Category Archives: Uncategorized

Inflammaging and Cannabinoids

Posted on by

Ageing Research Reviews“Aging is a complex phenomenon associated with a wide spectrum of physical and physiological changes affecting every part of all metazoans, if they escape death prior to reaching maturity. Critical to survival, the immune system evolved as the principal component of response to injury and defense against pathogen invasions. Because how significantly immune system affects and is affected by aging, several neologisms now appear to encapsulate these reciprocal relationships, such as Immunosenescence. The central part of Immunosenescence is Inflammaging -a sustained, low-grade, sterile inflammation occurring after reaching reproductive prime. Once initiated, the impact of Inflammaging and its adverse effects determine the direction and magnitudes of further Inflammaging. In this article, we review the nature of this vicious cycle, we will propose that phytocannabinoids as immune regulators may possess the potential as effective adjunctive therapies to slow and, in certain cases, reverse the pathologic senescence to permit a more healthy aging.”

https://pubmed.ncbi.nlm.nih.gov/34662745/

“The beneficial effects of cannabinoids may be considered as alternative therapy in treating age-related diseases.”

https://www.sciencedirect.com/science/article/pii/S1568163721002348?via%3Dihub

Novel CBG Derivatives Can Reduce Inflammation, Pain and Obesity

Posted on by

molecules-logo“Interest in CBG (cannabigerol) has been growing in the past few years, due to its anti-inflammatory properties and other therapeutic benefits.

Here we report the synthesis of three new CBG derivatives (HUM-223, HUM-233 and HUM-234) and show them to possess anti-inflammatory and analgesic properties.

In addition, HUM-234 also prevents obesity in mice fed a high-fat diet (HFD). The metabolic state of the treated mice on HFD is significantly better than that of vehicle-treated mice, and their liver slices show significantly less steatosis than untreated HFD or CBG-treated ones from HFD mice.

We believe that HUM-223, HUM-233 and HUM-234 have the potential for development as novel drug candidates for the treatment of inflammatory conditions, and in the case of HUM-234, potentially for obesity where there is a huge unmet need.”

https://pubmed.ncbi.nlm.nih.gov/34577072/

https://www.mdpi.com/1420-3049/26/18/5601

A potential role for cannabichromene in modulating TRP channels during acute respiratory distress syndrome

Posted on by

Special Issue Springer/Nature BMC Medical Informatics & Decision Making - Explainable-AI - human-centered.ai“Acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome whose potential to become one of the most grievous challenges of the healthcare system evidenced by the COVID-19 pandemic. Considering the lack of target-specific treatment for ARDS, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve quality of life and outcomes for ARDS patients. ARDS is a systemic inflammatory disease starting with the pulmonary system and involves all other organs in a morbid bidirectional fashion. Mounting evidence including our findings supporting the notion that cannabinoids have potential to be targeted as regulatory therapeutic modalities in the treatment of inflammatory diseases. Therefore, it is plausible to test their capabilities as alternative therapies in the treatment of ARDS. In this study, we investigated the potential protective effects of cannabichromene (CBC) in an experimental model of ARDS.

Results: Our data showed that CBC was able to reverse the hypoxia (increasing blood O2 saturation by 8%), ameliorate the symptoms of ARDS (reducing the pro-inflammatory cytokines by 50% in lung and blood), and protect the lung tissues from further destruction. Further analysis showed that CBC may wield its protective effects through transient receptor potential (TRP) cation channels, TRPA1 and TRPV1, increasing their expression by 5-folds in lung tissues compared to sham and untreated mice, re-establishing the homeostasis and immune balance.

Conclusion: Our findings suggest that inhalant CBC may be an effective alternative therapeutic target in the treatment of ARDS. In addition, Increased expression of TRPs cation channels after CBC treatment proposes a novel role for TRPs (TRPA1 and TRPV2) as new potential mechanism to interpret the beneficial effects of CBC as well as other cannabinoids in the treatment of ARDS as well as other inflammatory diseases. Importantly, delivering CBC through an inhaler device is a translational model supporting the feasibility of trial with human subjects, authorizing further research.”

https://pubmed.ncbi.nlm.nih.gov/34598736/

“Cannabinoids are naturally occurring compounds in Cannabis plants. Numerous studies suggest beneficial effects of cannabinoids in clinical settings.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-021-00101-0

The potential of cannabinoids and inhibitors of endocannabinoid degradation in respiratory diseases

Posted on by

European Journal of Pharmacology“The global incidence of respiratory diseases and complications is increasing. Therefore, new methods of treatment, as well as prevention, need to be investigated.

A group of compounds that should be considered for use in respiratory diseases is cannabinoids. There are three groups of cannabinoids – plant-derived phytocannabinoids, synthetic cannabinoids, and endogenous endocannabinoids including the enzymes responsible for their synthesis and degradation.

All cannabinoids exert their biological effects through either type 1 cannabinoid receptors (CB1) and/or type 2 cannabinoid receptors (CB2). In numerous studies (in vitro and in vivo), cannabinoids and inhibitors of endocannabinoid degradation have shown beneficial anti-inflammatory, antioxidant, anti-cancer, and anti-fibrotic properties.

Although in the respiratory system, most of the studies have focused on the positive properties of cannabinoids and inhibitors of endocannabinoid degradation. There are few research reports discussing the negative impact of these compounds. This review summarizes the properties and mechanisms of action of cannabinoids and inhibitors of endocannabinoid degradation in various models of respiratory diseases.

A short description of the effects selected cannabinoids have on the human respiratory system and their possible use in the fight against COVID-19 is also presented. Additionally, a brief summary is provided of cannabinoid receptors properties and their expression in the respiratory system and cells of the immune system.”

https://pubmed.ncbi.nlm.nih.gov/34648805/

“Phytocannabinoids are terpenophenolic compounds produced by specialized parts of the Cannabis sativa plant and are found in high concentrations in marijuana and hashish. In most of models, these compounds have shown positive biological properties. Anti-inflammatory, anti-oxidant, anti-cancer and anti-fibrotic actions are especially emphasized.”

https://www.sciencedirect.com/science/article/pii/S0014299921007160?via%3Dihub

Activity of THC, CBD, and CBN on Human ACE2 and SARS-CoV1/2 Main Protease to Understand Antiviral Defense Mechanism

Posted on by

“THC, CBD, and CBN were reported as promising candidates against SARS-CoV2 infection, but the mechanism of action of these three cannabinoids is not understood.

This study aims to determine the mechanism of action of THC, CBD, and CBN by selecting two essential targets that directly affect the coronavirus infections as viral main proteases and human angiotensin-converting enzyme2.

Tested THC and CBD presented a dual-action action against both selected targets. Only CBD acted as a potent viral main protease inhibitor at the IC50 value of 1.86 ± 0.04 µM and exhibited only moderate activity against human angiotensin-converting enzyme2 at the IC50 value of 14.65 ± 0.47 µM.

THC acted as a moderate inhibitor against both viral main protease and human angiotensin-converting enzymes2 at the IC50 value of 16.23 ± 1.71 µM and 11.47 ± 3.60 µM, respectively.

Here, we discuss cannabinoid-associated antiviral activity mechanisms based on in silico docking studies and in vitro receptor binding studies.”

https://pubmed.ncbi.nlm.nih.gov/34638139/

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-1581-3707

Cannabidiol inhibits SARS-Cov-2 spike (S) protein-induced cytotoxicity and inflammation through a PPARγ-dependent TLR4/NLRP3/Caspase-1 signaling suppression in Caco-2 cell line

Posted on by

Phytotherapy Research“Given the abundancy of angiotensin converting enzyme 2 (ACE-2) receptors density, beyond the lung, the intestine is considered as an alternative site of infection and replication for severe acute respiratory syndrome by coronavirus type 2 (SARS-CoV-2).

Cannabidiol (CBD) has recently been proposed in the management of coronavirus disease 2019 (COVID-19) respiratory symptoms because of its anti-inflammatory and immunomodulatory activity exerted in the lung.

In this study, we demonstrated the in vitro PPAR-γ-dependent efficacy of CBD (10-9 -10-7 M) in preventing epithelial damage and hyperinflammatory response triggered by SARS-CoV-2 spike protein (SP) in a Caco-2 cells. Immunoblot analysis revealed that CBD was able to reduce all the analyzed proinflammatory markers triggered by SP incubation, such as tool-like receptor 4 (TLR-4), ACE-2, family members of Ras homologues A-GTPase (RhoA-GTPase), inflammasome complex (NLRP3), and Caspase-1.

CBD caused a parallel inhibition of interleukin 1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), and IL-18 by enzyme-linked immunosorbent assay (ELISA) assay. By immunofluorescence analysis, we observed increased expression of tight-junction proteins and restoration of transepithelial electrical resistance (TEER) following CBD treatment, as well as the rescue of fluorescein isothiocyanate (FITC)-dextran permeability induced by SP.

Our data indicate, in conclusion, that CBD is a powerful inhibitor of SP protein enterotoxicity in vitro.”

https://pubmed.ncbi.nlm.nih.gov/34643000/

https://onlinelibrary.wiley.com/doi/10.1002/ptr.7302

Inducing Effects of Illegal Drugs to Improve Mental Health by Self-Regulation Therapy: A Pilot Study

Posted on by

ijerph-logo“This study consists of a brief psychological intervention, which uses Self-Regulation Therapy (SRT, procedure based on suggestion and classical conditioning), to improve coping with stress and emotionality by reproducing the positive effects of illegal drugs: cannabis, cocaine, ecstasy.

Results: SRT was superior to non-intervention for the 4 coping strategies (η2 = 0.829, 0.453, 0.411 and 0.606) and for positive (η2 = 0.371) and negative emotionality (η2 = 0.419). An improvement in scores was evidenced in the follow-up scores compared to the pre-intervention measures.

Conclusions: This study shows for the first time that it is possible to use illegal drugs, considered harmful to public health, to improve young people’s coping capacity and emotionality by reproducing their positive effects with SRT.”

https://pubmed.ncbi.nlm.nih.gov/34639687/

https://www.mdpi.com/1660-4601/18/19/10387

Efficacy of Δ 9 -Tetrahydrocannabinol (THC) Alone or in Combination With a 1:1 Ratio of Cannabidiol (CBD) in Reversing the Spatial Learning Deficits in Old Mice

Posted on by

Archive of "Frontiers in Aging Neuroscience".“Decline in cognitive performance, an aspect of the normal aging process, is influenced by the endocannabinoid system (ECS). Cannabinoid receptor 1 (CB1) signaling diminishes with advancing age in specific brain regions that regulate learning and memory and abolishing CB1 receptor signaling accelerates cognitive aging in mice.

We recently demonstrated that prolonged exposure to low dose (3 mg/kg/day) Δ9-tetrahydrocannabinol (THC) improved the cognitive performances in old mice on par with young untreated mice. Here we investigated the potential influence of cannabidiol (CBD) on this THC effect, because preclinical and clinical studies indicate that the combination of THC and CBD often exhibits an enhanced therapeutic effect compared to THC alone.

We first tested the effectiveness of a lower dose (1 mg/kg/day) THC, and then the efficacy of the combination of THC and CBD in 1:1 ratio, same as in the clinically approved medicine Sativex®. Our findings reveal that a 1 mg/kg/day THC dose still effectively improved spatial learning in aged mice. However, a 1:1 combination of THC and CBD failed to do so.

The presence of CBD induced temporal changes in THC metabolism ensuing in a transient elevation of blood THC levels. However, as CBD metabolizes, the inhibitory effect on THC metabolism was alleviated, causing a rapid clearance of THC. Thus, the beneficial effects of THC seemed to wane off more swiftly in the presence of CBD, due to these metabolic effects.

The findings indicate that THC-treatment alone is more efficient to improve spatial learning in aged mice than the 1:1 combination of THC and CBD.”

https://pubmed.ncbi.nlm.nih.gov/34526890/

“In conclusion, our observations indicate that 1 mg/kg/day THC dose is still effective in improving the spatial learning in aged mice. With regard to the efficacy, THC-alone has proved to be more efficient in improving spatial learning in aged mice than its 1:1 combination with CBD. However, the possibility of THC/CBD being efficient in other ratios or at the earliest time-points, like immediately after the treatment cease, cannot be negated. Possibly, reducing the dose of CBD may improve the efficacy of the THC/CBD combination.”

https://www.frontiersin.org/articles/10.3389/fnagi.2021.718850/full

Cannabidiol enhances verbal episodic memory in healthy young participants: A randomized clinical trial

Posted on by

Journal of Psychiatric Research“Cannabis contains a multitude of different compounds. One of them, cannabidiol – a non-psychoactive substance – might counteract negative effects of Δ-9-Tetrahydrocannabinol on hippocampus-dependent memory impairment.

The aim of the present study was to investigate the effect of vaping cannabidiol on verbal episodic memory in healthy young subjects.

We used a double-blind, placebo-controlled, randomized crossover trial in 39 healthy young subjects. Participants received once a single dose of cannabidiol e-liquid (0.25 ml, 5% cannabidiol, 12.5 mg cannabidiol) and once placebo for vaping after learning 15 unrelated nouns. The primary outcome measure was the short delay verbal memory performance (number of correctly free recalled nouns) 20 min after learning. 34 participants (mean age: 22.26 [3.04]) completed all visits and entered analyses (17 received cannabidiol and 17 received placebo first).

Cannabidiol enhanced verbal episodic memory performance (placebo: 7.03 [2.34]; cannabidiol 7.71 [2.48]; adjusted group difference 0.68, 95% CI 0.01 to 1.35; R2β = .028, p = .048). Importantly, we did not detect medication effects on secondary outcome measures attention or working memory performance, suggesting that CBD has no negative impact on these basic cognitive functions.

The results are in line with the idea that vaping cannabidiol interacts with the central endocannabinoid system and is capable to modulate memory processes, a phenomenon with possible therapeutic potential. Further studies are needed to investigate optimal dose-response and time-response relationships.”

https://pubmed.ncbi.nlm.nih.gov/34536664/

“To conclude, while further research is needed to identify dose-response and time-response relationships, our results show that CBD can improve episodic memory, a drug effect with possible therapeutic potential.”

https://www.sciencedirect.com/science/article/pii/S002239562100546X?via%3Dihub

Cannabidiol Exposure During the Mouse Adolescent Period Is Without Harmful Behavioral Effects on Locomotor Activity, Anxiety, and Spatial Memory

Posted on by

Archive of "Frontiers in Behavioral Neuroscience".“Cannabidiol (CBD) is a non-intoxicating phytocannabinoid whose purported therapeutic benefits and impression of a high safety profile has promoted its increasing popularity.

CBD’s popularity is also increasing among children and adolescents who are being administered CBD, off label, for the treatment of numerous symptoms associated with autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, and depression. The relative recency of its use in the adolescent population has precluded investigation of its impact on the developing brain and the potential consequences that may present in adulthood. Therefore, there’s an urgency to identify whether prolonged adolescent CBD exposure has substantive impacts on the developing brain that impact behavioral and cognitive processes in adulthood.

Here, we tested the effect of twice-daily intraperitoneal administrations of CBD (20 mg/kg) in male and female C57BL/6J mice during the adolescent period of 25-45 days on weight gain, and assays for locomotor behavior, anxiety, and spatial memory. Prolonged adolescent CBD exposure had no detrimental effects on locomotor activity in the open field, anxiety behavior on the elevated plus maze, or spatial memory in the Barnes Maze compared to vehicle-treated mice. Interestingly, CBD-treated mice had a faster rate of learning in the Barnes Maze. However, CBD-treated females had reduced weight gain during the exposure period.

We conclude that prolonged adolescent CBD exposure in mice does not have substantive negative impacts on a range of behaviors in adulthood, may improve the rate of learning under certain conditions, and impacts weight gain in a sex-specific manner.”

https://pubmed.ncbi.nlm.nih.gov/34512286/

“Cannabidiol (CBD) is one of the most abundant cannabinoids naturally produced by the plant, Cannabis sativa, and the dominant phytocannabinoid produced by the hemp variety. We report that multiple daily doses of a moderate CBD dose throughout the adolescent developmental period does not negatively impact locomotor behavior, anxiety, and spatial learning in healthy C57BL/6J mice. Further, the faster acquisition rate of a spatial learning task may highlight CBD’s potential protective benefits against stressors.”

https://www.frontiersin.org/articles/10.3389/fnbeh.2021.711639/full