabolites have a high antioxidant capacity and the main ones include phenolic compounds, terpenes, and alkaloids (Oreopoulou et al. 2021).

Biological activities in vivo

A study tested the extracts as antipyretics in young Rattus norvegicus males, in addition to testing the antinociceptive, anticonvulsant, and antispasmodic capacity in Mus musculus specimens. The aqueous extract of the roots was able to reduce contortions caused by acetic acid in M. musculus at a concentration of 12.5 mg/kg and did not have the same result at higher concentrations. A similar result was observed when the antinociceptive capacity was tested, in which a reduction in pain was observed at a concentration of 12.5 mg/kg. In the hot plate pain latency test, the rodents had an increase in pain latency at all concentrations of the extract (12.5, 25 and 50 mg/kg). No antipyretic or spasmolytic activity was observed with this extract at any of the concentrations (Menezes et al. 2021).

Also in murine models, the action of the aqueous extract of C. sativa roots was used to attempt the reduction of abdominal contractions caused by primary dysmenorrhea, which was effective at concentrations of 12.5, 25 and 50 mg/kg, demonstrating an antidysmenorrheal effect at all concentrations and not showing spasmolytic effect (Araújo et al. 2024).

Conclusion

This review highlights the bioactive compounds and medicinal potential of Cannabis sativa roots, broadening current understanding of this historically important yet scientifically underexplored plant organ. While C. sativa has long been recognized as a medicinal species, research has largely focused on the psychoactive properties of its aerial parts, overshadowing the pharmacological relevance of its roots.

Evidence to date demonstrates that C. sativa roots possess antioxidant, anti-inflammatory, antinociceptive, and antispasmodic activities, as well as promising antibacterial and antifungal properties, with no reports of cytotoxicity or genotoxicity. Their rich content of secondary metabolites, including terpenes, phytosterols, phenolic compounds, alkaloids, and cannabinoids, positions the roots as a valuable source of pharmacologically active molecules with potential therapeutic applications.

Strengths, limitations, and future prospects

This review contributes by integrating scattered evidence on the phytochemistry and pharmacological activities of C. sativa roots, providing a comprehensive overview rather than isolated discussions of extraction techniques or single therapeutic uses. However, the heterogeneity of geographical origins and environmental conditions across the reviewed studies represents a major limitation, as factors such as climate, soil composition, and harvest time strongly influence phytochemical profiles and complicate comparisons. Despite these gaps, the findings underscore that systematic and standardized studies on C. sativa roots may yield novel bioactive compounds with significant pharmacological value.

Future research should prioritize detailed phytochemical characterization, mechanistic pharmacological studies, and controlled in vivo and clinical evaluations. Ultimately, the roots of C. sativa represent a neglected pharmacognostic resource with considerable potential to contribute to drug discovery and the development of new therapeutic strategies.

Authors’ contributions

TAH designed and wrote the manuscript. LGP, DFR, and CMS contributed to the revision of individual sections. All authors contributed to the revision of the entire manuscript and read and approved the final manuscript. Disclosure Statement: No potential conflicts of interest were reported by the authors. Funding: The authors received no funding to support this work.

Funding

This study has not had any funds.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Chana de Medeiros da Silva, Daniela Fernandes Ramos and Lia Gonçalves Possuelo contributed equally to this work.

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Data Availability Statement

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