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

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“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.”

https://pubmed.ncbi.nlm.nih.gov/42477783

https://link.springer.com/article/10.1186/s42238-026-00470-4

Effects of cannabidiol in comparison to hormonal therapy on estrogen decline-induced memory impairments and endocannabinoid system in rats

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“The aim of this study was to investigate the effects of cannabidiol (CBD) on memory deficits induced by ovariectomy and to directly compare its effects with those of hormone therapy, in order to better understand potential shared mechanisms related to menopause-associated cognitive decline, with a particular focus on the endocannabinoid system.

Three-month-old female Wistar rats were randomly assigned to four experimental groups: SHAM-Veh (Vehicle), OVX-Veh, OVX-E2 (estradiol), and OVX-CBD. Animals underwent either bilateral ovariectomy or sham surgery. Following a three-week recovery period, rats received daily subcutaneous injections of CBD (10 mg/kg), estradiol (10 μg/kg), or vehicle for 21 consecutive days. Behavioral assessments included object recognition and fear-motivated memory tests. Twenty-four hours after the final treatment, animals were euthanized for neurochemical and molecular analyses. Levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured using high-performance liquid chromatography. Gene expression of cannabinoid receptors CB1 and CB2, as well as enzymes involved in the synthesis and degradation of endocannabinoids (NAPE-PLD, DAGL-A, FAAH, and MGLL), was evaluated in the hippocampus by RT-qPCR.

The results demonstrated that CBD treatment produced memory improvements in the object recognition task comparable to those observed with estradiol. Ovariectomy-induced impairments in fear-motivated memory were completely reversed by both CBD and estradiol treatments. Additionally, CBD reduced the expression of FAAH and MGLL, resulting in increased hippocampal levels of AEA and 2-AG, effects similar to those observed with hormone therapy. Estradiol also increased NAPE-PLD expression, contributing to elevated AEA levels.

Overall, the findings suggest that CBD exerts a protective effect on memory comparable to standard estrogen therapy, supporting its therapeutic potential for menopause-related cognitive impairments.”

https://pubmed.ncbi.nlm.nih.gov/42476954

https://onlinelibrary.wiley.com/doi/10.1111/jne.70234


Endocannabinoid system modulation in bruxism: a neurobiological hypothesis and translational model of ECS-targeted intervention

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“Bruxism is a multifactorial motor behavior of predominantly central origin, characterized by repetitive masticatory muscle activity and associated with dysregulation of dopaminergic, serotonergic, GABAergic, and glutamatergic pathways involved in motor control, emotional regulation, and stress responsivity.

The endocannabinoid system (ECS) has emerged as a key homeostatic neuromodulator capable of integrating these neurotransmitter systems, thereby influencing pain processing, sleep-wake dynamics, and motor output.

This article develops a neurobiological hypothesis based on a narrative integrative synthesis of clinical, experimental, and translational evidence regarding ECS involvement in the pathophysiology of bruxism.

Findings from randomized clinical trials suggest that topical cannabidiol (CBD) may modulate motor neuron excitability and reduce pain-related outcomes, while case-based and experimental evidence supports the interaction between cannabinoid signaling and neural circuits implicated in motor control and behavioral regulation.

Building on this evidence, we propose a hypothesis-driven translational model in which ECS-mediated neuromodulation may influence central mechanisms underlying bruxism, including motor pattern generation, stress responsivity, and nociceptive processing.

Rather than providing prescriptive therapeutic recommendations, this model is intended as a hypothesis-generating construct that integrates current knowledge on ECS signaling within the broader neurobiology of motor control. Although heterogeneity in study design and outcome measures limits definitive conclusions, the available evidence supports the ECS as a plausible modulatory system in bruxism, with potential implications for future mechanistic and clinical research in centrally mediated motor disorders.”

https://pubmed.ncbi.nlm.nih.gov/42459362

“In summary, the integration of neurobiological knowledge about bruxism with advances in understanding the endocannabinoid system supports the development of a hypothesis-driven translational model in which ECS-mediated neuromodulation may represent a relevant pathway for influencing centrally mediated motor behaviors.”

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2026.1854001/full


Hemp: A Sustainable Plant with High Industrial Value in Food Processing

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“In the era of SDGs, useful plants which provide valuable industrial outputs and at the same time pose less impact on the environment should be explored.

Hemp seems one of the most relevant gluten-free crop plants to meet such requirements. Its high nutritional value is comparable to soy. Moreover, almost the whole body of the hemp plant has a wide array of utility: industrial production of food, fiber, and construction materials. In view of environmental sustainability, hemp requires less pesticides or water in cultivation compared to cotton, a representative fiber plant.

This short review investigates hemp’s sustainability as a plant as well as its utility value as a highly nutritional material in the food industry. Recent application research of hemp protein in food processing includes plant milk, emulsifiers, fortification of gluten-free bread, plant-based meat production, as well as membrane formation.

These studies have revealed distinctive properties of hemp protein, especially in relation to disulfide (S-S)/sulfhydryl (-SH)-mediated interactions with protein from other sources. While its cultivation area and industrial use were limited for a while over confusion with marijuana, the market for industrial hemp is growing rapidly because it has been highly reevaluated in multiple areas of industry.

Conclusively, with its sustainability as a plant as well as its distinctive useful property of the seed protein, hemp has promising value in the development of new foods.”

https://pubmed.ncbi.nlm.nih.gov/36766179

“Hemp is a sustainable plant requiring less water or pesticides in cultivation compared to cotton. It has a short growth period and almost its whole plant body has versatile utility value. Hemp seeds are high-protein, low-carbohydrate, and rich in dietary fiber and unsaturated fatty acids. After expression of oil from the seeds, the residual mass is a useful protein-rich material for food processing. Moreover, hemp seed protein has distinctive characteristics suitable for developing new foods such as an emulsifier, plant-based meat, and gas-retaining membrane. The cysteine-rich protein feature realizes unique disulfide-mediated interactions with protein from other sources and is thus expected to facilitate development of new food materials. Meanwhile, hemp protein is reported to be less soluble, and a higher temperature is needed for processing compared to other plant protein. Therefore, suitable reaction conditions should be investigated for future application in the food industry. Further scientific understanding will facilitate expanded use of this less-investigated protein compared to soy protein. Conclusively, hemp is a suitable plant with versatile utility in this SDGs era. Hemp seeds and the protein are expected to be promising food materials in the food industry.”

https://www.mdpi.com/2304-8158/12/3/651


Prevention of Alzheimer’s Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation

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“Alzheimer’s disease (AD) is characterized by enhanced β-amyloid peptide (βA) deposition along with glial activation in senile plaques, selective neuronal loss, and cognitive deficits.

Cannabinoids are neuroprotective agents against excitotoxicity in vitro and acute brain damage in vivo.

This background prompted us to study the localization, expression, and function of cannabinoid receptors in AD and the possible protective role of cannabinoids after βA treatment, both in vivo and in vitro.

Here, we show that senile plaques in AD patients express cannabinoid receptors CB1 and CB2, together with markers of microglial activation, and that CB1-positive neurons, present in high numbers in control cases, are greatly reduced in areas of microglial activation. In pharmacological experiments, we found that G-protein coupling and CB1 receptor protein expression are markedly decreased in AD brains. Additionally, in AD brains, protein nitration is increased, and, more specifically, CB1 and CB2 proteins show enhanced nitration. Intracerebroventricular administration of the synthetic cannabinoid WIN55,212-2 to rats prevent βA-induced microglial activation, cognitive impairment, and loss of neuronal markers.

Cannabinoids (HU-210, WIN55,212-2, and JWH-133) block βA-induced activation of cultured microglial cells, as judged by mitochondrial activity, cell morphology, and tumor necrosis factor-α release; these effects are independent of the antioxidant action of cannabinoid compounds and are also exerted by a CB2-selective agonist. Moreover, cannabinoids abrogate microglia-mediated neurotoxicity after βA addition to rat cortical cocultures.

Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.”

“Cannabinoid receptors in AD brain.”

“Cannabinoids, the active components of marijuana and their analogs, exert a wide spectrum of central and peripheral effects by activating specific cannabinoid receptors, two of which have been well characterized to date: CB1 and CB2.”

“Cannabinoids exert neuroprotection under different experimental conditions. Thus, cannabinoid receptor activation protects hippocampal or granule cerebellar neurons from excitotoxicity”

“This background prompted us to study the characteristics and localization of cannabinoid receptors in AD brain, with particular emphasis on any relationship with microglial activation.”

“Cannabinoid treatment prevents βA-induced microglial activation and neurotoxicity in vitro.”

“Cannabinoid treatment prevents βA-induced toxic effects in vivo.”

“Because cannabinoids combine both anti-inflammatory and neuroprotective actions, our findings may set the basis for the use of these compounds as a therapeutic approach for AD.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC6726060

https://www.jneurosci.org/content/25/8/1904.long

Phenylpropionamides of Cannabis sativa L. seeds exert a cytoprotective effect through modulation of the AMPK/mTOR/ULK1 autophagy pathway and attenuate apoptosis in MPP+-induced SH-SY5Y cells

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“Objective: This study aimed to investigate whether phenylpropionamides (PHS) exert therapeutic effects on Parkinson’s disease (PD) by targeting autophagy-related pathways, using network pharmacology and in vitro experiments.

Methods: Network pharmacology (NP) analysis and molecular dynamics simulation (MDS) were applied to elucidate the potential mechanisms by which PHS treats PD. Subsequently, SH-SY5Y cells were treated with MPP+ to establish a neurotoxin model. Cell viability was assessed using the CCK-8 assay. Mitochondrial membrane potential (MMP) in SH-SY5Y cells was measured using JC-1 staining. Western blot (WB) was used to detect the expression of Bax, cleaved caspase-3, caspase-3, LC3-II, p62, Beclin-1, AMPK, mTOR, and ULK1 signaling proteins in SH-SY5Y cells.

Results: NP analysis suggested that the potential anti-PD effects of PHS were associated with cleaved caspase-3, Bcl-2, mTOR, and Beclin-1. Furthermore, KEGG and PPI analyses demonstrated that PHS may exert anti-PD effects by modulating the AMPK/mTOR/ULK1 autophagy signaling pathway. Molecular docking (MolD) and MDS showed that the key PHS component (Cannabisin I) had a stable interaction with caspase-3, Bcl-2, AMPK, mTOR, ULK1, and Beclin-1. The in vitro experiments showed that PHS suppressed the expression of cleaved caspase-3 and Bax, promoted Bcl-2 expression, activated the autophagy pathway, increased the levels of LC3-II and Beclin-1, increased mitochondrial membrane potential and decreased the levels of p62. Notably, PHS promoted autophagy by increasing AMPK and ULK1 while inhibiting mTOR protein levels. Therefore, PHS may represent a promising candidate for neuroprotective intervention in neurodegenerative disorders.

Conclusion: This study suggests that PHS may exert anti-PD effects, possibly through triggering autophagy via the AMPK/mTOR/ULK1 signaling pathway.”

https://pubmed.ncbi.nlm.nih.gov/42456387

“Historically, the seeds of Cannabis sativa L. have been used in traditional Chinese medicine (TCM). They are frequently utilized in various dietary applications, including cannabis seed oil, bread, and yogurt. Because they are rich in unsaturated fatty acids (UFAs) and essential amino acids (EAAs), they have been sought after by people. In addition, they have been reported to exhibit neuroprotective and immunomodulatory effects, as well as benefits for gastrointestinal health.

Furthermore, UFAs and EAAs, the seeds of Cannabis sativa L., are abundant in a category of compounds known as phenylpropionamides (PHS). Research has demonstrated that PHS compounds possess the ability to inhibit apoptosis in the SH-SY5Y cell model of PD, which is triggered by 1-methyl−4-phenylpyridinium (MPP+), by modulating the autophagy pathway. Previous studies have identified 22 PHS in cannabis seeds and demonstrated that PHS ameliorated MPTP-induced PD symptoms by promoting autophagy.”

https://www.sciencedirect.com/science/article/abs/pii/S0040816626004490?via%3Dihub

Delta-9-tetrahydrocannabinol delineates D-galactose and aluminium chloride-induced cognitive dysfunction and neurodegeneration in the hippocampus of the Wistar rat model

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“Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by neurodegeneration and a decline in cognition and memory. D-galactose (D-gal) and aluminium chloride (AlCl3) have been used to induce cognitive deterioration in rat models that mimic the alterations observed in AD.

This study assessed the neurotherapeutic effect of Δ9-tetrahydrocannabinol (Δ9THC) on cognitive abilities, brain morphology, neurogenesis activity and neuropathological markers in Wistar rats induced by D-gal plus AlCl3.

Male albino Wistar rats received D-gal (60 mg/kg, intraperitoneally) and AlCl3 (200 mg/kg, orally) daily for 10 weeks. The rats were then treated with increasing concentrations of Δ9THC (0.75, 1.5 and 3.0 mg/kg) for 28 days. Cognitive performance was evaluated using the novel object recognition and modified elevated plus maze tests. Dentate gyrus viable granule cells, neurogenesis markers, amyloid precursor protein and phosphorylated tau (p‑tau Thr231) were assessed histologically and molecularly.

Δ9THC treatment improved cognitive performance, prevented granule cell loss in the dentate gyrus, increased neurogenesis-related markers (GFAP+, DCX+, calbindin+ and NeuN immunoreactivity), and reduced amyloid precursor protein and p‑tau Thr231 expression.

These findings suggest that Δ9THC possesses promising therapeutic potential against Alzheimer’s disease.”

https://pubmed.ncbi.nlm.nih.gov/42454694


Progressive weight loss is attenuated by THC treatment in rats with activity-based anorexia

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“Anorexia nervosa (AN) is a severe psychiatric disorder with limited effective pharmacological treatments.

Given the role of the endocannabinoid system (ECS) in regulating energy balance and its possible involvement in AN pathophysiology, cannabinoid-based interventions may hold therapeutic potential.

Using the preclinical activity-based anorexia (ABA) model, we investigated whether Δ⁹-tetrahydrocannabinol (THC) could attenuate the progression of ABA-induced weight loss.

Female rats were exposed to the ABA paradigm, which combines restricted food access (2 h/day) with unrestricted access to running wheels. After 3 days, when ABA rats had lost 10-12% of their baseline body weight, they received daily injections of either THC or vehicle. Rats were removed from the paradigm after losing 23% of their body weight or on the morning of day 8, whichever occurred first.

THC treatment significantly attenuated weight loss and prolonged survival in the paradigm.

These beneficial effects of THC were mediated by a selective suppression of excessive dark- and light-phase wheel running with no additional effects on food intake.

These findings provide the first evidence that initiating THC treatment after significant weight loss in the ABA paradigm can halt the progression of weight loss through a selective decrease in energy expenditure.

Importantly, treatment was initiated after (rather than before) the emergence of ABA-induced weight loss, thus enhancing the translational relevance of the model and our findings.

Together, these findings suggest that pharmacological activation of the ECS may represent a promising treatment for individuals with AN.”

https://pubmed.ncbi.nlm.nih.gov/42448208

“THC treatment, initiated after ∼12% body weight loss in rats with activity-based anorexia (ABA), reduced further weight loss and prolonged survival.”

“Findings support endocannabinoid-targeted therapies for anorexia nervosa.”

https://www.sciencedirect.com/science/article/abs/pii/S0031938426002313?via%3Dihub


Edible Oil-Based Extraction of Cannabis sativa L. Roots: Effect of Solvent and Temperature on Friedelin Yield and Antioxidant Activity

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“The roots of Cannabis sativa L., historically overlooked, are gaining attention as a potential source of bioactive compounds with antioxidant, antimicrobial, and anti-inflammatory properties.

While previous studies have focused on extractions using ethanol, water, or supercritical CO2, the feasibility of edible oil-based extraction remains largely unexplored.

This study evaluated the extraction of root compounds using hemp seed oil, MCT coconut oil, and grape seed oil at six temperatures (50-90 °C).

Extracts were analyzed by GC-MS for compound identification and quantification, and antioxidant activity was assessed using the DPPH assay, ABTS test and β-carotene bleaching method, with results statistically evaluated by ANOVA. Friedelin was successfully extracted with all oils, with grape seed oil yielding the highest concentration (0.810 mg/g dry roots), achieving recoveries higher than those previously reported for ethanol-based extractions.

All extracts demonstrated positive antioxidant activity, with grape seed oil, both alone and combined with extracts, showing higher values across the three methods. ANOVA revealed a significant effect of solvent type on both Friedelin concentration and antioxidant capacity.

These results demonstrate that edible oils are effective solvents for extracting bioactive compounds from C. sativa roots, supporting their potential application in cosmetic or medicinal formulations.”

https://pubmed.ncbi.nlm.nih.gov/42123839

“In conclusion, this research validates the feasibility of extracting bioactive compounds from cannabis roots using accessible edible oils, achieving Friedelin recoveries higher than those previously reported for alcoholic extractions. These findings provide an important foundation for the development of Cannabis sativa L. root-based products for cosmetic or medicinal applications.”

https://www.mdpi.com/1420-3049/31/9/1473


Cannabis sativa: A Source of Antiparasitic Compounds?

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“Cannabis sativa (hemp, marijuana, ganja) is a plant with industrial, medicinal, and recreational uses that synthesizes phytocannabinoids, a group of compounds from which tetrahydrocannabinol (THC) and cannabidiol (CBD) outstand by their known high and low psychoactive properties.

These and other cannabinoids (endocannabinoids and synthetic derivatives with modulating effects over cannabinoid receptors CB1/2) have been tested in vitro using cultured parasites and in vivo in rodent models of protozoosis affecting the central nervous system as are amoebic encephalopathy, cerebral malaria, brain toxoplasmosis as well as Chagas disease and Leishmaniasis. Helminthiasis mainly includes Nippotrongyloidosis and Schistosomiasis and even their effects on ticks as Boophilus have been reported.

The parasiticidal effect of C. sativa extracts and cannabinoids is consistently found although some points of concern arise from animal models because CB1 or CB2 inactivation/inhibition led to distinct outcomes –beneficial or deleteriousin parasite load and host survival, depending on the organism studied. Possible parasitic targets of cannabinoids include arginase, acetylcholinestherase and haemozoin, a product of hemoglobin digestion.

Collectively, these data highlight that the potential use of cannabinoids against parasitic infections should consider the effects of these compounds on their known targets at the endocannabinoid system (CB1/2) and the likely target(s) in parasites.”

“Plant-derived compounds have multiple beneficial activities for human health, including new candidates for the treatment of parasitic diseases. Among these are macrocyclic lactones terpenes and polyphenols. Unlike most plant species, C. sativa (hemp, marijuana or ganja) is a rich source of both products of industrial interest and phytomedicinal compounds as well”

“At the light of experimental evidence, the potential application of cannabinoids in parasitosis is generally promising on the basis of their parasiticidal in vitro activities”

https://biomedres.us/fulltexts/BJSTR.MS.ID.007960.php