Adherence to Psychotropic Medication Before and During COVID-19: A Population-Wide Retrospective Observational Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic and associated public health measures have shifted the way people access health care. We aimed to study the effects of the COVID-19 pandemic on psychotropic medication adherence. METHODS: A retrospective cohort study using administrative data from the Manitoba Centre for Health Policy Manitoba Population Research Data Repository was conducted. Outpatients who received at least 1 prescription for an antidepressant, antipsychotic, anxiolytic/sedative-hypnotic, cannabinoid, lithium, or stimulants from 2015 to 2020 in Manitoba, Canada, were included. Adherence was measured using the proportion of individuals with a mean possession ratio of ≥0.8 over each quarter. Each quarter of 2020 after COVID-19-related health measures were implemented was compared with the expected trend using autoregression models for time series data plus indicator variables. Odds ratio of drug discontinuation among those previously adherent in 2020 was compared with each respective quarter of 2019. RESULTS: There were 1,394,885 individuals in the study population in the first quarter of 2020 (mean [SD] age, 38.9 [23.4] years; 50.3% female), with 36.1% having a psychiatric diagnosis in the preceding 5 years. Compared with the expected trend, increases in the proportions of individuals adherent to antidepressants and stimulants were observed in the fourth quarter (October-December) of 2020 (both P < 0.001). Increases in the proportions of individuals with anxiolytic and cannabinoid adherence were observed in the third quarter (July-September) of 2020 (both P < 0.05), whereas a decrease was seen with stimulants in the same quarter ( P < 0.0001). No significant changes were observed for antipsychotics. All drug classes except lithium had decreases in drug discontinuation in previously adherent patients during the pandemic compared with 2019. CONCLUSIONS: Improved adherence to most psychotropic medications in the 9 months after public health restrictions were enacted was observed. Patients who were already adherent to their psychotropic medications were less likely to discontinue them during the pandemic.

Antiviral activities of hemp cannabinoids.

Hemp is an understudied source of pharmacologically active compounds and many unique plant secondary metabolites including more than 100 cannabinoids. After years of legal restriction, research on hemp has recently demonstrated antiviral activities in silico, in vitro, and in vivo for cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and several other cannabinoids against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), human immunodeficiency virus (HIV), and γ-herpes viruses. Mechanisms of action include inhibition of viral cell entry, inhibition of viral proteases, and stimulation of cellular innate immune responses. The anti-inflammatory properties of cannabinoids are also under investigation for mitigating the cytokine storm of COVID-19 and controlling chronic inflammation in people living with HIV. Retrospective clinical studies support antiviral activities of CBD, Δ9-THC, and cannabinoid mixtures as do some prospective clinical trials, but appropriately designed clinical trials of safety and efficacy of antiviral cannabinoids are urgently needed.

Cannabis as antivirals.

Cannabis is a plant notorious for its psychoactive effect, but when used correctly, it provides a plethora of medicinal benefits. With more than 400 active compounds that have therapeutic properties, cannabis has been accepted widely as a medical treatment and for recreational purposes in several countries. The compounds exhibit various clinical benefits, which include, but are not limited to, anticancer, antimicrobial, and antioxidant properties. Among the vast range of compounds, multiple research papers have shown that cannabinoids, such as cannabidiol and delta-9-tetrahydrocannabinol, have antiviral effects. Recently, scientists found that both compounds can reduce severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral infection by downregulating ACE2 transcript levels and by exerting anti-inflammatory properties. These compounds also act as the SARS-CoV-2 main protease inhibitors that block viral replication. Apart from cannabinoids, terpenes in cannabis plants have also been widely explored for their antiviral properties. With particular emphasis on four different viruses, SARS-CoV-2, human immunodeficiency virus, hepatitis C virus, and herpes simplex virus-1, this review discussed the role of cannabis compounds in combating viral infections and the potential of both cannabinoids and terpenes as novel antiviral therapeutics.

Synthetic cannabinoids and ST elevation myocardial infarction.

Synthetic cannabinoids cannot be detected on a standard urine drug screen (UDS), making them a convenient drug of abuse. We report the first case of ST elevation myocardial infarction (STEMI) in a young patient due to coronary artery thrombosis secondary to synthetic cannabinoid use and concurrent COVID-19 infection. A 38-year-old previously healthy male developed severe chest pain and was found to have anterior STEMI and COVID-19 infection. Coronary angiography showed acute thrombotic occlusion of the mid-left anterior descending artery that was managed with thrombectomy and stent placement. He only required supportive care for COVID-19. A comprehensive literature search revealed 34 additional cases of STEMI with synthetic cannabinoid use; majority were males (97%) with mean age of 29 years. 29 patients (85.3%) underwent coronary angiography and majority had left anterior descending artery (LAD) involvement (55%), with 13 (44.8%) undergoing stent placement. We highlight STEMI as a potentially lethal complication of synthetic cannabinoids; prompt angiography may be lifesaving.

Selective CB2 Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury.

Acute respiratory distress syndrome (ARDS) and sepsis are risk factors contributing to mortality in patients with pneumonia. In ARDS, also termed acute lung injury (ALI), pulmonary immune responses lead to excessive pro-inflammatory cytokine release and aberrant alveolar neutrophil infiltration. Systemic spread of cytokines is associated with systemic complications including sepsis, multi-organ failure, and death. Thus, dampening pro-inflammatory cytokine release is a viable strategy to improve outcome. Activation of cannabinoid type II receptor (CB2) has been shown to reduce cytokine release in various in vivo and in vitro studies. Herein, we investigated the effect of HU-308, a specific CB2 agonist, on systemic and pulmonary inflammation in a model of pneumonia-induced ALI. C57Bl/6 mice received intranasal endotoxin or saline, followed by intravenous HU-308, dexamethasone, or vehicle. ALI was scored by histology and plasma levels of select inflammatory mediators were assessed by Luminex assay. Intravital microscopy (IVM) was performed to assess leukocyte adhesion and capillary perfusion in intestinal and pulmonary microcirculation. HU-308 and dexamethasone attenuated LPS-induced cytokine release and intestinal microcirculatory impairment. HU-308 modestly reduced ALI score, while dexamethasone abolished it. These results suggest administration of HU-308 can reduce systemic inflammation without suppressing pulmonary immune response in pneumonia-induced ALI and systemic inflammation.

Analysis and Identification of Bioactive Compounds of Cannabinoids in Silico for Inhibition of SARS-CoV-2 and SARS-CoV.

Despite the approval of multiple vaccinations in different countries, the majority of the world's population remains unvaccinated due to discrepancies in vaccine distribution and limited production capacity. The SARS-CoV-2 RBD-ACE2 complex (receptor binding domain that binds to ACE2) could be a suitable target for the development of a vaccine or an inhibitor. Various natural products have been used against SARS-CoV-2. Here, we docked 42 active cannabinoids to the active site of the SARS-CoV-2 and SARS-CoV complex of RBD-ACE2. To ensure the flexibility and stability of the complex produced after docking, the top three ligand molecules with the best overall binding energies were further analyzed through molecular dynamic simulation (MDS). Then, we used the webserver Swissadme program and binding free energy to calculate and estimate the MMPBSA and ADME characteristics. Our results showed that luteolin, CBGVA, and CBNA were the top three molecules that interact with the SARS-CoV-2 RBD-ACE2 complex, while luteolin, stigmasterol, and CBNA had the strongest contact with that SARS-CoV. Our findings show that luteolin may be a potential inhibitor of infections caused by coronavirus-like pathogens such as COVID-19, although further in vivo and in vitro research is required.

Use of Alcohol, Cannabinoids, Psychostimulants, and Sedatives before and during the COVID-19 Pandemic among Students in 40 European Countries.

In March 2020, the WHO announced the COVID-19 pandemic, which has been ongoing for over 2 years. To stop the spread of the virus, the governments of many countries decided to introduce reasonable social restrictions that were suitable for pandemic waves. This led to radical changes in people's lives, especially among students, who are very active in society. Before COVID-19, being of student age was associated with the highest frequency of stimulants use. It is important to note that drugs are taken disparately in various areas. Therefore, using the Computer-Assisted Web Interview type of study, the impact of the pandemic on the use of alcohol, cannabinoids, psychostimulants (e.g., amphetamine, methamphetamine, ecstasy) and sedatives (e.g., zolpidem, zopiclone, alprazolam, lorazepam, etc.) was assessed among students from European countries. The questionnaire included single- and multiple-answer questions. The first part concerned sociodemographic questions, while the second included questions about the use of stimulants in the last 3 months prior to participation in the study. Distribution of the survey covered the period from 31 January 2016 to 30 April 2021. A total of 17,594 European students participated in the study. The vast majority of participants were women (80.4%) and students of non-medical universities (77.2%) living in Eastern European countries (86.1%). Of all students, 15,613 (89.6%) reported alcohol drinking, 2538 (14.1%) the use of cannabinoids, 650 (3.6%) psychostimulants, and 2252 (12.5%) sedatives in the past three months. It has been shown that women are far less likely to use alcohol (OR 0.81), psychostimulants (OR 0.44) and cannabinoids (OR 0.49), while they are more likely to use sedatives (OR 1.41). During the COVID-19 pandemic, the consumption of alcohol (OR 0.55) and psychostimulants (OR 0.72) decreased and that of sleep medications increased (OR 1.17). To conclude, the COVID-19 pandemic influenced the pattern of stimulants used by students in European countries. The restriction of social interactions contributed to the decrease in the consumption of alcohol and psychostimulants but increased the use of sedatives and the frequency of their use. Women were found to use sedatives more often, while men preferred to drink alcohol and use cannabinoids or psychostimulants. It has also been shown that students of Central and Eastern Europe more often use alcohol and sedatives, while in Southern European countries psychostimulants and cannabinoids are preferred.

Cannabinoid hyperemesis syndrome in North America: evaluation of health burden and treatment prevalence.

BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is a poorly understood vomiting disorder associated with chronic cannabis use. AIMS: To characterise patients experiencing CHS in North America and to obtain a population-based estimate of CHS treatment prevalence in Canada before and during the Covid-19 pandemic METHODS: Internet survey of 157 CHS sufferers in Canada and the United States. Administrative health databases for the province of Alberta (population 5 million) were accessed to measure emergency department (ED) visits for vomiting, with a concurrent diagnostic code for cannabis use. Three time periods of 1 year were assessed: prior to recreational cannabis legalisation (2017-2018), after recreational legalisation (2018-2019) and during the first year of the Covid-19 pandemic (2020-2021). RESULTS: Problematic cannabis use (defined as a CUDIT-R score ≥8) was universal among the survey cohort, and 59% and 68% screening for moderate or worse anxiety or depression, respectively. The overall treatment prevalence of CHS across all ages increased from 15 ED visits per 100,000 population (95% CI, 14-17) prior to legalisation, to 21 (95% CI, 20-23) after legalisation, to 32 (95% CI, 31-35) during the beginning of the Covid-19 pandemic (p < 0.001). Treatment prevalence among chronic cannabis users was as high as 6 per 1000 in the 16-24 age group. CONCLUSION: Survey data suggest patients with CHS almost universally suffer from a cannabis use disorder, which has significant treatment implications. Treatment prevalence in the ED has increased substantially over a very short time period, with the highest rates seen during the Covid-19 pandemic.

Cannabinoids as Emergent Therapy Against COVID-19.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory distress syndrome coronavirus 2 (SARS-Cov-2), was identified for the first time in late 2019 in China, resulting in a global pandemic of massive impact. Despite a fast development and implementation of vaccination strategies, and the scouting of several pharmacological treatments, alternative effective treatments are still needed. In this regard, cannabinoids represent a promising approach because they have been proven to exhibit several immunomodulatory, anti-inflammatory, and antiviral properties in COVID-19 disease models and related pathological conditions. This mini-review aims at providing a practical brief overview of the potential applications of cannabinoids so far identified for the treatment and prevention of COVID-19, finally considering key aspects related to their technological and clinical implementation.

Toxic Habits and Well-Being Measures in Spanish Healthcare University Students during the COVID-19 Pandemic.

BACKGROUND: Unhealthy lifestyles are strongly entrenched in healthcare universities and have sometimes been linked to stress or lack of sleep. This study investigated the prevalence of toxic habits (smoking, patterns of harmful alcohol use, and illicit drug use), stress levels, perceived health status, and sleep duration and assessed the connections between toxic habits and said well-being measures, as well as healthcare students' perception of the influence of the COVID-19 pandemic on these health-related behaviors. METHODS: In a cross-sectional study, healthcare students from Alfonso X University (Spain) completed a health survey composed of Alcohol Use Disorders Identification Test (AUDIT-C), Perceived Stress Scale (PSS-10), self-perceived health status, and the number of hours of sleep. RESULTS: A total of 997 healthcare students completed the survey, of which 982 were analyzed. Being a smoker (32.2%) was associated with worse health status and insufficient sleep. Risk drinkers (33.2%) were associated with being female, and the consumption of cannabinoids (6.7%), with being male. These three toxic habits were related to each other. High levels of stress (28.2%) were correlated with worse ratings in the perception of health status (29.2%) and with insufficient sleep (45.8%), and all of them were associated with the female sex. Respectively, 49.3% and 44.2% of students recognized a worsening in their perception of stress and their sleep habits during the pandemic. CONCLUSION: Healthcare universities must carry out health promotion programs for stress management, sleep habits, and unhealthy lifestyles.

Identification of SARS-CoV-2 Main Protease Inhibitors from a Library of Minor Cannabinoids by Biochemical Inhibition Assay and Surface Plasmon Resonance Characterized Binding Affinity.

The replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by its main protease (Mpro), which is a plausible therapeutic target for coronavirus disease 2019 (COVID-19). Although numerous in silico studies reported the potential inhibitory effects of natural products including cannabis and cannabinoids on SARS-CoV-2 Mpro, their anti-Mpro activities are not well validated by biological experimental data. Herein, a library of minor cannabinoids belonging to several chemotypes including tetrahydrocannabinols, cannabidiols, cannabigerols, cannabichromenes, cannabinodiols, cannabicyclols, cannabinols, and cannabitriols was evaluated for their anti-Mpro activity using a biochemical assay. Additionally, the binding affinities and molecular interactions between the active cannabinoids and the Mpro protein were studied by a biophysical technique (surface plasmon resonance; SPR) and molecular docking, respectively. Cannabinoids tetrahydrocannabutol and cannabigerolic acid were the most active Mpro inhibitors (IC50 = 3.62 and 14.40 µM, respectively) and cannabigerolic acid had a binding affinity KD=2.16×10-4 M). A preliminary structure and activity relationship study revealed that the anti-Mpro effects of cannabinoids were influenced by the decarboxylation of cannabinoids and the length of cannabinoids' alkyl side chain. Findings from the biochemical, biophysical, and computational assays support the growing evidence of cannabinoids' inhibitory effects on SARS-CoV-2 Mpro.

Cross-Talk between the (Endo)Cannabinoid and Renin-Angiotensin Systems: Basic Evidence and Potential Therapeutic Significance.

This review is dedicated to the cross-talk between the (endo)cannabinoid and renin angiotensin systems (RAS). Activation of AT1 receptors (AT1Rs) by angiotensin II (Ang II) can release endocannabinoids that, by acting at cannabinoid CB1 receptors (CB1Rs), modify the response to AT1R stimulation. CB1R blockade may enhance AT1R-mediated responses (mainly vasoconstrictor effects) or reduce them (mainly central nervous system-mediated effects). The final effects depend on whether stimulation of CB1Rs and AT1Rs induces opposite or the same effects. Second, CB1R blockade may diminish AT1R levels. Third, phytocannabinoids modulate angiotensin-converting enzyme-2. Additional studies are required to clarify (1) the existence of a cross-talk between the protective axis of the RAS (Ang II-AT2 receptor system or angiotensin 1-7-Mas receptor system) with components of the endocannabinoid system, (2) the influence of Ang II on constituents of the endocannabinoid system and (3) the (patho)physiological significance of AT1R-CB1R heteromerization. As a therapeutic consequence, CB1R antagonists may influence effects elicited by the activation or blockade of the RAS; phytocannabinoids may be useful as adjuvant therapy against COVID-19; single drugs acting on the (endo)cannabinoid system (cannabidiol) and the RAS (telmisartan) may show pharmacokinetic interactions since they are substrates of the same metabolizing enzyme of the transport mechanism.

The Role of Cannabis sativa L. as a Source of Cannabinoids against Coronavirus 2 (SARS-CoV-2): An In Silico Study to Evaluate Their Activities and ADMET Properties.

Cannabis sativa L. is an annual herbaceous plant that belongs to the family Cannabinaceae. In this study, the potential use of forty-five cannabinoids, previously identified from Cannabis sativa to alleviate COVID-19 infection via prohibition of crucial SARS-CoV-2 proteins using molecular docking, was examined. In silico studies were performed on three vital enzymes that serve as principle therapeutic targets to prevent SARS-CoV-2 replication. These enzymes are the main protease SARS-CoV-2 MPro, papain-like protease SARS-CoV-2 PLpro and angiotensin-converting enzyme 2 (ACE2). Regarding SARS-CoV-2 MPro, cannabichromanon (32) showed the best fitting within its active centers, followed by cannabinolic acid (22) and cannabinol (21), displaying ∆G of -33.63, -23.24, and -21.60 kcal/mol, respectively. Concerning SARS-CoV-2 PLpro, cannabichromanon (32) followed by cannabinolic acid (22) and cannabicyclolic acid (41) revealed the best binding within its active pockets owing to multiple bond formation with ∆G values of -28.36, -22.81, and -19.89 kcal/mol. Furthermore, cannabichromanon (32), cannabinolic acid (22), and cannabinol (21) showed considerable fitting within the active sites of angiotensin-converting enzyme 2 (ACE2) evidenced by their significant ∆G values that were estimated as -41.77, -31.34, and -30.36 kcal/mol, respectively. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) evaluation was performed on the tested cannabinoids to further explore their pharmacokinetics, pharmacodynamics, and toxicity properties. The results indicated the considerable pharmacokinetic, pharmacodynamic, and toxicity properties of cannabinol (21), cannabinolic acid (22), cannabichromanon (32), and cannabicyclolic acid (41) that showed best fitting scores within the active sites of the tested enzymes. Multivariate data analysis revealed that cannabichromanon and cannabinolic acid showed a discriminant nature and hence can be incorporated in pharmaceutical dosage forms to alleviate COVID-19 infection.

Prevalence of Five Commonly Analyzed Cannabinoids in Forensic Toxicology Casework from Orange County CA, USA, from 2016 to 2019.

Over the last 25 years, marijuana laws have been changing throughout the USA. California started legalizing medicinal marijuana in 1996 and has since continued to relax laws. Compared to Washington and Colorado, there are little data on how the changing laws have affected the cannabinoid detection rate in California. This paper looks at the prevalence of five cannabinoids (Δ9-tetrahydrocannabinol (THC), 11-hydroxy-tetrahydrocannabinol (hydroxy-THC), 11-nor-9-carboxy-tetrahydrocannabinol (carboxy-THC), cannabinol and cannabidiol) in Orange County, CA, from 2016 to 2019. From 2016 to 2017, after legalizing recreational marijuana, there was an increase in the presence of THC, carboxy-THC and hydroxy-THC in postmortem and major crime cases, consisting mostly of sexual assaults. However, driving under the influence of drugs (DUID) saw a slight decrease. In 2018, when shops could be licensed to sell marijuana to anyone over 21 years old, there was an increase seen in all five cannabinoids for DUID and postmortem cases. The age group from 21 to 30 years showed the most prevalent cannabinoid use in all case types for all years except in major crime cases in 2019, where <21 year-old age group was the most prevalent. Surprisingly, the >50-year-old group in death investigation cases was a close second in prevalence in all years, which differs from DUID and major crime cases.

Cannabinoids Alleviate the LPS-Induced Cytokine Storm via Attenuating NLRP3 Inflammasome Signaling and TYK2-Mediated STAT3 Signaling Pathways In Vitro.

Cannabinoids, mainly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), are the most studied group of compounds obtained from Cannabis sativa because of their several pharmaceutical properties. Current evidence suggests a crucial role of cannabinoids as potent anti-inflammatory agents for the treatment of chronic inflammatory diseases; however, the mechanisms remain largely unclear. Cytokine storm, a dysregulated severe inflammatory response by our immune system, is involved in the pathogenesis of numerous chronic inflammatory disorders, including coronavirus disease 2019 (COVID-19), which results in the accumulation of pro-inflammatory cytokines. Therefore, we hypothesized that CBD and THC reduce the levels of pro-inflammatory cytokines by inhibiting key inflammatory signaling pathways. The nucleotide-binding and oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling has been implicated in a variety of chronic inflammatory diseases, which results in the release of pyroptotic cytokines, interleukin-1ß (IL-1ß) and IL-18. Likewise, the activation of the signal transducer and activator of transcription-3 (STAT3) causes increased expression of pro-inflammatory cytokines. We studied the effects of CBD and THC on lipopolysaccharide (LPS)-induced inflammatory response in human THP-1 macrophages and primary human bronchial epithelial cells (HBECs). Our results revealed that CBD and, for the first time, THC significantly inhibited NLRP3 inflammasome activation following LPS + ATP stimulation, leading to a reduction in the levels of IL-1ß in THP-1 macrophages and HBECs. CBD attenuated the phosphorylation of nuclear factor-κB (NF-κB), and both cannabinoids inhibited the generation of oxidative stress post-LPS. Our multiplex ELISA data revealed that CBD and THC significantly diminished the levels of IL-6, IL-8, and tumor necrosis factor-α (TNF-α) after LPS treatment in THP-1 macrophages and HBECs. In addition, the phosphorylation of STAT3 was significantly downregulated by CBD and THC in THP-1 macrophages and HBECs, which was in turn attributed to the reduced phosphorylation of tyrosine kinase-2 (TYK2) by CBD and THC after LPS stimulation in these cells. Overall, CBD and THC were found to be effective in alleviating the LPS-induced cytokine storm in human macrophages and primary HBECs, at least via modulation of NLRP3 inflammasome and STAT3 signaling pathways. The encouraging results from this study warrant further investigation of these cannabinoids in vivo.

Anti-Inflammatory and Antiviral Effects of Cannabinoids in Inhibiting and Preventing SARS-CoV-2 Infection.

The COVID-19 pandemic caused by the SARS-CoV-2 virus made it necessary to search for new options for both causal treatment and mitigation of its symptoms. Scientists and researchers around the world are constantly looking for the best therapeutic options. These difficult circumstances have also spurred the re-examination of the potential of natural substances contained in Cannabis sativa L. Cannabinoids, apart from CB1 and CB2 receptors, may act multifacetedly through a number of other receptors, such as the GPR55, TRPV1, PPARs, 5-HT1A, adenosine and glycine receptors. The complex anti-inflammatory and antiviral effects of cannabinoids have been confirmed by interactions with various signaling pathways. Considering the fact that the SARS-CoV-2 virus causes excessive immune response and triggers an inflammatory cascade, and that cannabinoids have the ability to regulate these processes, it can be assumed that they have potential to be used in the treatment of COVID-19. During the pandemic, there were many publications on the subject of COVID-19, which indicate the potential impact of cannabinoids not only on the course of the disease, but also their role in prevention. It is worth noting that the anti-inflammatory and antiviral potential are shown not only by well-known cannabinoids, such as cannabidiol (CBD), but also secondary cannabinoids, such as cannabigerolic acid (CBGA) and terpenes, emphasizing the role of all of the plant's compounds and the entourage effect. This article presents a narrative review of the current knowledge in this area available in the PubMed, Scopus and Web of Science medical databases.

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

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.

Potential Neuroprotective Effect of Cannabinoids in COVID-19 Patients.

The global pandemic caused by the SARS-CoV-2 virus began in early 2020 and is still present. The respiratory symptoms caused by COVID-19 are well established. However, neurological manifestations that may result from direct or indirect neurological damage after SARS-CoV-2 infection have been reported frequently. The main proposed pathophysiological processes leading to neurological damage in COVID-19 are cerebrovascular disease and indirect inflammatory/ autoimmune origin mechanisms. A growing number of studies confirm that neuroprotective measures should be maintained in COVID-19 patients. On the other hand, cannabinoids have been the subject of various studies that propose them as potentially promising drugs in chronic neurodegenerative diseases due to their powerful neuroprotective potential. In this review, we addresses the possible mechanism of action of cannabinoids as a neuroprotective treatment in patients infected by SARS-CoV-2. The endocannabinoid system is found in multiple systems within the body, including the immune system. Its activation can lead to beneficial results, such as a decrease in viral entry, a reduction of viral replication, and a reduction of pro-inflammatory cytokines such as IL-2, IL-4, IL-6, IL-12, TNF-α, or IFN-c through CB2R expression induced during inflammation by SARS-CoV-2 infection in the central nervous system.

Implications of Cannabis and Cannabinoid Use in COVID-19: Scoping Review.

OBJECTIVE: to identify and synthesize studies on the effects of cannabis use and its relation with SARS-CoV-2, as well as the therapeutic possibilities of using cannabinoids in the prevention and treatment of COVID-19. METHODS: scoping review, in the BVS, PubMed, SCIELO, CINAHL, SCOPUS, Web of Science, MedNar, CAPES and ProQuest databases, with no language restriction and year limitation. Narrative synthesis was performed. RESULTS: cannabis use causes changes in the respiratory and vascular system, it reduces the production of cytokines, which affects the users' immune system, increasing the susceptibility to infection and progression of COVID-19. However, studies have suggested the use of cannabinoids in the prophylaxis and treatment of COVID-19, due to their anti-inflammatory effect. CONCLUSIONS: the use of inhaled cannabis increases the progression and severity of the infection. On the other hand, the benefits of cannabinoids seem promising to modulate the immune system, but it needs further studies.

"I got a bunch of weed to help me through the withdrawals": Naturalistic cannabis use reported in online opioid and opioid recovery community discussion forums.

A growing body of research has reported on the potential opioid-sparing effects of cannabis and cannabinoids, but less is known about specific mechanisms. The present research examines cannabis-related posts in two large online communities on the Reddit platform ("subreddits") to compare mentions of naturalistic cannabis use by persons self-identifying as actively using opioids versus persons in recovery. We extracted all posts mentioning cannabis-related keywords (e.g., "weed", "cannabis", "marijuana") from December 2015 through August 2019 from an opioid use subreddit and an opioid recovery subreddit. To investigate how cannabis is discussed at-scale, we identified and compared the most frequent phrases in cannabis-related posts in each subreddit using term-frequency-inverse document frequency (TF-IDF) weighting. To contextualize these findings, we also conducted a qualitative content analysis of 200 random posts (100 from each subreddit). Cannabis-related posts were about twice as prevalent in the recovery subreddit (n = 908; 5.4% of 16,791 posts) than in the active opioid use subreddit (n = 4,224; 2.6% of 159,994 posts, p < .001). The most frequent phrases from the recovery subreddit referred to time without using opioids and the possibility of using cannabis as a "treatment." The most frequent phrases from the opioid subreddit referred to concurrent use of cannabis and opioids. The most common motivations for using cannabis were to manage opioid withdrawal symptoms in the recovery subreddit, often in conjunction with anti-anxiety and GI-distress "comfort meds," and to enhance the "high" when used in combination with opioids in the opioid subreddit. Despite limitations in generalizability from pseudonymous online posts, this examination of reports of naturalistic cannabis use in relation to opioid use identified withdrawal symptom management as a common motivation. Future research is warranted with more structured assessments that examines the role of cannabis and cannabinoids in addressing both somatic and affective symptoms of opioid withdrawal.