Tag Archives: endocannabinoid system

Ten-year outcomes of medical cannabis for chronic low back pain: opioid reduction, pain relief, and functional improvement in 1,000 patients

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A 2026 study published in the European Spine Journal followed 1,000 patients with chronic low back pain who had been using opioids for at least a year before beginning medical cannabis treatment. Researchers tracked changes in opioid use, pain, disability, and other medications over as long as 10 years.

Among the 638 patients who completed the full 10-year follow-up, average opioid use fell by 89.8%, while pain scores dropped by 84.2%. More than 91% of patients achieved at least a 50% reduction in opioid use, and 96.6% achieved at least a 30% reduction in pain. Disability scores also improved substantially over the study period.

The reductions were not limited to opioids. Use of benzodiazepines, gabapentinoids, antidepressants, and other pain medications also declined. With a decade of follow-up, this study provides unusually long-term evidence that medical cannabis may play an important role in reducing pain, improving function, and decreasing dependence on multiple medications in people living with chronic low back pain.

“Purpose: To evaluate 10-year outcomes of medical cannabis therapy on opioid use, pain intensity, functional disability, concomitant medication use, and adverse events in cannabis-naïve chronic low back pain (CLBP) patients, with particular attention to clinically meaningful outcomes defined by established minimal clinically important difference (MCID) thresholds.

Methods: Single-center longitudinal observational study of 1,000 consecutive cannabis-naïve CLBP patients from a registry database (2015-2024), reported following STROBE guidelines.

Primary outcome: morphine milligram equivalents (MMEQ).

Secondary outcomes: Numeric Rating Scale (NRS) for pain intensity, Oswestry Disability Index (ODI) for functional disability, cannabis dosing patterns, adverse events, and concomitant medication use. Pre-specified MCID thresholds: ≥50% MMEQ reduction, ≥ 30% NRS reduction, ≥ 10-point ODI improvement. Statistical analyses included paired t-tests for completers and linear mixed-effects models for sensitivity analyses.

Results: Of 1,000 enrolled patients, 638 (63.8%) completed 10-year follow-up. Among completers, MMEQ decreased from 62.8 ± 35.7 to 6.4 ± 7.1 mg/day (- 89.8%, p < 0.001); NRS from 8.71 ± 1.23 to 1.37 ± 1.71 (- 84.2%, p < 0.001); ODI from 52.9 ± 11.9% to 36.8 ± 14.9% (16.1-point reduction, – 30.4%, p < 0.001). MCID responders: 91.2% for MMEQ, 96.6% for NRS, 62.1% for ODI. Substantial polypharmacy reductions occurred: tramadol/tapentadol – 84.0% points (pp), benzodiazepines – 73.5 pp, SSRIs – 71.9 pp, gabapentinoids – 30.7 pp. True tolerability adverse events occurred in 11.4% of visits; serious psychiatric events in 0.02%.

Conclusions: In this uncontrolled observational study, medical cannabis therapy was associated with reductions in opioid use, pain intensity, and functional disability over 10 years, accompanied by polypharmacy reduction and acceptable tolerability. Effect sizes substantially exceeded RCT benchmarks (e.g., – 0.6 NRS difference vs. placebo in a recent phase 3 trial), suggesting observational biases contribute to these findings. These hypothesis-generating data warrant validation in randomized controlled trials.”

https://pubmed.ncbi.nlm.nih.gov/42734834

“In this 10-year single-arm observational study, medical cannabis therapy was associated with reductions in opioid use (− 89.8%), pain intensity (− 84.2%), and functional disability (− 30.4%), with high proportions of patients achieving pre-specified MCID thresholds. Substantial polypharmacy reductions and acceptable tolerability were observed.”

https://link.springer.com/article/10.1007/s00586-026-10290-y

The Endocannabinoid System is No Longer the Limiting Factor: Why Policy and Stigma Continue to Delay Cannabinoid-Based Medicine

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The science of the endocannabinoid system has advanced dramatically, but cannabinoid-based medicine is still being held back by forces outside the laboratory. This new Clinical Therapeutics commentary argues that the biological understanding of the endocannabinoid system is no longer the main limiting factor. The larger barriers are now policy, regulation, funding, access, and stigma.

According to the authors, restrictive and fragmented rules make cannabinoid research harder to conduct, while limited access to standardized products complicates rigorous clinical trials. At the same time, stigma within medicine can discourage research, education, prescribing, and open discussion with patients.

The message is simple: the remaining evidence gaps are not purely scientific. They are also structural. If cannabinoid-based medicine is going to move forward, policy and medical culture will have to catch up with what researchers already understand about the endocannabinoid system.

“Purpose: To examine whether the persistent gap between the extensive mechanistic knowledge of the Endocannabinoid System (ECS) and the limited number of high-quality randomized clinical trials of cannabinoid-based therapies primarily reflects scientific uncertainty or, instead, structural regulatory, economic, and social barriers.

Methods: This commentary critically synthesizes historical, regulatory, and contemporary evidence on cannabinoid research, integrating data from regulatory documents, international policy reports, clinical and observational studies, systematic reviews, and qualitative investigations. Particular emphasis is placed on barriers affecting access to standardized products, conduct of randomized clinical trials, public funding, product standardization, and healthcare professionals’ perceptions.

Findings: Although the ECS has been extensively characterized for more than three decades and cannabinoids demonstrate plausible pharmacological mechanisms across multiple therapeutic areas, clinical translation remains disproportionately limited. Persistent regulatory restrictions, inherited from prohibition policies, continue to delay access to standardized research material, increase the cost and complexity of clinical trials, and shift evidence generation toward observational designs. Regulatory fragmentation further compromises product standardization and study reproducibility, whereas persistent social and professional stigma reduces research activity, medical education, prescribing confidence, and patient disclosure, perpetuating a self-reinforcing cycle between limited evidence generation and clinical distrust.

Implications: The principal obstacle to cannabinoid-based medicine is no longer the biological understanding of the ECS but the structural environment surrounding cannabinoid research. Progress toward evidence-based clinical implementation will depend on regulatory harmonization, greater public investment in randomized clinical research, standardized pharmaceutical-quality products, and educational initiatives capable of reducing stigma among healthcare professionals. Recognizing the structural rather than scientific origin of the evidence gap is essential for informing future research priorities, editorial policies, and international regulatory strategies.”

https://pubmed.ncbi.nlm.nih.gov/42728140

“The ECS is no longer the main obstacle to cannabinoid therapeutics. Stigma and regulation continue to delay clinical translation. Standardized clinical research requires international regulatory reform. Medical education is crucial for evidence-based cannabinoid therapies.”

https://www.clinicaltherapeutics.com/article/S0149-2918(26)00317-6/fulltext

Combined Cannabidiol and Δ9-Tetrahydrocannabinol Modulate Inflammation and Nociceptive Signaling in Human Dental Pulp Cells

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A new study using human dental pulp cells found that combining cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) produced stronger anti-inflammatory effects than either cannabinoid alone. The combination reduced the pro-inflammatory cytokines IL-6, IL-12, and IL-1β while increasing the anti-inflammatory cytokine IL-10.

CBD and THC together also influenced important pathways involved in pain signaling and healing. Researchers reported increased expression of the cannabinoid receptors CNR1 and CNR2, modulation of TRPV1, and enhanced cell proliferation and migration. The combination also promoted mineralized nodule formation and increased markers associated with odontogenic differentiation and new blood-vessel formation.

The researchers concluded that combined CBD and THC show promise for promoting dental pulp healing by simultaneously influencing inflammation, nociceptive signaling, tissue repair, angiogenesis, and cell migration. The findings provide new evidence that cannabinoids may have potential applications in future vital pulp therapies designed to preserve and regenerate living dental tissue.

“Introduction: Dental pulp inflammation, caused by caries, trauma, or restorative operations, produces pain and slows regeneration. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), cannabinoids of Cannabis sativa, have effects on inflammation and pain relief. However, the impact of these factors on dental pulp healing is not understood. This study investigated the combined effects of CBD and THC in controlling inflammation and nociception during dental pulp repair.

Methods: Human dental pulp cells were stimulated with lipopolysaccharide (LPS) and treated with CBD (2.5 μg/mL), THC (0.6 μg/mL), and their combination. Pro-inflammatory cytokines (IL-6, IL-12 and IL-1β) and anti-inflammatory cytokine IL-10 were analysed using qPCR and ELISA, while anti-nociceptive markers (CNR1, CNR2, and TRPV1) were evaluated by qPCR and Western blot. Cell viability, proliferation, and migration assays were performed to evaluate treatment effects on cellular behaviours associated with pulpal repair and regenerative potential.

Results: Compared with either treatment alone, the CBD/THC combination more effectively attenuated pro-inflammatory cytokines IL-6, IL-12, and IL-1β, enhanced CNR1 and CNR2 expression, modulated TRPV1, and increased IL-10 expression. Viability assays determined optimal non-cytotoxic concentrations for treatment. The combination enhanced cell proliferation and migration, promoted mineralized nodule formation, and significantly upregulated markers associated with tissue repair, odontogenic differentiation (DMP1), and angiogenesis (VEGF and bFGF).

Conclusion: Combined CBD and THC show promise for promoting dental pulp healing by modulating inflammation and nociceptive signaling, while supporting odontogenic differentiation, angiogenesis, and cell migration in human dental pulp cells. These findings provide in vitro evidence supporting combined cannabinoid treatment as a therapeutic strategy for vital pulp therapies.”

https://pubmed.ncbi.nlm.nih.gov/42722230

https://www.jendodon.com/article/S0099-2399(26)00500-5/abstract

Phytocannabinoids and bone health

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A 2026 review published in Current Osteoporosis Reports examines growing evidence that phytocannabinoids may support bone health by influencing bone remodeling, inflammation, fracture healing, and bone loss.

The review highlights the endocannabinoid system as an important regulator of bone metabolism. Research involving CBD and THC shows that cannabinoids can affect osteoblasts, which build bone, and osteoclasts, which break bone down.

The review also discusses early human research showing that medical cannabis products containing THC and CBD reduced a blood marker associated with bone resorption. Together, the findings point to cannabinoids and the endocannabinoid system as promising areas for further bone-health research.

“Purpose of the review: Phytocannabinoids have received attention for their therapeutic properties, however, it is unclear how they affect bone homeostasis. Additionally, increased use of cannabis and hemp-derived products have raised questions about their impact on musculoskeletal health. This review summarizes recent studies that investigate the impact of phytocannabinoids on bone.

Recent findings: The most well studied phytocannabinoid in relation to bone health is cannabidiol (CBD). In vitro data suggests CBD inhibits osteoclasts and promotes osteoblast activity. Rodent studies have demonstrated CBD may be useful for managing bone loss associated with osteoporosis and periodontitis, as well as reducing fracture pain and promoting healing. Recent studies suggest other phytocannabinoid isolates and extracts containing multiple phytocannabinoids have varying effects on bone. The first clinical study in this area reported that a medical cannabis product reduced markers of bone turnover in healthy adults. Cannabinoids bind to receptors in the endocannabinoid system which is involved in regulation of bone metabolism. Phytocannabinoids may improve bone health; however, additional work is required to determine factors such as the optimal dose, timing, and route of administration.”

https://pubmed.ncbi.nlm.nih.gov/42709344

“Due to their diverse pharmacological properties, phytocannabinoids may have therapeutic value for bone-related disorders.”

 https://link.springer.com/article/10.1007/s11914-026-00982-1

A chronic low dose of Δ9-tetrahydrocannabinol (3 mg / kg / 21 d) reorganizes the disturbed wound healing process and accelerates wound closure in old female mice

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A chronic low dose of Δ9-THC accelerated wound closure in old female mice and helped reorganize an age-disrupted healing process. The biggest improvement occurred during the inflammatory phase, when aged wounds normally heal more slowly and remain inflamed longer.

THC changed the timing and amount of immune-cell activity in the wound, reduced inflammatory cytokines, and significantly increased infiltration of mesenchymal stem cells (MSCs) involved in tissue repair. The treatment did not increase growth-factor release, suggesting the benefit came mainly from better coordination of inflammation and cell migration.

The researchers concluded that THC improved wound healing by restoring a more normal sequence of immune-cell infiltration and cytokine release. The findings suggest that stimulating the aging endocannabinoid system may help support skin regeneration and tissue repair in older organisms.

“Wound healing in old mice is characterized by disturbed tissue homeostasis, manifested by delayed immune cell infiltration and reduced growth factor secretion, leading to a delayed onset and prolonged duration of the inflammatory phase.

The endocannabinoid system (ECS) is an important regulator of tissue homeostasis and cell migration and is also considered to be subject to aging processes, which may contribute to observable aging phenomena. Therefore, stimulating the aged ECS could represent a therapeutic option to support tissue regeneration in aging.

Female old mice received a low-dose of medical THC daily for 3 weeks, before four excisional full skin wounds were created. At day 1, 3 and 7 post-surgery, the wound closure rate was analyzed and wound samples were examined immunohistochemically for the numbers of granulocytes, M1-macrophages and mesenchymal stem cells (MSCs). The concentrations of inflammatory cytokines and regenerative growth factors were determined by ELISA.

Administration of THC improved the wound healing rate of old mice between day 1 and 7, which was associated with an altered timing and quantity of infiltrating immune cells and decreased levels of inflammatory cytokines in wound tissue on days 1 and 3 post-injury.

THC treatment significantly increased MSC infiltration but had no effect on the growth factor release.

The present study confirmed the anti-inflammatory activity of THC in vivo.

The THC-treatment improved wound healing in old mice by coordinating the temporal sequence of immune cell infiltration and cytokine release. Thus, restoration of ECS signaling could be an effective strategy to support age-related skin regeneration.”

https://pubmed.ncbi.nlm.nih.gov/40653209/

“A chronic low dose of THC accelerates the wound closure rate during the inflammatory phase in old mice.”

https://www.sciencedirect.com/science/article/pii/S0531556525001615?via%3Dihub

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∆9-Tetrahydrocannabinol Increases Growth Factor Release by Cultured Adipose Stem Cells and Adipose Tissue in vivo

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Δ9-THC increased the release of growth factors from cultured adipose-derived stem cells and from adipose tissue in vivo. These growth factors are involved in processes such as cell survival, tissue repair, blood-vessel formation, and regeneration.

The researchers found that THC changed the secretory activity of adipose stem cells rather than simply affecting their growth. This suggests that THC may influence how these cells communicate with surrounding tissue and support repair through the factors they release.

The findings point to a potential role for THC in regenerative signaling and tissue-healing biology, particularly through adipose-derived stem cells and the local tissue environment. The study adds another dimension to cannabinoid research by showing that THC can affect not just mature cells, but also the reparative signals produced by stem-cell populations.

“Background: Because of its biocompatibility and its soft and dynamic nature, the grafting of adipose tissue is regarded an ideal technique for soft-tissue repair. The adipose stem cells (ASCs) contribute significantly to the regenerative potential of adipose tissue, because they can differentiate into adipocytes and release growth factors for tissue repair and neovascularization to facilitate tissue survival. The present study tested the effect of administering a chronic low dose of ∆9-tetrahydrocannabinol (THC) on these regenerative properties, in vitro and in vivo.

Methods: Human ASCs were exposed to increasing concentrations of THC. Resazurin conversion was applied to investigate the effect on metabolic activity, cell number was assessed by crystal violet staining, tri-linear differentiation was evaluated by specific colorimetric approaches, and the release of growth factors was analyzed by ELISA. Two groups of mice were treated daily either with a low dose of THC (3 mg/kg) or a vehicle solution. After 3 weeks, adipose tissue was obtained from excised fat deposits, homogenized and tested for growth factor contents.

Results: THC decreased ASC proliferation but increased metabolic activity as well as adipogenic and chondrogenic differentiation. A low concentration of THC (1 µM) enhanced the growth factor release by ASCs. The concentration of these cytokines was also increased in adipose tissue of mice treated with THC.

Conlusion: Our results indicate that chronic activation of the endocannabinoid system promoted differentiation and growth factor release of ASCs, which could be of specific value for enhancing the regenerative potential of adipose tissue.”

https://pubmed.ncbi.nlm.nih.gov/39825991/

“Our findings may offer a new approach for improved application of adipose tissue in regenerative medicine.”

https://link.springer.com/article/10.1007/s13770-024-00692-8

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Δ 9 -Tetrahydrocannabinol alleviates hyperalgesia in a humanized mouse model of sickle cell disease

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Δ9-THC reduced pain hypersensitivity in a humanized mouse model of sickle cell disease. In mice expressing more than 99% human sickle hemoglobin, acute THC treatment dose-dependently reduced both mechanical and cold hypersensitivity and also produced substantial antinociceptive effects in a tail-flick pain test.

At 1 mg/kg, THC reduced pain sensitivity without altering anxiety-like behavior or long-term memory. With repeated treatment, THC continued to provide sustained relief from mechanical hypersensitivity, although tolerance developed to its effects on cold hypersensitivity.

The researchers concluded that THC may represent a potential option for managing chronic pain associated with sickle cell disease. These findings are especially notable because sickle cell pain is often severe and difficult to control, while current treatment frequently depends on opioid analgesics.

“People with sickle cell disease (SCD) often experience chronic pain as well as unpredictable episodes of acute pain, which significantly affect their quality of life and life expectancy. Current treatment strategies for SCD-associated pain primarily rely on opioid analgesics, which have limited efficacy and cause serious adverse effects.

Cannabis has emerged as a potential alternative, yet its efficacy remains uncertain. In this study, we investigated the antinociceptive effects of Δ9-tetrahydrocannabinol (THC), cannabis’ intoxicating constituent, in male HbSS mice, which express >99% human sickle hemoglobin, and male HbAA mice, which express normal human hemoglobin A, as a control.

Acute THC administration (0.1-3 mg-kg-1, intraperitoneal, i.p.) dose-dependently reduced mechanical and cold hypersensitivity in HbSS, but not HbAA mice. In the tail-flick assay, THC (1 and 3 mg-kg-1, i.p.) produced substantial antinociceptive effects in HbSS mice. By contrast, THC (1 mg-kg-1, i.p.) did not alter anxiety-like behavior (elevated plus maze) or long-term memory (24-h novel object recognition). Subchronic THC treatment (1 and 3 mg-kg-1, i.p.) provided sustained relief of mechanical hypersensitivity but led to tolerance in cold hypersensitivity in HbSS mice.

Together, the findings identify THC as a possible therapeutic option for the management of chronic pain in SCD. Further research is warranted to elucidate its mechanism of action and possible interaction with other cannabis constituents. 

Significance Statement The study explores THC’s efficacy in alleviating pain in sickle cell disease (SCD) using a humanized mouse model. Findings indicate that acute THC administration reduces mechanical and cold hypersensitivity in SCD mice without impacting emotional and cognitive dysfunction. Subchronic THC treatment offers sustained relief of mechanical hypersensitivity but leads to cold hypersensitivity tolerance. These results offer insights into THC’s potential as an alternative pain management option in SCD, highlighting both its benefits and limitations.”

https://pubmed.ncbi.nlm.nih.gov/38955494/

“The results indicate that acute THC administration alleviates mechanical and cold hypersensitivity in HbSS mice in a dose-dependent manner without affecting emotional and cognitive dysfunction also present in these mice.”

https://www.sciencedirect.com/science/article/abs/pii/S0022356524178147

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The Use of Tetrahydrocannabinol Is Associated with an Increase in Survival Time in Palliative Cancer Patients: A Retrospective Multicenter Cohort Study

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A large retrospective multicenter study of 9,419 palliative cancer patients found that THC use was associated with longer survival. The researchers reported the strongest association among patients receiving more than 4.7 mg of THC per day.

In patients who survived between 7 and 100 days, median survival was 40 days in the THC group compared with 25 days in patients who did not receive THC. The study also examined THC alongside palliative-care treatment rather than as a replacement for standard care.

These findings add an important human-data signal to the growing research on cannabinoids in cancer care. While the study was observational, the association between THC use and longer survival makes this a significant finding for palliative oncology and cannabinoid research.

“Introduction: Tetrahydrocannabinol (THC) is often prescribed for ambulatory palliative patients to improve sleep quality and appetite and to reduce anxiety, stress, and pain. However, it is not known if THC has also an effect on the mortality of these patients.

Method: The objective was the impact of THC on mortality of ambulatory palliative patients. For this purpose, data from the palliative treatment documentation from 5 ambulatory palliative care teams in Brandenburg, Germany were used for this analysis. Survival time was calculated for 3 groups of patients: (1) without THC; (2) with THC in a low dosage (≤4.7 mg per day); and (3) THC in higher doses (≥4.7 mg per day). The analysis was done for 2 cohorts of patients. Cohort 1: all patients with a survival time of at least 7 days after inclusion in specialized ambulatory palliative care (SAPC) and cohort 2: a subgroup of patients with a survival time between 7 and 100 days. Kaplan-Meier curves were created, and multivariate analysis was done to investigate the impact of THC on mortality.

Results: A total of 9,419 patients with a survival time of at least 7 days after inclusion in SAPC were included in the analysis (cohort 1). 7,085 among them had a survival time between 7 and 100 days (cohort 2). In both cohorts, survival time was significantly prolonged by THC, but only when the daily THC dose was above the median of 4.7 mg. Survival time was 15 days longer in cohort 2 (40 vs. 25 days), when more than 4.7 mg THC were prescribed per day.

Conclusion: Use of THC is associated with a significant increase in survival time in ambulatory palliative patients which survive longer than 7 days the initiation of THC prescription and which use of THC >4.7 mg/day.”

https://pubmed.ncbi.nlm.nih.gov/38655402/

“Thus, in view of its significant prolongation of patient survival time, THC therapy should be included as part of the first-line therapy for ambulatory palliative patients.”

https://karger.com/mca/article/7/1/59/896816/The-Use-of-Tetrahydrocannabinol-Is-Associated-with

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Impacts of delta 9-tetrahydrocannabinol against myocardial ischemia/reperfusion injury in diabetic rats: Role of PTEN/PI3K/Akt signaling pathway

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In diabetic rats with myocardial ischemia/reperfusion injury, Δ9-THC significantly reduced heart damage and improved cardiac function. THC pretreatment decreased infarct size as well as blood markers of heart injury, including LDH and cardiac troponin-I.

THC also reduced myocardial apoptosis and oxidative stress, two major contributors to tissue damage when blood flow returns to the heart after a period of ischemia. These protective effects were accompanied by reduced PTEN expression and activation of the PI3K/Akt signaling pathway, which is involved in cell survival.

When researchers blocked PI3K signaling, THC’s cardioprotective effect disappeared, strengthening the evidence that this pathway played an important role in the response. The findings show that THC protected the diabetic rat heart against ischemia/reperfusion injury through multiple measurable effects on cardiac damage, oxidative stress, cell death, and survival signaling.

“Despite the current optimal therapy, patients with myocardial ischemia/reperfusion (IR) injury still experience a high mortality rate, especially when diabetes mellitus is present as a comorbidity. Investigating potential treatments aimed at improving the outcomes of myocardial IR injury in diabetic patients is necessary.

Our objective was to ascertain the cardioprotective effect of delta 9-tetrahydrocannabinol (THC) against myocardial IR injury in diabetic rats and examine the role of phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in mediating this effect.

Diabetes was induced in male Wistar rats (8-10 weeks old, 200-250 g; n = 60) by a single injection of streptozotocin. The duration of the diabetic period was 10 weeks. During the last 4 weeks of diabetic period, rats were treated with THC (1.5 mg/kg/day; intraperitoneally), either alone or in combination with LY294002, and then underwent IR intervention. After 24 h of reperfusion, infarct size, cardiac function, lactate dehydrogenase (LDH) and cardiac-specific isoform of troponin-I (cTn-I) levels, myocardial apoptosis, oxidative stress markers, and expression of PTEN, PI3K, and Akt proteins were evaluated.

THC pretreatment resulted in significant improvements in infarct size and cardiac function and decreases in LDH and cTn-I levels (P < 0.05). It also reduced myocardial apoptosis and oxidative stress, accompanied by the downregulation of PTEN expression and activation of the PI3K/Akt signaling pathway (P < 0.05). LY294002 pretreatment abolished the cardioprotective action of THC.

This study revealed the cardioprotective effects of THC against IR-induced myocardial injury in diabetic rats and also suggested that the mechanism may be associated with enhanced activity of the PI3K/Akt signaling pathway through the reduction of PTEN phosphorylation.”

https://pubmed.ncbi.nlm.nih.gov/38149557/

“Delta 9-tetrahydrocannabinol (THC) is the main psychoactive component of cannabis and has been shown to have potential therapeutic effects in various medical conditions. THC has been shown to have anti-inflammatory and antioxidant properties, which may reduce the inflammation and oxidative stress associated with myocardial IR injury. Recent studies have suggested that THC improves glucose metabolism and insulin sensitivity and reduces blood glucose concentrations, oxidative stress, and inflammation associated with diabetic cardiomyopathy.”

https://www.cjphysiology.org/article.asp?issn=0304-4920;year=2023;volume=66;issue=6;spage=446;epage=455;aulast=Zhao

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An Ultra-Low Dose of ∆9-Tetrahydrocannabinol Alleviates Alzheimer’s Disease-Related Cognitive Impairments and Modulates TrkB Receptor Expression in a 5XFAD Mouse Model

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An ultra-low dose of Δ9-THC improved Alzheimer’s disease-related cognitive impairment in 5xFAD mice, including animals treated after memory problems were already established. The study found improvements in learning and memory without relying on repeated high-dose THC exposure.

The researchers also found changes in TrkB receptor expression, a signaling pathway closely tied to brain plasticity, learning, memory, and neuronal survival. These changes suggest that THC’s effects may involve more than temporary symptom relief and may influence mechanisms connected to cognitive function.

The findings add to a growing body of preclinical research showing that very low doses of THC can produce different biological effects than higher doses, particularly in the aging and Alzheimer’s-disease brain. In this model, a single ultra-low dose was enough to improve cognitive performance and alter a key neurotrophic signaling pathway.

“Alzheimer’s disease (AD) is the most common form of dementia, but there is still no available treatment.

Δ9-tetrahydrocannabinol (THC) is emerging as a promising therapeutic agent.

Using THC in conventional high doses may have deleterious effects. Therefore, we propose to use an ultra-low dose of THC (ULD-THC). We previously published that a single injection of ULD-THC ameliorated cognitive functioning in several models of brain injuries as well as in naturally aging mice.

Here, 5xFAD AD model mice received a single treatment of ULD-THC (0.002 mg/kg) after disease onset and were examined in two separate experiments for cognitive functions, neurotropic, and inflammatory factors in the hippocampus.

We show that a single injection of ULD-THC alleviated cognitive impairments in 6- and 12-month-old 5xFAD mice. On the biochemical level, our results indicate an imbalance between the truncated TrkB receptor isoform and the full receptor, with AD mice showing a greater tendency to express the truncated receptor, and ULD-THC improved this imbalance. We also investigated the expression of three AD-related inflammatory markers and found an ameliorating effect of ULD-THC.

The current research demonstrates for the first time the beneficial effects of a single ultra-low dose of THC in a mouse model of AD after disease onset.”

https://pubmed.ncbi.nlm.nih.gov/36012711/

“The current research demonstrates for the first time the beneficial effects of a single ultra-low dose of THC in a mouse model of AD after disease onset. As THC is a cheap, widely available substance already approved for use in other conditions, this research brings us closer to understanding its mechanisms and will possibly lead to new treatments.”

https://www.mdpi.com/1422-0067/23/16/9449/htm

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