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The pandemic caused by Sars-CoV-2 (COVID-19) has been a great concern for public and mental health systems worldwide. The identification of risk groups is essential for the establishment of preventive and therapeutic strategies, as for substance users. During COVID-19 pandemic, there was an increase in the use of psychoactive substances during the lockdown, including cannabis. This commentary reviews relevant findings and discusses scientific evidence on the risks of worse clinical and psychiatric complications due to coronavirus disease COVID-19 in subjects who use cannabis. Although they are not included as a risk group in the health recommendations for that disease, they may have a more vulnerable respiratory system to viral diseases. There are certain similarities between the harmful cardiovascular and respiratory effects of cannabis use and those of smoking. Due to the different modes of smoking, cannabis chemicals are retained in the body for longe and may also contain other toxic substances such as tar, a substance found in tobacco and which has been associated with the development of lung cancer, bronchitis and pulmonary emphysema. Therefore, we discuss if individuals who use cannabis regularly might be more vulnerable to COVID-19 infection. This population deserves more clinical attention worldwide and this manuscript can help clinicians become more aware of cannabis risks during pandemics and develop specific intervention strategies. Compounds in cannabis can prevent infection from the virus that causes Covid-19 by blocking its entry into cells, according to a study published this week by researchers affiliated with Oregon State University. COVID-19 pandemic has resulted in devastating mortality and morbidity consisting of socioeconomic and health effects that have included respiratory/pulmonary, cardiovascular, mental health and neurological consequences such as anxiety, depression, and substance use. Extensive efforts are underway to …

Multiple clinical risks for cannabis users during the COVID-19 pandemic

The pandemic caused by Sars-CoV-2 (COVID-19) has been a great concern for public and mental health systems worldwide. The identification of risk groups is essential for the establishment of preventive and therapeutic strategies, as for substance users. During COVID-19 pandemic, there was an increase in the use of psychoactive substances during the lockdown, including cannabis. This commentary reviews relevant findings and discusses scientific evidence on the risks of worse clinical and psychiatric complications due to coronavirus disease COVID-19 in subjects who use cannabis. Although they are not included as a risk group in the health recommendations for that disease, they may have a more vulnerable respiratory system to viral diseases. There are certain similarities between the harmful cardiovascular and respiratory effects of cannabis use and those of smoking. Due to the different modes of smoking, cannabis chemicals are retained in the body for longe and may also contain other toxic substances such as tar, a substance found in tobacco and which has been associated with the development of lung cancer, bronchitis and pulmonary emphysema. Therefore, we discuss if individuals who use cannabis regularly might be more vulnerable to COVID-19 infection. This population deserves more clinical attention worldwide and this manuscript can help clinicians become more aware of cannabis risks during pandemics and develop specific intervention strategies.

Introduction

The pandemic caused by Sars-CoV-2 (COVID19) has caused the collapse of health systems worldwide. Alongside the clinical risk, the appearance or intensification of psychiatric symptoms has also been generating a mental health pandemic within another. The identification of risk groups is essential for the establishment of preventive and therapeutic strategies, for people who are infected by the COVID-19 virus, as well as for users os psychoative substances (PS). During the COVID-19 pandemic, it was identified that the consumption of PS, such as tobacco, cannabis, and cocaine increased the risk of contamination of influenza and was associated with a worse clinical prognosis [1]. A study found that patients with a recent use of PS were at significant risk greater risk of developing COVID-19 compared to patients without a recent substance use disorder (SUD) diagnosis, after adjusting for age, sex, race and types of insurance. Although cannabis users have a lower odds ratio than other drugs (opioids, tobacco, alcohol and cocaine) the risk is five times greater than in people who do not use PS [2]. Thus, cannabis users can be at risk of clinical complications if infected with COVID-19 due to deteriorating health status.

A review conducted in 2019 found that with the increasing increase in cannabis use in the population there has been an increasing number of studies associating cannabis use with serious and life-threatening cardiovascular complications, including acute coronary syndromes, potentially lethal cardiac arrhythmias and ischemic strokes. There are certain similarities between the harmful cardiovascular and respiratory effects of cannabis use and those of smoking. Despite the difference in active ingredients (tetrahydrocannabinol vs. nicotine), along with, due to the different modes of smoking, cannabis chemicals are retained in the body for longer [3]. Furthermore, cannabis may also contain other toxic substances such as tar, a substance found in tobacco and which has been associated with the development of lung cancer, bronchitis and pulmonary emphysema [4]. Although, it is necessary to consider that cannabis is widely used by young populations.

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A recent review shows a significant association between cannabis use and symptoms of chronic bronchitis after adjustment for tobacco. Some studies have found a modest reduction in specific airway conductance in relation to marijuana, probably reflecting endoscopic evidence of bronchial mucosa edema among habitual cannabis smokers [5]. The immunosuppressive effects of delta-9 tetrahydrocannabinol (THC) increase the possibility of an increased risk of pneumonia, but further studies are needed to assess this potential risk. Several case series have demonstrated pneumothorax / pneumomediastinum and bullous lung disease in cannabis smokers, but these associations require epidemiological studies for firmer evidence of possible causation. Another recent study reports that the use of vaping causes lung injuries similar to COVID-19 symptoms [6].

Moreover, most of the people who use cannabis also report tobacco use concurrently. This fact may increase the risk of exposure to toxic substances, as certain co-users (for example, blunt users) tend to have higher levels of carbon monoxide in exhaled air and cannabis smoke may have higher levels of some carcinogens than tobacco smoke [7]. Previous studies have indicated that long-term cannabis use is associated with high mortality rates, heart disease [8], metabolic syndromes and changes in the immune system [9]. In this sense, when compared to the general population, we can consider that this population may be more vulnerable to infection morbidity and mortality.

In addition to worsening the clinical outcome (especially involving respiratory risk) [10], cannabis use can generate or increase psychiatric disorders (mainly psychotic symptoms) [11], intense emotional and behavioral reactions were reported during the pandemic, such as fear, boredom, loneliness, anxiety, insomnia, anger and aggression [12]. These symptoms might be especially intense in people who use cannabis, as it is a population that has high rates of psychiatric comorbidities, is particularly sensitive to dysphoric emotional states and has a low tolerance for frustration and stress [13]. Futhermore, it has been described that people who use cannabis may have high rates of psychiatric disorder comorbidities such as simultaneous substance use (mainly tobacco and alcohol), anxiety disorders, mood disorders and personality disorders, potentiating higher risk symptoms in the current scenario [14].

A study conducted in the USA found that 36% of adults had symptoms of anxiety disorders compared to 8% of adults in January–June 2020 (N = 17,067). Anxiety can lead to increased substance use, beginning to use SPA, relapses or even increasing the amount of SPA used. [15]. Another study, carried out with 1054 Canadian adolescents, for a previous period and after the beginning of the practices of social distancing, showed that there was an increase in the use of alcohol and cannabis by this population and although 43% of the sample reported using cannabis and alcohol alone, 23% of the sample reported using it with friends during the period of social isolation, thus placing adolescents at risk of contracting COVID-19. Besides, solitary substance use in adolescence during the pandemic, which is associated with mental health problems and coping, can also be a notable concern, worthy of further investigation [16].

Nevertheless, recent studies also report that the use of cannabinoids offers good results in the treatment of COVID-19, although the endocannabinoid system (ECS) is involved in the regulation of several physiological processes, including sleep and the immune response, its role during infections has not been fully studied. It is well known that the use of this substance increases the susceptibility to infections due to the impact on the modulation of the immune system. Regarding the medicinal or recreational use of cannabis, its influence on the course of an infection, whether caused by bacteria, viruses, parasites, and fungi, has been reported. In this sense, there is evidence to suggest the involvement of ECS in the control and elimination of infectious agents but few studies are available to date. The question therefore arises as to whether ECS increases the severity of viral or bacterial infections and whether consumption of cannabis or synthetic cannabis derivatives / products can influence this risk.

The ECS has a modulating effect on the immune system, but subjects who take cannabinoids or cannabis are not considered immunosuppressed [17]. There are currently no studies available on the incidence and course COVID-19 infection in individuals taking cannabinoids. Pre-existing non-medical consumption of cannabinoids should not be increased, but decreased, during the COVID-19 pandemic, considering potential respiratory complications. One should avoid sharing cigarettes, pipes, or any equipment used for the use of cannabis, as well as any psychoactive substance, as it might be a potential form of transmission of the virus, since the greatest form of dissemination is through droplets of saliva. Likewise, cannabidiol (CBD) cannot be recommended as a possible medication, as the impact on immunity in the case of COVID-19 infection is unclear [18].

In this context, it is essential that this population is recognized according to their clinical and psychiatric vulnerability. It is vital to think about prevention and protection strategies, as well as the recovery of clinical and mental symptoms. In order to prevent the period of social distance from intensifying consumption and all other risks related to it, several measures must be taken. Among them, one must consider: the information must be used as a form of prevention, damage reduction policy, pharmacological approach, brief intervention, possibly online, during the most critical peak of the pandemic. Therefore, it is relevant to refer these patients to highly complex health treatment centers to evaluate and treat them according to the specificity of this population. The clinical and psychiatric aspects of addiction and its relationship with COVID-19 should be noted. There are few studies conducted to date on the increased risk of COVID-19-related morbidity and mortality in this population, although the gray literature has shown data showing the increase in cannabis use in the United States during this period. Epidemiological studies should be carried out to assess a potential increase in cannabis use by the population and investments should be intensified, as well as directed to psychoeducation, to preventive and therapeutic approaches to this substance and its consequences, enhanced by the inherent pandemic risks.

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Conclusion

Our manuscript contains clinically relevant notes on the risks of worse clinical complications due to COVID-19 in marijuana users. Although not included as a risk group in global health recommendations, marijuana users may be more vulnerable to contagion and worsening of their clinical condition due to covid-19 infection are at high risk, this can be explained both by the action of the psychoactive substance on central nervous system and not immune system, as well as due to the method of use that this substance is usually used. In addition, the behavior of marijuana users can make them even more vulnerable to SARS-CoV-2 infection. At this stage that Pandemia is in, with increasing rates of morbidity due to contagion by COVID-19, this population deserves more clinical attention worldwide. Therefore, our letter manuscript can help doctors become more aware of this group and can develop a specific approach.

Study Finds Cannabis Compounds Prevent Infection By Covid-19 Virus

Compounds in cannabis can prevent infection from the virus that causes Covid-19 by blocking its entry into cells, according to a study published this week by researchers affiliated with Oregon State University. A report on the research, “Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants,” was published online on Monday by the Journal of Natural Products.

The researchers found that two cannabinoid acids commonly found in hemp varietals of cannabis, cannabigerolic acid, or CBGA, and cannabidiolic acid, also known as CBDA, can bind to the spike protein of SARS-CoV-2, the virus that causes Covid-19. By binding to the spike protein, the compounds can prevent the virus from entering cells and causing infection, potentially offering new avenues to prevent and treat the disease.

Compounds in cannabis can prevent infection by the virus that causes Covid-19, according to research . [+] published this week.

“Orally bioavailable and with a long history of safe human use, these cannabinoids, isolated or in hemp extracts, have the potential to prevent as well as treat infection by SARS-CoV-2,” the researchers wrote in an abstract of the study.

The study was led by Richard van Breemen, a researcher with Oregon State’s Global Hemp Innovation Center in the College of Pharmacy and Linus Pauling Institute, in collaboration with scientists at the Oregon Health & Science University. Van Breeman said that the cannabinoids studied are common and readily available.

“These cannabinoid acids are abundant in hemp and in many hemp extracts,” van Breemen said, as quoted by local media. “They are not controlled substances like THC, the psychoactive ingredient in marijuana, and have a good safety profile in humans.”

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Cannabinoids Effective Against New Variants

Van Breemen added that CBDA and CBGA blocked the action of emerging variants of the virus that causes Covid-19, saying that “our research showed the hemp compounds were equally effective against variants of SARS-CoV-2, including variant B.1.1.7, which was first detected in the United Kingdom, and variant B.1.351, first detected in South Africa.”

CBGA and CBDA prevented infection from the virus that causes Covid-19 by binding to its . [+] characteristic spike protein.

The spike protein is the same part of the virus target by Covid-19 vaccines and antibody therapies. In addition to the spike protein, SARS-CoV-2 has three more structural proteins as well as 16 nonstructural proteins and several compounds van Breemen characterized as “accessory” proteins, all of which are potential targets for drugs developed to prevent Covid-19.

“Any part of the infection and replication cycle is a potential target for antiviral intervention, and the connection of the spike protein’s receptor binding domain to the human cell surface receptor ACE2 is a critical step in that cycle,” van Breeman said. “That means cell entry inhibitors, like the acids from hemp, could be used to prevent SARS-CoV-2 infection and also to shorten infections by preventing virus particles from infecting human cells. They bind to the spike proteins so those proteins can’t bind to the ACE2 enzyme, which is abundant on the outer membrane of endothelial cells in the lungs and other organs.”

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Although further research is needed, van Breemen noted that study shows the cannabinoids could be developed into drugs to prevent or treat Covid-19.

“These compounds can be taken orally and have a long history of safe use in humans,” van Breemen noted. “They have the potential to prevent as well as treat infection by SARS-CoV-2. CBDA and CBGA are produced by the hemp plant as precursors to CBD and CBG, which are familiar to many consumers. However, they are different from the acids and are not contained in hemp products.”

Van Breeman also noted that the research showed the cannabinoids were effective against new variants of the virus, which he said are “one of the primary concerns” in the pandemic for health officials and clinicians.

“These variants are well known for evading antibodies against early lineage SARS-CoV-2, which is obviously concerning given that current vaccination strategies rely on the early lineage spike protein as an antigen,” said van Breemen. “Our data show CBDA and CBGA are effective against the two variants we looked at, and we hope that trend will extend to other existing and future variants.”

The researcher added that “resistant variants could still arise amid widespread use of cannabinoids but that the combination of vaccination and CBDA/CBGA treatment should make for a much more challenging environment for SARS-CoV-2.”

COVID-19 and Cannabidiol (CBD)

COVID-19 pandemic has resulted in devastating mortality and morbidity consisting of socioeconomic and health effects that have included respiratory/pulmonary, cardiovascular, mental health and neurological consequences such as anxiety, depression, and substance use. Extensive efforts are underway to develop preventive vaccines and therapeutics such as remdesivir, dexamethasone, convalescent plasma, and others to treat COVID-19 but many report residual mental health problems after recovery. Cannabis products such as cannabidiol (CBD) are being advertised for the treatment of COVID-19 associated mental health problems and substance use disorders. This commentary will briefly clear the myth that CBD can ameliorate a wide range of COVID-19 associated health effects including anxiety, depression, or any substance use disorder, and show that there is a clear lack of sufficient unbiased clinical evidence from well-designed double-blind, placebo-controlled clinical trials to prove the antianxiety or antidepression therapeutic properties of CBD and support its wide use as medicine to treat COVID-19- associated mental health conditions or substance use disorders. Finally, we suggest that addiction physicians must play an important role in dealing with their patients requesting CBD prescription for treating any of these conditions.

Copyright © 2020 American Society of Addiction Medicine.

Conflict of interest statement

Research grants to the institution from Merck, Inc., Gillead Sciences, and Airbutus pharmaceuticals. Other authors report no conflicts of interest.

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