Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Cannabinoids as anti-ROS in Aged Pancreatic Islet Cells

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Life Sciences“Cannabinoids are the chemical compounds with a high affinity for cannabinoid receptors affecting the central nervous system through the release of neurotransmitters. However, the current knowledge related to the role of such compounds in the regulation of cellular aging is limited. This study aimed to investigate the effect of cannabidiol and tetrahydrocannabinol on the function of aged pancreatic islets.

Main methods: The expression of p53, p38, p21, p16, and Glut2 genes and β-galactosidase activity were measured as hallmarks of cell aging applying real-time PCR, ELISA, and immunocytochemistry techniques. Pdx1 protein expression, insulin release, and oxidative stress markers were compared between young and aged rat pancreatic islet cells.

Key findings: Upon the treatment of aged pancreatic islets cells with cannabidiol and tetrahydrocannabinol, the expression of p53, p38, p21 and the activity of β-galactosidase were reduced. Cannabidiol and tetrahydrocannabinol increase insulin release, Pdx1, Glut2, and thiol molecules expression, while the oxidative stress parameters were decreased. The enhanced expression of Pdx1 and insulin release in aged pancreatic islet cells reflects the extension of cell healthy aging due to the significant reduction of ROS.

Significance: This study provides evidence for the involvement of cannabidiol and tetrahydrocannabinol in the oxidation process of cellular aging.”

https://pubmed.ncbi.nlm.nih.gov/32553926/

https://www.sciencedirect.com/science/article/abs/pii/S0024320520307190?via%3Dihub

“Reactive oxygen species (ROS) are chemically reactive chemical species containing oxygen. ROS can damage lipid, DNA, RNA, and proteins, which, in theory, contributes to the physiology of aging.” https://en.wikipedia.org/wiki/Reactive_oxygen_species

A Cross-Sectional and Prospective Comparison of Medicinal Cannabis Users and Controls on Self-Reported Health

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View details for Cannabis and Cannabinoid Research cover image“Despite widespread legalization, the impact of medicinal cannabis use on patient-level health and quality of life (QOL) has not been carefully evaluated.

The objective of this study was to characterize self-reported demographics, health characteristics, QOL, and health care utilization of Cannabis Users compared with Controls.

Results: Cannabis Users self-reported significantly better QOL [t(1054)=−4.19, p<0.001], greater health satisfaction [t(1045)=−4.14, p<0.001], improved sleep [children: t(224)=2.90, p<0.01; adults: [t(758)=3.03, p<0.01], lower average pain severity [t(1150)=2.34, p<0.05], lower anxiety [t(1151)=4.38, p<0.001], and lower depression [t(1210)=5.77, p<0.001] compared with Controls. Cannabis Users reported using fewer prescription medications (rate ratio [RR]=0.86; 95% confidence interval [CI]: 0.77–0.96) and were less likely to have a past-month emergency department visit (RR=0.61; 95% CI: 0.44–0.84) or hospital admission (RR=0.54; 95% CI: 0.34–0.87). Controls who initiated cannabis use after baseline showed significant health improvements at follow-up, and the magnitude of improvement mirrored the between-group differences observed at baseline.

Conclusions: Cannabis use was associated with improved health and QOL. Longitudinal testing suggests that group differences may be due to the medicinal use of cannabis. Although bias related to preexisting beliefs regarding the health benefits of cannabis in this sample should be considered, these findings indicate that clinical trials evaluating the efficacy of defined cannabinoid products for specific health conditions are warranted.

The key finding of this study is that medicinal cannabis use was associated with more positive ratings of health and QOL, assessed across multiple domains. Prospective analyses found that Controls showed improvement in health and QOL if they initiated medicinal cannabis use, and that Cannabis Users showed diminished health and QOL if they stopped cannabis use.”

https://www.liebertpub.com/doi/full/10.1089/can.2019.0096

“The Health Benefits of Medical Marijuana As Reported by Users. Using cannabis for medical reasons has been linked in a study to outcomes including better sleep, less anxiety, and taking fewer prescription medications.” https://www.newsweek.com/health-benefits-medical-marijuana-users-1511647

Cannabinoid CP55940 Selectively Induces Apoptosis in Jurkat Cells and in Ex Vivo T-cell Acute Lymphoblastic Leukemia Through H 2 O 2 Signaling Mechanism

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 Leukemia Research‘T-cell acute lymphoblastic leukemia (T-ALL) is a highly heterogeneous malignant hematological disorder arising from T-cell progenitors.

This study was aimed to evaluate the cytotoxic effect of CP55940 on human peripheral blood lymphocytes (PBL) and on T-ALL cells (Jurkat).

In conclusion, CP55940 selectively induces apoptosis in Jurkat cells through a H2O2-mediated signaling pathway.

Our findings support the use of cannabinoids as a potential treatment for T-ALL cells.”

https://pubmed.ncbi.nlm.nih.gov/32540572/

https://www.sciencedirect.com/science/article/abs/pii/S0145212620300941?via%3Dihub

“CP 55,940 is a synthetic cannabinoid which mimics the effects of naturally occurring THC (one of the psychoactive compounds found in cannabis)”  https://en.wikipedia.org/wiki/CP_55,940

Association Between Cannabis Use and Healthcare Utilization in Patients With Irritable Bowel Syndrome: A Retrospective Cohort Study

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Cureus | LinkedIn“Irritable bowel syndrome (IBS) is a frequent cause of abdominal pain and altered bowel habits, which is associated with significant healthcare utilization.

The effects of the active compound of cannabis, Δ9-tetrahydrocannabinol (THC), on gut motility and tone have been studied in several experimental models. It is unknown whether these effects correlate with improved healthcare utilization among cannabis users.

The purpose of this study is to evaluate the impact of cannabis use on inpatient length of stay and resource utilization for patients with a primary discharge diagnosis of IBS.

Cannabis users were less likely to have the following: upper gastrointestinal endoscopy (17.9% vs. 26.1%; adjusted odds ratio [aOR]: 0.51 [0.36 to 0.73]; p<0.001) and lower gastrointestinal endoscopy (21.1% vs. 28.7%; aOR: 0.54 [0.39 to 0.75]; p<0.001). Additionally, cannabis users had shorter length of stay (2.8 days vs. 3.6 days; p=0.004) and less total charges (US$20,388 vs. US$23,624). There was no difference in the frequency of CT abdomen performed.

Cannabis use may decrease inpatient healthcare utilization in IBS patients. These effects could possibly be through the effect of cannabis on the endocannabinoid system.”

https://pubmed.ncbi.nlm.nih.gov/32528750/

“Our study provides evidence to suggest that cannabis use may decrease healthcare utilization and costs among hospitalized patients with IBS. These findings are likely attributable to the effects of cannabis’ active compound, THC, on gastrointestinal motility and colonic compliance. The role of cannabis in the treatment for IBS has potential for significant impact at the individual and population level given the burden of IBS on individual quality of life and healthcare expenditures.”

https://www.cureus.com/articles/30417-association-between-cannabis-use-and-healthcare-utilization-in-patients-with-irritable-bowel-syndrome-a-retrospective-cohort-study

Migraine Frequency Decrease Following Prolonged Medical Cannabis Treatment: A Cross-Sectional Study

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brainsci-logo“Medical cannabis (MC) treatment for migraine is practically emerging, although sufficient clinical data are not available for this indication. This cross-sectional questionnaire-based study aimed to investigate the associations between phytocannabinoid treatment and migraine frequency.

Compared to non-responders, responders (n = 89, 61%) reported lower current migraine disability and lower negative impact, and lower rates of opioid and triptan consumption. Subgroup analysis demonstrated that responders consumed higher doses of the phytocannabinoid ms_373_15c and lower doses of the phytocannabinoid ms_331_18d (3.40 95% CI (1.10 to 12.00); p < 0.01 and 0.22 95% CI (0.05-0.72); p < 0.05, respectively).

Conclusions: These findings indicate that MC results in long-term reduction of migraine frequency in >60% of treated patients and is associated with less disability and lower antimigraine medication intake. They also point to the MC composition, which may be potentially efficacious in migraine patients.”

https://pubmed.ncbi.nlm.nih.gov/32526965/

https://www.mdpi.com/2076-3425/10/6/360

Long-term Assessment of the Cognitive Effects of Nabiximols in Patients With Multiple Sclerosis: A Pilot Study

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Clinical Neurology and Neurosurgery “Moderate to severe spasticity is commonly reported in Multiple Sclerosis (MS) and its management is still a challenge. Cannabinoids were recently suggested as add-on therapy for the treatment of spasticity and chronic pain in MS but there is no conclusive scientific evidence on their safety, especially on cognition and over long periods.

The aim of this prospective pilot study was to assess the long-term effects of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray (Sativex®) on cognition, mood and anxiety.

Results: Twenty per protocol patients were followed up and evaluated at baseline, 6 and 12 months. Domains involving processing speed and auditory verbal memory significantly improved within the first 6 months of therapy (SDMT: p < 0.001; CVLT: p = 0.0001). Mood and anxiety did not show any significant variation. Additionally, the NRS score significantly improved since the beginning (p < 0.0001).

Conclusions: These results are encouraging in supporting possible long-term benefits of Sativex on cognition and a wider role than symptom alleviator. Further studies on larger groups of patients would be necessary in order to test this intriguing possibility.”

https://pubmed.ncbi.nlm.nih.gov/32526487/

“Under Nabiximols some cognitive domains improved after 12 months, and the therapy was safely tolerated.”

https://www.sciencedirect.com/science/article/abs/pii/S0303846720303334?via%3Dihub

Localisation of Cannabinoid and Cannabinoid-Related Receptors in the Equine Dorsal Root Ganglia

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Publication cover image“Growing evidence recognises cannabinoid receptors as potential therapeutic targets for pain. Consequently, there is increasing interest in developing cannabinoid receptor agonists for treating pain.

As a general rule, to better understand the actions of a drug, it would be of extreme importance to know the cellular distribution of its specific receptors. The localisation of cannabinoid receptors in the dorsal root ganglia of the horse has not yet been investigated.

Conclusions: This study highlighted the expression of cannabinoid receptors in the sensory neurons and glial cells of the dorsal root ganglia. These findings could be of particular relevance for future functional studies assessing the effects of cannabinoids in horses to manage pain.”

https://pubmed.ncbi.nlm.nih.gov/32524649/

https://beva.onlinelibrary.wiley.com/doi/abs/10.1111/evj.13305

Δ9‐TETRAHYDROCANNABINOLIC ACID ALLEVIATES COLLAGEN‐INDUCED ARTHRITIS: ROLE OF PPARγ AND CB1 RECEPTORS

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British Journal of Pharmacology “Δ9‐THCA‐A, the precursor of Δ9‐THC, is a non‐psychotropic phytocannabinoid that shows PPARγ agonistic activity. Herein, we investigated Δ9‐THCA ability to modulate classic cannabinoid receptors (CB1 and CB2) and evaluated its anti‐arthritis activity.

Experimental Approach

Cannabinoid receptors binding and intrinsic activity, as well as their downstream signaling were analyzed in vitro and in silico . The anti‐arthritis properties of Δ9‐THCA‐A were studied in human chondrocytes and in the murine model of collagen‐induced arthritis (CIA). Plasmatic disease biomarkers were identified by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) based on proteomic and ELISA assays.

Key Results

Functional and docking analyses showed that Δ9‐THCA‐A can act as an orthosteric CB1 agonist and also as a positive allosteric modulator in the presence of CP‐55,940. In addition, Δ9‐THCA‐A seemed to be an inverse agonist for CB2. In vivo experiments showed that Δ9‐THCA‐A reduced arthritis in CIA mice. Δ9‐THCA‐A prevented the infiltration of inflammatory cells; synovium hyperplasia and cartilage damage. Furthermore, Δ9‐THCA‐A inhibited the expression of inflammatory and catabolic genes on knee joints. The anti‐arthritic effect of Δ9‐THCA‐A was ablated by either SR141716 or T0070907. Analysis of plasmatic biomarkers as well as determination of cytokines and anti‐collagen antibodies confirmed that Δ9‐THCA‐A mediates its activity mainly through PPARγ and CB1 pathways.

Conclusion and Implications

Δ9‐THCA‐A modulates CB1 receptor through the orthosteric and allosteric binding sites. In addition, our studies document that Δ9‐THCA‐A exerts anti‐arthritis activity through CB1/PPARγ pathways, highlighting its potential for the treatment of chronic inflammatory diseases such as Rheumatoid Arthritis (RA).”

https://pubmed.ncbi.nlm.nih.gov/32510591/

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.15155

 British Pharmacological Society | Journals

Conversion of Cannabidiol (CBD) Into Psychotropic Cannabinoids Including Tetrahydrocannabinol (THC): A Controversy in the Scientific Literature

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PubMed Overview “Cannabidiol (CBD) is a naturally occurring, non-psychotropic cannabinoid of the hemp plant Cannabis sativa L. and has been known to induce several physiological and pharmacological effects. While CBD is approved as a medicinal product subject to prescription, it is also widely sold over the counter (OTC) in the form of food supplements, cosmetics and electronic cigarette liquids. However, regulatory difficulties arise from its origin being a narcotic plant or its status as an unapproved novel food ingredient.

Regarding the consumer safety of these OTC products, the question whether or not CBD might be degraded into psychotropic cannabinoids, most prominently tetrahydrocannabinol (THC), under in vivo conditions initiated an ongoing scientific debate. This feature review aims to summarize the current knowledge of CBD degradation processes, specifically the results of in vitro and in vivo studies. Additionally, the literature on psychotropic effects of cannabinoids was carefully studied with a focus on the degradants and metabolites of CBD, but data were found to be sparse.

While the literature is contradictory, most studies suggest that CBD is not converted to psychotropic THC under in vivo conditions. Nevertheless, it is certain that CBD degrades to psychotropic products in acidic environments. Hence, the storage stability of commercial formulations requires more attention in the future.”

https://pubmed.ncbi.nlm.nih.gov/32503116/

 

Cannabinoid as Beneficial Replacement Therapy for Psychotropics to Treat Neuropsychiatric Symptoms in Severe Alzheimer’s Dementia: A Clinical Case Report

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CrossFit | 190629“Alzheimer’s Dementia (AD) is a devastating neurodegenerative disease that affects approximately 17% of people aged 75-84. Neuropsychiatric symptoms (NPS) such as delusions, agitation, anxiety, and hallucinations are present in up to 95% of patients in all stages of dementia. To date, any approved and effective pharmacological interventions for the treatment of NPS are still not available.

We describe a clinical case of a female patient diagnosed with AD with continuous cognitive decline and dementia-related behavioral symptoms. Between 2008 and 2019, the patient was examined half-yearly at the memory clinic of the Medical University of Innsbruck. At each visit, cognitive state and pharmacological treatment were evaluated. In addition, NPs were assessed by using the neuropsychiatric inventory (NPI). In 2018, the patient progressed to severe AD stage and presented with progressive NPs (anxiety, suspected delusions, agitation, aggressive behavior, and suspected pain due to long immobility).

Consequently, off-label treatment with low-dose dronabinol was initiated, which facilitated a reduction of psychopharmacological treatment from six to three psychotropics. At the same time, the patient’s emotional state improved, while disruptive behavior, aggression, and sedation decreased significantly. This case report underpins the need for randomized, controlled trials to explore the effect of cannabinoid receptor agonists on behavioral and psychological symptoms in patients with severe AD.”

https://pubmed.ncbi.nlm.nih.gov/32477187/

“Cannabinoids have a distinct pharmacologic profile that may offer an alternative pharmacologic approach to antipsychotics and sedatives for treating NPs in patients with AD. In addition, the beneficial effect on appetite and pain may significantly improve quality of life of AD-patients and their caregivers.”

https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00413/full