Search Results (38)

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

Malignant gliomas, including glioblastoma multiforme (GBM), are highly aggressive brain tumors with a poor prognosis and limited treatment options. This study investigates the antitumor potential of bioactive compounds derived from Cannabis sativa and Piper nigrum using molecular docking, cell viability assays, and transcriptomic and expression analyses from public databases in humans and cell lines. Cannabichromene (CBC), cannabigerol (CBG), cannabidiol (CBD), and Piper nigrum derivates exhibited strong binding affinities relative to glioblastoma-associated targets GPR55 and PINK1. In vitro analyses demonstrated their cytotoxic effects on glioblastoma cell lines (U87MG, T98G, and CCF-STTG1), as well as on neuroblastoma (SH-SY5Y) and oligodendroglial (MO3.13) cell lines, revealing interactions among these compounds. The differential expression of GPR55 and PINK1 in tumor versus normal tissues further supports their potential as biomarkers and therapeutic targets. These findings provide a basis for the development of novel therapies and suggest unexplored molecular pathways for the treatment of malignant glioma. Full article

Cannabinoids are widely recognized for their potential therapeutic effects, making them significant and valuable candidates for medical research and applications across various fields. This review aims to analyze the pharmacokinetics of Cannabidiol (CBD), Cannabigerol (CBG), and Cannabichromene (CBC), along with their corresponding acidic forms, Cannabidiolic acid (CBDA), Cannabigerolic acid (CBGA), and Cannabichromenic acid (CBCA). Among these cannabinoids, CBD is the most extensively studied. Nevertheless, research involving all the mentioned cannabinoids has shown that their pharmacokinetic parameters are highly variable, depending significantly on factors such as dose, formulation, route of administration, and diet. Furthermore, challenges such as brain penetration and first-pass metabolism have been highlighted. In conclusion, this review demonstrates significant progress in understanding the pharmacokinetics of non-psychotropic cannabinoids. However, it also underscores the need for further research, particularly on CBG, CBC, and their respective acidic forms, with the most significant gap being in clinical investigations. Expanding these studies is essential to facilitate their optimized use in medical treatments. Full article

Cannabichromene (CBC) is one of the main cannabinoids found in the cannabis plant, and although less well known than tetrahydrocannabinol (THC) and cannabidiol (CBD), it is gaining attention for its potential therapeutic benefits. To date, CBC’s known mechanisms of action include anti-inflammatory, analgesic, antidepressant, antimicrobial, neuroprotective, and anti-acne effects through TRP channel activation and the inhibition of inflammatory pathways, suggesting that it may have therapeutic potential in the treatment of inflammatory skin diseases, such as atopic dermatitis (AD), but its exact mechanism of action remains unclear. Therefore, in this study, we investigated the effects of CBC on Th2 cytokines along with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways involved in AD pathogenesis. We used a 2,4-Dinitrochlorobenzene (DNCB)-induced BALB/c mouse model to topically administer CBC (0.1 mg/kg or 1 mg/kg). The results showed that skin lesion severity, ear thickness, epithelial thickness of dorsal and ear skin, and mast cell infiltration were significantly reduced in the 0.1 mg/kg CBC-treated group compared with the DNCB-treated group (p < 0.001). In addition, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed a significant decrease in the mRNA expression of Th2 cytokines (TSLP, IL-4, IL-13) and inflammatory mediators (IFN-γ, IL-1β, IL-6, IL-17, IL-18, and IL-33) (p < 0.05). Western blot analysis also revealed a significant decrease in JAK1, JAK2, STAT1, STAT2, STAT3, and STAT6 protein expression (p < 0.05). These results suggest that CBC is a promising candidate for the treatment of AD and demonstrates the potential to alleviate AD symptoms by suppressing the Th2 immune response. Full article

Due to the typical production of Cannabis sativa L. for medical use in an artificial environment, it is crucial to optimize environmental and nutritional factors to enhance cannabinoid yield and quality. While the effects of light intensity and nutrient composition on plant growth are well-documented for various crops, there is a relative lack of research specific to Cannabis sativa L., especially in controlled indoor environments where both light and nutrient inputs can be precisely manipulated. This research analyzes the effect of different light intensities and nutrient solutions on growth, flower yield, and cannabinoid concentrations in seeded chemotype III cannabis (high CBD, low THC) in a controlled environment. The experiment was performed in a licensed production facility in the Czech Republic. The plants were exposed to different light regimes during vegetative phase and flowering phase (light 1 (S1), photosynthetic photon flux density (PPFD) 300 µmol/m²/s during vegetative phase, 900 µmol/m²/s in flowering phase and light 2 (S2) PPFD 500 µmol/m²/s during vegetative phase, 1300 µmol/m²/s during flowering phase) and different nutrition regimes R1 (fertilizer 1) and R2 (fertilizer 2). Solution R1 (N-NO₃⁻ 131.25 mg/L; N-NH₄⁺ 6.23 mg/L; P₂O₅ 30.87 mg/L; K₂O 4112.04 mg/L; CaO 147.99 mg/L; MgO 45.68 mg/L; SO₄²⁻ 45.08 mg/L) was used for the whole cultivation cycle (vegetation and flowering). Solution R2 was divided for vegetation phase (N-NO₃⁻ 171.26 mg/L; N-NH₄⁺ 5.26 mg/L; P₂O₅ 65.91 mg/L; K₂O 222.79 mg/L; CaO 125.70 mg/L; MgO 78.88 mf/L; SO₄²⁻ 66.94 mg/L) and for flowering phase (N-NO₃⁻ 97.96 mg/L; N-NH₄⁺ 5.82 mg/L; P₂O₅ 262.66 mg/L; K₂O 244.07 mg/L; CaO 138.26 mg/L; MgO 85.21 mg/L; SO₄²⁻ 281.54 mg/L). The aim of this study was to prove a hypothesis that light will have a significant impact on the yield of flowers and cannabinoids, whereas fertilizers would have no significant effect. The experiment involved a four-week vegetative phase followed by an eight-week flowering phase. During the vegetative and flowering phases, no nutrient deficiencies were observed in plants treated with either nutrient solution R1 (fertilizer 1) or R2 (fertilizer 2). The ANOVA analysis showed that fertilizers had no significant effect on the yield of flowers nor cannabinoids. Also, light intensity differences between groups S1 (light 1) and S2 (light 2) did not result in visible differences in plant growth during the vegetative stage. However, by the fifth week of the flowering phase, plants under higher light intensities (S2—PPFD 1300 µmol/m²/s) developed noticeably larger and denser flowers than plants in the lower light intensity group (S1). The ANOVA analysis also confirmed that the higher light intensities positively influenced cannabidiol (CBD), tetrahydrocannabinol (THC), cannabigerol (CBG), and cannabichromene (CBC) when the increase in the concentration of individual cannabinoids in the harvested product was 17–43%. Nonetheless, the study did not find significant differences during the vegetative stage, highlighting that the impact of light intensities is phase-specific. These results are limited to controlled indoor conditions, and further research is needed to explore their applicability to other environments and genotypes. Full article

The study highlights the need for quality control in evaluating medicinal plant products, especially CBD oils, before market release. Due to varying regulatory requirements, product labeling can sometimes be misleading, especially regarding cannabinoid concentrations such as CBD and THC. This research focused on developing a validated high-performance liquid chromatography (HPLC) method for accurately identifying and quantifying key cannabinoids in Commercial Veterinary CBD Oil. The main compounds identified included Cannabidivarin (CBDV), Cannabidiolic Acid (CBD-A), Cannabigerolic Acid (CBG-A), Cannabigerol (CBG), Cannabidiol (CBD), Tetrahydrocannabivarin (THCV), Cannabinol (CBN), ∆⁹-Tetrahydrocannabinol (d9-THC) ∆8-Tetrahydrocannabinol (d8-THC), Cannabicyclol (CBL), Cannabichromene (CBC), and Tetrahydrocannabinolic Acid (THCA), determined in line with the International Conference on Harmonization’s (ICH) guidelines. The method was validated for linearity, accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ). It was determined to be linear, with a correlation coefficient (R²) > 0.999. The LOD and LOQ values calculated from the calibration curve ranged from 0.05 to 0.13 and 0.50 to 0.61 µg/mL, respectively. The method also exhibited acceptable precision, with relative standard deviation values lower than or equal to 2%. The method’s accuracy was assessed through recovery percentages and fell within an acceptable range of 98–102 if the RSD was 2%. This study’s rigorous methodology and comprehensive findings significantly contribute to cannabinoid analysis. This validated protocol was used to analyze cannabinoids in 14 commercial veterinary CBD oil products from the Republic of North Macedonia. The performance parameters demonstrated that the method is reliable for quantitatively measuring cannabinoids in CBD oil. The analysis showed that the cannabinoid levels in the products were consistent with the manufacturers’ declared specifications, with no significant discrepancies in labeling. Full article

This review provides an overview of cannabis-based phytocannabinoids, focusing on their mechanisms of action, therapeutic applications, and production processes, along with the environmental factors that affect their quality and efficacy. Phytocannabinoids such as THC (∆⁹-tetrahydrocannabinol), CBD (cannabidiol), CBG (cannabigerol), CBN (cannabinol), and CBC (cannabichromene) exhibit significant therapeutic potential in treating various physical and mental health conditions, including chronic pain, epilepsy, neurodegenerative diseases, skin disorders, and anxiety. The cultivation of cannabis plays a crucial role in determining cannabinoid profiles, with indoor cultivation offering more control and consistency than outdoor methods. Environmental factors such as light, water, temperature, humidity, nutrient management, CO₂, and the drying method used are key to optimizing cannabinoid content in inflorescences. This review outlines the need for broader data transfer between the health industry and technological production, especially in terms of what concentration and cannabinoid ratios are effective in treatment. Such data transfer would provide cultivators with information on what environmental parameters should be manipulated to obtain the required final product. Full article

Cannabis sativa (C. sativa L.) has garnered significant attention worldwide due to its widespread use as a pharmaceutical agent. With the increasing clinical application of C. sativa and cannabinoid therapeutics, there is strong interest in the development of superior plant varieties and optimisation of growth conditions to enhance secondary metabolite yield. Our RNA sequencing analysis revealed differential expression of hormone-related transcripts in developing C. sativa trichomes, suggesting the involvement of hormone signalling pathways in cannabinoid production. Leveraging the potency of exogenous hormones on plants, this study sought to determine if the application of cytokinin (CK), gibberellic acid (GA) and jasmonic acid (JA) modified trichome morphology and the cannabinoid profile over an 8-week period following the induction of flowering. Exogenous hormone application led to alterations in trichome morphology, with each treatment significantly reducing trichome head width by the final week of assessment. Interestingly, GA application also resulted in a significant reduction in the concentration of Δ-9-tetrahydrocannabinol (THC), Δ-9-tetrahydrocannabinolic acid (THCA), cannabidiol (CBD) and cannabidiolic acid (CBDA) by week 8 post floral induction, however, JA and CK treatment did not consistently modulate the accumulation of these cannabinoids. The minor cannabinoids, cannabidivaranic acid (CBDVA), cannabicyclolic acid (CBLA), cannabicyclol (CBL), cannabichromene (CBC), cannabigerolic acid (CBGA) and cannabigerol (CBG), were also affected by hormone treatments, with varying degrees of accumulation observed. These findings underscore the intricate interplay between phytohormones and secondary metabolite biosynthesis in C. sativa. Our study highlights the potential of hormone modulation as a strategy to enhance cannabinoid yield and offers some insights into the regulatory mechanisms governing cannabinoid biosynthesis in C. sativa trichomes. Full article

Colorectal cancer (CRC) is a global problem. Oncology currently practices conventional methods of treating this carcinoma, including surgery, chemotherapy, and radiotherapy. Unfortunately, their efficacy is low; hence, the exploration of new therapies is critical. Recently, many efforts have focused on developing safe and effective anticancer compounds. Some of them include cannabinoids. In the present study, we obtained cannabinoids, such as cannabidiol (CBD), abnormal cannabigerol (abn-CBG), cannabichromene (CBC), and cannabicitran (CBT), by chemical synthesis and performed the biological evaluation of their activity on colon cancer cells. In this study, we analyzed the effects of selected cannabinoids on the lifespan and metabolic activity of normal colonic epithelial cells and cancer colon cells. This study demonstrated that cannabinoids can induce apoptosis in cancer cells by modulating mitochondrial dehydrogenase activity and cellular membrane integrity. The tested cannabinoids also influenced cell cycle progression. We also investigated the antioxidant activity of cannabinoids and established a relationship between the type of cannabinoid and nitric oxide (NO) production in normal and cancerous colon cells. To conclude, it seems that, due to their interesting properties, the cannabinoids studied may constitute an interesting target for further research aimed at their use in alternative or combined therapies for human colon cancer. Full article

This study delves into the transformative effects of supercritical carbon dioxide (scCO₂) cannabis extracts and prebiotic substances (dextran, inulin, trehalose) on gut bacteria, coupled with a focus on neuroprotection. Extracts derived from the Białobrzeska variety of Cannabis sativa, utilising supercritical fluid extraction (SFE), resulted in notable cannabinoid concentrations (cannabidiol (CBD): 6.675 ± 0.166; tetrahydrocannabinol (THC): 0.180 ± 0.006; cannabigerol (CBG): 0.434 ± 0.014; cannabichromene (CBC): 0.490 ± 0.017; cannabinol (CBN): 1.696 ± 0.047 mg/gD). The assessment encompassed antioxidant activity via four in vitro assays and neuroprotective effects against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The extract boasting the highest cannabinoid content exhibited remarkable antioxidant potential and significant inhibitory activity against both enzymes. Further investigation into prebiotic deliveries revealed their proficiency in fostering the growth of beneficial gut bacteria while maintaining antioxidant and neuroprotective functionalities. This study sheds light on the active compounds present in the Białobrzeska variety, showcasing their therapeutic potential within prebiotic systems. Notably, the antioxidant, neuroprotective, and prebiotic properties observed underscore the promising therapeutic applications of these extracts. The results offer valuable insights for potential interventions in antioxidant, neuroprotective, and prebiotic domains. In addition, subsequent analyses of cannabinoid concentrations post-cultivation revealed nuanced changes, emphasising the need for further exploration into the dynamic interactions between cannabinoids and the gut microbiota. Full article

Cannabichromene (CBC) is a minor cannabinoid within the array of over 120 cannabinoids identified in the Cannabis sativa plant. While CBC does not comprise a significant portion of whole plant material, it is available to the public in a purified and highly concentrated form. As minor cannabinoids become more popular due to their potential therapeutic properties, it becomes crucial to elucidate their metabolism in humans. Therefore, the goal of this was study to identify the major CBC phase I-oxidized metabolite generated in vitro following incubation with human liver microsomes. The novel metabolite structure was identified as 2′-hydroxycannabicitran using gas chromatography–mass spectrometry and nuclear magnetic resonance spectroscopy. Following the identification, in silico molecular modeling experiments were conducted and predicted 2′-hydroxycannabicitran to fit in the orthosteric site of both the CB₁ and CB₂ receptors. When tested in vitro utilizing a competitive binding assay, the metabolite did not show significant binding to either the CB₁ or CB₂ receptors. Further work necessitates the determination of potential activity of CBC and the here-identified phase I metabolite in other non-cannabinoid receptors. Full article

Silver has been shown to improve the antibiotic effects of other drugs against both Gram- positive and -negative bacteria. In this study, we investigated the antibiotic potential of cannabidiol (CBD), cannabichromene (CBC) and cannabigerol (CBG) and their acidic counterparts (CBDA, CBCA, CBGA) against Gram-positive bacteria and further explored the additive or synergistic effects of silver nitrate or silver nanoparticles using 96-well plate growth assays and viability (CFUs- colony-forming units). All six cannabinoids had strong antibiotic effects against MRSA with minimal inhibitory concentrations (MICs) of 2 mg/L for CBG, CBD and CBCA; 4 mg/L for CBGA; and 8 mg/L for CBC and CBDA. Using 96-well checkerboard assays, CBC, CBG and CBGA showed full or partial synergy with silver nitrate; CBC, CBDA and CBGA were fully synergistic with silver nanoparticles against MRSA. Using CFU assays, combinations of CBC, CBGA and CBG with either silver nitrate or silver nanoparticles, all at half or quarter MICs, demonstrated strong, time-dependent inhibition of bacterial growth (silver nitrate) and bactericidal effects (silver nanoparticles). These data will lead to further investigation into possible biomedical applications of specific cannabinoids in combination with silver salts or nanoparticles against drug-resistant Gram-positive bacteria. Full article

Phytocannabinoids, a diverse group of naturally occurring compounds extracted from the Cannabis plant, have attracted interest due to their potential pharmacological effects and medicinal uses. This comprehensive review presents the intricate pharmacological profiles of phytocannabinoids while exploring the diverse impacts these substances have on biological systems. From the more than one hundred cannabinoids which were identified in the Cannabis plant so far, cannabidiol (CBD) and tetrahydrocannabinol (THC) are two of the most extensively studied phytocannabinoids. CBD is a non-psychoactive compound, which exhibits potential anti-inflammatory, neuroprotective, and anxiolytic properties, making it a promising candidate for a wide array of medical conditions. THC, known for its psychoactive effects, possesses analgesic and antiemetic properties, contributing to its therapeutic potential. In addition to THC and CBD, a wide range of additional phytocannabinoids have shown intriguing pharmacological effects, including cannabichromene (CBC), cannabigerol (CBG), and cannabinol (CBN). The endocannabinoid system, made up of the enzymes involved in the production and breakdown of endocannabinoids, cannabinoid receptors (CB1 and CB2), and endogenous ligands (endocannabinoids), is essential for preserving homeostasis in several physiological processes. Beyond their effects on the endocannabinoid system, phytocannabinoids are studied for their ability to modify ion channels, neurotransmitter receptors, and anti-oxidative pathways. The complex interaction between phytocannabinoids and biological systems offers hope for novel treatment approaches and lays the groundwork for further developments in the field of cannabinoid-based medicine. This review summarizes the state of the field, points out information gaps, and emphasizes the need for more studies to fully realize the therapeutic potential of phytocannabinoids. Full article

Cannabis sativa contains minor cannabinoids that have potential therapeutic value in pain management. However, detailed experimental evidence for the antinociceptive effects of many of these minor cannabinoids remains lacking. Here, we employed artificial intelligence (AI) to perform compound–protein interaction estimates with cannabichromene (CBC) and receptors involved in nociceptive signaling. Based on our findings, we investigated the antinociceptive properties of CBC in naïve or neuropathic C57BL/6 male and female mice using von Frey (mechanical allodynia), tail-flick (noxious radiant heat), formalin (acute and persistent inflammatory pain), and acetone (cold thermal) tests. For von Frey assessments, CBC dose (0–20 mg/kg, i.p.) and time (0–6 h) responses were measured in male and female neuropathic mice. For tail-flick, formalin, and acetone assays, CBC (20 mg/kg, i.p.) was administered to naïve male and female mice 1 h prior to testing. The results show that CBC (10 and 20 mg/kg, i.p.) significantly reduced mechanical allodynia in neuropathic male and female mice 1–2 h after treatment. Additionally, CBC treatment caused significant reductions in nociceptive behaviors in the tail-flick assay and in both phase 1 and phase 2 of the formalin test. Finally, we found a significant interaction in neuropathic male mice in the acetone test. In conclusion, our results suggest that CBC targets receptors involved in nociceptive signaling and imparts antinociceptive properties that may benefit males and females afflicted with diverse forms of acute or chronic/persistent pain. Full article

Cannabichromene (CBC), a non-psychoactive cannabinoid found in Cannabis sativa, has recently been shown to possess several medicinal properties. However, how CBC produces anti-inflammatory effects and the mechanisms of this remain poorly studied. Therefore, we extracted and purified the CBC from the Cannabis sativa cv. pink pepper (hemp cultivar). The efficacy of CBC in reducing inflammation in RAW 264.7 macrophages and a λ-carrageenan-induced mouse model was then evaluated. CBC had no cytotoxicity up to a concentration of 20 μM and inhibited nitric oxide production by approximately 50% at a concentration of 20 μM. In addition, CBC treatment significantly inhibited causes of inflammation such as inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) at both the mRNA and protein levels. Moreover, CBC suppressed LPS-stimulated inflammation in RAW 264.7 cells by downregulating the nuclear factor kappa B (NF-kB) and mitogen-activated protein kinase pathways (MAPK). Furthermore, our in vivo experiments confirmed that the λ-carrageenan-induced increase in the levels of the cytokines iNOS, IL-1β, and IL-6 was abrogated following treatment with CBC. Therefore, CBC has potential anti-inflammatory effects and may be useful for preventing or treating inflammation. Full article