“An efficient method for the simultaneous extraction of cannabinoids and terpenes from the leaves and flowers of Cannabis sativa L. (var. Felina 32) was developed.
Extraction parameters, including solvent type, temperature, and pressure, were optimized, revealing that hexane enables high-yield cannabinoid recovery. Moreover, terpene composition was influenced by the extraction temperature. Two extracts with the highest cannabinoid content were selected for further study, Feli1 (64.76%) and Feli2 (61.32%), both obtained using hexane. Feli1, extracted at -55 °C, had a monoterpene-to-sesquiterpene ratio of 16.7% to 83.3%, while Feli2, extracted at 25 °C, showed a higher monoterpene content (25.2%) and lower sesquiterpene content (74.8%).
Both extracts demonstrated selective antiproliferative activity against cancer cell lines, with reduced toxicity toward normal breast epithelial cells (MCF-10A). Feli2 showed slightly stronger antiproliferative effects, likely due to its higher monoterpene content. At low concentrations, both extracts stimulated the growth of MV4-11 leukemia and MDA-MB-468 triple-negative breast cancer (TNBC) cells, while higher concentrations led to growth inhibition. These stimulatory effects were weaker than those observed for pure Δ9-THC or CBD.”
“Prior studies showed contradictory results regarding the impact of cannabinoids on thromboembolic events in trauma patients. The goal of the study was to investigate the association of cannabinoids to venous thromboembolism (VTE).
Records for all trauma patients admitted to the level one trauma center aged 14 years and above between October 18, 2019 and December 29, 2023 with urine drug screening (UDS) and blood alcohol concentration (BAC) results were included for collection. Patients testing positive for cannabinoids and patients testing negative for cannabinoids that were also negative for other illicit drugs and for alcohol were included in the final analysis primarily examining VTE occurrence, along with secondary outcomes in mortality, hospital length of stay, discharge disposition, and coagulation-related biomarkers. One-to-one propensity score matching analysis was performed.
Patient population was mostly white (78.8%), mostly male (71.5%), had a median age of 46, and a median ISS of 17. Out of 302 patients, 226 tested negative and 76 tested positive for cannabinoids. In the matched analysis, no difference was observed in rates of VTE (7.4% vs 4.4%, P = .683) or in platelet count (median [IQR], 260 [215-304] vs 260 [211-306], P = .790). No significant differences were found between the groups on coagulation profiles, complications, or other outcomes.
This study failed to identify significant differences between coagulation-related biomarkers and VTE incidence of adolescent and adult, trauma patients who tested positive for cannabinoids vs those that tested negative for cannabinoids.”
“Background/Objectives: Hemp (Cannabis sativa L. subsp. sativa) is a plant within the Cannabis sativa species and utilized for several applications, including antioxidation, antihypertension, and anti-inflammation. To our knowledge, no prior study has assessed the acute and sub-chronic oral safety of hemp leaf oil in Sprague-Dawley rats under Thailand-compliant THC levels. This study investigates the acute and sub-chronic effects of Hemp leaf oil (HLO) on the heart, liver, and kidneys of male and female Sprague-Dawley rats.
Methods: Six-week-old male and female Sprague-Dawley rats were administered HLO (1.5 mL/kg) intragastrically, either as a single dose or a repeat dose over 28 days.
Results: No changes in body or organ weights were observed following acute and sub-chronic HLO administration in sex-matched groups. Moreover, blood pressure and heart rate remained comparable across groups after acute and sub-chronic HLO treatment. Both acute and sub-chronic administration of HLO did not influence electrolyte balance, liver enzymes, total protein, albumin, blood urea nitrogen, or creatinine levels. Hematoxylin and eosin staining revealed the normal morphology of the heart, liver, and kidneys in rats subjected to HLO, during both acute and sub-chronic treatment.
Conclusions: In conclusion, our data suggested that both acute and sub-chronic administration of HLO at 1.5 mL/kg could be safe for the vital organs. These findings support the potential use of HLO in therapeutic applications, particularly in scenarios when the safety of essential organs is at stake.”
“These results support the safety effect of HLO treatment and the prospective application of HLO in preclinical research or clinical settings. This safety profile supports the extension of research into many domains, including dose-escalation studies and extended chronic toxicity assessments. This will strengthen the evidence base for any future clinical development of HLO.”
“Background: Perioperative tobacco use has been identified as an independent risk factor for adverse events after total hip arthroplasty (THA). It is unknown if perioperative cannabis users share similar levels of risk for adverse events after THA.
Methods: Patients undergoing THA were identified from the 2010 to 2021 PearlDiver M151 administrative data set. Patient subcohorts were categorized based on presence or absence of cannabis and/or tobacco use, as determined by coding. These subcohorts were equally matched based on patient age, sex, and Elixhauser Comorbidity Index scores to form groups of nonusers, tobacco users, tobacco and cannabis users, as well as cannabis users. The incidences of adverse events within 90 days postoperatively were obtained and compared using univariate and multivariate analyses that controlled for age, sex, and Elixhauser Comorbidity Index. Bonferroni correction was applied.
Results: Of 494,431 THA patients, nonusers were 442,000 (89.40%), tobacco users 46,925 (9.50%), tobacco and cannabis users 3,390 (0.69%), and cannabis users 2,116 (0.43%). After matching, there were 1,897 in each group. By multivariate analyses, tobacco-only users were at significantly greater risk of severe adverse events, sepsis, and pneumonia (P < 0.001 for each). Tobacco and cannabis users were at significantly greater risk of severe adverse events, myocardial infarction, pneumonia, and readmission (P < 0.001 for each). Conversely, cannabis-only users were not at significantly greater risk for any of the combined or individual adverse events assessed.
Discussion: This study confirmed that THA patients with tobacco-only use were at greater risk of perioperative adverse events and that these were relatively similar to those with concurrent tobacco and cannabis use. However, cannabis-only users were not at greater risk, a finding that is of clinical interest given the evolving access and increasing use of this agent.”
“Cannabidiol (CBD) is a non-psychotropic compound found in plants of the Cannabis genus, extensively studied for its therapeutic potential. Research has shown that CBD possesses anti-inflammatory, antioxidant, and regenerative properties, and may contribute to the recovery of neural and bone tissues.
In light of the aging population and the resulting rise in neurodegenerative and osteodegenerative conditions, exploring novel therapeutic strategies that promote cellular regeneration is increasingly important.
This review aims to compile and critically analyze key studies published in recent decades regarding the effects of CBD on the regeneration of the central and peripheral nervous systems, as well as bone tissue.
Findings from in vivo studies indicate that CBD can attenuate inflammatory responses, inhibit oxidative stress, and modulate cellular pathways involved in tissue repair, thereby supporting neuronal and bone regeneration. Moreover, evidence suggests that CBD may protect cells from structural damage, enhancing the functional recovery of affected tissues.
Despite scientific advances highlighting cannabidiol as a promising agent for bone and nerve regeneration, its therapeutic application still faces significant limitations. The primary challenge lies in the lack of robust clinical trials in humans, as most existing evidence is derived from in vitro and in vivo studies, making it difficult to confirm its efficacy and safety in clinical contexts. Additionally, CBD’s low bioavailability-due to first-pass hepatic metabolism-hinders dose standardization and reduces the predictability of therapeutic outcomes.
Compounding these issues are regulatory constraints and the persistent social stigma surrounding cannabis-derived compounds, which further impede their integration and acceptance in regenerative medicine. Therefore, future research is essential to validate the therapeutic benefits of CBD and to establish its clinical applicability in treating neurological and bone disorders.”
“Collectively, these effects underscore the potential of CBD as a regenerative agent in pathological conditions related to aging, trauma, and neurodegenerative or musculoskeletal disorders. This review offers a comprehensive synthesis of current findings, emphasizing the innovative potential of cannabidiol (CBD) as a minimally invasive and multifunctional therapeutic strategy for the regeneration of nerve and bone tissues.”
“Background: Cannabinoids, such as tetrahydrocannabinol (∆-9-THC) and cannabidiol (CBD) have been proposed for topical medicinal use as a treatment for tissue inflammation. In this context, keratinocytes are the first cells that encounter cannabinoids. The present study evaluated the dose-response relationship between different concentrations of THC and CBD and their effects on human skin and gingival keratinocyte growth and migration, to identify suitable non-toxic concentrations of cannabinoids.
Methods: Human gingival and skin keratinocytes were exposed to CBD or THC at different concentrations for 24 h, and then cell adhesion, morphology, and growth/viability were assessed. The effects of cannabinoids on keratinocyte migration were evaluated at 6, 12, and 24 h. Cytotoxicity of CBD and THC against keratinocyte cells was assessed using an LHD cytotoxicity test. Cell metabolic profiles were evaluated using Mito and Glyco Stress Assays. The anti-inflammatory effects of cannabis derivatives were assessed against LPS-stimulated keratinocytes. Data analysis was performed by one-way ANOVA.
Results: Only high concentrations (10 and 20 μg/mL) of CBD and THC were cytotoxic to gingival and skin keratinocytes, reduced cell adhesion and growth, and were associated with a delay in cell migration after wounding. Cells exposed to high concentrations (20 μg/mL) of cannabinoids displayed high levels of lactate dehydrogenase (LDH) activity and changes in mitochondrial activities. CBD induced a metabolic shift in skin keratinocyte cells toward glycolysis, while reducing mitochondrial oxidative phosphorylation. In contrast, THC did not alter the metabolic profile of skin keratinocytes. Interestingly, both CBD and THC significantly reduced the LPS-induced inflammatory response by decreasing secretion of IL-6 and IL-8 by gingival and skin keratinocytes.
Conclusions: Gingival and skin keratinocytes interact differently with cannabinoids. Only high concentrations of cannabinoids were cytotoxic, suggesting that the use of low concentrations of CBD and THC for topical medicinal applications may help control tissue inflammation.”
“Overall, results from this study suggest that CBD and THC may be used in different formulations (e.g., as a moisturizing lotion or spray) in order to manage tissue inflammation caused by pathological conditions, such as lichen planus, dermatitis, and psoriasis.”
“Background: The efficacy of cannabinoids as appetite stimulants in chronic wasting disorders is well established; however, their role in systemic sclerosis (SSc) remains to be elucidated. We aimed to evaluate the efficacy of cannabis oil on appetite, inflammatory markers, quality of life (QoL), and adverse events in patients with SSc compared to placebo.
Methods: A randomized placebo-controlled trial was conducted in 27 SSc patients with anorexia or malnutrition, according to sample size analysis. Patients with overlap connective tissue diseases, malignancies, or severe medical conditions were excluded. Participants were randomized 1:1 to receive either cannabis oil or placebo (two drops sublingual twice daily). The endpoints included changes in appetite grading using the visual analogue scale (VAS), body weight (BW), daily calorie intake, inflammatory markers, and QoL assessed using the EuroQol-5 Dimension (EQ-5D).
Results: Thirteen patients in each group completed the study (66.7% were female, and 77.9% had diffuse cutaneous SSc). The cannabinoid group trended toward greater improvements in appetite, satisfaction with eating, ability to eat more, BW, daily calorie intake, health VAS, and reduced inflammatory markers than the placebo group, although the differences were not statistically significant. Transferrin, transforming growth factor-β, and serum albumin levels did not differ between the groups. The VAS score for hunger significantly increased in the treatment group (p < 0.001) but not in the placebo group. One patient in the treatment group developed severe hyponatremia and was withdrawn from the study.
Conclusion: Cannabis oil showed a trend toward improving appetite, BW, calorie intake, and QoL in SSc patients with anorexia, though most results were not statistically significant. Hunger VAS scores increased significantly, and inflammatory markers showed some reduction. Larger studies are needed to confirm these findings.”
“Cannabis oil demonstrated a trend toward improving appetite, satisfaction with eating, body weight, daily calorie intake, and quality of life in SSc patients with anorexia or malnutrition.”
“Background: Opioid related fatalities remain a public health crisis in the US. Currently, the only way to restore breathing following an opioid induced persistent apnea is with the administration of the opioid antagonist naloxone, but it also reverses analgesia, euphoria, and induces precipitated withdrawal in opioid dependent individuals.
Methods: Using whole-body plethysmography, we assessed changes in breathing frequency in awake behaving mice resulting from a single fentanyl dose (50 mg/kg i.p.) that followed i.p. pretreatment with saline, vehicle, naloxone (100 mg/kg), cannabidiol (CBD) (250 mg/kg), or CBD + naloxone. Then we assessed the delay to opioid-induced persistent apnea (OIPA) and the median lethal dose (LD50) of fentanyl during a continuous i.c.v. infusion of fentanyl (100 ng/min), in urethane anesthetized mice, following pretreatment with saline, vehicle, naloxone (100 mg/kg), CBD (250 mg/kg), or CBD + naloxone i.p.
Results: Here we show acute pretreatment with CBD is as effective as naloxone at preventing opioid-induced respiratory depression from fentanyl in awake mice, and increasing LD50 of fentanyl in urethane anesthetized mice. When pre-administered together, CBD + naloxone, increased LD50 of fentanyl even more than CBD or naloxone alone in urethane anesthetized mice.
Conclusion: CBD may be an effective preventative therapy for OIPA by increasing the time before apnea onset and potentially enhancing the efficacy of naloxone as an additional strategy to save lives.”
“This proof of concept using CBD as a prophylactic therapeutic for prevention of fatal OIPA in mice has considerable potential for public health benefit.”
“Non-psychotropic Cannabis sativa L. chemotypes have gained increasing interest due to their diverse profiles of bioactive compounds. While cannabinoids such as cannabidiol (CBD), cannabigerol (CBG), are known for their biological effects, the role of other cannabinoids such cannabichromene (CBC) remains underexplored as for chemotype V, which lacks in cannabinoids but is characterized by other minor phytochemicals.
This study aimed to evaluate the individual and combined contributions of cannabinoids and non-cannabinoid phenolics to the antioxidant, antimicrobial, and anti-inflammatory properties of extracts derived from four C. sativa chemotypes, including a cannabinoid-free variant as a comparison.
Ethanolic extracts were obtained from four hemp chemotypes: CBD-rich (CS1), CBG-rich (CS2), CBC-rich (CS3), and cannabinoid-free (CS4). Phytochemical profiling was conducted using UHPLC-HRMS. Antioxidant properties were assessed via DPPH, ABTS, and FRAP assays. Antimicrobial activity was tested against Gram-positive and Gram-negative bacteria through MIC, MBC, and time-kill assays. Anti-inflammatory activity was evaluated in LPS-stimulated RAW 264.7 macrophages via gene expression analysis of pro- and anti-inflammatory mediators (IL1b, IL6, Cox2, IL10, IL1Ra).
Phytochemical analysis confirmed the chemotype-specific profiles, with CS3 showing the highest levels of canniprene and the early discovered 5-methoxy-dihydrodenbinobin. Antioxidant assays revealed that cannabinoids were the main contributors to radical scavenging capacity, though CS3 exhibited additional ferric ion reducing power likely due to non-cannabinoid phenolics. Antibacterial activity was confined to Gram-positive bacteria, where CS1 showed the highest efficacy, and CS4 showed no activity, highlighting the critical role of cannabinoids. All extracts reduced LPS-induced Il1b, Il6, and Cox2 gene expression, but only cannabinoid-rich extracts upregulated the anti-inflammatory cytokines IL10 and IL1Ra, indicating a cannabinoid-dependent effect.
Both cannabinoids and non-cannabinoid phenolics contribute to the biological activity of Cannabis sativa extracts, with cannabinoids playing a central role in antimicrobial responses and stronger anti-inflammatory effect as a pure cannabinoid or as an extract. From this point of view, the cannabinoid-free chemotype V could be a valuable functional control for isolating the effects of cannabinoids, reinforcing the need for integrative analyses in evaluating the therapeutic potential of cannabis-derived formulations.”
“In this study, we provided a phytochemical characterization and biological activity of non-psychoactive Cannabis sativa L. extracts from III, IV, V and the emerging CBC chemotype. The phytochemical profile confirmed the distinct percentage of cannabinoid and non-cannabinoid composition of each chemotype, with the CS3 sample exhibiting the highest levels of canniprene and 5-methoxy-dihydrodenbinobin. Antioxidant assays demonstrated that cannabinoids significantly contribute to the radical scavenging capacity of the extracts, with an additional support from non-cannabinoid phenolics as testified by the CS4. Antimicrobial assays showed that only the cannabinoid-containing extracts exhibited potent bactericidal activity against Gram-positive pathogens, including drug-resistant MRSA, while the cannabinoid-free extract lacked such activity. Furthermore, all extracts, including the cannabinoid-free one, were able to suppress LPS-induced pro-inflammatory gene expression in macrophages. However, only the cannabinoid-rich extracts promoted the anti-inflammatory cytokines IL-10 and IL-1Ra, underscoring a cannabinoid-dependent immunomodulatory effect.
Taken together, these results highlight the importance of cannabinoid in the biological properties of Cannabis sativa with a contribution apported by non-cannabinoid phenolic compounds. Moreover, the anti-inflammatory, antimicrobial, and antioxidant effects observed with both pure cannabinoids and cannabinoid-containing extracts support their potential use in topical formulation for the treatment of chronic inflammatory skin disorders, such as atopic dermatitis and psoriasis. These conditions are often exacerbated by skin dysbiosis and colonization by Gram-positive bacteria like Staphylococcus aureus, which contribute to skin barrier dysfunction and amplify immune dysregulation (Zhang et al. 2025). Therefore, while the cannabinoid-free chemotype V serves as a valuable control for dissecting the specific contributions of individual cannabinoids within CS extracts, our findings pave the way for future investigations into the therapeutic potential of selected cannabis-derived products—particularly in the context of antimicrobial resistance and inflammatory diseases associated with dysbiosis.”
“Intestinal fibrosis is a common and serious complication of inflammatory bowel diseases, often leading to strictures that require endoscopic or surgical intervention.
Despite advances in anti-inflammatory therapies, effective antifibrotic treatments is currently not available. Therefore, new treatment methods for intestinal fibrosis are sought with the endocannabinoid system (ECS) as a potential therapeutic target.
Cannabinoid receptors 1 and 2 (CB1/2) are classic receptors of the ES involved in the modulation of intestinal inflammation and permeability of the mucosal barrier. Experimental evidence from liver and lung models suggests that CB1 receptor activation promotes fibrosis through enhancement of the TGF-β/Smad pathway, interaction with the renin-angiotensin system, and upregulation of profibrotic markers, such as collagen and α-SMA.
In contrast, CB2 receptor signaling appears to exert protective effects by limiting inflammation, fibroblast activation, and extracellular matrix deposition. Recent findings also suggest cross-talk between cannabinoid signaling and platelet-derived growth factor pathways, which are key drivers of myofibroblast proliferation and fibrogenesis. Although these mechanisms are well-established in hepatic, pulmonary and skin fibrosis, data from small and large intestine is scarce. However, direct evidence in intestinal fibrosis is scarce, representing a major knowledge gap.
Elucidating ECS mechanisms in the alimentary tract could enable targeted antifibrotic strategies, complement current therapies, and reduce progression to fibrostenotic disease.”
“The ECS is widespread in the human body, which proves its many functions in the body. Due to its presence in the digestive system and immune cells, it can influence the modulation of inflammation and the process of fibrosis in IBD. Numerous studies, both in animal models, cell cultures and in human tissue, show that the activation or inhibition of individual elements of the ECS can affect the process of intestinal fibrosis. Hence, the ECS may be a potential target aiming at the fibrosis reduction.”
