Cannabis Use Is Inversely Associated with Overweight and Obesity in Hepatitis B Virus-Infected Patients (ANRS CO22 Hepather Cohort)

View details for Cannabis and Cannabinoid Research cover image“Chronic hepatitis B virus (HBV) infection may evolve into cirrhosis and hepatocellular carcinoma, and this progression may be accelerated by specific risk factors, including overweight and obesity. Although evidence for a protective effect of cannabis use on elevated body weight has been found for other populations, no data are available for HBV-infected patients. 

Aims: We aimed to identify risk factors (including cannabis use) for overweight and obesity in patients with HBV chronic infection. 

Methods: Using baseline data from the French ANRS CO22 Hepather cohort, we performed two separate analyses, one using “central obesity” (based on waist circumference) and the other “overweight” and “obesity” (based on body mass index) as outcomes. Logistic and multinomial regressions were used to model central obesity and overweight/obesity, respectively. 

Results: Among the 3706 patients in the study population, 50.8% had central obesity, 34.7% overweight, and 14.4% obesity. After multivariable adjustment, current cannabis use was associated with a 59% lower risk of central obesity compared with no lifetime use (adjusted odds ratio [95% CI]: 0.41 [0.24 to 0.70]). It was also associated with a 54% and 84% lower risk of overweight (adjusted relative risk ratio [95% CI]: 0.46 [0.27 to 0.76]) and obesity (0.16 [0.04 to 0.67]), respectively. 

Conclusions: Cannabis use was associated with lower risks of overweight and obesity in patients with HBV chronic infection. Future studies should test whether these potential benefits of cannabis and cannabinoid use translate into reduced liver disease progression in this high-risk population.”

https://pubmed.ncbi.nlm.nih.gov/34648718/

https://www.liebertpub.com/doi/10.1089/can.2021.0094

Novel CBG Derivatives Can Reduce Inflammation, Pain and Obesity

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

β-Caryophyllene Induces Apoptosis and Inhibits Angiogenesis in Colorectal Cancer Models

ijms-logo“Beta-Caryophyllene (BCP), a naturally occurring sesquiterpene abundantly found in cloves, hops, and cannabis, is the active candidate of a relatively new group of vascular-inhibiting compounds that aim to block existing tumor blood vessels.

Previously, we have reported the anti-cancer properties of BCP by utilizing a series of in-vitro anti-tumor-related assays using human colorectal carcinoma cells. The present study aimed to investigate the effects of BCP on in-vitro, ex-vivo, and in-vivo models of anti-angiogenic assays and evaluate its anti-cancer activity in xenograft tumor (both ectopic and orthotopic) mice models of human colorectal cancer.

BCP showed a remarkable reduction in tumor size and fluorescence molecular tomography signal intensity in all the mice treated with BCP, in a dose-dependent relationship, in ectopic and orthotopic tumor xenograft models, respectively. The histological analysis of the tumor from BCP-treated mice revealed a clear reduction of the density of vascularization. In addition, BCP induced apoptosis through downregulation of HSP60, HTRA, survivin, and XIAP, along with the upregulation of p21 expressions.

These results suggest that BCP acts at multiple stages of angiogenesis and could be used as a promising therapeutic candidate to halt the growth of colorectal tumor cells.”

https://pubmed.ncbi.nlm.nih.gov/34638895/

https://www.mdpi.com/1422-0067/22/19/10550

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

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

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

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

“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

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

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

Lung cancer patient who had declined conventional cancer treatment: could the self-administration of ‘CBD oil’ be contributing to the observed tumour regression?

b-on, bliblioteca do conhecimento online | BMJ“Conventional lung cancer treatments include surgery, chemotherapy and radiotherapy; however, these treatments are often poorly tolerated by patients. Cannabinoids have been studied for use as a primary cancer treatment. Cannabinoids, which are chemically similar to our own body’s endocannabinoids, can interact with signalling pathways to control the fate of cells, including cancer cells. We present a patient who declined conventional lung cancer treatment. Without the knowledge of her clinicians, she chose to self-administer ‘cannabidiol (CBD) oil’ orally 2-3 times daily. Serial imaging shows that her cancer reduced in size progressively from 41 mm to 10 mm over a period of 2.5 years. Previous studies have failed to agree on the usefulness of cannabinoids as a cancer treatment. This case appears to demonstrate a possible benefit of ‘CBD oil’ intake that may have resulted in the observed tumour regression. The use of cannabinoids as a potential cancer treatment justifies further research.”

https://pubmed.ncbi.nlm.nih.gov/34649854/

“Patient’s perspective

“I was not very interested in traditional cancer treatments as I was worried about the risks of surgery, and I saw my late husband suffer through the side effects of radiotherapy. My relative suggested that I should try ‘cannabidiol (CBD) oil’ to treat my cancer, and I have been taking it regularly ever since. I am ‘over the moon’ with my cancer shrinking, which I believe was caused by the ‘CBD oil’. I am tolerating it very well and I intend to take this treatment indefinitely.””

https://casereports.bmj.com/content/14/10/e244195

“Cannabis oil led to lung cancer regression in 80-year-old woman: Report”

https://www.freepressjournal.in/world/cannabis-oil-led-to-lung-cancer-regression-in-80-year-old-woman-report

“Case Report: Lung Cancer Shrinks in Patient Using CBD Oil”

https://www.medscape.com/viewarticle/960949

“Daily use of cannabidiol (‘CBD’) oil may be linked to lung cancer regression”

https://www.bmj.com/company/newsroom/daily-use-of-cannabidiol-cbd-oil-may-be-linked-to-lung-cancer-regression/

Characterization of cannabinoid receptors expressed in Ewing sarcoma TC-71 and A-673 cells as potential targets for anti-cancer drug development

Life Sciences“Aims: Characterizing cannabinoid receptors (CBRs) expressed in Ewing sarcoma (EWS) cell lines as potential targets for anti-cancer drug development.

Main methods: CBR affinity and function were examined by competitive binding and G-protein activation, respectively. Cannabinoid-mediated cytotoxicity and cell viability were evaluated by LDH, and trypan blue assays, respectively.

Key findings: qRT-PCR detected CB1 (CB1R) and CB2 receptor (CB2R) mRNA in TC-71 cells. However, binding screens revealed that CBRs expressed exhibit atypical properties relative to canonical receptors, because specific binding in TC-71 could only be demonstrated by the established non-selective CB1/CB2R radioligand [3H]WIN-55,212-2, but not CB1/CB2R radioligand [3H]CP-55,940. Homologous receptor binding demonstrated that [3H]WIN-55,212-2 binds to a single site with nanomolar affinity, expressed at high density. Further support for non-canonical CBRs expression is provided by subsequent binding screens, revealing that only 9 out of 28 well-characterized cannabinoids with high affinity for canonical CB1 and/or CB2Rs were able to displace [3H]WIN-55,212-2, whereas two ligands enhanced [3H]WIN-55,212-2 binding. Five cannabinoids producing the greatest [3H]WIN-55,212-2 displacement exhibited high nanomolar affinity (Ki) for expressed receptors. G-protein modulation and adenylyl cyclase assays further indicate that these CBRs exhibit distinct signaling/functional profiles compared to canonical CBRs. Importantly, cannabinoids with the highest affinity for non-canonical CBRs reduced TC-71 viability and induced cytotoxicity in a time-dependent manner. Studies in a second EWS cell line (A-673) showed similar atypical binding properties of expressed CBRs, and cannabinoid treatment produced cytotoxicity.

Significance: Cannabinoids induce cytotoxicity in EWS cell lines via non-canonical CBRs, which might be a potential therapeutic target to treat EWS.”

https://pubmed.ncbi.nlm.nih.gov/34592231/

Cannabinoid receptors (CBRs) were detected in EWS TC-71 and A-673 cells. CBRs expressed in EWS cell lines exhibit atypical binding and signaling characteristics. Ligands with highest affinity for these non-canonical CBRs induce EWS cell death.”

https://www.sciencedirect.com/science/article/abs/pii/S0024320521009802?via%3Dihub