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Rooted in therapeutics: comprehensive analyses of Cannabis sativa root extracts reveals potent antioxidant, anti-inflammatory, and bactericidal properties

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“Following the legalization of recreational Cannabis in Canada in 2018, the associated waste, including Cannabis roots, has significantly increased. Cannabis roots, comprising 30%-50% of the total plant, are often discarded despite their historical use in Ayurvedic medicine for treating inflammatory and infectious disorders.

This study evaluates the phytochemical and therapeutic properties of Cannabis root extracts from a high tetrahydrocannabinolic acid, low cannabidiolic acid cultivar (variety Alien Gorilla Glue).

We performed ultra high-performance liquid chromatography coupled with mass spectrometry (UPLC-QTOF-MS) to identify the chemical components of the Cannabis roots. Extracts using water, ethanol and acid-base solvents were tested for antioxidant activity through free radical scavenging, metal chelation, and lipoperoxidation inhibition assays. Mitochondrial membrane protection was assessed using flow cytometry with the MitoPerOx probe in THP-1 monocytic leukemia cells. Anti-inflammatory potential was evaluated by measuring interleukin-6 levels in lipopolysaccharide-stimulated THP-1 cells. Bactericidal/fungicidal efficacy against Escherichia coli, Staphylococcus aureus, and Candida albicans was determined using the p-iodonitrophenyltetrazolium assay. Additionally, we investigated the anticholinesterase activity of Cannabis root extracts, given the potential role of plant alkaloids in inhibiting cholinesterase, an enzyme targeted in Alzheimer’s disease treatments. UPLC-QTOF-MS analysis suggested the presence of several phenolic compounds, cannabinoids, terpenoids, amino acids, and nitrogen-containing compounds.

Our results indicated significant antioxidant, bactericidal, and anticholinesterase properties of Cannabis root extracts from both soil and hydroponic cultivation.

Extracts showed strong antioxidant activity across multiple assays, protected mitochondrial membrane in THP-1 cells, and exhibited anti-inflammatory and bactericidal/fungicidal efficacy. Notably, soil-cultivated roots displayed superior anti-inflammatory effects.

These findings demonstrate the remarkable antioxidant, anti-inflammatory, and anti-microbial activities of Cannabis roots, supporting their traditional uses and challenging their perception as mere waste. This study highlights the therapeutic potential of Cannabis roots extracts and suggests avenues for further research and application.”

https://pubmed.ncbi.nlm.nih.gov/39351095/

“In conclusion, this study sheds light on the chemical profile and significant therapeutic potential of Cannabis root extracts, confirming the validity of their traditional uses and challenging their conventional status as waste products of Cannabis cultivation.

The results presented in this work add evidence to the broad spectrum of biological systems in which Cannabis-sourced derivatives have a potential effect, not only because of cannabinoids, but also because of the possible action of phenolic and nitrogen-containing compounds. Through comprehensive investigation, we have demonstrated their remarkable antioxidant, anticholinesterase, and anti-inflammatory activities, along with their ability to protect mitochondrial membranes.

These findings underscore the importance of reevaluating the utilization of Cannabis roots in various therapeutic contexts, potentially offering new avenues for drug discovery and development. By recognizing the value of these often-overlooked plant components, we may uncover novel treatments for a range of medical conditions, thereby contributing to the advancement of natural product pharmacology and healthcare innovation. Further research in this area is warranted to elucidate the underlying mechanisms and explore the full therapeutic potential of Cannabis root extracts.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1465136/full

Repeated Administration of a Full-Spectrum Cannabidiol Product, Not a Cannabidiol Isolate, Reverses the Lipopolysaccharide-Induced Depressive-Like Behavior and Hypolocomotion in a Rat Model of Low-Grade Subchronic Inflammation

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“Background: Mounting evidence suggests that the phytocannabinoid cannabidiol (CBD) holds promise as an antidepressant agent in conditions underlined by inflammation. Full-spectrum CBD extracts might provide greater behavioral efficacy than CBD-only isolates and might require lower doses to achieve the same outcomes due to the presence of other cannabinoids, terpenes, and flavonoids. However, investigations in this area remain limited. 

Methods: We evaluated the behavioral response to the administration for 7 days of 15 and 30 mg/kg of a CBD isolate and a full-spectrum CBD product in a rat model of subchronic lipopolysaccharide (LPS, 0.5 mg/kg/day/7 days, intraperitoneal)-induced depressive-like and sickness behavior. The forced swim test was used to assess depressive-like behavior, the open field test (OFT) to assess locomotion, and the elevated plus maze to assess anxiety-like behavior. 

Results: The full-spectrum CBD extract at both doses, but not the CBD isolate, reversed the LPS-induced depressive-like behavior in the forced swim test. Moreover, the full-spectrum CBD extract at the higher dose but not the CBD isolate restored the subchronic LPS-induced hypolocomotion in the OFT. Repeated administration of both formulations elicited an anxiogenic-like trend in the elevated plus maze. 

Conclusion: Full-spectrum CBD products might have greater therapeutic efficacy in resolving inflammation-induced depressive and sickness behavior compared to a CBD-only isolate.”

https://pubmed.ncbi.nlm.nih.gov/39347620/

https://www.liebertpub.com/doi/10.1089/can.2024.0086

Hemp Seed (Cannabis sativa L.) Varieties: Lipids Profile and Antioxidant Capacity for Monogastric Nutrition

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“The present research aimed to study the proximate composition, fatty acid profile, antiox-idant activity, total phenolic and N-trans-Caffeoyltyramine content of three distinct varieties of hemp seeds (Carmaenecta, Enectaliana and Enectarol, grown in a Mediterranean area (Central Italy), as feed in the diet of farm animals. Proximate composition was determined using the official methods of analyses; the fatty acid profile was determined by gas chromatography, total phenolic content (TPC) and the scavenging activity (DPPH• and ABTS•+) by the colorimetric method, and N-trans-Caffeoyltyramine content by HPLC analysis. The hemp seed Enectarol showed the highest total lipid content and the best antioxidant activity with the highest TPC, N-trans-Caffeoyltyramine content, and ABTS•+, and the lowest peroxidation index and DPPH•; Carmaenecta showed the best fatty acid profile and nutritional indices (atherogenic and thrombogenic indices and hypocholesterolemic/hypercholesterolemic ratio), and Enectaliana showed the highest crude protein and dietary fiber content. The differences observed in the chemical composition, fatty acid profile and antioxidant activity are because of the varieties, considering that all other growing conditions were the same. The results obtained suggest that hemp seed can be used as a source of lipid and protein in animal diets due to their valuable antioxidant activity and as a rich source of essential fatty acids.”

https://pubmed.ncbi.nlm.nih.gov/39335288/

“(Cannabis sativa L.), due to its distinctive nutritional profile, can be considered an interesting and promising alternative resource for agriculture in human and animal nutrition.

In conclusion, the results highlight that hemp seeds can be used in the food industry as a source of oil and protein and as a supplement in feed mixtures for the valuable antioxidant activity and fatty acid profile, promoting better health in farm animals.”

https://www.mdpi.com/2076-2615/14/18/2699

Cannabis-Containing Cream for CKD-Associated Pruritus: A Double-Blind, Placebo Controlled Trial

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“Rationale & objective: This study aims to compare the efficacy of a cannabis cream and a placebo in the treatment of chronic kidney disease (CKD)-associated pruritus.

Study design: A double-blind randomized controlled study.

Setting & participants: Sixty hemodialysis patients with the worst itching intensity numerical rating scale (WI-NRS) ≥3.

Exposure: Patients received cannabis cream or placebo.

Outcomes: The primary endpoint was the WI-NRS score at week 4. The secondary endpoints included the WI-NRS at week 2, the Skindex-10 score at weeks 2 and 4, and the mean difference score between baseline and week 4 for the WI-NRS and the Skindex-10 score.

Analytical approach: We used unpaired t tests or Mann Whitney U tests, along with χ2 or Fisher exact tests as appropriate. The adjusted mean differences were determined using ANCOVA, adjusting for baseline scores.

Results: Among 60 participants, the mean age was 61.6 ± 14.4 years and the mean baseline WI-NRS was 6.7 ± 1.7. The placebo and cannabis cream groups were similar at baseline, although more individuals in the placebo group had diabetes. At 4 weeks, the WI-NRS dropped to 2.6 in the cannabis group and 3.6 in the placebo group (the mean difference after adjustment for baseline scores:-1.1, 95% CI, -2.1 to -0.2; P = 0.02). Skindex-10 scores at week 4 were also lower in the cannabis group, but after adjustment for baseline scores, statistical significance was not maintained. No side effects were observed in either group.

Limitations: A single study with a small sample size restricts its generalizability. Variances in participants’ diabetes statuses might have affected the itch outcomes. The absence of cannabinoid level assessment in blood prevents conclusive determination of the potential systemic impacts. A 4-week follow-up period inadequately captures long-term effect.

Conclusions: In CKD-associated pruritus, the topical cream containing cannabis significantly reduced the severity of itching symptoms compared to the placebo.”

https://pubmed.ncbi.nlm.nih.gov/39328960/

https://www.kidneymedicinejournal.org/article/S2590-0595(24)00105-5/fulltext

Effect of Cannabistilbene I in Attenuating Angiotensin II-Induced Cardiac Hypertrophy: Insights into Cytochrome P450s and Arachidonic Acid Metabolites Modulation

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“Introduction: This research investigated the impact of Cannabistilbene I on Angiotensin II (Ang II)-induced cardiac hypertrophy and its potential role in cytochrome P450 (CYP) enzymes and arachidonic acid (AA) metabolic pathways. Cardiac hypertrophy, a response to increased stress on the heart, can lead to severe cardiovascular diseases if not managed effectively. CYP enzymes and AA metabolites play critical roles in cardiac function and hypertrophy, making them important targets for therapeutic intervention. 

Methods: Adult human ventricular cardiomyocyte cell line (AC16) was cultured and treated with Cannabistilbene I in the presence and absence of Ang II. The effects on mRNA expression related to cardiac hypertrophic markers and CYP were analyzed using real-time polymerase chain reaction, while CYP protein levels were measured by Western blot analysis. AA metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 

Results: Results showed that Ang II triggered hypertrophy, as evidenced by the increase in hypertrophic marker expression, and enlarged the cell surface area, effects that were alleviated by Cannabistilbene I. Gene expression analysis indicated that Cannabistilbene I upregulated CYP1A1, leading to increased enzymatic activity, as evidenced by 7-ethoxyresorufin-O-deethylase assay. Furthermore, LC-MS/MS analysis of AA metabolites revealed that Ang II elevated midchain (R/S)-hydroxyeicosatetraenoic acid (HETE) concentrations, which were reduced by Cannabistilbene I. Notably, Cannabistilbene I selectively increased 19(S)-HETE concentration and reversed the Ang II-induced decline in 19(S)-HETE, suggesting a unique protective role. 

Conclusion: This study provides new insights into the potential of Cannabistilbene I in modulating AA metabolites and reducing Ang II-induced cardiac hypertrophy, revealing a new candidate as a therapeutic agent for cardiac hypertrophy.”

https://pubmed.ncbi.nlm.nih.gov/39324890/

https://www.liebertpub.com/doi/10.1089/can.2024.0148

“Cannabistilbene I (CBG-I) is a naturally occurring derivative of the plant cannabis. It is a polyphenol compound found in the resinous glandular trichomes of the cannabis plant. CBG-I is known for its potent antioxidant, anti-inflammatory, and neuroprotective properties, making it a promising area of research in various fields.

Cannabistilbene I was first isolated and identified in 1975 by scientists from the University of Mississippi. It is a distinct compound from other cannabinoids and is found in different cannabis varieties. CBG-I is the precursor to THC, CBD, and other cannabinoids, which makes it essential in the biosynthesis of these compounds.”

https://www.smolecule.com/products/s579399


Cannabidiol Modulation of Nicotine-Induced Toxicity: Assessing Effects on Behavior, Brain-Derived Neurotrophic Factor, and Oxidative Stress in C57BL/6 Male Mice

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“High doses of nicotine administered to rodents serve as a model for studying anxiety and test compounds’ potential anxiolytic effects. At these doses, anxiety in rodents is accompanied by disruption of brain-derived neurotrophic factor (BDNF). The endocannabinoids and nicotine modulate several central nervous system processes via their specific receptors, impacting locomotion, anxiety, memory, nociception, and reward.

Cannabidiol (CBD), an active ingredient of Cannabis sativa L., is devoid of psychoactive actions and has gained attention for its anxiolytic, antioxidant, and anti-inflammatory properties, among others. This work aims to examine the potential anxiety-reducing properties of CBD in a well-established experimental mouse model of anxiety-like behavior induced by high doses of nicotine on male C57BL/6 mice.

In this context, the open-field behavioral test was specially conducted to assess CBD’s effects on anxiety-like behavior and locomotion. Brain neuronal plasticity, modulated by BDNF, along with a diverse array of blood’s metabolic markers, was examined as a means of evaluating systemic toxicity under various treatments. Finally, oxidative stress was evaluated through the measurement of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), while pro-inflammatory cytokine assessments were conducted to evaluate redox status and immune system function.

Our research suggests that CBD shows potential in reducing anxiety-like behaviors induced by high doses of nicotine, by mitigating changes in BDNF protein levels in cerebral hemispheres and cerebellum. At the same time, CBD targets specific liver enzymes, maintains tissue’s systemic toxicity (i.e., renal, kidney, and pancreatic), balances redox status (SOD, GSH, and MDA), and regulates the secretion of pro-inflammatory cytokines (TNF-alpha and IL-6).”

https://pubmed.ncbi.nlm.nih.gov/39297526/

https://onlinelibrary.wiley.com/doi/10.1002/jnr.25384

[Transepithelial transport in vivo and in vitro and anti-inflammatory activity of cannabidiol]

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“This study used Caco-2 cells and normal rats to investigate the in vitro absorption characteristics and in vivo pharmacokinetic characteristics of cannabidiol(CBD) and explore the anti-inflammatory mechanism of CBD. The safe concentration range of CBD was determined by the CCK-8 assay, and then the effects of time, concentration, temperature, endocytosis inhibitors, and transport inhibitors on the transepithelial absorption and transport of CBD were assessed. The blood drug concentration was measured at different time points after oral administration in rats for pharmacokinetic profiling, and the pharmacokinetic parameters were calculated. The Caco-2 cell model of inflammation injury was established with lipopolysaccharide(LPS). The effects of CBD on lactate dehydrogenase(LDH) activity, transendothelial electrical resistance(TEER), and levels of inflammatory cytokines of the modeled cells were exami-ned, on the basis of which the anti-inflammatory mechanism of CBD was deciphered.

The results showed that within the concentration range tested in this study, the CBD uptake by Caco-2 cells reached saturation at the time point of 2 h. Moreover, the CBD uptake was positively correlated with concentration and temperature and CBD could be endocytosed into the cells. CBD could penetrate Caco-2 cells through active transport pathways involving multidrug resistance-associate protein 2(MRP2) and breast cancer resistance protein(BCRP), while the addition of P-gp inhibitors had no effect on CBD transport. Rats exhibited rapid absorption of CBD, with the peak time(t_(max)) of(1.00±0.11) h, and fast elimination of CBD, with a half-life(t_(1/2)) of only(1.86±0.16) h. In addition, CBD significantly ameliorated the increased LDH activity and decreased TEER that were caused by inflammatory response. It maintained the intestinal barrier by down-regulating the expression of pro-inflammatory cytokines interleukin-8(IL-8), interleukin-1 beta(IL-1β) and tumor necrosis factor-α(TNF-α), thus exerting anti-inflammatory effects.”

https://pubmed.ncbi.nlm.nih.gov/39307812/

Unleashing the therapeutic role of cannabidiol in dentistry

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“Cannabidiol (CBD) found in Cannabis sativa is a non-psychoactive compound which is capable of binding to CB1 and CB2 receptors. CBD has recently gained interest in dentistry although it has not been explored sufficiently yet.

The therapeutic effects of CBD include anti-inflammatory, analgesic, antioxidant, biological and osteoinductive properties. The aim of this review is to highlight these effects with respect to various oral conditions and shed light on the current limitations and prospects for the use of CBD in maintaining oral health.”

https://pubmed.ncbi.nlm.nih.gov/39296277/

“CBD are potent non-psychoactive drug which when used in appropriate proportions under proper guidelines hold the potential to drastically change the current state of dental sciences. However, future researches are imperative focusing on the nature, mechanism, formulations as well as modes of administration to understand this drug thoroughly. Nonetheless, due to its properties such as anti-inflammation, antioxidation, biological nature, analgesia as well as osteoinduction; it is a drug with promising future in dentistry.”

https://www.sciencedirect.com/science/article/pii/S2212426824001258?via%3Dihub

Cannabidiol for the Treatment of Cervical Spondyloarthritis-Related Pain: A Case Report

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“Spondyloarthritis (SA) is a chronic inflammatory disease that predominantly affects the spinal column. SA-related pain can be intense, persistent, and disabling. Studies with cannabis have been conducted involving patients with refractory epilepsy, multiple sclerosis, Parkinson’s disease, sleep disorders, and chronic pain.

Cannabidiol is the major non-psychotropic component of cannabis, has anti-inflammatory and analgesic properties, and exerts anxiolytic and mood-stabilizing effects. This paper reports a case of a 72-year-old male with SA, with mild stenoses of the spinal canal at C4-C5 and C5-C6 and stenoses of the left neural foramina at C3-C4, C4-C5, C5-C6, and C6-C7.

The use of cannabidiol in our patient achieved satisfactory results in the control of pain related to cervical spondyloarthritis.”

https://pubmed.ncbi.nlm.nih.gov/39295690/

https://www.cureus.com/articles/278440-cannabidiol-for-the-treatment-of-cervical-spondyloarthritis-related-pain-a-case-report#!/

Therapeutic potential of cannabis for surgical wound healing in rats

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“This study was conducted to evaluate the wound-healing activities of a Cannabis sativa L. plant extract and cannabidiol on incision wounds.

An incision was created and sutured in rats under anaesthesia. Routine wound care procedures were applied for 10 days, followed by histological wound examinations. The cellular bioactivities of the hemp extract and CBD were assessed for MCP-1, EGF, BFGF, IL-8, and COL-1 using ELISA on the rat skin wound healing activity. A one-way ANOVA was used for the data analysis.

The EGF values in the plasma were similar in the povidone-iodine, hemp seed oil, and hemp essential oil groups (P > 0.05). However, the EGF levels were lower in the CBD group compared to the other groups (P < 0.001, P < 0.005). The MCP-1 values in the hemp seed oil, hemp essential oil, and CBD were similar (P > 0.05), whereas povidone iodine exhibited lower MCP-1 levels compared to the other groups (P < 0.001, P < 0.005). It was determined that the plasma BFGF, IL-8, and COL 1 values of the groups were similar (P > 0.05).

To our knowledge, this study is the first to evaluate the effects of CBD, seed oil, and hemp leaf extract on incision wound healing. It demonstrates that hemp extract holds greater potential benefits for wound healing compared to CBD.”

https://pubmed.ncbi.nlm.nih.gov/39296630/

http://vetmed.agriculturejournals.cz/artkey/vet-202408-0002_therapeutic-potential-of-cannabis-for-surgical-wound-healing-in-rats.php