Tag Archives: THC

The Effects of Cannabis Use on Cognitive Function in Healthy Aging: A Systematic Scoping Review

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Archives of Clinical Neuropsychology“Background: Older adults (≥50 years) represent the fastest-growing population of people who use cannabis, potentially due to the increasing promotion of cannabis as medicine by dispensaries and cannabis websites. Given healthy aging and cannabis use are both associated with cognitive decline, it is important to establish the effects of cannabis on cognition in healthy aging.

Objective: This systematic scoping review used preferred reporting items for systematic reviews and meta-analyses guidelines to critically examine the extent of literature on this topic and highlight areas for future research.

Results: Six articles reported findings for older populations (three human and three rodent studies), highlighting the paucity of research in this area. Human studies revealed largely null results, likely due to several methodological limitations. Better-controlled rodent studies indicate that the relationship between ∆9-tetrahydrocannabinol (THC) and cognitive function in healthy aging depends on age and level of THC exposure. Extremely low doses of THC improved cognition in very old rodents. Somewhat higher chronic doses improved cognition in moderately aged rodents. No studies examined the effects of cannabidiol (CBD) or high-CBD cannabis on cognition.

Conclusions: This systematic scoping review provides crucial, timely direction for future research on this emerging issue. Future research that combines neuroimaging and cognitive assessment would serve to advance understanding of the effects of age and quantity of THC and CBD on cognition in healthy aging.”

https://pubmed.ncbi.nlm.nih.gov/33159510/

“THC; the main psychoactive cannabis compound; exerted pro-cognitive effects on memory and learning in older populations.”

https://academic.oup.com/acn/advance-article/doi/10.1093/arclin/acaa105/5960018

Cannabinoids Inhibited Pancreatic Cancer via P-21 Activated Kinase 1 Mediated Pathway

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ijms-logo“The anti-cancer effects of cannabinoids including CBD (Cannabidiol) and THC ((-)-trans-∆9-tetrahydrocannabinol) have been reported in the case of pancreatic cancer (PC).

The connection of these cannabinoids to KRas oncogenes that mutate in more than 90% of PC, and their effects on PD-L1, a key target of immune checkpoint blockade, have not been thoroughly investigated. Using cell lines and mouse models of PC, the effects of CBD and THC on cancer growth, the interaction between PC cells and a stromal cell, namely pancreatic stellate cells (PSCs), and the mechanism(s) involved were determined by cell-based assays and mouse study in vivo.

CBD and THC inhibited the proliferation of PC, PSC, and PSC-stimulated PC cells. They also suppressed pancreatic tumour growth in mice. Furthermore, CBD and/or THC reduced the expression of PD-L1 by either PC or PSC cells. Knockout of p-21 activated kinase 1 (PAK1, activated by KRas) in PC and PSC cells and, in mice, dramatically decreased or blocked these inhibitory effects of CBD and/or THC.

These results indicated that CBD and THC exerted their inhibitions on PC and PSC via a p-21 activated kinase 1 (PAK1)-dependent pathway, suggesting that CBD and THC suppress Kras activated pathway by targeting PAK1. The inhibition by CBD and THC of PD-L1 expression will enhance the immune checkpoint blockade of PC.”

https://pubmed.ncbi.nlm.nih.gov/33126623/

https://www.mdpi.com/1422-0067/21/21/8035

Ingestion of a THC-Rich Cannabis Oil in People with Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

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Issue Cover “Objective: To determine the benefit of a tetrahydrocannabinol (THC)-rich cannabis oil on symptoms and quality of life of fibromyalgia patients.

Conclusions: Phytocannabinoids can be a low-cost and well-tolerated therapy to reduce symptoms and increase the quality of life of patients with fibromyalgia. Future studies are still needed to assess long-term benefits, and studies with different varieties of cannabinoids associated with a washout period must be done to enhance our knowledge of cannabis action in this health condition.”

https://pubmed.ncbi.nlm.nih.gov/33118602/

“To our knowledge, this is the first randomized controlled trial to demonstrate the benefit of cannabis oil—a THC-rich whole plant extract—on symptoms and on quality of life of people with fibromyalgia. We conclude that phytocannabinoids can be a low-cost and well-tolerated therapy for symptom relief and quality of life improvement in these patients, and we suggest that this therapy could be included as an herbal medicine option for the treatment of this condition”

https://academic.oup.com/painmedicine/article/21/10/2212/5942556

A Critical Review of the Role of the Cannabinoid Compounds Δ 9-Tetrahydrocannabinol (Δ 9-THC) and Cannabidiol (CBD) and their Combination in Multiple Sclerosis Treatment

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molecules-logo“Many people with MS (pwMS) use unregulated cannabis or cannabis products to treat the symptoms associated with the disease. In line with this, Sativex, a synthetic combination of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) has been approved to treat symptoms of spasticity.

In animals, CBD is effective in reducing the amounts of T-cell infiltrates in the spinal cord, suggesting CBD has anti-inflammatory properties. By doing this, CBD has shown to delay symptom onset in animal models of multiple sclerosis and slow disease progression. Importantly, combinations of CBD and Δ9-THC appear more effective in treating animal models of multiple sclerosis.

While CBD reduces the amounts of cell infiltrates in the spinal cord, Δ9-THC reduces scores of spasticity. In human studies, the results are less encouraging and conflict with the findings in animals. Drugs which deliver a combination of Δ9-THC and CBD in a 1:1 ratio appear to be only moderately effective in reducing spasticity scores, but appear to be almost as effective as current front-line treatments and cause less severe side effects than other treatments, such as baclofen (a GABA-B receptor agonist) and tizanidine (an α2 adrenergic receptor agonist).

The findings of the studies reviewed suggest that cannabinoids may help treat neuropathic pain in pwMS as an add-on therapy to already established pain treatments.

Long term double-blind placebo studies are greatly needed to further our understanding of the role of cannabinoids in multiple sclerosis treatment.”

https://pubmed.ncbi.nlm.nih.gov/33113776/

https://www.mdpi.com/1420-3049/25/21/4930

Update on cannabis and cannabinoids for cancer pain

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Current Issue Cover Image “The prevalence of cancer pain will continue to rise as pain is common among the survivorship and general cancer population. As interest in cannabis and cannabinoids for medicinal use including pain management continues to rise, there is growing need to update and review the current state of evidence for their use. The literature was searched for articles in English with key words cannabis, cannabinoids, and cancer pain. The sources of articles were PubMed, Embase, and open Google search.

Recent findings: In a double-blind randomized placebo-controlled trial including a 3-week treatment period of nabiximol for advanced cancer patients with pain refractory to optimized opiate therapy, improvements in average pain were seen in the intention to treat population (P = 0.0854) and per- protocol population (P = 0.0378).

Summary: To date, preclinical data has demonstrated evidence to suggest promising potential for cancer pain and the urgent need to translate this into clinical practice. Unfortunately, due to limited data, for adults with advanced cancer being treated with opiate therapy, the addition of cannabis or cannabinoids is not currently supported to address cancer pain effectively.”

https://pubmed.ncbi.nlm.nih.gov/33110020/

https://journals.lww.com/co-anesthesiology/Abstract/2020/12000/Update_on_cannabis_and_cannabinoids_for_cancer.19.aspx

Attenuation of Oxidative Stress by Cannabinoids and Cannabis Extracts in Differentiated Neuronal Cells

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pharmaceuticals-logo“In this proof-of-concept study, the antioxidant activity of phytocannabinoids, namely cannabidiol (CBD) and Δ9- tetrahydrocannabinol (THC), were investigated using an in vitro system of differentiated human neuronal SY-SH5Y cells.

We showed that THC had a high potency to combat oxidative stress in both in vitro models, while CBD did not show a remarkable antioxidant activity. The cannabis extracts also exhibited a significant antioxidant activity, which depended on the ratio of the THC and CBD. However, our results did not suggest any antagonist effect of the CBD on the antioxidant activity of THC. The effect of cannabis extracts on the cell viability of differentiated human neuronal SY-SH5Y cells was also investigated, which emphasized the differences between the bioactivity of cannabis extracts due to their composition.

Our preliminary results demonstrated that cannabis extracts and phytocannabinoids have a promising potential as antioxidants, which can be further investigated to develop novel pharmaceuticals targeting oxidative stress therapy.”

https://pubmed.ncbi.nlm.nih.gov/33105840/

https://www.mdpi.com/1424-8247/13/11/328

Cannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells

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molecules-logo“This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis.

The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol (CBG), cannabinol (CBN), and cannabidiol (CBD), and displayed favorable dose reduction indices and limited cytotoxicity against the non-cancerous breast cell line, MCF-10A. C6 exerted its effects in the MCF-7 cell line by inducing cell cycle arrest in the G2 phase, followed by the induction of apoptosis.

Morphological observations indicated the induction of cytoplasmic vacuolation, with further investigation suggesting that the vacuole membrane was derived from the endoplasmic reticulum. In addition, lipid accumulation, increased lysosome size, and significant increases in the endoplasmic reticulum chaperone protein glucose-regulated protein 78 (GRP78) expression were also observed.

The selectivity and ability of cannabinoids to halt cancer cell proliferation via pathways resembling apoptosis, autophagy, and paraptosis shows promise for cannabinoid use in standardized breast cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/33066359/

https://www.mdpi.com/1420-3049/25/20/4682

Antioxidant and antimicrobial activity of two standardized extracts from a new Chinese accession of non-psychotropic Cannabis sativa L

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Phytotherapy Research “The purpose of this study was to evaluate the antioxidant and antimicrobial properties of two extracts from a new Chinese accession (G-309) of Cannabis sativa L. (Δ9 -tetrahydrocannabinol <0.2%) with high content of propyl side chain phytocannabinoids.

Dried flowering tops, as such and after hydrodistillation of the essential oil, were extracted with acidic hexane to produce the Cannabis Chinese hexane extract 1 (CChHE1) and 2 (CChHE2), respectively. The phytochemical profile of CChHE1 and CChHE2 was investigated by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-diode array detector-electrospray ionization-tandem mass spectrometry (LC-DAD-ESI-MS/MS) analyses. The antioxidant properties were assessed by several in vitro cell-free assays. The antimicrobial activity was evaluated against Gram-positive and Gram-negative bacteria and the yeast Candida albicans.

Phytochemical analyses highlighted a high content of cannabidivarinic acid (CBDVA) and tetraydrocannabivarinic acid (THCVA) in CChHE1, and cannabidivarin (CBDV) and tetraydrocannabivarin (THCV) in CChHE2. Both extracts showed remarkable antioxidant activity and strong antimicrobial properties (MIC 39.06 and MBC 39.06-78.13 μg/ml) against both ATCC and methicillin-resistant clinical strains of Staphylococcus aureus.

In conclusion, standardized extracts of C. sativa Chinese accession could be promising for their possible use as novel antibacterial agents for the treatment of widespread S. aureus infections.”

https://pubmed.ncbi.nlm.nih.gov/33034400/

https://onlinelibrary.wiley.com/doi/10.1002/ptr.6891

Signaling Through the Type 2 Cannabinoid Receptor Regulates the Severity of Acute and Chronic Graft versus Host Disease

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Blood“Graft versus host disease (GVHD) pathophysiology is a complex interplay between cells that comprise the adaptive and innate arms of the immune system. Effective prophylactic strategies are therefore contingent upon approaches that address contributions from both immune cell compartments.

In the current study, we examined the role of the type 2 cannabinoid receptor (CB2R) which is expressed on nearly all immune cells and demonstrated that absence of the CB2R on donor CD4+ or CD8+ T cells, or administration of a selective CB2R pharmacological antagonist, exacerbated acute GVHD lethality. This was accompanied primarily by the expansion of proinflammatory CD8+ T cells indicating that constitutive CB2R expression on T cells preferentially regulated CD8+ T cell alloreactivity. Using a novel CB2R-EGFP reporter mouse, we observed significant loss of CB2R expression on T cells, but not macrophages, during acute GVHD, indicative of differential alterations in receptor expression under inflammatory conditions.

Therapeutic targeting of the CB2R with the agonists, tetrahydrocannabinol (THC) and JWH-133, revealed that only THC mitigated lethal T cell-mediated acute GVHD. Conversely, only JWH-133 was effective in a sclerodermatous chronic GVHD model where macrophages contribute to disease biology. In vitro, both THC and JWH-133 induced arrestin recruitment and ERK phosphorylation via CB2R, but THC had no effect on CB2R-mediated inhibition of adenylyl cyclase.

These studies demonstrate that the CB2R plays a critical role in the regulation of GVHD and suggest that effective therapeutic targeting is dependent upon agonist signaling characteristics and receptor selectivity in conjunction with the composition of pathogenic immune effector cells.”

https://pubmed.ncbi.nlm.nih.gov/33027805/

https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2020004871/464166/Signaling-Through-the-Type-2-Cannabinoid-Receptor?redirectedFrom=fulltext

An Agathokakological tale of ∆9 -THC: Exploration of Possible Biological Targets

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“∆ 9 -Tetrahydrocannabinol (∆9 -THC), the active phytocannabinoid in cannabis, is virtually an adjunct to the endogenous endocannabinoid signaling system.

By interacting with G-protein-coupled receptors CB1 and CB2, ∆9 -THC affects peripheral and central circulation by lowering sympathetic activity, altering gene expression, cell proliferation, and differentiation, decreasing leukocyte migration, modulating neurotransmitter release thereby modulating cardiovascular functioning, tumorigenesis, immune responses, behavioral and locomotory activities respectively.

∆ 9 -THC is effective in suppressing chemotherapy-induced vomiting, retards malignant tumor growth, inhibits metastasis, and promotes apoptosis. Other mechanisms involved are targeting cell cycle at the G2-M phase in human breast cancer, downregulation of E2F transcription factor 1 (E2F1) in human glioblastoma multiforme, and stimulation of ER stress-induced autophagy.

∆ 9 -THC also plays a role in ameliorating neuroinflammation, excitotoxicity, neuroplasticity, trauma, and stroke and is associated with reliving childhood epilepsy, brain trauma, and neurodegenerative diseases.

∆9 -THC via CB1 receptors affects nociception, emotion, memory, and reduces neuronal excitability and excitotoxicity in epilepsy. It also increases renal blood flow, reduces intraocular pressure via a sympathetic pathway, and modulates hormonal release, thereby decreasing the reproductive function and increasing glucose metabolism.

Versatile medical marijuana has stimulated abundant research demonstrating substantial therapeutic promise, suggesting the possibilities of first-in-class drugs in diverse therapeutic segments. In this review, we represent the current pharmacological status of the phytocannabinoid, ∆ 9 -THC, and synthetic analogs in cancer, cardiovascular, and neurodegenerative disorders.”

https://pubmed.ncbi.nlm.nih.gov/33001012/

https://www.eurekaselect.com/186455/article