As the COVID-19 pandemic continues to impact global health, researchers are delving deeper into the biological systems that might influence the disease’s progression and outcomes. One such system is the endocannabinoid system (ECS), which has recently been highlighted in studies exploring its role in COVID-19 pathology and potential therapeutic interventions.
Cannabis Users and COVID-19 Severity
Recent large-scale research has provided compelling evidence suggesting that cannabis use may be associated with improved outcomes in COVID-19 patients. The most extensive study to date, conducted by Igwe and Alaribe (2024), analyzed data from 1,698,560 COVID-19-related hospitalizations using the National Inpatient Sample. This study found that cannabis use was associated with lower mortality among hospitalized COVID-19 patients [1].
These findings are supported by an earlier, smaller study by Shover et al. (2022), which examined 1,831 COVID-19 patients requiring hospital admission. Their research indicated that cannabis use was associated with decreased disease severity and better clinical outcomes in hospitalized COVID-19 patients [2].
However, it’s important to note that not all studies have reached the same conclusions. A study by Griffith et al. (2024), which analyzed 72,501 patients diagnosed with COVID-19, found that cannabis use was associated with increased risk of hospitalization and ICU admission [3]. This highlights the complexity of the relationship between cannabis use and COVID-19 outcomes.
The conflicting results underscore the need for further research to fully understand the mechanisms by which cannabis might influence COVID-19 severity. Factors such as the type of cannabinoids consumed (e.g., THC vs. CBD), method of consumption, and individual patient characteristics likely all play roles in determining therapeutic outcomes.
While the largest study by Igwe and Alaribe provides strong evidence for potential benefits, it’s crucial to interpret the findings cautiously. The observed associations do not prove causation, and more research is needed to elucidate the specific effects of different cannabinoids on the progression of COVID-19. It’s worth noting that these observational studies have limitations, and randomized controlled trials would be necessary to establish definitive causal relationships.
Cannabinoids and ECS Modulation
Cannabis exerts its therapeutic effects primarily through modulation of the ECS/eCBome, a complex suprasystem of receptors, endocannabinoids, and enzymes involved in maintaining homeostasis across our entire physiology. Cannabinoids, such as cannabidiol (CBD) and tetrahydrocannabinol (THC), interact with ECS receptors, influencing immune responses and inflammation. These interactions are thought to be key factors in the observed benefits of cannabis use in mitigating COVID-19 symptoms.
New Research Unveils ECS Dysfunction in COVID-19
A recent research study by Velasco et al., published in Nature Scientific Reports, provides compelling evidence that COVID-19 disease brings about significant alterations to the ECS [4]. The study found that levels of 2-arachidonoylglycerol (2-AG) were significantly elevated in COVID-19 patients, particularly during the acute phase, suggesting its involvement in the inflammatory response. Conversely, levels of anandamide (AEA) and N-palmitoylethanolamide (PEA) were decreased in post-acute patients, indicating persistent ECS dysregulation.
Figure 2: Circulating eCB levels per milligram of total protein in COVID-19 patients (acute n=30; post-acute n=16) compared to healthy donors (control n=16). Univariate analysis was performed using the Kruskall-Wallis test and Dunn test was used to calculate adjusted p-values: *p<0.05; **p<0.001. 2-AG: 2-arachidonoylglycerol, AEA: N-arachidonoylethanolamine, PEA: N-palmitoylethanolamine, OEA: N-oleoylethanolamine. Reproduced from Velasco et al. (2024) under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Scientific Rationale for Medical Cannabis
The findings from Velasco et al. provides a clear scientific rationale for the use of medical cannabis in COVID-19 treatment. By modulating ECS activity, cannabinoids potentially helps to alleviate inflammation and improve clinical outcomes. This aligns with previous research, such as the scoping review by Scott et al., which highlighted the potential of cannabinoids in managing both early SARS-CoV-2 infection and long COVID-19 [5].
Other ECS-Modulating Interventions
Cannabis is far from the only ECS-modulating intervention that can be employed to potentially combat COVID-19. Lifestyle changes such as diet, mindfulness, and exercise have also been shown to modulate ECS activity. These interventions can influence ECS function by promoting overall health and reducing inflammation, which may help mitigate the severity of COVID-19 symptoms. Additionally, pharmacological agents targeting ECS receptors or enzymes involved in endocannabinoid metabolism are being explored for their therapeutic potential.
Potential Role of Cannabis in Post-COVID Condition
A recent review by Cárdenas-Rodríguez et al. explores the possible role of cannabis in managing neuroinflammation in patients with post-COVID condition (PCC) [6]. The study suggests that cannabinoids, with their antioxidative, anti-inflammatory, and immunomodulatory properties, could be promising adjuvants for PCC, potentially reducing symptoms like headaches, fatigue, and anxiety.
Implications for Treatment
The modulation of the ECS presents a promising therapeutic target for COVID-19. Cannabinoids and other ECS-modulating interventions could offer novel approaches to managing both acute and post-acute phases of the disease, potentially reducing the severity of symptoms and improving recovery. Further research is needed to fully understand the mechanisms at play and to develop targeted therapies. As research into the ECS’s role in COVID-19 progresses, it’s important to consider the current state of ECS knowledge among healthcare professionals. [Read about the global analysis of healthcare professionals’ ECS knowledge].
Conclusion
The clear involvement of the ECS in COVID-19 pathology opens up new avenues for therapeutic interventions. As research continues to unravel the complexities of this system, cannabinoids and other ECS-modulating strategies are likely to emerge as valuable tools in the fight against COVID-19 and its long-term effects. The recent studies by Velasco et al., Scott et al., and Cárdenas-Rodríguez et al. underscore the importance of continued exploration into the ECS as a potential therapeutic target.
Future research directions should focus on:
- Conducting randomized controlled trials to establish causal relationships between cannabis use and COVID-19 outcomes.
- Investigating the specific effects of different cannabinoids (e.g., CBD vs. THC) on COVID-19 progression.
- Exploring potential ECS-targeted therapies for both acute COVID-19 and “long COVID”.
These efforts will be crucial in developing evidence-based treatments and interventions that leverage the ECS to combat COVID-19 and its long-term consequences.
References
- Igwe JK, Alaribe U. Cannabis use associated with lower mortality among hospitalized Covid-19 patients using the national inpatient sample: an epidemiological study. J Cannabis Res. 2024;6(1):18. Published 2024 Apr 6. doi:10.1186/s42238-024-00228-w
- Shover CM, Yan P, Jackson NJ, et al. Cannabis consumption is associated with lower COVID-19 severity among hospitalized patients: a retrospective cohort analysis. J Cannabis Res. 2022;4(1):46. Published 2022 Aug 5. doi:10.1186/s42238-022-00152-x
- Griffith NB, Baker TB, Heiden BT, et al. Cannabis, Tobacco Use, and COVID-19 Outcomes [published correction appears in JAMA Netw Open. 2024 Jul 1;7(7):e2427937. doi: 10.1001/jamanetworkopen.2024.27937]. JAMA Netw Open. 2024;7(6):e2417977. Published 2024 Jun 3. doi:10.1001/jamanetworkopen.2024.17977
- Velasco, M., Posada-Ayala, M., Pérez-Fernández, E., et al. (2024). Circulating endocannabinoid levels in SARS-CoV-2 infection and their potential role in the inflammatory response. Sci Rep, 14, 19558.
- Scott, C., Hall, S., Zhou, J., Lehmann, C. (2023). Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19-A Scoping Review. J Clin Med, 13(1), 227.
- Cárdenas-Rodríguez, N., Ignacio-Mejía, I., Correa-Basurto, J., et al. (2024). Possible Role of Cannabis in the Management of Neuroinflammation in Patients with Post-COVID Condition. Int J Mol Sci, 25(7), 3805.