We conducted a thorough literature search using PubMed Central (PMC), PubMed, MEDLINE, and Google Scholar. We used Keywords such as ‘Myocardial Infarction,’ ‘Cannabis’, and ‘Marijuana’. These keywords were used individually and in combination to gather relevant articles. Medical Subject Heading (MeSH) search terms’ Cannabis’ and ‘Myocardial Infarction’ were used to collect data. Type of studies included were randomized controlled trials, letters to the editor, review articles, observational studies, and case reports. The results of the keyword searches are summarized in Table Table1 1 .
CB1R and CB2R receptors are found on the platelet surface, which are the primary sites for activating platelet aggregation. In animal models, it is found that THC increases cyclooxygenase-1 and cyclooxygenase-2 (COX-1, COX-2) activity leading to thromboxane A2 and many prostaglandin productions . It is shown that THC acting on CB receptors leads to increased platelet aggregation through increased platelet P-selectin and glycoprotein IIa/IIIb expression. Furthermore, THC leads to the formation of 2-arachidonoylglycerol (2-AG), which is a precursor for arachidonic acid . Initially, the effects of 2-AG on the aggregation of platelets start with Phosphatidylinositol 3 Kinase/AKT pathway. This pathway leads to conformational changes in platelet structure by myosin light chain kinase phosphorylation and actin polymerization. This conformational change results in the secretion of adenosine triphosphate (ATP) and platelet aggregation . This increased arachidonic acid production and COX activity result in a pro-inflammatory state in the human body. It leads to vascular endothelial damage, central and peripheral vasoconstriction, and importantly platelet aggregation, which collectively increases the risk of atherosclerosis and other cardiovascular events, including myocardial infarction. If more research is done to understand better the complex mechanisms of platelet aggregation and inflammatory effects of cannabis on the cannabinoid receptors, many serum markers and risks factor for cardiovascular disease like myocardial infarction due to cannabis abuse can be determined to help the increasing cannabis users in the nation.
Mechanism of Action of Cannabis on the Cannabinoid Receptors
Over the past decade, marijuana use has increased rapidly. Legalizing possession, consumption, and distribution of marijuana in various states of the United States is the prime reason. Our study finds a strong relationship between marijuana use and the incidence of myocardial infarction and mortality of patients after cannabis-induced MI. Many cases in our research show that after marijuana use, even for the first time, there can be an event of MI, indicating that marijuana use should be considered a significant risk for MI. Mortality of patients after cannabis-induced MI could not be determined effectively due to insufficient data, but provided data says that there is a decrease in in-hospital mortality post-cannabis-induced MI. Various studies have proposed the pathophysiology of how these events occur. It is safe to say that cannabinoids act on the cannabinoid receptors to affect the cardiovascular system. They cause a mismatch in oxygen supply and demand in the myocardium, which can lead to ischemia. It can also increase platelet aggregation, which can lead to atherosclerosis, ultimately MI. The majority of the public use this for recreational purposes, thinking it is a safe drug, especially teenagers and older people. Public awareness about the ill-effects of marijuana is the need of the hour, and all physicians should always recognize those effects and advise their patients properly.
According to earlier studies, CB1R and CB2R are involved in modulating inflammatory processes in the body. Activation of CB1R results in atherosclerotic and inflammatory effects, whereas activation of CB2R leads to immunosuppression and anti-inflammatory effect. CB1R and CB2R mediate downstream signaling at the cellular level by activating their respective ligands at the cellular level . There are ongoing researches done in the area of immunomodulation by the receptors (CB1R and CB2R). Furthermore, few reviews have outlined that the downstream effects of CB receptor activation possibly lead to systemic pro-inflammatory states . It is postulated that there is an increase in tumor necrosis factor α (TNFα) and interleukin (IL)-12 levels from CB-induced activation of G-protein coupled receptor 55 (GPR55); this, in turn, increases the endocytic function of the monocytes. This can eventually lead to atherosclerosis and foam cell production, which can precipitate MI in the long run .
Remove and destroy infected plants
Irradiate leaves for 3–4 s with UV-C light daily
The greatest challenge remains in dealing with pathogens that infect cannabis inflorescences (Table S1) since economic losses from tissue destruction and a build-up of colony-forming units pre and post harvest can be as high as 20%. Research on this topic is limited by government regulations in Canada which restrict the cultivation of flowering cannabis plants to producers with approved licenses; researchers have limited capacity to grow such plants. Indoor climate management to provide dry conditions is recommended to reduce Botrytis bud rot, since reduced relative humidity and moisture deposition on the inflorescences can reduce spore germination and infection. 81 Under field conditions, Botrytis bud rot can be a devastating disease under cool and wet weather on cannabis and hemp 25, 39 ; cultivation under warm dry conditions would alleviate disease pressure. Cannabis strains have noticeable differences in Botrytis bud rot susceptibility: those that produce large tightly packed inflorescences develop more disease that those with smaller and loosely arranged inflorescences. In the latter, improved air movement within the canopy is assumed to be the underlying reason. It may be useful to evaluate pruning or deleafing methods to enhance air circulation, similar to that demonstrated for grapevines and Botrytis bunch rot reduction. 82 Removal and destruction of diseased inflorescences and early harvest are currently practiced by licensed producers to reduce the potential for spore production and pathogen spread. These physical methods can minimize disease outbreaks but are labor-intensive. The application of fungicidal or fungistatic compounds is restricted to the use of vaporized sulphur for powdery mildew control and potassium bicarbonate and hydrogen peroxide applications for powdery mildew and potentially Botrytis reduction. Concerns over possible fungicide residue carry-over in the inflorescence tissues used for medical or recreational purposes has limited the registration of synthetic fungicides. A reassessment of the utility of fungicides during cannabis production to enable producers to manage diseases is warranted.
8.2 Prevention of infection/symptom development
Government regulations require quantification of total yeast, mold, bacteria and other pathogens in dried cannabis samples to ensure they do not pose potential risks to human health. Certified laboratories perform a set of microbial isolations to enumerate total culturable yeast and mold (TCYM) and total bacteria, as well as coliforms, expressed as colony-forming units (cfu). 7 These certifications are required by provincial (state) and federal regulatory agencies in Canada and the USA, as well as in Europe, 10 Israel 47 and other countries. The assessment methods can be vastly different and require standardization to ensure consistency and reproducibility, as well as to provide recovery rates and validation based on known standard samples. There is ongoing debate on whether culture methods provide the most representative assessment of microbial load present on cannabis buds. 7, 35 Many of these methods are adapted from the food manufacturing industry, yet the microbial flora on plants are vastly different. The diversity of microbes that are present on fresh inflorescences of cannabis can be ascertained through sampling methods (Fig. S3). Many of these microbes can survive the postharvest drying phase but the relationship of microbial loads on buds preharvest to those postharvest has not been established. Research to develop models to predict final cfu/g from preharvest assessments would be useful. The fungal species found on dried cannabis buds in commercial production are diverse and exceed 35 different species. 25 Other researchers have described the yeast and bacterial loads. 7, 35, 48 There are recommendations that molecular approaches utilizing quantitative PCR (q-PCR) would be more informative for microbial determination on cannabis inflorescences compared to plating assays. 7, 35 Regulatory agencies have not provided a framework of recommended methods or best practices for quantification of these microbes and thus the variability in findings will persist. This can make interpretation of QA results from commercial laboratories challenging for cannabis producers. Instances of the same batch of dried flowers yielding different mold counts from two different laboratories indicate that regulated and standardized procedures are required. The total cultural assessment data also do not identify the actual yeast or mold species present, which can be quite varied. 25 For example, a potential beneficial biological control agent such as Trichoderma harzianum, if it is present in high numbers on buds, may cause a product to fail to meet the limit requirements. Other commercial products containing the fermentation end-products from Lactobacillus spp. may result in higher yeast and mold counts after application, perhaps as a result of nutrients and other secondary products causing a ‘flush’ of resident microbes to grow. These changes in microbial loads from the application of bio-rationale treatments need to be monitored to assess their impact on product quality. Currently, such studies are lacking. Also needed are studies to assess the changes in microbial flora during inflorescence development up to harvest.
Reduce ambient relative humidity, improve air circulation
Historically, cannabis cultivation began in outdoor growing in areas where climatic conditions allowed plants to grow for at least 120 days to complete flowering. 4 This was followed by indoor cultivation in growing facilities with controlled environmental conditions and supplemental lighting to optimize plant growth. Most indoor cultivation currently utilizes hydroponic soil-free culture, e.g. rockwool or cocofibre, although soil culture is common, especially for organic production. A combination of indoor environments, which includes expansive greenhouse production, and outdoor (field) environments is used to cultivate cannabis in Canada. Each production environment faces challenges from plant pathogens, with indoor and greenhouse systems sharing more diseases in common compared to field-grown cannabis. The nature of these diseases is described in more detail in this review.