Cannabidiol effects in stem cells: A systematic review

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“Stem cells play a critical role in human tissue regeneration and repair. In addition, cancer stem cells (CSCs), subpopulations of cancer cells sharing similar characteristics as normal stem cells, are responsible for tumor metastasis and resistance to chemo- and radiotherapy and to tumor relapse.

Interestingly, all stem cells have cannabinoid receptors, such as cannabidiol (CBD), that perform biological functions. The aim of this systematic review was to analyze the effect of CBD on both somatic stem cells (SSCs) and CSCs.

Of the 276 articles analyzed, 38 were selected according to the inclusion and exclusion criteria. A total of 27 studied the effect of CBD on SSCs, finding that 44% focused on CBD differentiation effect and 56% on its protective activity. On the other hand, 11 articles looked at the effect of CBD on CSCs, including glioblastoma (64%), lung cancer (27%), and breast cancer (only one article).

Our results showed that CBD exerted a differentiating and protective effect on SCCs. In addition, this molecule demonstrated an antiproliferative effect on some CSCs, although most of the analyses were performed in vitro.

Therefore, although in vivo studies should be necessary to justify its clinical use, CBD and its receptors could be a specific target to act on both SSCs and CSCs.”

https://pubmed.ncbi.nlm.nih.gov/39653426/

https://iubmb.onlinelibrary.wiley.com/doi/10.1002/biof.2148

Exploring β-caryophyllene: a non-psychotropic cannabinoid’s potential in mitigating cognitive impairment induced by sleep deprivation

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“Sleep deprivation or sleep loss, a prevalent issue in modern society, is linked to cognitive impairment, leading to heightened risks of errors and accidents. Chronic sleep deprivation affects various cognitive functions, including memory, attention, and decision-making, and is associated with an increased risk of neurodegenerative diseases, cardiovascular issues, and metabolic disorders.

This review examines the potential of β-caryophyllene, a dietary non-psychotropic cannabinoid, and FDA-approved flavoring agent, as a therapeutic solution for sleep loss-induced cognitive impairment. It highlights β-caryophyllene’s ability to mitigate key contributors to sleep loss-induced cognitive impairment, such as inflammation, oxidative stress, neuronal death, and reduced neuroplasticity, by modulating various signaling pathways, including TLR4/NF-κB/NLRP3, MAPK, Nrf2/HO-1, PI3K/Akt, and cAMP/PKA/CREB.

As a naturally occurring, non-psychotropic compound with low toxicity, β-caryophyllene emerges as a promising candidate for further investigation. The review underscores the therapeutic potential of β-caryophyllene for sleep loss-induced cognitive impairment and provides mechanistic insights into its action on crucial pathways, suggesting that β-caryophyllene could be a valuable addition to strategies aimed at combating cognitive impairment and other health issues due to sleep loss.”

https://pubmed.ncbi.nlm.nih.gov/39653971/

https://link.springer.com/article/10.1007/s12272-024-01523-z

“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


Marijuana Use and Complication Risk Following Tibia Shaft Fracture Fixation

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“Objectives: The aim of this study was to investigate the relationship between preoperative marijuana use and complications following tibia shaft fracture fixation.

Methods: Design: Retrospective cohort study.

Setting: Two academic Level I trauma centers.

Patient selection criteria: Adults age ≥18 years who underwent tibia shaft fracture (OTA/AO 42) fixation from 2014-2022 and had a minimum 3-months postoperative follow-up were included. Patients were considered marijuana users if they had current self-reported marijuana use or a urine toxicology screen positive for cannabinoids documented at initial presentation.

Outcome measures and comparisons: Bivariate statistics and multivariate regression were used to evaluate the effect of marijuana use on 90-day postoperative thromboembolic and surgical complications, unplanned readmissions, and emergency department (ED) visits. Complications related to fracture union were evaluated in patients with ≥ 6 months follow-up. Multivariate analysis controlled for tobacco use, open fracture, and American Society of Anesthesiologist class ≥ 3.

Results: Among 388 patients included in the study, the mean age was 37.6 years (range, 18-90), and most patients were men (66.5%). Ninety-six patients (25%) were identified as marijuana users. Marijuana users were significantly younger (30.5 years vs 40 years, P < .001) and more likely to be male (79% vs 62%, P = .002) and use tobacco currently (73% vs 31%, P < .001) than non-users. Marijuana users experienced higher rates of 90-day surgical complications (11.5% vs 4.8%, P = .030) and deep infection (8.3% vs 2.1%, P = .008) compared with non-users. No significant difference was observed between groups in the rates of thromboembolic complications, nonunion, or delayed union (P > .05). On multivariate analysis, marijuana use was not associated with odds of developing any 90-day surgical complication (OR 2.01; 95% CI 0.83-4.84) or deep infection (OR 2.97; 95% CI 0.95-9.25).

Conclusions: Preoperative marijuana use was not found to be associated with risk of thromboembolic, surgical, or fracture union-related complications in patients undergoing tibia shaft fracture fixation.”

https://pubmed.ncbi.nlm.nih.gov/39651897/

https://journals.lww.com/jorthotrauma/abstract/9900/marijuana_use_and_complication_risk_following.456.aspx

Rapid seizure resolution with cannabidiol in medically refractory epilepsy with myoclonic-atonic seizures

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“Epilepsy with myoclonic-atonic seizures (EMAS) is an early childhood epilepsy syndrome with an explosive onset of multiple seizure types in a previously healthy child. EMAS often evolves to a drug-resistant epileptic encephalopathy before a variable degree of remission around 3 years from onset.

Highly purified cannabidiol (CBD, available in United States as Epidiolex®) has demonstrated efficacy and tolerability as an adjunct in medically refractory EMAS. We present two cases of medically refractory EMAS achieving rapid seizure freedom (7-30 days) with CBD, illustrating CBD as a potential effective monotherapy in EMAS.”

https://pubmed.ncbi.nlm.nih.gov/39641913/

https://onlinelibrary.wiley.com/doi/10.1002/epd2.20321

Phytoremediation Evaluation of Forever Chemicals using hemp (Cannabis sativa L.): Pollen Bioaccumulation and the Risk to Bees

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“Per- and polyfluoroalkyl substances (PFAS), often termed “forever chemicals,” are a diverse group of persistent fluorinated compounds, including the well-known perfluorooctanesulfonic acid (PFOS), which has been identified as lethal to bee larvae. However, the risk of PFAS exposure through pollen, a bee’s primary food source, has not been thoroughly investigated.

In controlled greenhouse experiments, Cannabis sativa L. (hemp) plants were cultivated in soil contaminated with eight PFAS compounds. Phytoremediation potential was assessed by measuring bioconcentration factors (BCF) in both the total above-ground biomass and pollen.

The study found that BCF for total PFAS in hemp pollen was significant (>20.8), with over 45% of the total PFAS uptake of around 3,248 μg/kg concentrated in the pollen. Based on these figures, the estimated daily intake (EDI) of PFOS for western honeybees (Apis mellifera) was found to be about 124.5 μg/kg body weight per day.

These findings underscore a critical global threat to pollinator health, with significant implications for agriculture and biodiversity.”

https://pubmed.ncbi.nlm.nih.gov/39638132/

Evidence for therapeutic use of cannabidiol for nail-patella syndrome-induced pain in a real-world pilot study

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“Nail-patella syndrome (NPS) is a rare genetic disease characterized by dysplastic nails, patella abnormalities, skeletal malformation, and chronic pain. Although chronic pain in NPS is mainly due to bone and musculoskeletal symptoms, it can also result from neurological dysfunction. Conventional analgesics are often insufficient to relieve NPS-associated chronic pain.

Cannabinoids, which act on the serotonergic and/or noradrenergic pain systems, may therefore represent valuable non-psychoactive alternatives for managing pain in these patients. The effectiveness and safety of synthetic cannabidiol (CBD) for the management of NPS-associated pain was assessed using real-world data from a pilot cohort of patients with NPS who received a 3-month treatment with oral CBD.

The treatment (median dose of 900 mg/day) was associated with a significant reduction in pain intensity (mean score of 7.04 ± 0.24 at initiation versus 4.04 ± 0.38 at 3 months, N = 28, p < 0.0001), which correlated with changes in the peripheral concentration of noradrenaline (r = 0.705, 95% CI [0.44-0.86], p < 0.0001).

Health-related quality of life and other NPS-associated symptoms also improved in most patients. CBD treatment was well tolerated and no elevations in liver enzyme levels were reported. Synthetic CBD therefore appears to be a safe and effective treatment option for managing NPS-associated chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/39627343/

“Oral treatment with synthetic CBD was associated with a significant reduction in pain in most of the patients with NPS included in our study, and led to improvements in most of the NPS-associated symptoms analyzed. Hence, synthetic oral CBD appears to be a safe and effective treatment option for NPS-associated pain, and may be an alternative to conventional analgesics for managing chronic pain in this pathology.”

https://www.nature.com/articles/s41598-024-79239-9

Cannabigerol (CBG): A Comprehensive Review of Its Molecular Mechanisms and Therapeutic Potential

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“Cannabigerol (CBG), a non-psychoactive cannabinoid found in cannabis, has emerged as a promising therapeutic agent with a diverse range of potential applications. Unlike its well-known counterpart tetrahydrocannabinol (THC), CBG does not induce intoxication, making it an attractive option in the clinic.

Recent research has shed light on CBG’s intriguing molecular mechanisms, highlighting its potential to modulate multiple physiological processes.

This review delves into the current understanding of CBG’s molecular interactions and explores its therapeutic power to alleviate various conditions, including cancer, metabolic, pain, and inflammatory disorders, amongst others.

We discuss how CBG interacts with the endocannabinoid system and other key signaling pathways, such as CB1, CB2, TPR channels, and α2-adrenoceptor, potentially influencing inflammation, pain, neurodegeneration, and other ailments. Additionally, we highlight the ongoing research efforts aimed at elucidating the full spectrum of CBG’s therapeutic potential and its safety profile in clinical settings.

Through this comprehensive analysis, we aim to provide a deeper understanding of CBG’s role in promoting human health and pave the way for future research endeavors.”

https://pubmed.ncbi.nlm.nih.gov/39598860/

https://www.mdpi.com/1420-3049/29/22/5471

Improving the Biopharmaceutical Properties of Cannabinoids in Glioblastoma Multiforme Therapy With Nanotechnology: A Drug Delivery Perspective

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“Glioblastoma multiforme (GBM) is the most prevalent primary brain tumor in adults and is known for its rapid proliferation and infiltrative nature. Current therapeutic strategies include surgical resection followed by radio- and chemotherapy. Still, they are hindered by GBM biological characteristics and physical-chemical properties of chemotherapeutic drugs, leading to limited efficacy and poor prognosis.

Cannabinoids have emerged as potential anti-GBM agents, exhibiting antiangiogenic, antimetastatic, and antiproliferative effects. However, their hydrophobicity and poor oral bioavailability pose significant challenges for clinical applications. This study evaluates the potential of nanocarriers in enhancing the solubility and targeted delivery of cannabinoids for GBM therapy.

The innovative combination of nanotechnology with cannabinoid-based treatment offers a promising strategy to improve therapeutic outcomes. We addressed the application of nanocarriers to deliver cannabinoids, which can enhance passage across the blood-brain barrier and enable targeted therapy. Studies demonstrate the potential of nanocarriers in improving solubility, stability, and controlled release of cannabinoids, highlighting the advancements in nanocarrier design for optimized delivery to glioma cells.

Cannabinoids can exert their antitumor effect, including the induction of apoptosis through the ceramide and p8-regulated pathways and the modulation of immune responses. The evidence found in this study supports the potential of cannabinoid-based nanotechnologies in GBM therapeutic regimens as a strategy to enhance its efficacy and patient outcomes.”

https://pubmed.ncbi.nlm.nih.gov/39620407/

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/ddr.70023

Evaluation of Cytoprotective Effects of Cannabidiol on Neuroinflammation and Neurogenesis Process in Rat Offsprings

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“Natural compounds include complex chemical compounds that exist in plants, animals and microbes. Due to their broad spectrum of pharmacological and biochemical actions, they have been widely used to treat multifactorial diseases, including cancer. In addition, their demonstrated neuroprotective properties strongly support their use in the treatment of neurological diseases.

The present study investigated the effect of CBD, which can easily cross the placental barrier and is known to have anti-inflammatory effects, on fetal neuroinflammation and neurogenesis in a systemic inflammation model during pregnancy.

Herein, 12 weeks adult pregnant rats (n=30) were randomly divided into 5 groups with 6 rats in each group as follows: Control, LPS (lipopolysaccharide, i.p.), LPS+CBD 5mg/kg (i.p.), LPS+CBD10 mg/kg (i.p.) and LPS+CBD30 mg/kg (i.p.). After the injections, blood samples of rats were collected, fetuses and placentas were taken by hysterectomy. Histopathological analysis, immunohistochemical staining, ELISA and immunoblotting analysis were performed to investigate neuroinflammatory and neurogenesis parameters in fetal brain and placenta tissues.

Our findings indicated that CBD administration importantly suppressed the inflammatory process in the rat fetal brain by decreasing interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels and diminishing nuclear factor kappa B (NF-κB) activation. Moreover, CBD inhibited lipopolysaccharide (LPS)-induced increasing levels of neuroinflammation-associated proteins, including glial fibrillary acidic protein (GFAP), S100B and cAMP-response element binding protein (CREB).

These results suggest that CBD usage in pregnancy with inflammation conditions may be an effective therapeutic option for preventing conditions that may cause neuroinflammation in the fetal brain and adversely affect neurogenesis.”

https://pubmed.ncbi.nlm.nih.gov/39615608/

“Cannabidiol suppresses LPS-induced systemic inflammation in the fetal brain and placenta tissues. Cannabidiol reduces the level of neuroinflammatory markers in fetal brain tissues.”

https://www.sciencedirect.com/science/article/abs/pii/S0890623824002284?via%3Dihub


Acute cannabidiol treatment reverses behavioral impairments induced by embryonic valproic acid exposure in male mice

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“Cannabidiol (CBD), the major non-psychotomimetic compound of the Cannabis sativa plant, has shown promising effects in addressing various symptoms associated with autism spectrum disorder (ASD).

This neurodevelopmental disorder typically impacts cognitive, behavioral, social communication, and motor skills domains. However, effective treatments for the wide range of symptoms associated with the disorder are limited and may trigger undesirable effects.

Embryonic exposure to valproic acid (VPA, 500 mg/kg at 12° day embryonic age) in rodents is a consolidated environmental model for studying behavioral and molecular characteristics related to ASD. Therefore, this study aimed to evaluate whether acute CBD could reverse behavioral impairments in adult mice (eight weeks) exposed to VPA in the embryonic period in four distinct trials.

In independent groups of animals, the following assays were conducted: I) Pre-Pulse Inhibition Test (PPI), II) Marble Burying, III) Social Interaction, IV) Actimeter Test, and V) Novel Object Recognition Test (NOR). In the PPI paradigm, mice exposed to VPA showed PPI impairment, and CBD (30 and 60 mg/kg) reversed this disruption. CBD (60 mg/kg) respectively decreased the number of buried marbles, improved social interaction time, but failed to reduce stereotyped-like movements in the VPA group. In NOR test CBD at both doses reversed the impairment in index of recognition induced in VPA group.

These findings suggest that acute CBD administration can ameliorate behavioral impairments associated with ASD in a well-established animal model for studying this neurodevelopmental disorder.”

https://pubmed.ncbi.nlm.nih.gov/39615556/

https://www.sciencedirect.com/science/article/abs/pii/S0091305724002132?via%3Dihub