Category Archives: Uncategorized

Adult Neurogenesis Is Regulated by the Endocannabinoid and Kisspeptin Systems

Posted on by
Reply
pubmed logo

“Neurogenesis is considered the most robust form of plasticity in the adult brain. To better decipher this process, we evaluated the potential crosstalk of Kisspeptin and Endocannabinoid Systems (KPS and ECS, respectively) on hippocampal neurogenesis.

Male adolescent rats were exposed to kisspeptin-10 (KP10) and the endocannabinoid anandamide (AEA) administered alone or in combination with the type 1 cannabinoid receptor (CB1R) antagonist SR141716A. The expression of Kiss1 and Kisspeptin receptor (Kiss1R) has been characterized for the first time in rat hippocampus together with the expression of the CB1R and the Transient Receptor Potential Vanilloid 1 ion channel receptor (TRPV1).

Results show that both systems inhibit neurogenesis by reducing the extracellular signal-regulated kinase (ERK) signaling. Despite little differences in the expression of Kiss1R and CB1R, TRPV1 is enhanced by both KP10 and AEA treatments, suggesting TRPV1 as a common thread. KP10 administration reduces CB1R expression in the dentate gyrus, while AEA does not. KPS, unlike ECS, promotes the expression of estrogen receptor α (ER-α) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), also upregulating sirtuin 1 (SIRT1), brain-derived-neurotrophic factor (BDNF), and c-Jun.

These findings suggest that the interaction between ECS and KPS could be involved in the fine-tuning of neurogenesis, highlighting a novel role for KPS.”

https://pubmed.ncbi.nlm.nih.gov/40362219/

https://www.mdpi.com/1422-0067/26/9/3977

Microbial Biosynthesis of Rare Cannabinoids

Posted on by
Reply
pubmed logo

“∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD) are the most abundant natural cannabinoids isolated from the different cultivars of the Cannabis plant. Other natural ∆9-THC analogs, especially those with different alkyl chain substitutions, display different and potent bioactivity. However, these rare cannabinoids are typically isolated at minuscule amounts and are difficult to synthesize. Targeted microbial biosynthesis can therefore be an attractive route to access such molecules.

Here, we report the development of a Saccharomyces cerevisiae host to biosynthesize two rare cannabinoids from simple sugars. The yeast host is engineered to accumulate excess geranyl pyrophosphate (GPP), to overexpress a fungal pathway to 2,4-dihydroxy-6-alkyl-benzoic acids, as well as the downstream UbiA-prenyltransferase and THCA synthase. Two rare cannabinoid acids, the C1-substituted ∆9-tetrahydrocannabiorcolic acid (∆9-THCCA, ∼16 mg/L) and the C7-substituted ∆9-tetrahydrocannabiphorolic acid (∆9-THCPA, ∼5 mg/L) were obtained from this host; the latter was thermally decarboxylated to give ∆9-tetrahydrocannabiphorol (∆9-THCP).

Given the diversity of fungal biosynthetic gene clusters (BGCs) that can produce resorcylic acids, this microbial platform offers potential to produce other rare and new-to-nature cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/40359163/

https://academic.oup.com/jimb/advance-article/doi/10.1093/jimb/kuaf013/8129704?login=false

Effect of hemp seed oil on accelerating wound healing: Evaluation of wound size reduction, epithelialization, granulation tissue formation, and vascularization in murine models

Posted on by
Reply
pubmed logo

“Essential oils have gained interest in wound management, with prior studies exploring combinations of hemp seed oil (Cannabis sativa) and other oils. However, single-oil strategies may offer simpler formulation, reducing the risk of interactions while preserving therapeutic benefits.

The aim of this study was to explore the effect of hemp seed oil on accelerating wound healing, focusing on wound size reduction, epithelialization, granulation tissue formation, and vascularization in murine models.

An in vivo with a post-test-only control group was conducted using 36 male Mus musculus mice (3-4 months, 150-250 grams) which were divided into three groups: negative control (NC), positive control (PC, treated with chloramphenicol ointment twice daily), and treatment group (TG, treated with hemp seed oil 400,000 mg/mL twice daily). Mice were euthanized on day 3, 7, 14, and 21 for wound healing assessment, including macroscopic evaluation (visual observation, wound size, and wound healing rate) and microscopic evaluation (epithelialization, granulation tissue formation, and vascularization).

The present study found that the TG group demonstrated smaller wound sizes on day 14 (p < 0.001) and day 21 (p < 0.001). This group also enhanced wound healing rates observed on day 14 (p < 0.001) and day 21 (p = 0.001) compared to PC and NC groups. Epithelialization was significantly higher in the TG group compared to PC and NC groups on day 14 (p = 0.007), while granulation tissue formation showed significant improvement on day 3 (p = 0.045), day 14 (p = 0.028), and day 21 (p = 0.003). Additionally, TG group showed significantly greater new blood vessel formation on day 21 (p = 0.001) compared to the PC and NC groups.

In conclusion, hemp seed oil demonstrated significant potential in accelerating wound healing processes suggesting a superior effect compared to chloramphenicol ointment. Therefore, hemp seed oil may serve as a promising natural and cost-effective adjunct for wound management.”

https://pubmed.ncbi.nlm.nih.gov/40352225/

In Vivo and In Vitro Crosstalk Among CBD, Aβ, and Endocannabinoid System Enzymes and Receptors

Posted on by
Reply
pubmed logo

“Cannabidiol (CBD), a non-psychotropic compound derived from Cannabis sativa, has garnered attention as a potential therapeutic agent for various neurodegenerative diseases, including Alzheimer’s disease (AD).

Despite growing interest, additional research is required to clarify the specific mechanisms by which CBD influences the pathological accumulation of β-amyloid (Aβ) associated with AD. Moreover, the interactions between CBD and the endocannabinoid system (ECS), both in the presence and absence of Aβ expression, remain a subject of active investigation.

Elucidating these mechanisms may provide valuable insights for advancing both our understanding and the development of targeted interventions in neurodegenerative disease management. Using a multifaceted approach that integrates pharmacological interventions, immunofluorescence imaging, flow cytometry, and biochemical assays, we examined the effects of CBD on Aβ40 and Aβ42. Additionally, we analyzed the modulation of cannabinoid receptor 1(CB1 receptor) and fatty acid amide hydrolase (FAAH) in the presence or absence of Aβ expression, uncovering the intricate regulatory mechanisms of CBD.

Our findings indicate a nuanced response to CBD; while it may produce side effects in non-pathological cells, it demonstrates an ability to induce autophagy and apoptosis in Aβ-expressing cells via the activation of the Microtubule-associated protein 1 light chain 3 B(LC3B) and Caspase-3 pathways. Furthermore, our investigation into faah-1 involvement highlighted its role in alleviating pharyngeal dysfunction and counteracting weight loss in Aβ-expressing Caenorhabditis elegans(C. elegans) strains. These insights advance our understanding of CBD’s therapeutic potential in addressing neurodegenerative pathologies.”

https://pubmed.ncbi.nlm.nih.gov/40350019/

https://www.sciencedirect.com/science/article/abs/pii/S0014299925004741?via%3Dihub

Optimization of the Extraction Process and Comprehensive Evaluation of the Antimicrobial and Antioxidant Properties of Different Polar Parts of the Ethanol Extracts of Cannabis sativa L

Posted on by
Reply
pubmed logo

“The total flavonoids of Cannabis sativa L. were selected as the research object, and the extraction process of C. sativa L. was optimized on the basis of a single factor experiment utilizing a five-factor, three-level response surface method. Subsequently, the vitro antimicrobial and antioxidant activities of the flavonoids were evaluated.

The optimized extraction conditions were as follows: ratio of liquid to solid, 24.69:1 mL/g; soaking time, 102.12 min; extraction time, 165.96 min; ethanol concentration, 46.59%; extraction temperature, 86.87 °C. The extraction rate of C. sativa L. flavonoids (CSF) was found to be 5.51 ± 0.04 mg/g. The extraction of crude flavonoid (i.e., flavonoids extracted under the optimal extraction process) was conducted using four solvents, resulting in five C. sativa L. flavonoid extracts (petroleum ether, CSFp; n-butanol, CSFb; ethyl acetate, CSFe; aqueous phase, CSFw; and crude flavonoid, CSF). CSF contains 10 flavonoid components.

In vitro, all five CSF samples demonstrated good total reducing power, effective scavenging capacity against DPPH and ABTS+ radicals, and pronounced inhibitory effects against Escherichia coli, Bacillus subtilis, and Bacillus pumilus. Analytic Hierarchy Process (AHP) was employed to evaluate the five CSF samples in terms of antibacterial and antioxidant activity.

The results indicated that petroleum-ether-extracted C. sativa L. flavonoids (CSFp) exhibited the most pronounced antibacterial and antioxidant effects.”

https://pubmed.ncbi.nlm.nih.gov/40352509/

“Cannabis sativa L. is an annual herbaceous plant belonging to the mulberry family. It has been demonstrated that the plant contains a variety of physiologically active substances, including antibacterial, antithrombotic, antiallergic, and analgesic properties.”

“The results demonstrate that flavonoids present in C. sativa L. possess significant potential for utilization in both medical and industrial applications.”

https://pubs.acs.org/doi/10.1021/acsomega.4c10986

Quantitative and qualitative imaging in marijuana users and smokers

Posted on by
Reply
pubmed logo

“Objective: To evaluate the effect of marijuana use compared to cigarette smoking on imaging findings in the lungs.

Methods: By searching the electronic medical record, we identified patients who were marijuana users who never smoked; current smokers; and non-marijuana never smokers, who underwent chest CT in our healthcare system in 2019. We generated a random sample of 100 marijuana users as well as 100 each age- and sex-matched controls from the current smoker and never-smoker groups. Patients with extensive airspace disease on CT were excluded. Quantitative CT analysis was performed to measure total lung volume (TLV). A thoracic radiologist reviewed chest CTs in a blinded fashion for the presence of emphysema, centrilobular ground glass opacities, mosaic attenuation, bronchial wall thickening, and coronary calcification.

Results: Our study included 285 participants, comprising 89 non-smokers, 97 smokers, and 99 marijuana users. Despite propensity score matching, the marijuana user group was slightly younger than the smokers and non-smokers (mean age 59 versus 62 and 64 years, respectively, p = 0.04), with similar sex distribution across all groups. TLV was higher in smokers than marijuana users and non-smokers (p<.01 for both).

By visual analysis, 62 % of smokers had emphysema versus 4 % of marijuana users (p<.001). Additionally, centrilobular ground glass opacities were more prevalent in smokers (15 %) than in marijuana users (2 %) (p = 0.0008). No significant difference was noted in the occurrence of mosaic attenuation between smokers and marijuana users. In terms of coronary artery calcification, more smokers had moderate to severe coronary artery calcifications compared to marijuana users (43 % versus 25 %, p = 0.01).

Conclusion: While emphysema and hyperinflation were common in smokers, they were rare in marijuana users.”

https://pubmed.ncbi.nlm.nih.gov/40318925/

“Visual assessment revealed a significantly higher prevalence of emphysema in smokers (62 %) compared to marijuana users”

https://www.sciencedirect.com/science/article/abs/pii/S0363018825000738

Effects of legal access versus illegal market cannabis on use and mental health: A randomized controlled trial

Posted on by
Reply
pubmed logo

“Aims: We measured the effects of public health-oriented cannabis access compared with the illegal market on cannabis use and related mental health outcomes in adult cannabis users.

Design: This was a two-arm, parallel group, open-label, randomized controlled trial. Follow-up outcome measurement took place after 6 months.

Setting: The study was conducted in Basel-Stadt, Switzerland.

Participants: A total of 378 adult (aged ≥18 years) cannabis users were enrolled and randomized between August 2022 and March 2023, although only 374 users who completed baseline measures could be included.

Intervention and comparator: Participants were randomly assigned to the intervention group with public health-oriented recreational cannabis access in pharmacies (regulated cannabis products, safer use information, voluntary counseling, no advertisement; 189/188) or the illegal market control group (continued illicit cannabis sourcing; 189/186).

Measurements: The primary outcome was self-reported severity of cannabis misuse after 6 months, as measured by the Cannabis Use Disorders Identification Test – Revised (range 0-32). Secondary outcomes involved depressive, anxiety, and psychotic symptoms, cannabis consumption amount, alcohol, and drug use.

Findings: Ten participants were not followed (2.7%). Primary analysis included those with complete data (182 vs. 182). There was some evidence of a difference in cannabis misuse between the legal cannabis intervention group (mean [M] = 10.1) and the illegal market control group (M = 10.9; β = -0.69, 95% confidence interval [CI] = -1.4 to 0.0, P = 0.052). These results were supported by an intention-to-treat multiple imputation analysis (n = 374). Additional sub-group analysis by whether the participant used other drugs or not suggested that any reduction in cannabis misuse was confined to those in the legal cannabis intervention group who used other drugs (PInteraction < 0.001). We found no statistically significant changes in any of the secondary outcomes.

Conclusions: Public health-oriented recreational cannabis access may decrease cannabis use and cannabis-related harms, especially among those using other drugs.”

https://pubmed.ncbi.nlm.nih.gov/40289676/

“Our results indicate that public health-oriented RCL could be an effective policy model to make cannabis safer without increasing cannabis use and cannabis-related harms.”

https://onlinelibrary.wiley.com/doi/10.1111/add.70080

“Cannabis study finds legalization reduces problematic consumption, especially among those using other drugs”

https://medicalxpress.com/news/2025-05-cannabis-legalization-problematic-consumption-drugs.html

“Researchers uncover causal evidence that cannabis legalization reduces problematic consumption”

Researchers uncover causal evidence that cannabis legalization reduces problematic consumption

“Legal Cannabis Linked to Less Problematic Use, Better Mental Health”

Legal Cannabis Linked to Less Problematic Use, Better Mental Health

Efficacy of a Neuroimmune Therapy Including Pineal Methoxyindoles, Angiotensin 1-7, and Endocannabinoids in Cancer, Autoimmune, and Neurodegenerative Diseases

Posted on by
Reply
pubmed logo

“Purpose: Recent advancements in psycho-neuro-endocrine-immunology indicate that numerous noncommunicable diseases (NCDs) originate from disruptions in the cytokine immune network, resulting in chronic inflammatory responses. This persistent low-degree inflammation is attributed to deficiencies in crucial endogenous anti-inflammatory neuroendocrine systems, including the pineal gland, the endocannabinoid system, and the angiotensin-converting enzyme 2 / angiotensin 1-7 axis.

The administration of pineal methoxyindoles (melatonin, 5-methoxytryptamine), cannabinoids, and angiotensin 1-7 may entail potential therapeutic benefits for NCDs, particularly for patients who do not respond to conventional treatments.

Patients and methods: This study evaluates the safety and efficacy of a neuroimmune regimen comprising melatonin (100 mg/day at night), 5-methoxytryptamine (30 mg in the early afternoon), angiotensin 1-7 (0.5 mg twice daily), and cannabidiol (20 mg twice daily) in 306 patients with NCDs, including advanced cancer, autoimmune diseases, neurodegenerative disorders, depression, and cardiovascular disease.

Results: The neuroimmune regimen successfully halted cancer progression in 68% of cancer patients, who also reported improvements in mood, sleep, and relief from anxiety, pain, and fatigue. In patients with autoimmune diseases, the treatment effectively controlled the disease process, remarkable in cases of multiple sclerosis. Additionally, positive outcomes were observed in patients with Parkinson’s disease, Alzheimer’s disease, and depression.

Conclusion: Randomized controlled trials are required to assess this therapeutic approach for NCDs that includes endogenous neuroendocrine molecules regulating immune responses in an anti-inflammatory manner.”

https://pubmed.ncbi.nlm.nih.gov/40330271/

“This study highlights the potential of leveraging endogenous molecules to treat NCDs by modulating cell proliferation, inflammation, immune responses, metabolism, and neurological functions. The findings suggest that a neuroimmune regimen incorporating melatonin, angiotensin 1–7, and other bioactive compounds could offer a low-cost, minimally toxic therapeutic approach.”

https://www.dovepress.com/efficacy-of-a-neuroimmune-therapy-including-pineal-methoxyindoles-angi-peer-reviewed-fulltext-article-CIA

Effects of heat reflux extraction on the content, antioxidant, and immune activity of polyphenols and flavonoids from hempseed threshing residues

Posted on by
Reply
pubmed logo

“Objective: Hempseed threshing residues are rich in phytochemicals such as polyphenols and flavonoids. Phenolic and flavonoid compounds have been associated with antioxidant, antibacterial and anticancer activities. The re-use of the hempseed threshing residues as value-added materials is, not only cost-saving, but also environmentally beneficial. It is therefore important to develop an effective method for extraction of phenolic compounds and flavonoids from hempseed threshing residues.

Methods: In this investigation, the extraction of phenolic constituents and flavonoids from hempseed threshing residues using heat reflux extraction (HRE) were optimized through response surface methodology (RSM). Four HRE parameters to enhance the yield of crude extracts (CE), total phenolic content (TPC), and total flavonoids content (TFC) were evaluated. Additionally, the study evaluated the chemical compounds, antioxidant characteristics of the extracts, and the immune activity of the extracts was assessed by quantifying the levels of inflammatory cytokines, specifically IL-6, IL-10, and TNF-α.

Results: The best extraction parameters were determined as: for the extraction time of 69.71 min, a liquid-solid proportion of 5.12:1, a particle size of 1150 µm, and an ethanol concentration of 69.60%. Under these optimized conditions, the yields for CE, TPC, and TFC were 4.74%, 27.54%, and 16.02% respectively. The data conformed well to multiple regression models, showing that these extraction parameters markedly influence the yields of CE, TPC, and TFC. Most of the compounds found may belong to the class of polyphenol and flavonoids. Cellular assays indicated that extracts from hempseed threshing residue notably reduced pro-inflammatory factors (TNF-α, IL-6) and increased anti-inflammatory factors (IL-10) in RAW 264.7 cells.

Conclusion: This research lays a theoretical foundation for extracting polyphenols and flavonoids from hempseed threshing residue and for the comprehensive assessment of antioxidant and immune-enhancing products. However, the antioxidant and immune activity of hempseed threshing residues extracts under physiological conditions in vivo, and the relevant mechanism should be further studied.”

https://pubmed.ncbi.nlm.nih.gov/40333885/

“These findings highlight the potential of utilizing hempseed threshing residues in food or health product industries as natural alternatives to synthetic antioxidants.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0322134

Cannabinoids: Adaptogens or Not?

Posted on by
Reply
pubmed logo

“Since ancient times, humanity has been exploring natural substances with the aim of increasing stress resistance, enhancing biochemical homeostasis, and treating different diseases. In this way, the objective of the present review is to compare the biological effects of cannabinoids (CNBs) with adaptogens, this exploration allows us to consider the controversy if they can be classified together considering the effects on the body.

First, the work revises different features of adaptogens such as their chemical structure, ligand-receptors properties, and homeostasis-stress capabilities. Also, this review includes an overview of preclinical and clinical studies of the effect of adaptogens considering a broad spectrum of adverse biological, chemical, and physical factors.

Then, the work does a review of the CNBs effects on the body including the principal uses for the treatment of several diseases as neurodegenerative disorders, arthritis, cancer, cardiovascular affections, diabetes, anxiety, chronic pain, among others. In addition, the different characteristics of the specific endocannabinoid system are described explaining the wide CNBs body effects.

Finally, this review presents a comparative analysis between CNBs and adaptogens properties, expecting to contribute to understanding if CNBs can be classified as adaptogens.”

https://pubmed.ncbi.nlm.nih.gov/40332769/

https://www.liebertpub.com/doi/10.1089/can.2024.0108

“Adaptogens are herbs and plant-based substances believed to help the body manage stress and restore balance after stressful situations”

“Adaptogens are active ingredients in certain plants and mushrooms that may impact how your body deals with stress, anxiety and fatigue.”