Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Cannabis Use and Incident Atrial Fibrillation in a Longitudinal Cohort

Posted on by
Reply
pubmed logo

“Background: Cannabis use is increasing worldwide. While prior studies have reported an association between cannabis use and a higher risk of atrial fibrillation (AF), most were cross-sectional and generally relied on diagnostic coding to identify cannabis users, which may not be representative of the typical, recreational cannabis user.

Objective: To examine the association between recreational cannabis use and lifetime AF risk.

Methods: We evaluated the AF risk of participants of the UK Biobank cohort who completed the cannabis use lifestyle questionnaire. Cannabis exposure was categorized as “Occasional Use” for less than 100 times used, “Frequent Use” for more than 100 times used, and “Never” users. AF events were identified using International Classification of Diseases (ICD) codes. Cox models were used to estimate the hazard ratios (HR) between cannabis use and incident AF and were subsequently adjusted for age, sex, race, alcohol, coffee, smoking, education, and baseline cardiovascular comorbidities.

Results: A total of 150,554 participants (mean 63.4 ± 7.7 years, 57.4% female, and 22.2% using cannabis at least once) were followed for a mean 6.1 ± 0.6 years. After multivariable adjustment, there were no statistically significant differences in incident AF among occasional users (HR 0.98, 95% CI 0.89 to 1.08) nor frequent users (HR 1.03, 95% CI 0.81 to 1.32) compared to never users.

Conclusions: Among a large, prospective cohort, there was no evidence that cannabis use was associated with a higher risk of incident AF. An evaluation of cannabis ingestion methods and quantification was not possible using the current dataset.”

https://pubmed.ncbi.nlm.nih.gov/38142832/

https://www.heartrhythmjournal.com/article/S1547-5271(23)03058-8/fulltext

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

Posted on by
Reply
pubmed logo

“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

Targeting Nrf2 Signaling Pathway in Cancer Prevention and Treatment: The Role of Cannabis Compounds

Posted on by
Reply
pubmed logo

“The development and progression of cancer are associated with the dysregulation of multiple pathways involved in cell proliferation and survival, as well as dysfunction in redox balance, immune response, and inflammation. The master antioxidant pathway, known as the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, regulates the cellular defense against oxidative stress and inflammation, making it a promising cancer prevention and treatment target.

Cannabinoids have demonstrated anti-tumor and anti-inflammatory properties, affecting signaling pathways, including Nrf2.

Increased oxidative stress following exposure to anti-cancer therapy prompts cancer cells to activate antioxidant mechanisms. This indicates the dual effect of Nrf2 in cancer cells-influencing proliferation and apoptotic processes and protecting against the toxicity of anti-cancer therapy. Therefore, understanding the complex role of cannabinoids in modulating Nrf2 might shed light on its potential implementation as an anti-cancer support.

In this review, we aim to highlight the impact of cannabinoids on Nrf2-related factors, with a focus on cancer prevention and treatment. Additionally, we have presented the results of several research studies that combined cannabidiol (CBD) with other compounds targeting Nrf2. Further studies should be directed toward exploring the anti-inflammatory effects of cannabinoids in the context of cancer prevention and therapy.”

https://pubmed.ncbi.nlm.nih.gov/38136172/

https://www.mdpi.com/2076-3921/12/12/2052

The Basic Science of Cannabinoids

Posted on by
Reply
pubmed logo

“The cannabis plant has been used for centuries to manage the symptoms of various ailments including pain.

Hundreds of chemical compounds have been identified and isolated from the plant and elicit a variety of physiological responses by binding to specific receptors and interacting with numerous other proteins.

In addition, the body makes its own cannabinoid-like compounds that are integrally involved in modulating normal and pathophysiological processes.

As the legal cannabis landscape continues to evolve within the United States and throughout the world, it is important to understand the rich science behind the effects of the plant and the implications for providers and patients.

This narrative review aims to provide an overview of the basic science of the cannabinoids by describing the discovery and function of the endocannabinoid system, pharmacology of cannabinoids, and areas for future research and therapeutic development as they relate to perioperative and chronic pain medicine.”

https://pubmed.ncbi.nlm.nih.gov/38100799/

https://journals.lww.com/anesthesia-analgesia/fulltext/2024/01000/the_basic_science_of_cannabinoids.6.aspx

Impact of Low-Dose Dronabinol Therapy on Cognitive Function in Cancer Patients Receiving Palliative Care: A Case-Series Intervention Study

Posted on by
Reply
pubmed logo

“Background: Cannabis may offer therapeutic benefits to patients with advanced cancer not responding adequately to conventional palliative treatment. However, tolerability is a major concern. Cognitive function is a potential adverse reaction to tetrahydrocannabinol containing regimens. The aim of this study was to test cognitive function in patients being prescribed dronabinol as an adjuvant palliative therapy.

Methods: Adult patients with advanced cancer and severe related pain refractory to conventional palliative treatment were included in this case-series study. Patients were examined at baseline in conjunction with initiation of dronabinol therapy and at a two-week follow-up using three selected Wechsler’s adult intelligence scale III neurocognitive tests: Processing Speed Index (PSI), Perceptual Organization Index (POI), and Working Memory Index (WMI). Patients were also assessed using pain visual analog scale, Major Depression Inventory, and Brief Fatigue Inventory.

Results: Eight patients consented to take part in the study. Two patients discontinued dronabinol therapy, one due to a complaint of dizziness and another critical progression of cancer disease, respectively. The remaining six patients were successfully treated with a daily dosage of 12.5 mg dronabinol (p = 0.039). PSI (p = 0.020), POI (p = 0.034.), and WMI (p = 0.039).

Conclusions: Cognitive function improved in this group of patients with advanced cancer in conjunction with low-dose dronabinol therapy. The cause is likely multifactorial including reported relief of cancer-associated symptoms. Further clinical investigation is required.”

https://pubmed.ncbi.nlm.nih.gov/38098857/

https://www.liebertpub.com/doi/10.1089/pmr.2023.0024

Phytocannabinoids for the Treatment of Neuropathic Pain: A Scoping Review of Randomised Controlled Trials Published Between 2012 and 2023

Posted on by
Reply
pubmed logo

“Purpose of review: Neuropathic pain (NP) remains a challenge to treat, with 50% of patients experiencing limited efficacy from current treatments. Medicinal cannabis, which contains tetrahydrocannabinol (THC), cannabidiol (CBD) and other minor cannabinoids, is garnering attention as an alternative treatment for NP. This paper reviews the clinical evidence for phytocannabinoid treatment of NP.

Recent findings: Seventeen randomised controlled trials (RCT) were identified for inclusion in this review. Of these, ten studies using phytocannabinoid preparations containing THC alone had the most evidence for pain relief. Four studies investigating THC/CBD combinations showed some reductions in pain scores, although not all findings were statistically significant, whereas studies investigating CBD (two studies) or cannabidivarin (one study) showed no analgesic effect over placebo. However, CBD studies were of small sample size when compared to other studies in the review and short duration. Results for treatment of diabetic peripheral neuropathy patients with THC showed better improvements over those for NP induced by chemotherapy and multiple sclerosis, with these trials using vaporised whole plant cannabis. This formulation may have trace amounts of other minor cannabinoids, compared with synthetic cannabinoids such as dronabinol or nabilone that were investigated in other studies. This review provides an overview of RCTs that have investigated phytocannabinoid use for the treatment of NP. There appears to be evidence to necessitate further high quality RCTs into novel formulations of phytocannabinoids for the treatment of NP.”

https://pubmed.ncbi.nlm.nih.gov/38095748/

https://link.springer.com/article/10.1007/s11916-023-01196-1

Medical Cannabis: A Review from the American Society of Pain and Neuroscience

Posted on by
Reply
pubmed logo

“Cannabinoids have recently gained a renewed interest due to their potential applicability to various medical conditions, specifically the management of chronic pain conditions.

Unlike many other medications, medical cannabis is not associated with serious adverse events, and no overdose deaths have been reported.

However, both safety and efficacy data for medical cannabis treatment of chronic, nonmalignant pain conditions are lacking. Therefore, representatives from the American Society of Pain and Neuroscience summarize the evidence, according to level and grade, for medical cannabis treatment of several different pain conditions. Treatment of cancer-related pain has prospective evidentiary support for the use of medical cannabis. Although 3 large and well-designed randomized controlled trials investigated cannabis treatment of cancer-related pain, the evidence yielded only a grade D recommendation. Neuropathic pain has been investigated in prospective studies, but a lack of high-quality evidence renders cannabis treatment for this indication a grade C recommendation. Both safety and efficacy data are lacking for use of medical cannabis to treat chronic nonmalignant pain conditions.”

https://pubmed.ncbi.nlm.nih.gov/38094100/

https://www.dovepress.com/medical-cannabis-a-review-from-the-american-society-of-pain-and-neuros-peer-reviewed-fulltext-article-JPR

Cannabis use and atherosclerotic cardiovascular disease: a Mendelian randomization study

Posted on by
Reply
pubmed logo

“Background: Association between cannabis use and development of atherosclerotic cardiovascular disease (ASCVD) is inconsistent and challenging to interpret, given existing study limitations.

Methods: Sixty five independent single-nucleotide polymorphisms (SNPs), obtained from a genome-wide association study on lifetime cannabis use, were employed as genetic instruments to estimate the effects of genetically indexed cannabis use on risk of coronary artery disease (CAD) and acute ischemic stroke (IS) using a two-sample Mendelian randomization (MR) approach. Summary statistics on CAD (CARDIoGRAMplusC4D; 60,801 cases and 123,504 controls) and IS (MEGASTROKE; 34,217 cases and 406,111 controls) were obtained separately. A comprehensive review of the observational literature on cannabis use and CAD or IS was also performed and contrasted with MR results.

Results: There was no causal effect of cannabis use on the risk of CAD (odds ratio (OR) per ever-users vs. never-users 0.93; 95% confidence interval (CI), 0.83 to 1.03) or IS (OR 1.05; 95%CI, 0.93 to 1.19). Sensitivity analyses yielded similar results, and no heterogeneity and directional pleiotropy was observed. Our meta-analysis of observational studies showed no significant association between ever use of cannabis with risk of CAD (k = 6 studies; ORpooled = 1.23, 95%CI 0.78 to 1.69), nor with IS (k = 6 studies; ORpooled = 1.22, 95%CI 0.95 to 1.50).

Conclusion: Using a genetic approach approximating a clinical trial does not provide evidence consistent with a causal effect of genetic predisposition to cannabis use on CAD or IS development. Further studies are needed to replicate our findinds, an to investigate more precisely the risk of ASCVD in relation to the quantity, type, route of administration, or the age at exposure to cannabis.”

https://pubmed.ncbi.nlm.nih.gov/38093188/

https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-023-03641-w

Cannabis as a Source of Approved Drugs: A New Look at an Old Problem

Posted on by
Reply
pubmed logo

“Cannabis plants have been used in medicine since ancient times. They are well known for their anti-diabetic, anti-inflammatory, neuroprotective, anti-cancer, anti-oxidative, anti-microbial, anti-viral, and anti-fungal activities. A growing body of evidence indicates that targeting the endocannabinoid system and various other receptors with cannabinoid compounds holds great promise for addressing multiple medical conditions. There are two distinct avenues in the development of cannabinoid-based drugs. The first involves creating treatments directly based on the components of the cannabis plant. The second involves a singular molecule strategy, in which specific phytocannabinoids or newly discovered cannabinoids with therapeutic promise are pinpointed and synthesized for future pharmaceutical development and validation. Although the therapeutic potential of cannabis is enormous, few cannabis-related approved drugs exist, and this avenue warrants further investigation. With this in mind, we review here the medicinal properties of cannabis, its phytochemicals, approved drugs of natural and synthetic origin, pitfalls on the way to the widespread clinical use of cannabis, and additional applications of cannabis-related products.”

https://pubmed.ncbi.nlm.nih.gov/38067416/

https://www.mdpi.com/1420-3049/28/23/7686

THC improves behavioural schizophrenia-like deficits that CBD fails to overcome: a comprehensive multilevel approach using the Poly I:C maternal immune activation

Posted on by
Reply
pubmed logo

“Prenatal infections and cannabis use during adolescence are well-recognized risk factors for schizophrenia. As inflammation and oxidative stress (OS) contribute to this disorder, anti-inflammatory drugs have been proposed as potential therapies. This study aimed to evaluate the association between delta-9-tetrahydrocannabinol (THC) and schizophrenia-like abnormalities in a maternal immune activation (MIA) model. Additionally, we assessed the preventive effect of cannabidiol (CBD), a non-psychotropic/anti-inflammatory cannabinoid. THC and/or CBD were administered to Saline- and MIA-offspring during periadolescence. At adulthood, THC-exposed MIA-offspring showed significant improvements in sensorimotor gating deficits. Structural and metabolic brain changes were evaluated by magnetic resonance imaging, revealing cortical shrinkage in Saline- and enlargement in MIA-offspring after THC-exposure. Additionally, MIA-offspring displayed enlarged ventricles and decreased hippocampus, which were partially reverted by both cannabinoids. CBD prevented THC-induced reduction in the corpus callosum, despite affecting white matter structure. Post-mortem studies revealed detrimental effects of THC, including increased inflammation and oxidative stress. CBD partially reverted these pro-inflammatory alterations and modulated THC’s effects on the endocannabinoid system. In conclusion, contrary to expectations, THC exhibited greater behavioural and morphometric benefits, despite promoting a pro-inflammatory state that CBD partially reverted. Further research is needed to elucidate the underlying mechanisms involved in the observed benefits of THC.”

https://pubmed.ncbi.nlm.nih.gov/38064909/

https://www.sciencedirect.com/science/article/abs/pii/S0165178123005930?via%3Dihub