The synthetic cannabinoid WIN 55,212-2 attenuates cognitive and motor deficits and reduces amyloid load in 5XFAD Alzheimer mice

pubmed logo

“Background: Alzheimer’s disease (AD) is characterized by cognitive decline, with pathological features including amyloid β (Aβ) plaques and inflammation. Despite recent approvals of anti-amyloid antibodies, there remains a need for disease-modifying and easily accessible therapies. The endocannabinoid system presents a promising target for AD treatment, as it regulates various processes implicated in AD pathogenesis.

Aims: This study assesses the effects of the synthetic cannabinoid WIN 55,212-2 on AD pathology and behavior deficits in aged 5XFAD mice, a well-established AD model.

Methods: Male 9-month-old 5XFAD mice received either 0.2 mg/kg WIN 55,212-2 or a vehicle solution for 42 days. Memory, anxiety, and motor tests were conducted at 10 months to identify potential changes in behavior and cognition following WIN 55,212-2 treatment. Additionally, the effects of prolonged WIN 55,212-2 treatment on Aβ pathology and neuroinflammation in the brain were quantified immunohistochemically.

Results: Therapeutic WIN 55,212-2 treatment improved the motor performance of 5XFAD mice on the rotarod and rescued memory deficits in the water maze. However, WIN 55,212-2 treatment did not significantly affect anxiety-like behavior in 5XFAD mice. Additionally, prolonged treatment with WIN 55,212-2 reduced Aβ plaque pathology and astrogliosis in the cortex and hippocampus.

Conclusions: This study highlights the therapeutic potential of WIN 55,212-2 in AD by ameliorating cognitive and motor deficits and reducing neuropathology. These findings support a cannabinoid-based therapy as a promising strategy for AD treatment, with WIN 55,212-2 emerging as a potential candidate.”

https://pubmed.ncbi.nlm.nih.gov/39675388/

“Natural and synthetic cannabinoids exhibit anti-inflammatory, anti-oxidative, anti-proliferative and analgesic properties. The synthetic cannabinoid WIN 55,212-2, an agonist of both CB1 and CB2 receptors, has been shown to possess neuroprotective, anti-inflammatory, and antinociceptive properties. Furthermore, it has been shown to promote neurogenesis, reduce beta-amyloid and tau in vitro and in vivo

https://www.sciencedirect.com/science/article/abs/pii/S0091305724002387?via%3Dihub

Cost-efficient analysis of cannabinoids in therapeutic oils using HPLC with UV and mass spectrometry detection

pubmed logo

“Cannabis oil, derived from Cannabis sativa plants, is increasingly used for therapeutic purposes across a wide range of diseases.

Accurate quantification of cannabinoids is essential, especially for cannabis products sourced from informal markets where supply origins are uncertain.

This study aimed to develop a cost-effective, robust analytical methodology using liquid chromatography in combination with UV- and mass detectors for the quantification of key cannabinoids (THC, CBD and CBN) and the identification of THCA and CBDA.

Utilising an isocratic flow, the method achieved effective separation within 17 min, ensuring simplicity and reproducibility. The methodology validation was aligned with ICH guidelines’ requirements for selectivity, linearity, precision, accuracy, and matrix effects.

Successful application of this method to both homemade and commercial cannabis oil samples underscores its relevance for adjusting therapeutic doses and optimising CBD:THC ratios for specific disease treatments.”

https://pubmed.ncbi.nlm.nih.gov/39671430/

https://www.tandfonline.com/doi/full/10.1080/14786419.2024.2439024

Prenatal cannabis exposure and the risk of subsequent maltreatment

pubmed logo

“Background: Parental substance use can increase the risk of child maltreatment.

Objective: The purpose of this study was to assess racial bias in newborn drug testing and to investigate the association between prenatal tetrahydrocannabinol (THC) exposure and subsequent child maltreatment.

Participants and setting: This retrospective cohort study (n = 35,437) linked University of Michigan Hospital birth data and Michigan Department of Health and Human Services child maltreatment data relative to a 2018 policy change. Prior to 2018, prenatal THC exposure was routinely substantiated as physical abuse; after 2018 THC exposure was investigated but not automatically substantiated.

Methods: We defined prenatal THC exposure as a positive newborn meconium drug test for THC. The primary outcome was a substantiated Child Protective Services (CPS) report of maltreatment before and after the policy change. Demographic variables included parent age, race, ethnicity, zip code and insurance type. Covariates included prenatal urine drug test orders and results, and newborn drug test orders and results. Regression models estimated the rate of subsequent maltreatment and racial disparities associated with newborn testing.

Results: Regression analyses indicated that Black and multiracial newborns were significantly more likely to be tested for substance exposure at birth. Newborns with a test positive for THC only were not more likely to experience maltreatment after the policy change as compared with newborns that tested negative and newborns not tested.

Conclusions: The evidence strongly supports a policy to end routine CPS investigations for cannabis exposure and eliminate racially biased drug testing practices.”

https://pubmed.ncbi.nlm.nih.gov/39667085/

https://www.sciencedirect.com/science/article/abs/pii/S0145213424005684?via%3Dihub

Marijuana Use and Complication Risk Following Tibia Shaft Fracture Fixation

pubmed logo

“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

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

pubmed logo

“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 the Efficacy of a Full-Spectrum Low-THC Cannabis Plant Extract Using In Vitro Models of Inflammation and Excitotoxicity

pubmed logo

“Evidence has accumulated that Cannabis-derived compounds have the potential to treat neuroinflammatory changes present in neurodevelopmental conditions such as autism spectrum disorder. However, research is needed on the specific brain health benefits of strains of whole Cannabis extract that are ready for commercial production.

Here, we explore the anti-inflammatory and neuroprotective effects of NTI-164, a genetically unique high-cannabidiol (CBD), low-Δ9-tetrahydrocannabinol extract, and also CBD alone on BV-2 microglia and SHSY-5Y neurons. Inflammation-induced up-regulation of microglial inflammatory markers was significantly attenuated by NTI-164, but not by CBD. NTI-164 promoted undifferentiated neuron proliferation and differentiated neuron survival under excitotoxic conditions.

These effects suggest the potential for NTI-164 as a treatment for neuropathologies.”

https://pubmed.ncbi.nlm.nih.gov/39595610/

https://www.mdpi.com/2218-273X/14/11/1434

Cannabinoids as Antibacterial Agents: A Systematic and Critical Review of In Vitro Efficacy Against Streptococcus and Staphylococcus

pubmed logo

“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.”

https://pubmed.ncbi.nlm.nih.gov/39596719/

“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.”

https://www.mdpi.com/2079-6382/13/11/1023

Prenatal cannabinoid exposure and early language development

pubmed logo

“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.”

https://pubmed.ncbi.nlm.nih.gov/38078314/

https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1290707/full

Cannabis Use and Age-Related Changes in Cognitive Function From Early Adulthood to Late Midlife in 5162 Danish Men

pubmed logo

“Introduction: Cannabis is by far the most widely used and abused drug listed on the Drug Enforcement Administration’s Schedule I, which includes drugs with a high potential for abuse. There is evidence of short-term negative effects of cannabis use on cognition, but only a limited number of studies have explored the association between cannabis use and age-related cognitive decline. The aim of the present study was to investigate the relationship between cannabis use and age-related cognitive decline from early adulthood to late midlife.

Methods: The study population consisted of 5162 men who had participated in Danish follow-up studies on cognitive aging. These studies included scores on the military intelligence test Børge Prien’s Prøve from both the conscription assessment (mean age = 20 years; p1 and p99: 18 and 26 years) and from the follow-up (mean age = 64 years; p1 and p99: 55 and 72 years) as well as extensive data on lifestyle and health from the follow-up questionnaires. The association between cannabis use and age-related cognitive decline was investigated in linear regression models.

Results: Men with a history of cannabis use had less cognitive decline from early adulthood to late midlife compared to men without a history of cannabis use. Among cannabis users, neither age of initiation of cannabis use nor frequent use was significantly associated with a greater age-related cognitive decline.

Discussion and conclusions: In a sample of more than 5000 men followed for a mean of 44 years, we found no significant harmful effects of cannabis use on age-related cognitive decline.”

https://pubmed.ncbi.nlm.nih.gov/39508467/

“In the present study, we aimed to investigate the relationship between cannabis use and age-related cognitive decline from early adulthood to late midlife. This study contributes to the sparse knowledge on this subject and aligns with most existing studies, suggesting no association between cannabis use and greater cognitive decline. More specifically, in the present study, cannabis users experienced slightly less cognitive decline compared to nonusers, and the association remained significant when controlling for potential confounders. Among cannabis users, no significant association was found with cognitive decline for either age of initiation of cannabis use or frequent cannabis use. Further studies are needed to investigate whether these findings reflect that there are no adverse effects on cognitive decline or that the effects of cannabis are temporary and disappear after a prolonged period of time.”

https://onlinelibrary.wiley.com/doi/10.1002/brb3.70136

Cannabinoid for alcohol use disorder

pubmed logo

“Several pieces of evidence have implicated the endocannabinoid system on dopaminergic mesolimbic brain reward, as well as the potential role of cannabinoid receptors CB1 and CB2 on modulation of reinforced properties of drug abuse and consequently to the treatment of substance use disorder, including alcoholism.

Moreover, growing evidence has been proposed that cannabis or cannabinoid compounds may be helpful to treat alcohol use disorder (AUD).

Cannabis is prevalent among individuals who also consume alcohol. While some authors reported that cannabis may be a promising candidate as a substitute medication for AUD, some studies have demonstrated that concomitant use of alcohol and cannabis may increase the risk of adverse outcomes.

Considering that advances in the legalization and decriminalization movements regarding cannabis have led to increased availability worldwide, the current chapter aims to provide evidence on the benefits and risks of combining alcohol and cannabis, as well as the potential therapeutic use of cannabinoid compounds in treating AUD.”

https://pubmed.ncbi.nlm.nih.gov/39523058/

“Growing studies have indicated that medicinal cannabis could be reasoned as a substitute therapy for alcohol, especially among individuals who are trying to reduce drinking behavior. Based on these premises, medicinal cannabis might be safer and also produce less social harms, for this reason some studies have been pointed as a good candidate for substitute medication for alcohol.”

https://www.sciencedirect.com/science/article/abs/pii/S0074774224001089?via%3Dihub