Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Cannabidiol-Rich Cannabis sativa L. Extract Alleviates LPS-Induced Neuroinflammation Behavioral Alterations, and Astrocytic Bioenergetic Impairment in Male Mice

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“Neuroinflammation is a hallmark of various neurodegenerative disorders, yet effective treatments remain limited.

This study investigates the neuroprotective potential of a cannabidiol (CBD)-Rich Cannabis sativa L. (CS) extract in a lipopolysaccharide (LPS)-induced neuroinflammation mouse model.

The effects on anxiety-like behavior, cognitive function, and locomotor activity were assessed using behavioral tests (open field, elevated plus maze, novel object recognition, and Morris water maze). Antioxidant activity was measured by assaying glutathione (GSH) levels and lipid peroxidation by-products (TBARs). Anti-inflammatory properties were evaluated using quantitative reverse transcription polymerase chain reaction (QRt-PCR) for proinflammatory cytokines (IL-6 and TNF-α), glial fibrillary acidic protein (GFAP), and cannabinoid receptor 1 (CB1) mRNAs in the prefrontal cortex (PFC). Astrocytic bioenergetics were analyzed using extracellular flux assays. Additionally, computational inference with a deep learning approach was conducted to evaluate the synergistic interactions among CS phytocompounds on the CB1 receptors.

Compared with synthetic CBD, the CS extract (20.0 mg/kg) demonstrated superior efficacy in mitigating LPS-induced anxiety-like behavior, cognitive deficits, and locomotor impairments. It also significantly mitigated oxidative stress (increased GSH, reduced TBARs) and suppressed proinflammatory cytokines and GFAP mRNAs, indicating potent anti-inflammatory properties.

The extract modulated CB1 receptor expression and preserved metabolic homeostasis in cortical astrocytes, preventing their shift from glycolysis to oxidative phosphorylation under neuroinflammatory conditions. Computational modeling highlighted conformational changes in CB1 receptor residues induced by Delta-9-THC that enhanced CBD binding.

These findings underscore the potential of CS extract as a therapeutic candidate for managing neuroinflammation and its associated neurodegenerative consequences, warranting further clinical exploration.”

https://pubmed.ncbi.nlm.nih.gov/40195769/

https://onlinelibrary.wiley.com/doi/10.1002/jnr.70035

Effects of cannabinoids on immune checkpoint inhibitor response: CCTG pooled analysis of individual patient data

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“Background: Immune checkpoint inhibitors (ICIs) benefit patients across various tumor types. ICIs block cancer and T-cell interactions whereas cannabinoids may inhibit T-cell activation, reducing lysis of tumor cells. Interactions between cannabinoid use and dual ICI treatment remain unknown.

Methods: Individual patient data from 4 Canadian Cancer Trials Group (CCTG) trials of patients treated with dual ICI ± chemotherapy (n = 684) were pooled. Cochran – Mantel – Haenszel and log-rank tests (stratified by trial/treatment arms) correlated cannabinoid use with clinicopathologic characteristics, Best Overall Response (BOR)/iBOR per RECIST 1.1/iRECIST, Progression-Free Survival (PFS)/iPFS, Overall Survival (OS) and immune-related adverse events (irAEs).

Results: Sixty-five (9.5%) patients took cannabinoids at any time on trial, 32 (4.7%) of which were using cannabinoids at baseline. By multivariate analysis, cannabinoid use at baseline was significantly associated with improved iPFS (0.05), but not iBOR (p = 0.15), PFS (p = 0.12), OS (p = 0.35) or incidence of grade 1/2 or 3/4 irAEs (p = 0.96 and 0.65 respectively). Results were not significantly different with cannabinoid use at any time on trial.

Conclusion: Improved iPFS with cannabinoid use in patients treated with durvalumab plus tremelimumab ± chemotherapy did not translate into OS benefits. This study supports the safe use of cannabinoids in the context of combination ICI therapy.”

https://pubmed.ncbi.nlm.nih.gov/40184324/

“Plain Language Summary

Immune checkpoint inhibitors (ICI) have become an important treatment option for cancer patients and has been associated with improved survival outcomes across various tumor types. Cannabinoids are active components of cannabis and include tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabis use has increased in Canadian cancer patients and is often used for symptom management. Some studies have suggested that cannabinoids can alter the function of the immune system, which could impact the effectiveness of immune checkpoint inhibitors. Therefore, we aimed to evaluate whether cannabinoid use might impact the effectiveness of combination ICI treatment with durvalumab plus tremelimumab (with/without chemotherapy) using data from four clinical trials completed through the Canadian Cancer Trials Group (CCTG). We found no significant difference in response, survival outcomes or adverse events in patients who used cannabinoids with combination ICI treatment compared to cannabinoid non-users. This study supports the safe use of cannabinoids in the context of combination ICI therapy.”

https://www.tandfonline.com/doi/full/10.1080/1750743X.2025.2485012

Multifunctional cosmetic potential of extracellular vesicle‑like nanoparticles derived from the stem of Cannabis sativa in treating pigmentation disorders

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“While natural products and synthetic chemicals are used in functional cosmetics, their potential side effects remain a concern.

This has driven the need safer and more effective agents to treat skin disorders. Therefore, the present study aimed to explore the functional properties of Cannabis sativa stem‑derived nanoparticles (CSS‑NPs) and evaluate their potential as a cosmetic ingredient.

Using nanoparticle analysis, CSS‑NPs, with a mean diameter of ~120 nm exhibited notable resistance to external stress conditions, including pH fluctuation and enzymatic degradation by DNase, RNase and proteinase K. They also contained 48 distinct biochemical components. In vitro assays revealed that CSS‑NPs significantly downregulated the expression of genes and proteins associated with melanin synthesis in mouse B16F10 melanoma cells under α‑melanocyte stimulating hormone (α‑MSH)‑induced hyperpigmentation. These inhibitory effects were mediated by the activation of ERK and Akt signaling pathways. Furthermore, CSS‑NPs improved the viability of α‑MSH‑treated B16F10 cells; this was accompanied by the upregulation of antioxidant‑associated enzymes and a decrease in α‑MSH‑induced reactive oxygen species levels.

Collectively, these findings suggested that CSS‑NPs carry out a key role in mitigating skin pigmentation and enhancing antioxidant defenses by modulating the ERK/Akt axis during excessive melanin synthesis. Thus, CSS‑NPs represent a promising multifunctional cosmetic ingredient with potential in treating pigmentation disorders and protecting skin cells.”

https://pubmed.ncbi.nlm.nih.gov/40183388/

https://www.spandidos-publications.com/10.3892/mmr.2025.13512

Characterizing the Population of a Medical Cannabis Clinic in a Pediatric Hospital

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“Background: Medical cannabis (MC) is increasingly in use due to recent cultural and political changes. Other than patients with Lennox-Gastaut and Dravet syndrome, there is inadequate literature to provide evidence-based support for prescribing MC in pediatric patients. 

Objectives: Characterize the population receiving an MC recommendation in an ambulatory pediatric palliative care setting and quantify patient/family-reported outcomes. 

Design: Retrospective chart review of electronic medical record (EMR) data. Setting/Subjects: Total n = 46 consecutive patients receiving medical advice regarding MC (n = 42) in a specialized ambulatory clinic embedded in a palliative care division and n = 4 inpatient in a midwestern U.S. hospital between 2019 and 2022. Measurements: Demographics, diagnosis, symptoms, adverse reactions, patient-reported outcomes, and barriers abstracted from EMR. 

Results: Our sample included 46 palliative care patients with a mean age of 11.7 years (SD 5.4); 50% had a neurological diagnosis (n = 25); 37% (n = 14) hematological/oncologic; and 13% (n = 6), chronic pain. The most common type of MC recommended was 1:1 Cannabidiol (CBD): tetrahydrocannabinol (THC) tincture. There was a statistically significant decrease in inpatient floor days and cost. Totally, 35% of patients were able to decrease or discontinue other medications. Thematic analysis identified four barriers to use (product unavailable, difficulty obtaining state MC card, cost, and organizational) and subjective symptom improvement. 

Conclusions: These data characterize the palliative care MC clinic population at our pediatric hospital. Positive outcomes were noted across several symptom domains. MC seems to be associated with lower health care utilization, reduced polypharmacy, and increased quality of life and was used without significant adverse events. In a value-conscious health care environment, the data warrant further exploration.”

https://pubmed.ncbi.nlm.nih.gov/40180570/

https://www.liebertpub.com/doi/10.1089/jpm.2024.0533

Cannabinoid receptor deficiencies drive immune response dynamics in Salmonella infection

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“This study investigated the roles of cannabinoid receptors 1 and 2 (CB1R and CB2R) in regulating host responses to Salmonella Typhimurium in C57BL/6 mice.

The absence of both receptors significantly impaired host resilience, as evidenced by increased weight loss, deteriorated body condition, and reduced survival following infection.

Notably, CB1R deficiency resulted in more pronounced weight loss and heightened susceptibility to bacterial proliferation, as demonstrated by increased Salmonella dissemination to organs. In addition, both CB1R and CB2R knockout mice exhibited alterations in immune cell recruitment and cytokine production. CB1R-KO mice displayed increased T cell and macrophage populations, whereas CB2R-KO mice showed a reduction in NK cells, indicating receptor-specific effects on immune cell mobilization.

Cytokine profiling of macrophages post-infection revealed that CB1R-KO mice had reduced IL-10 levels, along with increased IL-6 and TGF-β, suggesting a dysregulated polarization state that combines pro-inflammatory and regulatory elements. In contrast, CB2R-KO mice exhibited a profile consistent with a more straightforward pro-inflammatory shift.

Furthermore, microbiota analysis demonstrated that CB2R-KO mice experienced significant gut dysbiosis, including reduced levels of beneficial Lactobacillus and Bifidobacterium species and an increase in pro-inflammatory Alistipes species post-infection. Functional microbiome analysis further indicated declines in key metabolic pathways, such as the Bifidobacterium shunt, L-glutamine biosynthesis, and L-lysine biosynthesis, suggesting microbiota-driven immune dysregulation.

Together, these findings highlight the distinct, non-redundant roles of CB1R and CB2R in modulating innate immunity, host defense, and microbiota composition during bacterial infections.

Significance statement: Understanding the role of cannabinoid receptors in immune regulation is important for identifying new therapeutic targets for bacterial infections. Our study demonstrates that CB1R and CB2R play distinct, non-redundant roles in host defense against Salmonella Typhimurium. The absence of these receptors impairs host resilience, increases bacterial dissemination, and alters immune cell recruitment and cytokine production. Notably, CB1R deficiency leads to enhanced weight loss, increased bacterial spread, and a dysregulated macrophage cytokine profile-characterized by reduced IL-10 and elevated IL-6 and TGF-β-while CB2R deficiency is associated with reduced NK cell numbers and a more pronounced pro-inflammatory cytokine profile. These findings reveal a receptor-specific balance in immune responses, suggesting that cannabinoid signaling modulates infection outcomes.

Targeting CB1R and CB2R pathways may offer novel strategies to enhance host immunity and improve treatments for bacterial infections in the future.”

https://pubmed.ncbi.nlm.nih.gov/40161677/

https://www.biorxiv.org/content/10.1101/2025.03.10.642352v1

Cannabinoids in Chronic Pain Management: A Review of the History, Efficacy, Applications, and Risks

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“Background/Objectives: Chronic pain remains a pervasive and challenging public health issue, often resistant to conventional treatments such as opioids, which carry substantial risks of dependency and adverse effects. Cannabinoids, bioactive compounds derived from the Cannabis sativa plant and their synthetic analogs, have emerged as a potential alternative for pain management, leveraging their interaction with the endocannabinoid system to modulate pain and inflammation. 

Methods: The current, evolving literature regarding the history, efficacy, applications, and safety of cannabinoids in the treatment of chronic pain was reviewed and summarized to provide the most current review of cannabinoids. 

Results: Evidence suggests that cannabinoids provide moderate efficacy in managing neuropathic pain, fibromyalgia, cancer-related pain, and multiple sclerosis-related spasticity. Patient-reported outcomes further indicate widespread perceptions of cannabinoids as a safer alternative to opioids, with potential opioid-sparing effects. However, the quality of existing evidence is limited by small sample sizes and methodological inconsistencies. Regulatory barriers, including the classification of cannabis as a Schedule I substance in the United States, continue to hinder robust research and clinical integration. Moreover, the risks associated with cannabinoids, such as psychiatric effects, addiction potential, and drug interactions, necessitate cautious application. 

Conclusions: Cannabinoids represent a promising, albeit complex, alternative for chronic pain management, particularly given the limitations and risks of traditional therapies such as opioids. However, significant deficiencies remain in the research. While smaller trials and systematic reviews indicate therapeutic potential, the quality of evidence is often low due to limited sample sizes, short study durations, and methodological inconsistencies. Large-scale, randomized controlled trials with long-term follow-up are urgently needed to confirm efficacy and safety across diverse patient populations and pain etiologies.”

https://pubmed.ncbi.nlm.nih.gov/40149508/

“The future for cannabis research is bright, and as regulatory frameworks adapt to balance access and oversight, cannabinoids may transition from an experimental adjunct to a well-established option in chronic pain care, provided scientific rigor and evidence-based policymaking remain at the forefront.”

https://www.mdpi.com/2227-9059/13/3/530

Parthanatos and apoptosis: unraveling their roles in cancer cell death and therapy resistance

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“Cell death is a fundamental process that needs to be maintained to balance cellular functions and prevent disease. There are several cell death pathways; however, apoptosis and parthanatos are the most prominent and have important roles in cancer biology. As an extremely well-regulated process, apoptosis removes damaged or abnormal cells via caspase activation and mitochondrial involvement.

Unlike in the healthy cells, the loss of ability to induce apoptosis in cancer permits tumor cells to survive and multiply out of control and contribute to tumor progression and therapy resistance. On the contrary, parthanatos is a caspase-independent metabolic collapse driven by poly (ADP-ribose) polymerase 1 (PARP1) overactivation, translocation of apoptosis-inducing factor (AIF), and complete DNA damage. Several cancer models are involved with parthanatos. Deoxypodophyllotoxin (DPT) induces parthanatos in glioma cells by excessive ROS generation, PARP1 upregulation, and AIF nuclear translocation.

Like in acute myeloid leukemia (AML), the cannabinoid derivative WIN-55 triggers parthanatos, and the effects can be reversed by PARP inhibitors such as olaparib.

Developing cancer treatment strategies involving advanced cancer treatment strategies relies on the interplay between apoptosis and parthanatos. However, such apoptosis-based cancer therapies tend to develop resistance, so there is an urgent need to look into alternative pathways like parthanatos, which may not always trigger apoptosis.

In overcoming apoptosis resistance, there is evidence that combining apoptosis-inducing agents, such as BH3 mimetics, with PARP inhibitors synergistically enhances cell death.

Oxidative stress modulators have been found to promote the execution of parthanatic and apoptotic pathways and allow treatment. In this review, apoptosis and parthanatos are thoroughly compared at the molecular level, and their roles in cancer pathogenesis as related to cancer therapeutic potential are discussed.

We incorporate recent findings to demonstrate that not only can parthanatos be used to manage therapy resistance and enhance cancer treatment via the combination of parthanatos and apoptosis but also that immunity and bone deposition can feasibly be employed against long-circulating cancer stem cells to treat diverse forms of metastatic cancers.”

https://pubmed.ncbi.nlm.nih.gov/40166425/

“Cannabinoids induce cell death in leukaemic cells through Parthanatos and PARP-related metabolic disruptions.”

https://pubmed.ncbi.nlm.nih.gov/38461169/

Early oral administration of THC:CBD formulations prevent pain-related behaviors without exacerbating paclitaxel-induced changes in weight, locomotion, and anxiety in a rat model of chemotherapy-induced neuropathy

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“Rationale: Paclitaxel-induced neuropathy stands out as the primary, dose-limiting side effect of this extensively used chemotherapy agent. Prolonged hypersensitivity and pain represent the most severe clinical manifestations. Effective preventive and therapeutic strategies are currently lacking.

Objectives: Our study aimed to assess the impact of early oral administration of pharmaceutical-grade formulations containing the phytocannabinoids THC and CBD in a rat model of paclitaxel-induced neuropathy.

Methods: The experimental design involved the co-administration of paclitaxel and cannabinoid formulations with different THC to CBD ratios (THC:CBD 1:1 and THC:CBD 1:20) to adult male rats. Mechanical and thermal sensitivity, locomotor activity, vertical exploratory behaviors, anxiety-related parameters, weight gain, food and water consumption, and liver functionality were assessed.

Results: Daily administration of THC:CBD 1:1 successfully prevented paclitaxel-induced cold allodynia, while THC:CBD 1:20 effectively prevented both thermal and mechanical hypersensitivities. Additionally, THC:CBD 1:1 formulation restored rearing behavior, significantly reduced by paclitaxel. Conversely, neither cannabinoid formulation was able to counteract paclitaxel-induced hypo-locomotion, reduced vertical exploratory activity, increased anxiety-like behaviors, attenuated weight gain, or decreased food and water intakes. However, the formulations employed did not induce further alterations or toxicity in animals receiving paclitaxel, and no signs of liver damage were detected.

Conclusions: Our results suggest a differential therapeutic effect of two THC:CBD formulations on pain-related behaviors and spontaneous activities, particularly in the context of peripheral neuropathy. These formulations represent a promising therapeutic strategy not only to managing pain but also for enhancing daily activities and improving the quality of life for cancer patients.”

https://pubmed.ncbi.nlm.nih.gov/40163146/

Cannabidiol/tetrahydrocannabinol-enrich extract decreases neuroinfalmmation and improves locomotor outcome following spinal cord injury

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“Neuroinflammation is one of the main players in lesion expansion and locomotor deficits after spinal cord injury (SCI), thus treatments to control the inflammatory process emerge as novel therapeutic strategies. In this context, the anti-inflammatory effects of tetrahydrocannabinol (THC) and cannabidiol (CBD), the main phytocannabinoids of Cannabis sativa, are increasingly recognized.

The aim of this work was to investigate the effects of a standardized Cannabis sativa extract (CSE), which is mainly composed by THC/CBD in equimolar concentration, on neuroinflammation, secondary damage and locomotor outcome after SCI in rats.

After acute SCI, CSE therapy increased the number of non-inflammatory (arginase-1 positive) microglial cells in the epicenter of the lesion and decreased the number of pro-inflammatory ones (arginase-1 negative) in the epicenter and in the rostral and caudal regions of the lesion. CSE also reduced the number of reactive astrocytes in the grey matter of the rostral and caudal regions.

These results are consistent with the downregulation of mRNAs of inflammatory mediators (IL-1β, TNFα, IL-6, C3) and the upregulation of anti-inflammatory markers (ARG-1, MRC). In the chronic phase, CSE treatment prevented cyst expansion and also increased the volume of spared grey and white matter. Regarding locomotor outcome, CSE-treated rats showed better locomotor scores (open field test), higher latency to fall (Rotarod test) and lower number of hindlimb foot misplacements (horizontal ladder walking test) than untreated injured rats.

These results suggest that this standardized CSE offers a promising perspective for reducing acute neuroinflammation and promoting functional recovery after SCI.”

https://pubmed.ncbi.nlm.nih.gov/40157632/

https://www.ibroneuroscience.org/article/S0306-4522(25)00258-1/abstract

Evaluating Vaporized Cannabinoid Therapy in Multiple Sclerosis: Findings from a Prospective Single-Center Clinical Study

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“Introduction: Multiple Sclerosis (MS) is associated with a wide range of debilitating symptoms, and conventional therapies often fail to adequately address the disease’s multifaceted challenges. Cannabidiol (CBD) 13.0% + Delta9-tetrahydrocannabinol (THC) 9.0% (CBD13/THC9), a vaporized cannabis-based medicinal product, presents a novel therapeutic option for managing MS symptoms. 

Methods: This single-center longitudinal study followed 69 MS patients over a six-month period. Participants were assessed at treatment initiation and at three- and six-month intervals. Key measures included muscle spasticity, urine bladder dysfunction, and the evaluation of disability progression rate. The evaluation included the Modified Ashworth Scale (MAS), the Post Void Residual (PVR) volume, and the Expanded Disability Status Scale (EDSS). 

Results: Significant improvement was observed across all outcome assessments. The EDSS score was decreased over time (p = 0.009), indicating a slight reduction in disability progression rate, while MAS scores showed substantial improvement in muscle spasticity (p < 0.001). Urine bladder function improved significantly, with PVR volume showing notable improvement between baseline and the six-month assessment (p < 0.001). Correlation analyses revealed that a gradual increase in vaporized CBD13/THC9 dose was correlated with slightly lower EDSS scores, while the adverse effects were negatively associated with the frequency of cannabinoid use. Finally, patients who were smokers used CBD13/THC9 more frequently. 

Conclusions: The vaporized CBD13/THC9 formulation demonstrated notable efficacy in slightly improving disability progression rate via reduction in muscle spasticity and urine bladder dysfunction in MS patients. This highlights its addon therapeutic value during rehabilitation in MS patients with debilitating disability symptoms.”

https://pubmed.ncbi.nlm.nih.gov/40142928/

https://www.mdpi.com/2077-0383/14/6/2121