Monthly Archives: February 2025

Cannabidiol protects lung against inflammation and apoptosis in a rat model of blunt chest trauma via Bax/Bcl-2/Cas-9 signaling pathway

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“Purpose: This study aimed to investigate the hypothesis that cannabidiol (CBD), with known anti-inflammatory and anti-apoptotic effects, would reduce the severity of acute lung injury in pulmonary contusion following blunt chest trauma.

Methods: Forty male Wistar Albino rats were randomly divided into four groups, each consisting of 10 rats: Sham, Trauma, Trauma + CBD, and CBD. The rats were treated with a single dose of 5 mg/kg CBD intraperitoneally 30 min before trauma. Then, the trauma were exposed to a weight of 200 g and a height of 1 m. After sacrifice, the lung tissues were removed for histopathological, immunohistochemical, biochemical, and genetic analyses.

Results: Pulmonary injury of trauma group led to increases in tumor necrosis factor α, caspase-3, caspase-9, Bcl-2-associated X protein expressions, total oxidant status, oxidative stress index levels, and decreases in B-cell lymphoma expression and total antioxidant levels. Additionally, inflammatory cell infiltration, damage-related emphysema, pronounced hyperemia, and increased septal tissue thickness were observed histopathologically. CBD treatment ameliorated all these findings.

Conclusion: CBD reduces lung damage in lung contusions caused by blunt chest trauma through its anti-inflammatory and antiapoptotic effects. More detailed studies investigating other important intracellular pathways are needed.”

https://pubmed.ncbi.nlm.nih.gov/39918746/

“In conclusion, it has been observed that CBD reduces lung damage in lung contusions caused by blunt chest trauma through its anti-inflammatory and antiapoptotic effects. In addition, the effects of a single dose of CBD were examined in this study, and more detailed molecular studies are needed in which longer-term use or higher doses are preferred, in addition to this study, which highlights the acute effects of CBD. The ability to perform analyses at the gene level at the protein level via the western blot method will increase the effectiveness of the study.”

https://link.springer.com/article/10.1007/s00068-025-02767-0

Cannabidiol interactions with oxycodone analgesia in an operant orofacial cutaneous thermal pain assay following oral administration in rats

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“Previous studies have driven the notion that the cannabis constituent cannabidiol could be an effective adjunct to opioid administration for managing pain.

Most of these studies have used experimental rodents with routes of administration, such as subcutaneous and intraperitoneal, that do not correspond with the routes used in clinical practice. In response to this, we tested the ability of cannabidiol co-administration to augment opioid analgesia via the more clinically-relevant oral route of administration.

To this end, male and female rats were orally gavaged with cannabidiol (25 mg/kg), oxycodone (1.4 mg/kg), or a combination of both, after which they were tested in an operant thermal orofacial pain assay in which they voluntarily exposed their faces to cutaneous thermal pain to receive a palatable reward.

All three drug conditions produced analgesic effects of varying degrees, being most profound in the combination group where a statistically significant enhancement over oxycodone-induced analgesia alone was evident. Additionally, oxycodone administration decreased lick frequencies – a measure of motor coordination of rhythmic movements – which too was magnified by co-administration of cannabidiol.

Together these studies provide further support of an ability of cannabidiol to augment opioid effects, particularly analgesia, when administered by a route relevant to human pain management. As such, they encourage the notion that cannabidiol could find utility as an opioid-sparing approach to treating pain.”

https://pubmed.ncbi.nlm.nih.gov/39914591/

“Cannabidiol is an orally active constituent of the cannabis plant”

“Cannabidiol potentiates opioid analgesia in an operant orofacial pain assay in rats”

“Cannabidiol as an opioid-sparing approach to treating pain is worthy of more study”

https://www.sciencedirect.com/science/article/abs/pii/S0091305725000152?via%3Dihub

Advances in cannabinoid receptors pharmacology: from receptor structural insights to ligand discovery

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“The medicinal and recreational uses of Cannabis sativa have been recognized for thousands of years.

Today, cannabis-derived medicines are used to treat a variety of conditions, including chronic pain, epilepsy, multiple sclerosis, and chemotherapy-induced nausea. However, cannabis use disorder (CUD) has become the third most prevalent substance use disorder globally.

Cannabinoid receptors are the primary targets that mediate the effects of cannabis and its analogs. Despite their importance, the mechanisms of modulation and the full therapeutic potential of cannabinoid receptors remain unclear, hindering the development of the next generation of cannabinoid-based drugs.

This review summarizes the discovery and medicinal potential of phytocannabinoids and explores the distribution, signaling pathways, and functional roles of cannabinoid receptors. It also discusses classical cannabinoid drugs, as well as agonists, antagonists, and inverse agonists, which serve as key therapeutic agents.

Recent advancements in the development of allosteric drugs are highlighted, with a focus on positive and negative allosteric modulators (PAMs and NAMs) that target CB1 and CB2 receptors. The identification of multiple allosteric sites on the CB1 receptor and the structural basis for allosteric modulation are emphasized, along with the structure-based discovery of ago-BAMs for CB1.

This review concludes by examining the future potential of allosteric modulators in cannabinoid drug development, noting that ongoing progress in cannabinoid-derived drugs continues to open new avenues for therapeutic use and paves the way for future research into their full medicinal potential.”

https://pubmed.ncbi.nlm.nih.gov/39910211/

https://www.nature.com/articles/s41401-024-01472-9

The effects of recreational cannabis laws on alcohol and tobacco use among US adults, 2012 to 2022

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“Introduction: Many states have legalized cannabis for medicinal and recreational purposes in the past decade. However, it is unclear how recreational cannabis laws (RCLs) may affect alcohol and tobacco use among adults.

Methods: This is a cross-sectional study of 4.8 million adults from the 2012-2022 Behavioral Risk Factor Surveillance System. A difference-in-differences approach was used to examine the impact of RCLs on the use of alcohol and tobacco, adjusting for individual-level characteristics and time-varying state-level factors. The analyses were performed in 2024.

Results: Three alcohol use outcomes (current drinking, binge drinking, and heavy drinking) and two tobacco use outcomes (current tobacco use and smokeless tobacco use) were examined. Considering passage of cannabis laws as RCL implementation,

RCLs were not associated with any alcohol or tobacco use outcomes in the fully adjusted model. However, considering operational dispensary as RCL implementation, RCLs were associated with a decrease of 0.95 percentage point (95% CI, 1.80 to 0.09) in current drinking and a decrease of 0.48 percentage point (95% CI, 0.85 to 0.10) in current cigarette use.

Subgroup analysis showed that RCLs were associated with reductions in current drinking, binge drinking, and current cigarette use in multiple groups. However, RCLs were associated with increases in current smokeless tobacco use for some groups.

Conclusions: The findings suggest that while the overall effects of RCLs on the use of alcohol and tobacco may be limited, there are heterogeneous associations of RCLs with drinking and smoking by age, sex, race and ethnicity, education, and income.”

https://pubmed.ncbi.nlm.nih.gov/39909135/

https://www.ajpmonline.org/article/S0749-3797(25)00038-8/abstract

Cannabidiol attenuates lipid metabolism and induces CB1 receptor-mediated ER stress associated apoptosis in ovarian cancer cells

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“Ovarian cancer (OC) is the most deadly gynecological tumor. OC cells utilize cellular metabolic reprogramming to gain a survival advantage, particularly through aberrant lipid metabolic process.

As the primary ingredient in exogenous cannabinoids, cannabidiol (CBD) has been confirmed to exhibit antitumor activity in preclinical studies. However, it is still unclear whether CBD can disrupt fatty acid metabolism and induce apoptosis in OC cells.

In this study, we have demonstrated that CBD significantly inhibits the proliferation of OCs through a cannabinoid receptor type 1 (CB1R)-mediated manner.

Fatty acid metabolic profiling and flow cytometry analysis revealed that CBD has the ability to decrease fatty acid levels and significantly suppress the transcription of genes involved in fatty acid uptake and synthesis in ES-2 cells. In addition, the analysis from RNA-seq and real-time RT-PCR revealed that CBD activated the endoplasmic reticulum (ER) stress pathway. Conversely, by supplementation with unsaturated fatty acid or blocking CB1R, ER stress or reactive oxygen species (ROS) signals with specific inhibitors could significantly relieve CBD induced, dose-dependent, ER stress associated apoptosis, G0-G1 phase arrest, and mitochondrial dysfunction.

Taken collectively, these data indicate that CBD may disrupt lipid metabolism, and lead to ER stress-related apoptosis in OCs. Our findings may provide a theoretical mechanism for anti-ovarian cancer using CBD.”

https://pubmed.ncbi.nlm.nih.gov/39910152/

“Preclinical studies have demonstrated that CBD, either as a monotherapy or in conjunction with other treatments, holds potential as a novel anti-tumor, anti-inflammatory, and analgesic agent. Our results demonstrated that CBD promoted OC cells apoptosis and G0-G1 phase arrest by disrupting the CBR1-mediated lipid metabolism and ER stress- and mitochondrial dysfunction-associated apoptosis signaling pathways (Fig. 8). Therefore, CBD may serve as a potential candidate for adjuvant therapy in the treatment of ovarian cancer. However, larger-scale clinical studies involving more patient samples and detailed dose-response relationship analyses are still needed to confirm the efficacy of CBD in cancer patients.”

https://www.nature.com/articles/s41598-025-88917-1

The Effects of Cannabinoids on Ischemic Stroke-Associated Neuroinflammation: A Systematic Review

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“Stroke represents a significant burden on global health and the economy, with high mortality rates, disability, and recurrence. Ischemic stroke is a serious condition that occurs when a blood vessel in the brain is interrupted, reducing the blood supply to the affected area.

Inflammation is a significant component in stroke pathophysiology. Neuroinflammation is triggered following the acute ischemic ictus, where the blood-brain barrier (BBB) breaks down, causing damage to the endothelial cells. The damage will eventually generate oxidative stress, activate the pathological phenotypes of astrocytes and microglia, and lead to neuronal death in the neurovascular unit. As a result, the brain unleashes a robust neuroinflammatory response, which can further worsen the neurological outcomes.

Neuroinflammation is a complex pathological process involved in ischemic damage and repair. Finding new neuroinflammation molecular targets is essential to develop effective and safe novel treatment approaches against ischemic stroke.

Accumulating studies have investigated the pharmacological properties of cannabinoids (CBs) for many years, and recent research has shown their potential therapeutic use in treating ischemic stroke in rodent models.

These findings revealed promising impacts of CBs in reducing neuroinflammation and cellular death and ameliorating neurological deficits.

In this review, we explore the possibility of the therapeutic administration of CBs in mitigating neuroinflammation caused by a stroke. We summarize the results from several preclinical studies evaluating the efficacy of CBs anti-inflammatory interventions in ischemic stroke.

Although convincing preclinical evidence implies that CBs targeting neuroinflammation are promising for ischemic stroke, translating these findings into the clinical setting has proven to be challenging. The translation hurdle is due to the essence of the CBs ability to cause anxiety, cognitive deficit, and psychosis. Future studies are warranted to address the dose-beneficial effect of CBs in clinical trials of ischemic stroke-related neuroinflammation treatment.”

https://pubmed.ncbi.nlm.nih.gov/39899062/

“Recently, there has been increased interest in the use of cannabinoids (CBs) in stroke and other neurological disorders with a robust neuroinflammatory component.”

“CBs are naturally occurring compounds derived from the cannabis plant (Cannabis sativa L.), which have been utilized historically for their therapeutic effects.”

“In this systematic review, CBs showed remarkable effects against ischemic stroke-induced neuroinflammation in animal models through selective and nonselective activation/inhibition of CB receptors. Most CBs have the advantage of working on multiple targets, affecting many aspects of stroke pathology (Fig. 2). However, a wide range of CBs modulating neuroinflammation were found to be acting more through CB2Rs than CB1Rs, which is attributed to the close involvement of CB2Rs with the inflammatory cascades. Interestingly, simultaneous activation, inhibition, or a combination of both effects on CB1R and CB2R has demonstrated potential neuroprotective effects. This phenomenon is attributed to the biphasic nature of CBs, which allows them to modulate excitatory and inhibitory neurotransmitters in the brain.”

https://link.springer.com/article/10.1007/s11481-025-10171-z

Cannabidiol-Induced Autophagy Ameliorates Tau Protein Clearance

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“Tau is a neuronal protein that confers stability to microtubules; however, its hyperphosphorylation and accumulation can lead to an impairment of protein degradation pathways, such as autophagy. Autophagy is a lysosomal catabolic process responsible for degrading cytosolic components, being essential for cellular homeostasis and survival.

In this context, autophagy modulation has been postulated as a possible therapeutic target for the treatment of neurodegenerative diseases.

Studies point to the modulatory and neuroprotective role of the cannabinoid system in neurodegenerative models and here it was investigated the effects of cannabidiol (CBD) on autophagy in a human neuroblastoma strain (SH-SY5Y) that overexpresses the EGFP-Tau WT (Wild Type) protein in an inducible Tet-On system way.

The results demonstrated that CBD (100 nM and 10 µM) decreased the expression of AT8 and total tau proteins, activating autophagy, evidenced by increased expression of light chain 3-II (LC3-II) protein and formation of autophagosomes.

Furthermore, the cannabinoid compounds CBD, ACEA (CB1 agonist) and GW-405,833 (CB2 agonist) decreased the fluorescence intensity of EGFP-Tau WT; and when chloroquine, an autophagic blocker, was used, there was a reversal in the fluorescence intensity of EGFP-Tau WT with CBD (1 and 10 µM) and GW-405,833 (2 µM), demonstrating the possible participation of autophagy in these groups.

Thus, it was possible to conclude that CBD induced autophagy in EGFP-Tau WT cells which increased tau degradation, showing its possible neuroprotective role. Hence, this study may contribute to a better understanding of how cannabinoids can modulate autophagy and present a potential therapeutic target in a neurodegeneration model.”

https://pubmed.ncbi.nlm.nih.gov/39900844/

“CBD induces autophagy promoting tau clearance in an in vitro model of tauopathy. Moreover, CBD, ACEA and GW-405,833 decreased tau expression, which was reversed by chloroquine indicating that autophagy participates in tau clearance.

Our results support the relevance of cannabinoid compounds in the autophagic process involved in the degradation of accumulated tau, which has been associated with several neuropathies. Therefore, autophagy is a potential therapeutic target of cannabinoids in neurodegenerative diseases.”

https://link.springer.com/article/10.1007/s12640-025-00729-3

The use of cannabidiol in patients with Lennox-Gastaut syndrome and Dravet syndrome in the UK Early Access Program: A retrospective chart review study

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“Purpose: To evaluate clinical outcomes from the UK Early Access Program in patients aged 2-17 years with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) treated with plant-derived highly purified cannabidiol (CBD; Epidyolex®; 100 mg/mL oral solution).

Methods: Retrospective chart review of data collected from baseline (1 month before CBD treatment initiation) until 12 months’ treatment, CBD discontinuation, death, or loss to follow up.

Results: At baseline, all 26 patients enrolled (LGS, n = 17; DS, n = 9; male, 73 %; mean [range] age, 11.8 [3.0-17.0] years) experienced motor seizures; 92 % were taking ≥ 1 antiseizure medication. Median (IQR) CBD dosage at 6 months (6 M; n = 12) was 6.0 (2.7) mg/kg/day, and 12 months (12 M; n = 9) 7.3 (2.1) mg/kg/day. Median (IQR) percentage change from baseline for motor seizures was – 56.7 % (60.7) at 6 M (n = 20), and – 60.0 % (53.3) at 12 M (n = 15). Patients experiencing ≥ 50 % and ≥ 75 % reduction in motor seizures were 13/20 (65 %) and 5/20 (25 %) at 6 M, respectively, and 10/15 (67 %) and 6/15 (40 %) at 12 M, respectively. Mean (SD) motor seizure-free days/month were 1.5 (4.3) at baseline (n = 24, missing data n = 2), 2.4 (6.3) at 6 M (n = 18), and 2.7 (5.5) at 12 M (n = 15). At 12 M, CBD retention for patients with follow-up data was 14/19 (74 %), whilst 7/26 (27 %) were lost to follow up. The number of patients reporting ≥ 1 adverse event of special interest (most common: gastrointestinal) was 14/20 (70 %) and 8/15 (53 %) at 6 M and 12 M, respectively.

Conclusion: Results demonstrate a reduction in motor seizures and a safety profile consistent with previous studies.”

https://pubmed.ncbi.nlm.nih.gov/39898301/

“Results on CBD effectiveness and safety are consistent with previous studies.”

https://www.sciencedirect.com/science/article/pii/S2589986424000881?via%3Dihub

Physiochemical properties of hemp extract (Cannabis sativa L) inflorescences grown in Northern Alabama

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“Medicinal plants are an excellent source of bioactive components and are gaining significant attention for food protection due to their bioactive properties.

In this context, hemp (Cannabis sp.) is being explored for such applications because of its well-known antibacterial and antioxidant activities. However, the bioactive efficacy of cultivars currently grown in Northern Alabama has not been widely studied. Therefore, the purpose of this study was to evaluate the physicochemical properties of two hemp cultivars (Hemp 5 and Hemp 17).

Hemp inflorescences grown at the Winfred Thomas Agricultural Research Station were used in this study. The antioxidant activity and content of the extracts were determined by ferric reducing antioxidant power, radical scavenging activity, total phenolic content, and total flavonoid content. Antibacterial activity against cocktails of Listeria monocytogenes (LM) and Salmonella enterica (SE) was evaluated by optical density and disc diffusion. All treatments were analyzed in triplicate, and analysis of variance was conducted with statistical significance based on p ≤ 0.05.

Results indicated that cultivars and defatting significantly affected (p ≤ 0.05) the antioxidant properties, with Hemp 17 DF (defatted) having the highest RSA (70.51 ± 4.24%) compared to the positive control of ascorbic acid (83.81 ± 5.85%). Antibacterial results based on optical density indicated that hemp extracts had a significantly (p ≤ 0.05) lower optical density compared to the negative controls (LM and SE).

These findings suggest that Northern Alabama hemp cultivars can potentially be utilized to enhance food safety and quality.

PRACTICAL APPLICATION: Northern Alabama cultivars of hemp extract can be utilized for the enhancement of the safety and quality application due to inherent antioxidant and antimicrobial properties.”

https://pubmed.ncbi.nlm.nih.gov/39898995/

https://ift.onlinelibrary.wiley.com/doi/10.1111/1750-3841.17642

In vitro characterization the antioxidant and antibacterial properties of hemp (Cannabis sativa spp.) varieties cultivated in Northern Alabama

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“Plants, especially those recognized for their medicinal properties, are an excellent source of bioactive components and are attracting considerable interest in the food industry due to their natural bioactivity.

In this context, hemp species (Cannabis sativa spp.) were investigated for such applications because of their well-documented antibacterial and antioxidant activities. However, the bioactive efficacy of varieties being introduced in Northern Alabama and their implications for food safety have not been studied.

The purpose of this study was to evaluate the antibacterial and antioxidative potential of four hemp varieties grown at the Alabama A&M University, Winfred Thomas Agricultural Research Station in Northern Alabama using three different extraction solvents (deionized water, acetone, and ethanol).

Antioxidant potential was evaluated by DPPH free radical scavenging activity (2, 2-diphenyl-1- picrylhydrazyl), Total phenolic and flavonoid contents. Antibacterial activity against cocktails of enteric pathogens, including Listeria monocytogenese, E. coli O157:H7, and Salmonella enterica was evaluated for optical density using a BioScreen-C microtiter. Also, the disc diffusion extraction yield was evaluated to determine the best extraction solvent. Data were expressed as mean ± standard error (n = 3) and ANOVA (P ≤ 0.05).

The ethanolic extracts exhibited the the highest extraction yield at 25.29 ± 0.70% (RE), while the antioxidant result demonstrated that the ethanolic extracts had the highest DPPH free radical scavenging activity at 64.03 ± 0.26% (RE).

The results of the antibacterial studies showed that ethanolic hemp extracts exhibited significantly higher growth inhibition against all foodborne pathogens > 70% (p ≤ 0.05).

The results show that the ethanolic extracts has significant extraction yield and bioactivity, highlighting ethanolic extract utilization in future antimicrobial nanofiber application.”

https://pubmed.ncbi.nlm.nih.gov/39891281/

“Hemp (Cannabis sativa). Cannabis sativa has been used for thousands of years to prevent disease in humans.”

“In various reports, hemp has been shown to contain phytochemical compounds (such as phenolics, flavonoids, and terpenophenolics) that effectively inhibit the growth of pathogenic bacteria and scavenge free radicals.

Hemp has been used in traditional medicine as a therapeutic agent with antibacterial, anti-inflammatory, and chemopreventive properties that can cure many ailments.

The ability of the hemp ethanolic extracts to scavenge the DPPH free radical indicates that they may have antioxidant properties. The inhibition of EC, SE, and LM in disc diffusion and growth inhibition assays by ethanolic hemp extracts suggests growth inhibitory effects of the extract, and pinpoints ethanol as the most effective extraction solvent for maceration extraction of northern Alabama varieties.

The obtained results support the idea that hemp grown in northern Alabama can be used as a plant-based natural preservative because of its antibacterial and antioxidant potential in food preservation. Future research is required to study quantitative antibacterial and antioxidant activities, mechanisms of antibacterial action, phytochemical profiles through analytical chromatography, and applications of hemp ethanol extract in nanotechnology.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00258-y