Monthly Archives: March 2025

Identification and Molecular Mechanism of Novel α-Glucosidase Inhibitory Peptides from the Hydrolysate of Hemp Seed Proteins: Peptidomic Analysis, Molecular Docking, and Dynamics Simulation

Posted on by
Reply
pubmed logo

“There is a growing demand for natural and potent α-glucosidase inhibitors due to the rising prevalence of diabetes.

In this study, newly identified α-glucosidase inhibitory peptides were identified from the tryptic hydrolysate of hemp seed proteins based on peptidomics and in silico analysis.

A total of 424 peptides, primarily derived from four cupin-type-1 domain-containing proteins, were identified, and 13 ultimately were selected for validation based on their higher PeptideRanker scores, solubility, non-toxicity, and favorable ADMET properties.

Molecular docking revealed that these 13 peptides primarily interacted with α-glucosidase via hydrogen bonding and hydrophobic interactions. Among them, three novel peptides-NPVSLPGR (-8.7 kcal/mol), LSAERGFLY (-8.5 kcal/mol), and PDDVLANAF (-8.4 kcal/mol)-demonstrated potent α-glucosidase inhibitory activity due to their lower binding energies than acarbose (-8.1 kcal/mol), the first approved α-glucosidase inhibitor for type 2 diabetes treatment.

The molecular mechanism analysis revealed that the peptides NPVSLPGR and LSAERGFLY inhibited α-glucosidase by simultaneously blocking substrate entry through occupying the entrance of the active site gorge and preventing catalysis by binding to active sites. In contrast, the peptide PDDVLANAF primarily exerted inhibitory effects by occupying the entrance of the active site gorge. Molecular dynamics simulation validated the stability of the complexes and provided additional insights into the molecular mechanism determined through docking.

These findings contribute essential knowledge for the advancement of natural α-glucosidase inhibitors and offer a promising approach to effectively manage diabetes.”

https://pubmed.ncbi.nlm.nih.gov/40076843/

“Based on the findings from computational studies, these peptides demonstrate promising α-glucosidase inhibitory potential and may serve as viable natural alternatives to synthetic inhibitors.”

https://www.mdpi.com/1422-0067/26/5/2222

UK Medical Cannabis Registry: An Analysis of Outcomes of Medical Cannabis Therapy for Hypermobility-Associated Chronic Pain

Posted on by
Reply
pubmed logo

“Objective: The study aims to evaluate the clinical outcomes in patients with hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) with chronic pain following treatment with cannabis-based medicinal products (CBMPs).

Methods: This was a case series conducted with the UK Medical Cannabis Registry. The primary outcomes were changes in the following validated patient-reported outcome measures at 1, 3, 6, 12, and 18 months compared with baseline: Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2), pain visual analog scale score (Pain-VAS), Brief Pain Inventory (BPI), five-level EQ-5D (EQ-5D-5L), Single-Item Sleep Quality Scale (SQS), General Anxiety Disorder Seven-Item Scale (GAD-7), and Patient Global Impression of Change. The incidence of adverse events was analyzed as secondary outcomes. Statistical significance was defined as P <0.050.

Results: A total of 161 patients met inclusion criteria. Improvements were observed in BPI severity and interference subscales, SF-MPQ-2, and Pain-VAS (P < 0.001). Changes were also seen in the EQ-5D-5L index value, SQS, and GAD-7 (P < 0.001). A total of 50 patients (31.06%) reported one or more adverse event with a total incidence of 601 (373.29%). The most frequent rating for adverse events was moderate (n = 258; 160.25%), with headache being the most common (n = 44; 27.33%).

Conclusion: An association was identified between patients with HSD/hEDS with chronic pain and improvements in pain-specific and general health-related quality of life following the commencement of CBMPs. CBMPs were also well tolerated at 18 months. These findings must be interpreted within the context of the limitations of study design but add further weight to calls for randomized controlled trials.”

https://pubmed.ncbi.nlm.nih.gov/40079426/

“Cannabis-based medicinal products (CBMPs) have emerged as a potential alternative for chronic pain management, acting on the endocannabinoid system (ECS), which plays a pivotal role in pain regulation.”

“This study reports an association between CBMP treatment and reported improvements in pain and HRQoL among patients with HSD/hEDS.”

https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr2.70024

A Multicenter Feasibility Study of a Novel Curriculum for Oncology Trainees Regarding Medical Cannabis

Posted on by
Reply
pubmed logo

“Background: Oncology providers often lack the confidence to make clinical recommendations about medical cannabis (MC). This study aimed to develop and evaluate the feasibility of implementing an educational curriculum on the use of MC in patient care for oncology trainees.

Methods: A multidisciplinary team designed an educational curriculum for MC use in oncology. The curriculum was piloted as a 1-hour interactive webinar across 8 United States-based hematology/oncology fellowship programs between 2022 and 2023. Incentivized surveys measuring feasibility outcomes, including cultural attitudes/norms, acceptability, compatibility, and self-efficacy (a composite index of self-confidence in discussing MC efficacy, risks, modes of use, and role in symptom management), were distributed before, immediately after, and 12 weeks post-webinar.

Results: Of 103 trainees, 75 (72.8%) completed the pretraining survey and 66 (64.1%) completed the posttraining survey. Most respondents believed discussions about the role of MC in symptom management were valuable (n=56; 74.7%), though few (14.7%) believed trainees were expected to engage in such discussions. Most participants rated the curriculum as helpful (92.4%), beneficial for oncology trainees (84.8%), and likely to be recommended to colleagues (87.9%). Post-webinar, 78.8% of participants reported an increased likelihood of initiating discussions with patients regarding MC. There were significant improvements in the composite self-confidence index from pre- to post-webinar (2.7% vs 65.2%; P<.001), which persisted in the follow-up surveys (n=36; response rate, 34.9%).

Conclusions: This multisite study demonstrates the feasibility of implementing a novel curriculum focused on MC for oncology trainees. These findings can guide the design of a prospective, multi-institutional study to evaluate knowledge expansion, retention, and behavioral changes resulting from the intervention.”

https://pubmed.ncbi.nlm.nih.gov/40073833/

“Our prior work demonstrated that training in MC use for patients with cancer is an area of unmet need among hematology/oncology trainees. The current study demonstrated the feasibility and acceptability of developing and delivering a virtual webinar curriculum on MC for hematology/oncology fellows. Most trainees enjoyed the format and found the content useful and applicable to their practice and education. We observed sustained improvements in self-reported confidence in conducting clinical discussions across all domains included in the curriculum. Furthermore, participants reported increased discussions about MC with patients following the training, aligning with recent expert consensus guidelines. Future efforts should focus on refining this curriculum based on emerging data in the field, developing similar interventions for other oncology health care professionals, and exploring strategies to sustain these educational initiatives. Such efforts are essential to ensure broad implementation, maximize knowledge retention, and facilitate meaningful behavioral changes in real-world clinical practice.”

https://jnccn.org/view/journals/jnccn/23/3/article-p82.xml

A Pilot Randomized Placebo-Controlled Crossover Trial of Medicinal Cannabis in Adolescents with Tourette Syndrome

Posted on by
Reply
pubmed logo

“Introduction: Medicinal cannabis (MC) has potential therapeutic effects in Tourette Syndrome (TS), however there has been limited research in adolescent patients. This pilot study aimed to investigate the feasibility of conducting a randomized placebo-controlled crossover trial of MC in adolescents with TS. 

Method: This was a phase I/II double-blind, cross-over pilot study comparing MC with matched placebo in adolescents aged 12-18 years with TS. The active medication was Δ9-tetrahydrocannabinol (THC) 10 mg/mL and CBD 15 mg/mL in peppermint-flavored medium-chain triglyceride oil. The dose titration schedule was stratified into two participant weight bands: below 50 kg (max THC 10 mg/day) or ≥50 kg (max THC 20 mg/day). Each treatment phase lasted 10 weeks, with a 4-week washout period. 

Results: Ten adolescents were randomized (mean age 14.8 years, 50% male) and seven completed the full study protocol. Two adolescents discontinued due to adverse events (one on MC, one placebo) and one was lost to follow-up. The most common adverse event was dizziness (67%). There were no serious adverse events. Among actively enrolled participants, protocol adherence was excellent: study visits 100%, blood test completions 100%, and online questionnaire completion 97.6%. Medication adherence was acceptable in 63.6%. Parents reported a high degree of study design acceptability. On the Clinical Global Impression-Improvement scale, three participants were rated as much improved on MC compared with one on placebo at 10 weeks. 

Discussion: The findings suggest that the study protocol is feasible and acceptable to patients with TS and their families. A fully powered study is needed to evaluate the efficacy of MC in adolescent TS.”

https://pubmed.ncbi.nlm.nih.gov/40082070/

https://www.liebertpub.com/doi/10.1089/can.2024.0188

Cannabis sativa L. Leaf Oil Displays Cardiovascular Protective Effects in Hypertensive Rats

Posted on by
Reply
pubmed logo

“Hemp (Cannabis sativa L.) leaf oil (HLO) contains several bioactive compounds such as phenolics, flavonoids, and quercetin. However, the effects of HLO on hypertensive conditions have not yet been investigated.

This study investigated the cardiovascular protective effects of HLO in a nitric oxide (NO) synthase inhibitor-induced hypertensive rat model.

Five weeks of HLO administration significantly prevented blood pressure elevation, improved cardiac function, and mitigated cardiac hypertrophy. Furthermore, HLO ameliorated vascular dysfunction by reducing sympathetic nerve stimulation-induced vasoconstriction, increasing endothelium-dependent vasorelaxation, as well as decreasing vascular wall thickness and vascular smooth muscle cell proliferation. HLO inhibited renin-angiotensin system (RAS) activation and downregulated angiotensin II type 1 (AT1) receptor and NADPH oxidase expression. Additionally, HLO normalized the circulating NO metabolites, decreased oxidative stress, and enhanced antioxidant status.

These findings suggest that HLO protects against cardiovascular dysfunction and preserves its morphology. The mechanism of action might involve the suppression of RAS overactivity and oxidative stress through the Ang II/AT1 receptor/NOX2 pathway in NO-deficient hypertension.”

https://pubmed.ncbi.nlm.nih.gov/40076524/

“In conclusion, HLO possesses a total phenolic content that demonstrates cardiovascular-protective effects against NOS inhibitor-induced hypertension. HLO exhibits an ACE inhibitory action and inhibits the Ang II/AT1 receptor/NOX2 pathway, alleviating cardiovascular hypertrophy and oxidative stress in a hypertensive rat model. Our findings suggest that HLO displays beneficial effects under a hypertensive condition.”

https://www.mdpi.com/1422-0067/26/5/1897

Low doses of cannabis extract ameliorate non-motor symptoms of Parkinson’s disease patients: a case series

Posted on by
Reply
pubmed logo

“Introduction: Parkinson’s disease (PD) is mainly characterized by motor symptoms including muscle rigidity, resting tremor and bradykinesia. However, the management of the non-motor symptoms represent a relevant clinical challenger in PD. These non-motor symptoms include cognitive and sleep disturbance and there is evidence that cannabinoids may represent alternative and effective treatments for non-motor symptoms of PD.

Methods: Therefore, this study addressed the effects of oral treatment with cannabis extract on cognition, insomnia, and daytime sleepiness in six patients with moderate PD. The patients were randomized to receive two different doses of a cannabis extract: THC:CBD 250:28 μg/day (n = 3) or 1000:112 μg/day (n = 3). The assessment of cannabis administration related to the cognitive field was measured by the Montreal Cognitive Assessment test (MoCA test), the insomnia was assessed by the Insomnia Severity Index (ISI), and daytime sleepiness was assessed using the Epworth sleepiness scale (ESS). All clinical evaluations were performed before treatment and at 15, 30, 60, and 90 days of treatment.

Results: The statistical analysis indicated a significant benefit of the cannabis extract treatment, at dose of 1000:112 μg/day after 60 days of treatment, on insomnia assessed by ISI. Moreover, the statistical analysis of data from ISI and MoCA tests showed a trend toward improvement over time, while no significant effect was observed in the ESS. There were no reports of significant adverse effects during the cannabis extract treatment.

Discussion: These results demonstrate benefits of short-time treatment (60 days) with low doses of cannabis extract on insomnia in PD patients. This study provide novel findings of the potential of combining CBD and THC as safe and effective treatments for non-motor symptoms of PD.”

https://pubmed.ncbi.nlm.nih.gov/40066073/

“In conclusion, these results demonstrate a possible benefit of short-time treatment (3 months) with low doses of cannabis extract on cognition and insomnia in PD patients. This study provide novel findings of the potential of combining CBD and THC as safe and effective treatments for non-motor symptoms of PD.”

https://www.frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2024.1466438/full

Beta-caryophyllene inhibits the permeability of the blood-brain barrier in MPTP-induced parkinsonism

Posted on by
Reply
pubmed logo

“Introduction: Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Although the precise pathogenesis of PD remains unclear, several studies demonstrate that oxidative stress, inflammation, low levels of antioxidants, and the presence of biomolecules that generate reactive oxygen species can disrupt the blood-brain barrier (BBB) as an essential feature of the disease.

Aims: This study aimed to test whether agonism to cannabinoid receptor type 2 (CB2) through the administration of β-caryophyllene (BCP) could correct BBB permeability in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonism induction model.

Methods: We conducted a molecular assessment of proteins (immunochemistry and western blot), BBB permeability, and related biomarkers of PD (lipid peroxidation) in the MPTP mouse model of the disease.

Results: Expression of zonula occludens (ZO-1) and occludin tight junction (TJ) proteins was dampened in the striatum and substantia nigra pars compacta of mice, while lipid peroxidation and BBB permeability increased in the striatum in the MPTP-treated group, and these effects were reversed under BCP administration. This phytocannabinoid was able to restore protein expression and immunoreactivity of tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP), as well as nuclear factor-erythroid 2-related factor (NRF2) translocation to the nucleus, and NADPH quinone oxidase 1 (NQO1) expression in mice treated with MPTP.

Conclusion: These results highlight the role of CB2 as a therapeutic target for PD, suggesting that its activation may ameliorate PD-related BBB disruption and oxidative stress, reducing the selective death of dopaminergic neurons.”

https://pubmed.ncbi.nlm.nih.gov/40054982/

“Beta-caryophyllene is a dietary cannabinoid.” https://www.ncbi.nlm.nih.gov/pubmed/18574142

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

Improved recognition memory and reduced inflammation following β-caryophyllene treatment in the Wistar-Kyoto rodent model of treatment-resistant depression

Posted on by
Reply
pubmed logo

“Persistent low mood, anxiety and cognitive deficits are common symptoms of depression and highly efficacious treatments that address symptoms including cognitive dysfunction are still required.

β-caryophyllene (BCP) is a terpene with anti-inflammatory and pro-cognitive properties; however, its efficacy on cognition in depression remains unclear.

This study aimed to investigate acute and chronic BCP treatment effects on cognitive, depressive- and anxiety-like behaviours, and inflammation in male and female Wistar-Kyoto (WKY) rats, a rodent model of treatment-resistant depression.

Rats were administered either BCP (50 mg/kg) or vehicle (control). Open field (OFT), social interaction, sucrose preference, novel object recognition (NOR) and elevated plus maze (EPM) tests were conducted after acute (1 h) and chronic (2 weeks) treatment. Peripheral plasma inflammatory cytokine levels were examined.

BCP acutely increased locomotor activity in the OFT but did not improve social interaction, whereas chronic BCP prevented increased latency to first interaction in females (not males). BCP did not improve sucrose preference or prevent anxiety-like behaviours in the EPM. BCP significantly increased novel object discrimination in the NOR test in male and female WKY rats and reduced cytokine levels after chronic treatment.

This study shows for the first time that chronic BCP treatment improved recognition memory and exerted anti-inflammatory properties in a rodent model of depressive-like behaviours. BCP did not significantly improve anxiety-like behaviours, social interaction or anhedonia in WKY rats of either sex.

These findings demonstrate the pro-cognitive effects of BCP in a rodent model of treatment-resistant depression worthy of further investigation.”

https://pubmed.ncbi.nlm.nih.gov/40049345/

https://www.sciencedirect.com/science/article/pii/S0278584625000661?via%3Dihub

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

Improvement in the Cognitive Function in Chronic Pain: Therapeutic Potential of the Endocannabinoid System

Posted on by
Reply
pubmed logo

“Chronic pain presents as a complex condition encompassing sensory (Zhang Z et al. Cell Rep 12;752-759, 2015) and emotional components, often accompanied by anxiety, depression, insomnia, and cognitive impairment. These factors significantly hinder daily activities and rehabilitation efforts.

The widespread prevalence of chronic pain imposes substantial clinical, societal, and economic burdens. While current analgesics have limitations and associated side effects such as tolerance, dependency, cognitive deficits, and a narrow therapeutic window, the search for new analgesic options remains imperative.

The endocannabinoid system (ECS), a key modulator in pain processing pathways, plays a crucial role in executive functions. This review specifically focuses on the cognitive impairments associated with chronic pain and highlights the pivotal role of the ECS in the cognitive aspects of pain. Additionally, the effectiveness of cannabinoid-based medications in improving executive functions in patients with chronic pain is evaluated.”

https://pubmed.ncbi.nlm.nih.gov/40059255/

https://link.springer.com/article/10.1007/s12035-025-04814-8

Spinal dorsal horn neurons involved in the alleviating effects of cannabinoid receptor agonists on neuropathic allodynia-like behaviors in rats

Posted on by
Reply
pubmed logo

“Mechanical allodynia, the pain caused by innocuous tactile stimuli, is a hallmark symptom of neuropathic pain that is often resistant to currently available treatments.

Cannabinoids are widely used for pain management; however, their therapeutic mechanisms for neuropathic mechanical allodynia remain unclear.

Using transgenic rats that enable to optogenetically stimulate touch-sensing Aβ fibers in the skin, we found that the intrathecal administration of the synthetic cannabinoid, WIN 55,212-2, alleviated the Aβ fiber-derived neuropathic allodynia. Furthermore, we injected adeno-associated virus vectors incorporating the rat cannabinoid receptor 1 (CB1 receptor) (encoded by Cnr1) promoter and tdTomato or short hairpin RNA targeting the CB1 receptor into the spinal dorsal horn (SDH) and demonstrated that the conditional knockdown of CB1 receptors in Cnr1+ SDH neurons attenuates the anti-allodynic effects of intrathecally administered WIN 55,212-2. Electrophysiological analysis revealed that Cnr1+ SDH neurons received excitatory synaptic inputs from the primary afferent Aβ fibers.

Collectively, our results suggest that the CB1 receptors in Cnr1+ SDH neurons are molecular and cellular targets of intrathecal WIN 55,212-2 to alleviate neuropathic allodynia.”

https://pubmed.ncbi.nlm.nih.gov/40058945/

https://linkinghub.elsevier.com/retrieve/pii/S1347861325000180

“WIN 55,212-2 is a chemical described as an aminoalkylindole derivative, which produces effects similar to those of cannabinoids such as tetrahydrocannabinol (THC) “