Use of Cannabis-Based Medical Products for Pediatric Health Conditions: A Systematic Review of the Recent Literature

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“Introduction: Cannabis policy is rapidly changing in the USA and across the globe, with 24 states legalizing cannabis for adult use and 38 states making medical cannabis available for those with qualified conditions. Building on prior evidence, we reviewed the recently published literature (from the past 5 years) focused on the treatment effects of naturally derived medical cannabis products within the pediatric population.

Methods: We conducted a systematic literature review of three electronic databases using MeSH terms and free-text. A study was eligible for inclusion if it investigated the efficacy of medical cannabis for any condition, it was published in 2019 or later, and the mean age of participants was under 21. We excluded studies that tested the effect of pharmaceutical cannabis-derived drug products.

Results: We identified a total of 10 studies that met our inclusion/exclusion criteria. Of the 10, 2 utilized a double-arm randomized control trial (RCT) design, 3 used a single-arm trial design, and the remaining were observational studies, a case series, or a qualitative design. Aside from autism spectrum disorder (ASD) (n = 4), studies focused on cancer, treatment-resistant epilepsy, and Sturge-Weber syndrome (SWS). Four of the five single- or double-arm trials used a CBD:THC compound in a specific ratio as treatment. Both RCTs found significant improvement in ASD-related validated measures. Other studies found general improvements in validated measures of efficacy for SWS and epilepsy. Minimal adverse events were reported.

Conclusion: In the pediatric population, emerging evidence, combined with existing literature, suggests medical cannabis may be beneficial for quality-of-life symptoms related to specific conditions, like cancer, ASD, treatment-resistant epilepsy, and SWS. More clinical trial data are necessary to establish medical cannabis as an addition to established medical guidelines.”

https://pubmed.ncbi.nlm.nih.gov/39659365/

“While more research is necessary, this review, together with other reviews of the literature , suggests that medical cannabis is potentially a viable treatment option alongside established medical treatment guidelines. This is especially true for pediatric ASD.”

https://karger.com/mca/article/7/1/257/917351/Use-of-Cannabis-Based-Medical-Products-for

Cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cells

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“Introduction: Cannabinoids are reported to suppress the growth of ovarian cancer cells, but it is unclear whether structural modifications can improve their cytotoxic effects.

Methods: Herein, an investigation into the antiproliferative effects of natural cannabinoids on human ovarian cancer Caov-3 cells identified cannabidiol (CBD) as the most promising cannabinoid. Furthermore, chemical modifications of CBD yielded a group of derivatives with enhanced cytotoxicity in Caov-3 cells.

Results: Two CBD piperazinyl derivatives (19 and 21) showed augmented antiproliferative effects with an IC50 of 5.5 and 4.1 µM, respectively, compared to CBD’s IC50 of 22.9 µM. Further studies suggest that modulation of apoptosis and ferroptosis may contribute to the cytotoxic effects of CBD and its derivatives. In addition, CBD and its derivatives (19 and 21) were explored for their potential synergistic antiproliferative effects in combination with chemotherapeutic agent cisplatin. Compounds 19 or 21 (5 µM) combined with cisplatin (1 µM) showed a synergistic effect with a combination index of 0.23 and 0.72, respectively. This effect was supported by elevated levels of reactive oxygen species in Caov-3 cells treated with cisplatin combined with 19 or 21.

Discussion: Findings from this study suggest that CBD derivatives with enhanced antiproliferative effects may exert synergistic effects with chemotherapeutic drugs, providing insight into the development of cannabinoid-based adjuvant agents for the management of ovarian cancer.”

https://pubmed.ncbi.nlm.nih.gov/39660007/

“In summary, this work supports the therapeutic potential of cannabinoids, both as standalone agents and in combination with conventional chemotherapy, for the management of ovarian cancer.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1496131/full

Cannabidiol (CBD) as an emerging nutraceutical ingredient from industrial hemp: regulation, production, extraction, nutraceutical properties, and functionality

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“Cannabidiol (CBD) in industrial hemp is a promising functional food ingredient with multifarious health benefits, including anticancer activity, antioxidant activity, anti-inflammatory properties, and anxiolytic effects.

In recent years, the application of CBD in the food industry has been emerging and several CBD fortified products are available across the globe. Currently, the scientific information associated with CBD are segregated, and there is a lack of connectivity between their recent explorations. Therefore, in this review, the findings associated with CBD that are crucial for extending its food applications are comprehensively discussed.

It begins by exploring the global regulatory landscape of CBD. Followingly, the factors that affect CBD production in the field, CBD isolation techniques from industrial hemp flowers, and their functional properties are comprehensively detailed. Importantly, this review examines reported delivery systems for enhancing the physicochemical properties and bioavailability of CBD, thus broadening its potential applications in the food industry.

Overall, this review would connect the patches of CBD information available from the field to food and would be resourceful for food scientists, regulatory agencies, and hemp farmers.”

https://pubmed.ncbi.nlm.nih.gov/39654401/

https://www.tandfonline.com/doi/full/10.1080/10408398.2024.2436130

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