An intriguing pattern has emerged for cannabis enthusiasts as a result of lockdowns and statewide safety restrictions for COVID-19.
Dr. Faisal Islam
Consumers, as of late, have been shopping for larger marijuana baskets per trip to the dispensaries in various states, including California, Colorado, Nevada, and Washington, . However, they are also cutting down on the number of trips, perhaps, as a preventive measure to reduce the risk of exposure to coronavirus during this pandemic. Sales dipped considerably by the end of March only to experience a resurgence after the issuing of stimulus checks and unemployment benefits.
For the past few years, cannabis consumption remained steady while the industry continued to thrive with robust sales of the drug. It is a recession-proof phenomenon, therefore presenting a unique opportunity for clinicians with respect to patient education and individualized care.1
An unfortunate carryover of the governmental restrictions, self-isolation, and social estrangement is that consumers are now turning to the dark web as a source for continuous supply of cannabis. Prepandemic, according to the U.N. 2020 World Drug Report, there was already a 30% increase in sales of cannabis between 2009 and 2018. COVID-19 has fractured the drug’s supply chain and created an inescapable void that is being filled by drug traffickers.2 A clinical dilemma is posed when a user procures counterfeit cannabis or a drug batch with impurities.
Riding the cytokine storm
Cytokines are a host of proteins with designated regulatory and immune responses that play an instrumental role in cell signaling. The aptly named “cytokine storm” conjures up the image of an imperiled immune system spiraling out of control; it is, in fact, an extreme immune response that culminates into a massive influx of cytokines released into the bloodstream. Without the presence of an immunologic threat, cytokines are responsible for maintaining homeostasis and the functionality of immune cells. However, acute cytokine release (i.e., cytokine storm), as is the case with severe COVID-19, jeopardizes organ function (for example, interstitial lung disease) with clinical symptoms, such as fever, cough, dyspnea, and myalgia.
Benefits and drawbacks of immunosuppressive agents
To inhibit cytokine release (e.g., interleukin-6 cytokine levels), immunosuppressive agents such as tocilizumab have been leveraged to damper the body’s overactive inflammatory response to perceived immunologic stressors, in particular, COVID-19. While the aforementioned agent was remarkably effective with respect to lung consolidation clearance in most of the patients tested, a host of untoward effects prevent its general applicability and use. However, a team of researchers from the University of Nebraska, Omaha, with the Texas Biomedical Research Institute, San Antonio, might have stumbled upon a strategic workaround for mitigating the immune response.
Zaid Choudhry
They have proposed that cannabidiol (CBD) be used in lieu of other agents with potentially toxic effects. Animal and human trials have established that CBD confers a relatively high margin of safety coupled with favorable tolerance, providing a viable option for effectively targeting the inflammatory processes of SARS-CoV-2–based pulmonary disease. Furthermore, efficacy increased when CBD was combined with a terpene formulation, especially with respect to the more traditional steroid therapy.3
SARS-CoV-2 exhibits binding affinity for the ACE2 receptor, which is expressed in the lungs as well as other known predilection sites of infection. Ongoing studies attempt to modulate ACE2 expression, thereby eliminating its conspicuous role as “viral gateways,” perhaps even more so in patients with lung pathologies (e.g., people with chronic obstructive pulmonary disease [COPD] and smokers) as they already are prone to increased respiratory morbidity. CBD lacks tetrahydrocannabinol (THC), or the psychoactive component of cannabis sativa, rendering the agent to be particularly attractive from a therapeutic perspective. In addition to being devoid of abuse potential, CBD exhibits remarkable anti-inflammatory properties. It should be noted that considerable overlap exists between tobacco and cannabis users, and it is too early to determine the impact on COVID-19. As opposed to cannabis’s effect on ACE2 levels, smoking exhibits a proinflammatory role by up-regulating ACE2 expression.3 However, there are currently numerous conflicting reports in circulation about the positive effect of nicotine on COVID-19 outcome; confounding variables will need to be explored further in patients with a history of using nicotine and cannabis together.
Dr. Zia Choudhry
From an immunologic perspective, the endocannabinoid system (ECS) plays an integral role in cell signaling by interacting with natural chemicals of the body, namely, cannabinoids with designated targets at the cannabinoid receptor 1 (CB1) and the CB2, respectively. The CB2 receptor is of particular interest as it is intimately involved in immune homeostasis; the primary goal of these COVID-19 studies is to modulate the endocannabinoid system via targeted CB2 therapies to produce an immunosuppressant effect.4 CB2 activation, be it by means of THC or CBD agonism, may prove to be beneficial by inhibiting the cytokine influx.
Unfortunately, there is a general dearth of data on COVID-19–exposed cannabis users, whether the drug is consumed for medication or recreational purposes. It has been suggested that cannabis intake might contribute toward the development of a cough, complicating the overall clinical outcome for those infected with the virus. The presence of a cough, even in an otherwise asymptomatic individual, facilitates viral spread. As for those cannabis users experiencing COVID-19 symptomatology, they can expect rapid clinical deterioration, including pronounced fatigue and a change in mental status.
According to pulmonary specialists and representatives of the American Lung Association, recreational cannabis use may be associated with a bronchitis-like inflammation (comparable with chronic bronchitis/COPD for chronic users) of the airways, along the lines of cigarette smoking.5 As far as cannabis smokers are concerned, the rationale for lung irritation is believed to stem from the relatively large portion of unburnt plant content that is inhaled in a given joint. If there is a superimposed infection, as is the case with COVID-19, the patient may experience further risk of adverse respiratory effects. This serves as a diagnostic dilemma for physicians, especially when they encounter patients who recently started dabbling with cannabis as a means of placating themselves or because they’ve heard rumors that it will somehow protect them from COVID-19. The entire assessment plan is slowed down as a result of the confounding variable (onset of a cough), which may arise independently of COVID-19 in cannabis users. Vulnerable populations include smokers and those with COPD or asthma, as they are more likely to require ventilator assistance during the course of COVID-19 therapy.5 Asthmatics and COPD patients are prone to bronchospasms because of sensitive airways.