UHPLC-Q-TOF-MS profiling and multifaceted antioxidant, antihyperglycemic and anticancer potential of Cannabis sativa sugar leaves: An unexplored source of cannabidiol, terpenes and polyphenols

Posted on by
Reply
Pharmacological Research - Natural Products

“Cannabis sativa is one of the most extensively researched plant species that holds promising therapeutic and ethnomedicinal significance.

Various parts of the species including fan leaves, flowers and trichomes are well documented for their richness in cannabidiol (CBD) and tetrahydrocannabidiol (THC) contents. However, an overlooked part of C. sativa, the sugar leaves, which are wasted during harvesting has plethora of CBD and THC and yet to investigated.

In this study we investigated the ethanol extract of sugar leaves of C. sativa (CSLE) for chemical composition through UHPLC-Q-TOF-MS analysis and pharmacological potential by using various in vitro antioxidant, antidiabetic, nitric oxide inhibition and anticancer studies. Furthermore, in silicomolecular docking analysis was performed for 10 selected compounds against α-glucosidase and α-amylase.

The UHPLC-Q-TOF-MS profiling of CSLE revealed the tentative identification of 37 compounds including CBD, THC, terpenes and flavonoids. The cytotoxicity studies presented highest activity against breast cancer cell lines (MDA-MB-231, IC50= 18.12 ± 1.13 µg/mL) followed by lung, liver and colorectal cancer cell lines.

Similarly, CSLE showed significant antidiabetic activity by inhibiting α-glucosidase (IC50= 3.13 ± 2.78 µg/mL) and α-amylase. The in vitro antioxidant assays gave highest activity in ABTS followed by DPPH method as well as potentially inhibited nitric oxide (NO) formation. The computational analysis revealed good docking interaction of CBD, THC, selected terpene and flavonoids against α-glucosidase and α-amylase.

Overall, the findings present the sugar leaves of C. sativa as the undisputed rich source of CBD, THC, terpenes and flavonoids with multifaceted therapeutic potential in diabetes, inflammation and different types of cancers. However, there is need of further investigations on toxicity profile and in-depth pharmacological evaluation through in vivo disease bearing animal models.”

https://www.sciencedirect.com/science/article/abs/pii/S2950199725001429

“The research titled “UHPLC-Q-TOF-MS profiling and multifaceted antioxidant, antihyperglycemic and anticancer potential of Cannabis sativa sugar leaves: An unexplored source of cannabidiol, terpenes and polyphenols” identifies sugar leaves of Cannabis sativa as a potential source for multiple therapeutic compounds, including cannabidiol, terpenes, and polyphenols. Through UHPLC-Q-TOF-MS analysis, the study found that these sugar leaf extracts exhibit antioxidant, antihyperglycemic (anti-diabetic), and anticancer activities against various cancer cell lines. The specific compounds present in the sugar leaves, when combined with other plant compounds like terpenes and flavonoids, demonstrate a phenomenon known as the entourage effect, which could enhance their therapeutic potential.”

Neuroavailable peptides from hempseed protein hydrolysates reduce hippocampal inflammation and glial activation in a scopolamine-induced Alzheimer’s disease

Posted on by
Reply
pubmed logo

“Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment, synaptic dysfunction, and neuronal loss. Neuroinflammation, driven by the activation of microglia and astrocytes, is a key contributor to AD pathology, amplifying oxidative stress and amyloid-β toxicity. Modulation of neuroinflammatory pathways thus represents a promising therapeutic strategy.

In this study, we evaluated the effects of a food-grade hempseed protein hydrolysate (HPH20A) on hippocampal inflammation and glial activation in a scopolamine-induced mouse model of AD.

Mice were orally supplemented with HPH20A (10 mg/kg/day) for 12 weeks. Hippocampal tissue was analyzed by RT-qPCR and immunohistochemistry to assess the expression of glial and inflammatory markers. To identify peptides capable of reaching the brain, we employed a double transwell in vitro system simulating intestinal and blood-brain barrier (BBB) transport, followed by LC-TIMS-MS/MS peptidomics, in silico bioactivity prediction, and molecular docking. HPH20A supplementation significantly attenuated the expression of pro-inflammatory markers, including GFAP, IBA1, TREM2, CD68, iNOS, COX2, and IL-6, and increased the anti-inflammatory cytokine IL-10. Peptidomic analysis identified two peptides, NVDTELAHKL and DSETVKRL, consistently present across intestinal, systemic, and brain compartments. These peptides were predicted to exhibit anti-inflammatory activity and demonstrated high-affinity binding to AD-related targets (APP, TREM2, and AChE) in docking simulations.

Taken together, these findings suggest that HPH20A exerts neuroprotective effects by modulating hippocampal inflammation inflammation, potentially through specific bioactive peptides capable of crossing the BBB.

Our results support the potential of hempseed-derived peptides as dietary modulators of neuroinflammation in early stages of neurodegenerative disease.”

https://pubmed.ncbi.nlm.nih.gov/40916308/

https://www.sciencedirect.com/science/article/pii/S0753332225006328?via%3Dihub

Cannabis administration is associated with reduced alcohol consumption: Evidence from a novel laboratory co-administration paradigm

Posted on by
Reply
pubmed logo

“Background: Alcohol and cannabis co-use is increasingly prevalent across the U.S., concomitant with trends towards recreational cannabis legalization. While some studies have shown that cannabis co-use is associated with reductions in alcohol consumption (i.e., substitution), others have observed increases in alcohol intake (i.e., complementarity) or no change. This study aims to address this gap in the literature through investigating the effects of legal-market cannabis on alcohol consumption and craving in the laboratory.

Method: Leveraging a within-subjects design, we enrolled non-treatment seeking individuals who use both alcohol and cannabis (n = 61) to complete two laboratory sessions, wherein they were provided an alcohol priming drink alone or after self-administering cannabis. Participants were then given the opportunity to self-administer up to 4 additional drinks. We assessed differences in alcohol self-administration and craving between sessions.

Results: Cannabis self-administration was associated with a significant reduction in number of drinks self-administered. Further, exploratory analyses revealed that individuals who drank less after using cannabis (“substituters”, n = 23) experienced reductions in craving after using cannabis and alcohol compared to alcohol alone, whereas individuals who drank the same number of drinks after using cannabis show minimal differences in craving. There were no significant group differences in blood-THC concentration post-cannabis use.

Conclusion: Results indicate that for some individuals who drink heavily, cannabis may serve as a substitute for alcohol, and craving reduction is a potential mechanism through which this could occur.”

https://pubmed.ncbi.nlm.nih.gov/40915022/

“Cannabis use was associated with a reduction in alcohol intake.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871625003138?via%3Dihub

Short-term residual effects of smoked cannabis on simulated driving performance

Posted on by
Reply
pubmed logo

“Rationale: Between periods of use, chronic cannabis consumers may display residual effects on selective cognitive functions, particularly memory and attention. Whether there are comparable deficits in real-world behaviors, such as driving, has not been thoroughly examined.

Objectives: The current study explored the association between driving simulator performance, cannabis use history, and demographic factors after ≥ 48 h of abstinence. Study I examined simulator performance across a broad range of use within 191 healthy cannabis users. Study II compared performance between participants with the highest cannabis use intensity and a non-cannabis-using comparison group.

Methods: In Study I, 191 healthy cannabis users completed a 25-minute simulated drive, following ≥ 48 h of abstinence. In Study II, a pilot study comprising a subset of 18 frequent cannabis users was compared to 12 non-using controls who completed identical driving measures in a separate study. In both studies, the main outcome was the Composite Drive Score (CDS), a global measure of driving performance comprising key driving-related variables, including standard deviation of lateral position.

Results: In Study I, there was no relationship between CDS, its subtests, measures of cannabis use history, or demographic variables (all ps > 0.10). In Study II, frequent cannabis users and the non-using comparison group did not differ on CDS or performance on its subtests (all ps > 0.40).

Conclusions: The current study did not find evidence of a residual effect of cannabis on simulated driving performance during a short period of cannabis abstinence. Future studies would benefit from inclusion of larger non-cannabis-using comparison groups.”

https://pubmed.ncbi.nlm.nih.gov/40913146/

https://link.springer.com/article/10.1007/s00213-025-06880-1

UK Medical Cannabis Registry: A clinical outcomes analysis for insomnia

Posted on by
Reply

“Insomnia affects approximately 10% of adults globally. Current treatments have their limitations, and there is growing evidence on the therapeutic potential of cannabis-based medicinal products for insomnia.

This study aimed to assess changes in sleep-specific and general patient-reported outcome measures (PROMs) in individuals prescribed cannabis-based medicinal products for insomnia and to assess the incidence of adverse events.

A case series was analysed with patients diagnosed with primary insomnia from the UK Medical Cannabis Registry (UKMCR). The primary outcome examined changes in the Single-Item Sleep Quality Scale (SQS), Generalised Anxiety Disorder-7 (GAD-7), and EuroQol-5 Dimension-5 Level (EQ-5D-5L). Changes in PROMs were assessed from baseline to 1-, 3-, 6-, 12- and 18-months. Adverse events were classified according to the CTCAE version 4.0. The inclusion criteria were met by 124 participants.

SQS scores showed improvement from baseline (2.66 ± 2.41) to 1- (5.67 ± 2.65; p < 0.001), 3- (5.41 ± 2.69; p < 0.001), 6- (4.80 ± 2.89; p < 0.001), 12- (4.24 ± 3.01; p < 0.001) and 18-months (3.81 ± 2.90; p < 0.001). GAD-7 scores improved from baseline to 1-, 3-, 6-, 12- and 18-months (p < 0.050). There were also improvements in EQ-5D-5L dimensions of usual activities, pain/discomfort, anxiety/depression, and index values (p < 0.001). Eleven (8.87%) participants reported a total of 112 (90.32%) adverse events, but none were disabling or life-threatening.

The study demonstrated improvements in subjective sleep quality and other captured PROMs in insomnia patients treated with cannabis-based medicinal products. Although the treatment was generally well-tolerated, randomised controlled trials are needed to confirm the effectiveness and safety of cannabis-based medicinal products.”

https://journals.plos.org/mentalhealth/article?id=10.1371/journal.pmen.0000390

“Study finds cannabis improves sleep where other drugs fail”

https://www.sciencedaily.com/releases/2025/09/250901104658.htm

Endocannabinoid signaling in epilepsy

Posted on by
Reply
pubmed logo

“Epilepsy, characterized by recurrent abnormal neuronal discharges, can lead to severe manifestations, including prolonged seizures that may become life-threatening. Despite the availability of numerous antiseizure drugs, many patients remain refractory to existing treatments, prompting the urgent search for novel therapeutic strategies.

One pivotal factor driving epileptogenesis is the disruption of the excitatory-inhibitory balance, resulting in excessive neuronal firing and hyperexcitability. In addition, neuroinflammation not only contributes to seizure generation but also exacerbates disease progression, forming a vicious cycle of neuronal damage.

The endocannabinoid (eCB) system, including eCBs, cannabinoid receptors, as well as biosynthetic and catabolic enzymes, has emerged as a crucial regulator of brain homeostasis.

By restoring excitatory-inhibitory balance and alleviating inflammation, eCB signaling influences key processes such as synaptic transmission, neuronal plasticity, and immune responses.

This dual capacity to regulate excitability and inflammatory pathways underscores its therapeutic potential for epilepsy.

In this review, we discussed the mechanisms by which eCB signaling regulates neuronal plasticity and inflammatory responses, emphasizing the interplay between these processes in epilepsy. We also discussed preclinical findings that support the therapeutic potential of targeting the eCB system.

By integrating insights from recent studies, we aim to provide a comprehensive overview of eCB-mediated neuroprotection and highlight future directions for epilepsy research and treatment.”

https://pubmed.ncbi.nlm.nih.gov/40886859/

https://www.sciencedirect.com/science/article/pii/S0969996125002918?via%3Dihub

Assessing Inflammatory Biomarkers at the Intersection of Marijuana and PrEP Use: Preliminary findings from the NCHAT-BIO study

Posted on by
Reply
pubmed logo

“Introduction: Past research has shown that inflammation is reduced among marijuana-using HIV-negative people but not those living with HIV. We take this work a step further by assessing differences based on pre-exposure prophylaxis (PrEP) use among HIV-negative individuals.

Methods: NCHAT is a nationally-representative cohort study of 3,642 adult respondents who are married or cohabiting. Their ages range from 20 to 60 years with 45% self-identifying as non-heterosexual. Biological data (n=573; CRP, IL-6, and EBV antibody levels) were collected via finger stick dried blood spots as part of NCHAT-BIO, a sub-study. Participants self-reported demographic characteristics, PrEP use, and marijuana use. Multivariable regression analyses were used to assess the relationship between these variables and each of the measured biomarkers, adjusting for known confounders.

Results: In adjusted models, neither lifetime or current PrEP use were associated with CRP, IL-6, or EBV antibody levels. Moreover, marijuana use did not differ among those who used PrEP versus those who did not. Among PrEP users, those who reported marijuana use had lower CRP than those who did not (B=-2.31; 95% CI:-4.23, -0.40). Among non-PrEP users, no association was observed between marijuana use and CRP.

Conclusion: The current preliminary data suggest inflammation is reduced among PrEP users who also use marijuana, but the same is not true among non-PrEP users. These findings may suggest that PrEP increases inflammation which is then partially mitigated by the individual cannabinoids or cannabidiols found in marijuana, although more research is needed to confirm this hypothesis.”

https://pubmed.ncbi.nlm.nih.gov/40905335/

https://journals.lww.com/jaids/abstract/9900/assessing_inflammatory_biomarkers_at_the.709.aspx

Effect of Preoperative Cannabis Use on Postoperative Pain and Outcomes Following Cardiothoracic Surgery

Posted on by
Reply
pubmed logo

“Cannabis use has grown both recreationally and medicinally in the United States over the past decades, alongside increased legalization and social acceptance. However, there remains little research investigating the effects of preoperative cannabis use on postoperative pain in patients undergoing surgery.

We conducted a single-center prospective study in adults undergoing cardiac surgery via sternotomy. Patients seen for preoperative consultation in clinic were asked a standardized survey about cannabis use. Clinical data was collected via chart review. Primary outcomes were morphine equivalents in the first 48 hours postoperatively and Visual Analog Scale (VAS) scores. Secondary outcomes were time to extubation, postoperative nausea/vomiting, ICU length of stay (LOS), reoperation, and in-hospital mortality. The non-cannabis user group had 50 patients, and the cannabis user group had 23 patients.

Average morphine equivalents in the first 48 hours were similar between cannabis users and non-users (60.98 vs 59.90; P = 0.93), as were VAS scores at 24 hours (5.52 vs 4.84; P = 0.414) and 48 hours (4.74 vs 3.90; P = 0.23). Average time to extubation (minutes) was nearly identical between cannabis users and non-users (718.41 vs 718.67; P = 0.99). There was also no significant difference in average LOS (days) between cannabis users and non-users (2.91 vs 3.48; P = 0.26). There were no differences in postoperative nausea/vomiting, reoperation, or in-hospital mortality.

In patients undergoing cardiac surgery via sternotomy, there was no effect of cannabis use on any outcomes, including morphine equivalents, Visual Analog Scale scores, time to extubation, ICU length of stay, postoperative nausea or vomiting, reoperation, or in-hospital mortality.”

https://pubmed.ncbi.nlm.nih.gov/40905360/

https://journals.sagepub.com/doi/10.1177/10892532251374952

Exploring therapeutic potential of Cannabis based therapy in autoimmune and rheumatic disorders

Posted on by
Reply
pubmed logo

“The medical use of cannabis is expanding across many countries, with some legalizing its use outright and others implementing medical licensure systems to approve treatment for eligible patients.

Despite this growing interest and utilization, there remains a lack of solid scientific evidence supporting its medical use, even though cannabis has been used therapeutically for thousands of years.

The goal of the following communication is to present updated data on the potential roles of cannabis-based treatments in various autoimmune and rheumatic conditions.

The information highlights that incorporating cannabis into the therapeutic armamentarium may offer benefits.

However, in many cases, despite encouraging perspectives and outcomes, the supporting evidence remains insufficient and requires further validation.

Due to social and legal barriers, the conduct of such rigorous clinical trials has been hindered, limiting the availability of high-quality evidence to guide medical practice.”

https://pubmed.ncbi.nlm.nih.gov/40907777/

https://www.sciencedirect.com/science/article/abs/pii/S1568997225001867?via%3Dihub

Cannabidiol dampens propagation of hippocampal hyperactivity and differentially modulates feedforward and feedback inhibition

Posted on by
Reply
pubmed logo

“Cannabidiol (CBD) decreases seizures in patients with severe pediatric-onset epilepsies including Dravet, Lennox-Gastaut, and Tuberous Sclerosis syndromes. However, the effects of CBD on neuronal activity and circuits remain obscure.

In the mouse hippocampus, we found that CBD causes a GPR55-independent decrease in CA1 pyramidal neuron firing frequency and a GPR55-dependent reduction in CA3 to CA1 hippocampal activity propagation. CBD-mediated decrease in high-frequency activity was mimicked by GPR55 antagonism and prevented by GPR55 deletion and blockade of GABAergic transmission. Dampening high-frequency activity was accompanied by increased recruitment of parvalbumin+ (PV)-INs and reduced recruitment of somatostatin+ (SST)-INs, leveraging the inhibitory subcircuit to limit propagation of hyperactivity. CBD-induced attenuation of high frequency spike propagation was mimicked by pharmacological enhancement and optogenetic engagement of PV-INs. Such increased on-demand recruitment of PV-INs dampened propagation of high-frequency activity to hippocampal CA1 similarly to CBD.

We predict that CBD potentially curbs propagation and perpetuation of seizure activity via these mechanisms.”

https://pubmed.ncbi.nlm.nih.gov/40909733/

https://www.biorxiv.org/content/10.1101/2025.08.26.672420v1