“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.”
“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.”
“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.”
“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.”
“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.”
“Cannabidiol suppresses LPS-induced systemic inflammation in the fetal brain and placenta tissues. Cannabidiol reduces the level of neuroinflammatory markers in fetal brain tissues.”
“Background: Phytochemicals derived from the plant Cannabis sativa hold promise in terms of medicinal value. Cannabinoids such as Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) are arguably the best characterized and known to possess wide-ranging therapeutic benefits. The mechanism of action for these therapeutic effects remains to be fully elucidated, however, the anti-inflammatory actions are of particular interest. Maximizing therapeutic effects while limiting adverse effects is crucial in pharmaceutical development. Fluorination of natural products often yields molecules with enhanced biological properties and provides opportunities for intellectual property protection not available to the natural product.
Methods: Herein, we describe four novel cannabinoids (a deoxy trifluoroCBN analog (F3CBN), the racemic cis-deoxy-trifluoro-THC (F3THC), and truncated pyridine analogs of an intermediate in route to the THC and CBN, SG126 and SG154. Importantly, we provide the initial assessment of the biologic activity of these molecules, by investigating the in vitro effects on metabolic activity (via 3-[4,5-dimethylthiazol-2-yl]-2,5,-diphenyltetrazolium bromide, MTT assay) and cytokine expression (via enzyme linked immunosorbent assay, ELISA) in human C20 microglial cells.
Results: The cannabinoids examined had minimal to no effect on metabolic activity up to 10 µM. Notably, F3CBN and F3THC potentiated interleukin-1 β (IL-1β)-induced expression of interferon-γ inducible protein 10 (CXCL10) and IL-6 expression whereas, SG126 and SG154 were inhibitory.
Conclusions: These findings are foundational for new lines of investigation into the therapeutic potential of four novel fluorinated cannabinoids.”
“Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder typically caused by a somatic mosaic mutation in R183Q GNAQ. At-risk children present at birth with a capillary malformation port-wine birthmark.
The primary diagnostic characteristic of the disorder includes leptomeningeal enhancement of the brain, which demonstrates abnormal blood vessels and results in impaired venous drainage and impaired local cerebral perfusion. Impaired cerebral blood flow is complicated by seizures resulting in strokes, hemiparesis and visual field deficits, hormonal deficiencies, behavioral impairments, and intellectual disability. Therefore, anti-seizure medication in combination with low-dose aspirin is a common therapeutic treatment strategy. Recently published data indicate that the underlying mutation in endothelial cells results in the hyperactivation of downstream pathways and impairment of the blood-brain barrier.
Cannabidiol (CBD) has been used to treat medically refractory seizures in SWS due to its anti-seizure, anti-inflammatory, and neuroprotective properties. Pilot research suggests that CBD improves cognitive impairment, emotional regulation, and quality of life in patients with SWS.
Recent preclinical studies also suggest overlapping molecular pathways in SWS and in CBD, suggesting that CBD may be uniquely effective for SWS brain involvement.
This review aims to summarize early data on CBD’s efficacy for preventing and treating epilepsy and neuro-cognitive impairments in patients with SWS, likely molecular pathways impacted, and provide insights for future translational research to improve clinical treatment for patients with SWS.”
“Aging is characterized by oxidative stress and immune function impairment, and is associated with increased morbidity. Cannabidiol (CBD) has anti-oxidant properties, but its role in aging has been scarcely studied.
This work aims to test the effect of CBD on the redox state and immunity during aging in rats. In this study, 15-month-old male Long Evans rats received 10 mg/kg b.w/day of CBD in their diet for 10 weeks and were compared with same-age control and 2-month-old rats serving as a young control group, both following a standard diet.
After treatment, they were sacrificed, and the spleen, thymus, and total blood cells were collected. Redox parameters such as glutathione reductase and peroxidase activities, reduced (GSH) and oxidized (GSSG) glutathione concentration, GSSG/GSH ratio, and lipid peroxidation were evaluated. Moreover, immune functions (chemotaxis, natural killer activity, and lymphoproliferation) were analyzed in the spleen.
Results show that the 15-month-old control rats exhibited increased oxidative stress and immunosenescence compared to the 2-month-old rats. However, the CBD-treated animals showed higher anti-oxidant defenses, lower oxidants in the spleen, thymus, and blood cells, and better immunity in the spleen than the corresponding age-matched controls.
Therefore, CBD administration neutralizes oxidative stress and improves immunity, suggesting it is a strategy for achieving healthy aging.”
“Background: Two major bacterial pathogens, Staphylococcus aureus and Streptococcus pyogenes, are becoming increasingly antibiotic-resistant. Despite the urgency, only a few new antibiotics have been approved to address these infections. Although cannabinoids have been noted for their antibacterial properties, a comprehensive review of their effects on these bacteria has been lacking.
Objective: This systematic review examines the antibacterial activity of cannabinoids against S. aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) strains, and S. pyogenes.
Methods: Databases, including CINAHL, Cochrane, Medline, Scopus, Web of Science, and LILACS, were searched. Of 3510 records, 24 studies met the inclusion criteria, reporting on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration of cannabinoids.
Results: Cannabidiol (CBD) emerged as the most effective cannabinoid, with MICs ranging from 0.65 to 32 mg/L against S. aureus, 0.5 to 4 mg/L for MRSA, and 1 to 2 mg/L for VRSA. Other cannabinoids, such as cannabichromene, cannabigerol (CBG), and delta-9-tetrahydrocannabinol (Δ9-THC), also exhibited significant antistaphylococcal activity. CBD, CBG, and Δ9-THC also showed efficacy against S. pyogenes, with MICs between 0.6 and 50 mg/L. Synergistic effects were observed when CBD and essential oils from Cannabis sativa when combined with other antibacterial agents.
Conclusion: Cannabinoids’ antibacterial potency is closely linked to their structure-activity relationships, with features like the monoterpene region, aromatic alkyl side chain, and aromatic carboxylic groups enhancing efficacy, particularly in CBD and its cyclic forms. These results highlight the potential of cannabinoids in developing therapies for resistant strains, though further research is needed to confirm their clinical effectiveness.”
“In conclusion, cannabinoids such as CBD, CBG, and Δ9-THC offer significant promise as alternatives or adjuncts to traditional antibiotics, particularly for targeting S. aureus, MRSA, and S. pyogenes. Their favourable safety profile positions them as potential candidates for antibacterial therapies, though rigorous clinical trials, standardised testing, and long-term safety studies are crucial to fully unlock their potential in combating AMR.”
“Introduction: The effect of prenatal cannabis exposure (PCE) on childhood neurodevelopment remains poorly understood. There is a paucity of studies describing the neurodevelopment impact of PCE in infancy. The Mullen Scale of Early Learning (MSEL) is a cognitive screening tool that can be used from birth to 68 months and includes language and motor domains. Here we aim to explore the association between PCE during pregnancy and neurodevelopmental outcomes at 12 months of age.
Methods: Participants were pregnant persons/infant pairs enrolled in The Safe Passage Study, a large prospective cohort study. Inclusion criteria included data available on PCE with associated MSEL scores at 12 months of age. Exposed participants were defined as early exposure (1st trimester only) or late exposure (2nd or 3rd trimester) and were randomly matched with unexposed participants. Multiple linear regression models were performed to test associations between prenatal cannabis exposure and the five Mullen subscales: gross motor, fine motor, expressive language, receptive language, and visual reception.
Results: Sixty-nine exposed and 138 randomly matched unexposed infants were included in the analyses. Mothers of children with PCE were younger with the mean age 23.7 years for early exposure (n = 51) and 22.8 years for late exposure (n = 18). Maternal characteristics with prenatal cannabis use include a high-school education, American Indian or Alaska Native descent, lower socioeconomic status and co-use of tobacco. There were no gestational age or sex difference among the groups. Expressive (95% CI: 2.54-12.76; p = 0.0036,) and receptive language scores (95% CI: 0.39-8.72; p = 0.0322) were significantly increased between late-exposed infants compared to unexposed infants following adjustment for covariates. Gross motor scores (95% CI: 1.75-13; p = 0.0105) were also significantly increased for early-exposed infants with no difference in visual reception scores.
Conclusion: Preclinical studies have shown abnormal brain connectivity in offspring exposed to cannabis affecting emotional regulation, hyperactivity, and language development. Results from this study link PCE to altered early language development within the first year of life. Exposed infants demonstrated increased expressive and receptive language scores at 12 months of age, which can translate to better performance in school. However, further research is needed to determine the implications of these results later in childhood.”
“Ethnopharmacological relevance: Hemp (Cannabis sativa L.) is increasingly being recognized for its medicinal properties beside utilizing it for food, oil, and textile fibers. The high level of cannabidiol (CBD) content in hemp’s flowers shows promising neuroprotective properties without causing psychotomimetic or addictive effects. Recently, products containing CBD and its precursor, cannabidiolic acid (CBDA), have been used to treat stress-related cognitive impairment. However, the therapeutic potential of hemp extract remains inadequately explored.
Aim of the study: To investigate the effect of CBD/CBDA-rich hemp extract on learning and memory, neuroendocrine alterations, and hippocampal neuropathological changes in the chronic restraint stress model.
Materials and methods: Chronic restraint stress (CRS) was induced in male Wistar rats by immobilizing them in a restrainer for 6 hours per day for 21 consecutive days. CBD/CBDA-rich hemp extract (10 and 30 mg/kg, intraperitoneal injection) was administered daily, 1 hour before restraint. After the last day of CRS, behavioral tests for cognition were conducted using the Y-maze and object recognition tests. Serum corticosterone (CORT) levels were measured by ELISA. Histopathological changes, neuronal density, and the activation of microglia and astrocytes were visualized using cresyl violet and immunohistochemical staining.
Results: A high dose of CBD/CBDA-rich hemp extract effectively ameliorated CRS-induced cognitive impairment and reversed HPA axis hyperactivity in CRS rats by reducing CORT levels and adrenal gland weight. Additionally, CBD/CBDA-rich hemp extract protected CRS-induced damage to hippocampal neurons. Further analysis showed that CBD/CBDA-rich hemp extract reduced specific markers of microglial activation (ionized calcium-binding adaptor molecule-1, Iba-1) and astrocytic structural protein (glial fibrillary acidic protein, GFAP) in CRS rats.
Conclusion: CBD/CBDA-rich hemp extracts remarkably reversed the stress-induced behavioral perturbations and hippocampal damage, suggesting its ameliorative effect on stress response.”
