ThePineapple - Journal Club #35: Myocardial infarction | Fibroblasts | Glial cells | Melanoma

Journal Club #35: Myocardial infarction, Fibroblasts, Glial cells, Melanoma

Week of 03-27-22

Welcome to journal club. A weekly curation of scientific research papers in the field of cannabis science. Fair warning, these are unedited, freshly destilled scientifc publications. In other words, this post is for the cannabis scientists among you, who are likely going to spent at least one day this week eating free pizza and discussing new publications in your respective biomedical graduate departments. So, if you are a graduate student, feel free to save yourself some time and pick one of these :)

Also, if you feel we missed a particularly juicy paper, then leave a comment with the doi: number or pubmed ID ! We'll update the "journal club" as the week goes on.

Why Do Marijuana and Synthetic Cannabimimetics Induce Acute Myocardial Infarction in Healthy Young People?

Weresa J, Pędzińska-Betiuk A, Mińczuk K, Malinowska B, Schlicker E. 

Cells. 2022 Mar 28;11(7):1142.

The use of cannabis preparations has steadily increased. Although cannabis was traditionally assumed to only have mild vegetative side effects, it has become evident in recent years that severe cardiovascular complications can occur. Cannabis use has recently even been added to the risk factors for myocardial infarction. This review is dedicated to pathogenetic factors contributing to cannabis-related myocardial infarction. Tachycardia is highly important in this respect, and we provide evidence that activation of CB1 receptors in brain regions important for cardiovascular regulation and of presynaptic CB1 receptors on sympathetic and/or parasympathetic nerve fibers are involved. The prototypical factors for myocardial infarction, i.e., thrombus formation and coronary constriction, have also been considered, but there is little evidence that they play a decisive role. On the other hand, an increase in the formation of carboxyhemoglobin, impaired mitochondrial respiration, cardiotoxic reactions and tachyarrhythmias associated with the increased sympathetic tone are factors possibly intensifying myocardial infarction. A particularly important factor is that cannabis use is frequently accompanied by tobacco smoking. In conclusion, additional research is warranted to decipher the mechanisms involved, since cannabis use is being legalized increasingly and Δ9-tetrahydrocannabinol and its synthetic analogue nabilone are indicated for the treatment of various disease states.

doi: 10.3390/cells11071142. PMID: 35406706; PMCID: PMC8997492.

Standardized Cannabis Smoke Extract Induces Inflammation in Human Lung Fibroblasts.

Aloufi N, Namkung Y, Traboulsi H, Wilson ET, Laporte SA, Kaplan BLF, Ross MK, Nair P, Eidelman DH, Baglole CJ. 

Front Pharmacol. 2022 Mar 28;13:852029.

Cannabis (marijuana) is the most commonly used illicit product in the world and is the second most smoked plant after tobacco. There has been a rapid increase in the number of countries legalizing cannabis for both recreational and medicinal purposes. Smoking cannabis in the form of a joint is the most common mode of cannabis consumption. Combustion of cannabis smoke generates many of the same chemicals as tobacco smoke. Although the impact of tobacco smoke on respiratory health is well-known, the consequence of cannabis smoke on the respiratory system and, in particular, the inflammatory response is unclear. Besides the combustion products present in cannabis smoke, cannabis also contains cannabinoids including Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). These compounds are hydrophobic and not present in aqueous solutions. In order to understand the impact of cannabis smoke on pathological mechanisms associated with adverse respiratory outcomes, the development of in vitro surrogates of cannabis smoke exposure is needed. Therefore, we developed a standardized protocol for the generation of cannabis smoke extract (CaSE) to investigate its effect on cellular mechanisms in vitro. First, we determined the concentration of Δ9-THC, one of the major cannabinoids, by ELISA and found that addition of methanol to the cell culture media during generation of the aqueous smoke extract significantly increased the amount of Δ9-THC. We also observed by LC-MS/MS that CaSE preparation with methanol contains CBD. Using a functional assay in cells for CB1 receptors, the major target of cannabinoids, we found that this CaSE contains Δ9-THC which activates CB1 receptors. Finally, this standardized preparation of CaSE induces an inflammatory response in human lung fibroblasts. This study provides an optimized protocol for aqueous CaSE preparation containing biologically active cannabinoids that can be used for in vitro experimentation of cannabis smoke and its potential impact on various indices of pulmonary health.

doi: 10.1002/glia.24172. Epub ahead of print. PMID: 35353392.

Endocannabinoid signaling in brain diseases: Emerging relevance of glial cells.

Bernal-Chico A, Tepavcevic V, Manterola A, Utrilla C, Matute C, Mato S. 

Glia. 2022 Mar 30.

The discovery of cannabinoid receptors as the primary molecular targets of psychotropic cannabinoid Δ9 -tetrahydrocannabinol (Δ9 -THC) in late 1980s paved the way for investigations on the effects of cannabis-based therapeutics in brain pathology. Ever since, a wealth of results obtained from studies on human tissue samples and animal models have highlighted a promising therapeutic potential of cannabinoids and endocannabinoids in a variety of neurological disorders. However, clinical success has been limited and major questions concerning endocannabinoid signaling need to be satisfactorily addressed, particularly with regard to their role as modulators of glial cells in neurodegenerative diseases. Indeed, recent studies have brought into the limelight diverse, often unexpected functions of astrocytes, oligodendrocytes, and microglia in brain injury and disease, thus providing scientific basis for targeting glial cells to treat brain disorders. This Review summarizes the current knowledge on the molecular and cellular hallmarks of endocannabinoid signaling in glial cells and its clinical relevance in neurodegenerative and chronic inflammatory disorders.

doi: 10.1002/glia.24172. Epub ahead of print. PMID: 35353392.

Impact of Cannabinoid Compounds on Skin Cancer.

Ramer R, Wendt F, Wittig F, Schäfer M, Boeckmann L, Emmert S, Hinz B. 

Cancers (Basel). 2022 Mar 31;14(7):1769.

Drugs targeting the endocannabinoid system are of interest as potential systemic chemotherapeutic treatments and for palliative care in cancer. In this context, cannabinoid compounds have been successfully tested as a systemic therapeutic option in preclinical models over the past decades. Recent findings have suggested an essential function of the endocannabinoid system in the homeostasis of various skin functions and indicated that cannabinoids could also be considered for the treatment and prophylaxis of tumour diseases of the skin. Cannabinoids have been shown to exert their anticarcinogenic effects at different levels of skin cancer progression, such as inhibition of tumour growth, proliferation, invasion and angiogenesis, as well as inducing apoptosis and autophagy. This review provides an insight into the current literature on cannabinoid compounds as potential pharmaceuticals for the treatment of melanoma and squamous cell carcinoma.

doi: 10.3390/cancers14071769. PMID: 35406541; PMCID: PMC8997154.