Author Archives: David

Innovative active bio-based food packaging material with Cannabis sativa L. seeds extract as an agent to reduce food waste

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“In the present study, ethanolic extracts from the extract of unshelled seeds of Cannabis sativa L. were used to produce films in order not to generate additional waste, taking into view a circular economy. Combinations of apple pectin and citrus pectin in a ratio of 80:20 were used. Film samples containing 0.5, 1.0 and 2.5 [wt%] of the extract were extruded. Antimicrobial, mechanical and barrier properties of the obtained films were tested. Samples with 0.5 [wt%] showed a WVTR of 16.98 [g/m2d]. The water vapour barrier properties of the films decreased with an increase in the amount of extract used. As the amount of extract increased, the transparency of the films decreased linearly to 12.84 [%] (0.5 [wt%]), 4.90 [%] (1.0 [wt%]) and 4.99 [%] (2.5 [wt%]). It was observed that the brightness of the samples decreased with increasing concentration, due to the presence of higher levels of phenolic compounds. Tests carried out showed that the prepared films exhibited inhibitory activity against all micrograms tested. All prepared films had antibacterial activity against the Salmonella typhimurium strain. Similarly, in the case of L. monocytogenes.”

https://pubmed.ncbi.nlm.nih.gov/39418822/

“In this study, packaging films were developed based on bio-based ingredients, including pectin (a combination of apple and citrus pectin in a ratio of 80:20), tragacanth gum and ethanol extracts from unshelled cannabis seeds. Ethanolic extracts from unshelled cannabis seeds were used in this study to avoid waste generation, in relation to a circular economy. The use of higher amounts of extract resulted in lower TS and EB values. With increasing amounts of extract, the transparency of the film decreased linearly and was 12.84 [%] (0.5 wt%), 4.90 [%] (1.0 wt%) and 4.99 [%] (2.5 wt%), respectively. The film was observed to have a significant colour change, confirmed by examination under a stereoscopic microscope. This was confirmed by colour tests of L a b. The highest value of the L* parameter (89.91) was obtained for the film sample without extract. All prepared films had a lethal effect on the Salmonella typhimurium strain. The same was the case for L. monocytogenes bacteria. The high antimicrobial activity of the films seems to be due to the active effect of the phenolic compounds present in the films that were found in the extract.”

https://www.sciencedirect.com/science/article/pii/S0927776524005721?via%3Dihub

Effect of Cannabidiol (CBD), a cannabis plant derivative, against Candida albicans growth and biofilm formation

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“This study aimed to evaluate the antifungal activities of cannabidiol (CBD) against C. albicans.

Yeast cells were treated once or twice with different concentrations (from 0 to 20 mg/ml) of CBD, showing a significant (p < 0.05) decreased the growth of C. albicans, with cell concentrations ranging from 5.1 × 106 cell/mL in the control to 1.8 × 106 cell/mL after one exposure to 20 µg/mL CBD. This growth reduction was greater after two exposures to CBD. After two exposures to 20 µg/mL CBD, the cell concentration was only 1.1 × 106 cell/mL. Such a growth decrease in C. albicans was confirmed by a reduced number of CFUs and a lower MTT value compared to the control. The growth inhibition was supported by a significant (p < 0.001) decrease in the yeast-to-hyphae transition, ranging from 20 ± 0.2% in the control to 2 ± 0.5% after exposure to 20 µg/mL CBD. Biofilm formation was also significantly reduced following CBD exposure.

CBD at 10 and 20 µg/mL promoted the death of C. albicans through an apoptosis/necrotic pathway.

Altogether, our results suggest the possible use of CBD, a cannabis derivative, to control C. albicans infection, including oral candidiasis.”

https://pubmed.ncbi.nlm.nih.gov/39418672/

https://cdnsciencepub.com/doi/10.1139/cjm-2024-0034

Association Between Medical Marijuana Cardholder Status and Antiemetic Overuse

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“Introduction: The conscientious prescribing of antiemetics by chemotherapy-induced nausea and vomiting (CINV) risk was highlighted in the American Society of Clinical Oncology (ASCO) “Choosing Wisely” recommendations. The pharmacologic properties of medical marijuana (MMJ) may allow for decreased incidence of CINV; however, little is known about the effects of MMJ on the use of antiemetics. This study aimed to determine if MMJ cardholder status, which enables access to MMJ, is associated with antiemetic overuse among patients with cancer. 

Materials and Methods: This population-based secondary data analysis examined a retrospective cohort derived from the linked Arkansas All Payers Claims Database (2013-2020) and MMJ cardholder registry (2013-2019). The cohort consisted of 20,558 patients with cancer aged 18 and older with a chemotherapy claim in an outpatient setting within 12 months of a cancer diagnosis. Exposure was a registration to receive an MMJ card that permitted access to MMJ. The primary outcome of interest was antiemetic overuse, as characterized by the ASCO recommendation. Antiemetic use associated with chemotherapy was identified through filled prescriptions and medical claims. Multivariable logistic regression, adjusted for baseline demographic and prescription characteristics, was used to calculate the adjusted odds ratios (aOR) of antiemetic overuse among MMJ cardholders compared with non-MMJ cardholders. 

Results: Among 20,558 eligible patients, 436 (2.1%) had an MMJ card at some point in the study period. Antiemetic overuse was identified in 7.5% of chemotherapy cycles. Compared with non-MMJ cardholders, MMJ cardholders were less likely to experience antiemetics overuse (aOR: 0.76, p < 0.001). Patients with fewer chemotherapy cycles and younger in age had higher odds of antiemetic overuse compared with those with more chemotherapy cycles. The risk of antiemetic overuse did not differ based on gender and rurality of residency. Route of chemotherapy administration, CINV risk category, and type of cancer also impacted the odds of antiemetic overuse. 

Discussion: The findings indicate that MMJ cardholders are significantly less likely to experience antiemetic overuse than non-MMJ cardholders. Further investigation into the use, effectiveness, and safety of cannabis for CINV mitigation is needed to inform patient and provider decision-making.”

https://pubmed.ncbi.nlm.nih.gov/39419579/

https://www.liebertpub.com/doi/10.1089/can.2024.0083

Maternal Prenatal Cannabis Use and Child Autism Spectrum Disorder

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“Importance: Despite an increase in maternal prenatal cannabis use and associations with adverse neonatal outcomes, research on child neurodevelopmental outcomes is limited.

Objective: To evaluate the association between maternal cannabis use in early pregnancy and child autism spectrum disorder (ASD).

Design, setting, and participants: This population-based retrospective birth cohort study included children born between 2011 and 2019 to pregnant Kaiser Permanente Northern California members screened for prenatal cannabis use during pregnancy. Statistical analysis was conducted February 2023 to March 2024.

Exposures: Maternal prenatal cannabis use was assessed at entrance to prenatal care (approximately 8- to 10-weeks’ gestation) via self-report and/or positive urine toxicology test. Use frequency was assessed.

Main outcomes and measures: Child ASD was defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes ascertained from the electronic health record. Associations between maternal prenatal cannabis use and child ASD were modeled using Cox proportional hazards regression adjusted for maternal sociodemographic, other substance use and disorders, prenatal care initiation, comorbidities, and clustering among maternal siblings.

Results: The study cohort included 178 948 singleton pregnancies among 146 296 unique pregnant individuals, including 48 880 (27.3%) Asian or Pacific Islander, 42 799 (23.9%) Hispanic, 9742 (5.4%) non-Hispanic Black, and 70 733 (39.5%) non-Hispanic White pregnancies. The median (IQR) maternal age at pregnancy onset was 31 (6) years; 8486 (4.7%) screened positive for cannabis use, 7054 (3.9%) via urine toxicology testing and 3662 (2.0%) by self-report. In the total study population, the frequency of self-reported use was monthly or less for 2003 pregnancies (1.1%), weekly for 918 pregnancies (0.5%), daily for 741 pregnancies (0.4%), and unknown for 4824 pregnancies (2.7%). ASD was diagnosed in 3.6% of children. After adjustment for maternal characteristics, maternal prenatal cannabis use was not associated with child ASD (hazard ratio [HR], 1.05; 95% CI, 0.84-1.32). When self-reported frequency of use was assessed, no statistically significant associations were observed after confounder adjustment. No sex-specific associations were documented (males: HR, 1.01; 95% CI, 0.77-1.32; and females: HR, 1.19; 95% CI, 0.77-1.85).

Conclusions and relevance: In this cohort study, maternal cannabis use assessed in early pregnancy was not associated with child ASD. Additional studies are needed to evaluate different patterns of use throughout pregnancy. Given the known adverse neonatal health effects of maternal prenatal cannabis use, clinicians should follow national guidelines and advise against use.”

https://pubmed.ncbi.nlm.nih.gov/39422906/

“Question  Is maternal cannabis use during early pregnancy associated with risk of child autism spectrum disorder (ASD)?

Findings  In this cohort study of 178 948 mother-child dyads, maternal prenatal cannabis use during early pregnancy was not associated with child ASD.

Meaning  These findings suggest that maternal cannabis use during early pregnancy was not associated with child ASD, but additional research should be conducted to replicate these findings.”

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2825075


Early Maternal Prenatal Cannabis Use and Child Developmental Delays

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“Importance: Maternal prenatal cannabis use is associated with adverse neonatal health effects, yet little is known about its association with child developmental outcomes.

Objective: To evaluate associations between maternal prenatal cannabis use in early pregnancy and child early developmental delays.

Design, setting, and participants: This cohort study included 119 976 children born to 106 240 unique individuals between January 2015 and December 2019 and followed up to aged 5.5 years or younger (through December 31, 2021) at Kaiser Permanente Northern California. Individuals were screened for prenatal cannabis use via self-report and urine toxicology at entrance into prenatal care (approximately 8- to 10-weeks’ gestation). Data were analyzed from February 2023 to March 2024.

Exposure: Maternal prenatal cannabis use defined as any use (self-reported or by urine toxicology testing) and use frequency.

Main outcomes: Early developmental delays (speech and language disorders, motor delays, global delays) in children up to age 5.5 years defined by International Statistical Classification of Diseases and Related Health Problems, Ninth Revision and Tenth Revision diagnoses codes ascertained from electronic health records.

Results: In this cohort of 119 976 pregnancies among 106 240 unique pregnant individuals, there were 29 543 Hispanic pregnancies (24.6%), 6567 non-Hispanic Black pregnancies (5.5%), 46 823 non-Hispanic White pregnancies (39.0%), 12 837 pregnancies (10.7%) to individuals aged 24 years or younger, and 10 365 pregnancies (8.6%) to individuals insured by Medicaid. Maternal prenatal cannabis use was documented for 6778 pregnancies (5.6%). Daily maternal prenatal cannabis use was reported for 618 pregnancies (0.5%), weekly for 722 pregnancies (0.6%), and monthly or less for 1617 pregnancies (1.3%). No association was observed between maternal prenatal cannabis use and child speech and language disorders (HR, 0.93; 95% CI, 0.84-1.03), global developmental delays (HR, 1.04; 95% CI, 0.68-1.59), or motor delays (HR, 0.86; 95% CI, 0.69-1.06). No association was detected between the frequency of maternal prenatal cannabis use and child early developmental delays.

Conclusions and relevance: In this cohort study, maternal prenatal cannabis use was not associated with an increased risk of child early developmental delays. Future research is needed to assess different patterns of cannabis use throughout pregnancy. Given the association between maternal prenatal cannabis use and other adverse outcomes, pregnant individuals should be educated on those risks.”

https://pubmed.ncbi.nlm.nih.gov/39422907/

 “Is maternal prenatal cannabis use during early pregnancy associated with child early developmental delays (ie, speech and language disorders, motor delays, global delays)?

Findings  In this cohort study of 119 976 mother-child dyads, maternal cannabis use during early pregnancy was not associated with child early developmental delays in children aged 5.5 years or younger.

Meaning  These findings suggest that maternal cannabis use in early pregnancy was not associated with an increased risk of child early developmental delays, but additional research on cannabis use throughout pregnancy, mode of administration, and product strength should be conducted.”

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2825076#google_vignette


Cannabinoids shift the basal ganglia miRNA m6A methylation profile towards an anti-inflammatory phenotype in SIV-infected Rhesus macaques

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“Epitranscriptomic modifications modulate diverse biological processes, such as regulation of gene expression, abundance, location and function. In particular, N6-methyladenosine (m6A) methylation has been shown to regulate various disease processes, including cancer and inflammation. While there is evidence that m6A modification is functionally relevant in neural development and differentiation, the role of m6A modification in HIV neuropathogenesis is unknown.

Here, we identified direct m6A modifications in miRNAs from BG tissues of Rhesus Monkeys (RMs) that were either vehicle-treated uninfected (VEH), SIV-infected combination anti-retroviral therapy (cART) treated (VEH/SIV/cART), or THC:CBD treated VEH/SIV/cART (THC:CBD/SIV/cART) RMs.

We detected m6A modifications across all BG tissues. SIV infection promoted an overall hypomethylated m6A profile. While the overall hypomethylated m6A profile was not significantly impacted by THC:CBD treatment, specific miRNAs, particularly those predicted to target proinflammatory genes showed markedly reduced m6A methylation levels compared to the VEH treated RMs. Additionally, we found that specific BG tissue miRNAs bearing m6A epi-transcriptomic marks were also transferred to BG-derived extracellular vesicles (EVs). Mechanistically, we identified the DRACH motif of the seed region of miR-194-5p to be significantly m6A hypomethylated, which was predicted to directly target STAT1, an important interferon-activated transcription factor known to drive neuroinflammation, in diseases ranging from Alzheimer to Parkinson and Huntington disease.

Notably, THC:CBD treatments significantly reduced m6A methylation of 43 miRNA species directly involved in regulating CNS network genes, thus providing a possible mechanist explanation on the beneficial effects of THC:CBD treatments noted in several disease involving neuroinflammation.

Our findings also underscore the need for investigating the qualitative, posttranscriptional modification changes in the RNA profiles along with the more traditional, qualitative alterations in pathological conditions or after various treatment regimens.”

https://pubmed.ncbi.nlm.nih.gov/39416016/

https://www.biorxiv.org/content/10.1101/2024.10.11.614514v1

Decoding the Therapeutic Potential of Cannabis and Cannabinoids in Neurological Disorders

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“For millennia, Cannabis sativa has served diverse roles, from medicinal applications to recreational use. Despite its extensive historical use, only a fraction of its components have been explored until recent times.

The therapeutic potential of Cannabis and its constituents has garnered attention, with suggestions for treating various conditions such as Parkinson’s disease, epilepsy, Alzheimer’s disease, and other Neurological disorders.

Recent research, particularly on animal experimental models, has unveiled the neuroprotective properties of cannabis. This neuroprotective effect is orchestrated through numerous G protein-coupled receptors (GPCRs) and the two cannabinoid receptors, CB1 and CB2.

While the capacity of cannabinoids to safeguard neurons is evident, a significant challenge lies in determining the optimal cannabinoid receptor agonist and its application in clinical trials. The intricate interplay of cannabinoids with the endocannabinoid system, involving CB1 and CB2 receptors, underscores the need for precise understanding and targeted approaches. Unravelling the molecular intricacies of this interaction is vital to harness the therapeutic potential of cannabinoids effectively.

As the exploration of cannabis components accelerates, there is a growing awareness of the need for nuanced strategies in utilizing cannabinoid receptor agonists in clinical settings. The evolving landscape of cannabis research presents exciting possibilities for developing targeted interventions that capitalize on the neuroprotective benefits of cannabinoids while navigating the complexities of receptor specificity and clinical applicability.”

https://pubmed.ncbi.nlm.nih.gov/39410886/

https://www.eurekaselect.com/article/143747

Cannabinoids and Genetic Epilepsy Models: A Review with Focus on CDKL5 Deficiency Disorder

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“Pediatric genetic epilepsies, such as CDKL5 Deficiency Disorder (CDD), are severely debilitating, with early-onset seizures occurring more than ten times daily in extreme cases. Existing antiseizure drugs frequently prove ineffective, which significantly impacts child development and diminishes the quality of life for patients and caregivers.

The relaxation of cannabis legislation has increased research into potential therapeutic properties of phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC).

CBD’s antiseizure properties have shown promise, particularly in treating drug-resistant genetic epilepsies associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). However, specific research on CDD remains limited. Much of the current evidence relies on anecdotal reports of artisanal products lacking accurate data on cannabinoid composition. Utilizing model systems like patient-derived iPSC neurons and brain organoids allows precise dosing and comprehensive exploration of cannabinoids’ pharmacodynamics.

This review explores the potential of CBD, THC, and other trace cannabinoids in treating CDD and focusing on clinical trials and preclinical models to elucidate the cannabinoid’s potential mechanisms of action in disrupted CDD pathways and strengthen the case for further research into their potential as anti-epileptic drugs for CDD. This review offers an updated perspective on cannabinoid’s therapeutic potential for CDD.”

https://pubmed.ncbi.nlm.nih.gov/39409097/

https://www.mdpi.com/1422-0067/25/19/10768

Interplay between cannabinoids and the neuroimmune system in migraine

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“Migraine is a common and complex neurological disorder that has a high impact on quality of life. Recent advances with drugs that target the neuropeptide calcitonin gene-related peptide (CGRP) have helped, but treatment options remain insufficient. CGRP is released from trigeminal sensory fibers and contributes to peripheral sensitization, perhaps in part due to actions on immune cells in the trigeminovascular system.

In this review, we will discuss the potential of cannabinoid targeting of immune cells as an innovative therapeutic target for migraine treatment. We will cover endogenous endocannabinoids, plant-derived phytocannabinoids and synthetically derived cannabinoids.

The focus will be on six types of immune cells known to express multiple cannabinoid receptors: macrophages, monocytes, mast cells, dendritic cells, B cells, and T cells. These cells also contain receptors for CGRP and as such, cannabinoids might potentially modulate the efficacy of current CGRP-targeting drugs. Unfortunately, to date most studies on cannabinoids and immune cells have relied on cell cultures and only a single preclinical study has tested cannabinoid actions on immune cells in a migraine model. Encouragingly, in that study a synthetically created stable chiral analog of an endocannabinoid reduced meningeal mast cell degranulation. Likewise, clinical trials evaluating the safety and efficacy of cannabinoid-based therapies for migraine patients have been limited but are encouraging.

Thus, the field is at its infancy and there are significant gaps in our understanding of the impact of cannabinoids on immune cells in migraine. Future research exploring the interactions between cannabinoids and immune cells could lead to more targeted and effective migraine treatments.”

https://pubmed.ncbi.nlm.nih.gov/39407099/

“Overall, the intersection of cannabinoids and immune cells presents a promising but under-investigated strategy for innovative migraine treatments. Indeed, a major limitation in the current landscape of cannabinoid research for migraine is the limited number of published studies and clinical trials. This can partly be attributed to the schedule 1 classification of cannabis products in the US and the illegalization of cannabis world-wide. In the future, this problem should improve as recent legal changes have led to the (re)legalization of cannabis for medical purposes, and the consumption of cannabis products has increased.”

https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-024-01883-3

The Modulatory Effects and Therapeutic Potential of Cannabidiol in the Gut

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“Cannabidiol (CBD) is a major non-psychotropic phytocannabinoid that exists in the Cannabis sativa plant.

CBD has been found to act on various receptors, including both cannabinoid and non-cannabinoid receptors. In addition, CBD has antioxidant effects that are independent of receptors. CBD has demonstrated modulatory effects at different organ systems, such as the central nervous system, immune system, and the gastrointestinal system. Due to its broad effects within the body and its safety profile, CBD has become a topic of therapeutic interest.

This literature review summarizes previous research findings with regard to the effect of CBD on the gastrointestinal (GI) system, including its effects at the molecular, cellular, organ, and whole-body levels. Both pre-clinical animal studies and human clinical trials are reviewed.

The results of the studies included in this literature review suggest that CBD has significant impact on intestinal permeability, the microbiome, immune cells and cytokines. As a result, CBD has been shown to have therapeutic potential for GI disorders such as inflammatory bowel disease (IBD).

Furthermore, through interactions with the gut, CBD may also be helpful in the treatment of disorders outside the GI system, such as non-alcoholic liver disease, postmenopausal disorders, epilepsy, and multiple sclerosis. In the future, more mechanistic studies are warranted to elucidate the detailed mechanisms of action of CBD in the gut. In addition, more well-designed clinical trials are needed to explore the full therapeutic potential of CBD on and through the gut.”

https://pubmed.ncbi.nlm.nih.gov/39404382/

“CBD has exhibited modulatory effects on both the intestinal barrier permeability and the gut microbiome. In addition, CBD has displayed therapeutic potential for the treatment of GI disorders such as IBD. Furthermore, CBD may produce therapeutic effects on diseases outside the GI system by regulating gut–liver, gut–bone, and gut–brain axes.”

https://www.mdpi.com/2073-4409/13/19/1618