Marijuana use and aspergillosis

This article was written in November 2016. Since then a number of US states have legalised marijuana for recreational use. The popularity of E-cigarettes, which may contain THC vaping cartridges, has also increased in recent years. These products have been linked to lung injuries, which are referred to as ‘e-cigarette or vaping product use-associated lung injury’ (EVALI).The liquids used within these cartridges can also be contaminated with bacterial and fungal toxins (14). In 2021, a fatal case of invasive pulmonary aspergillosis was reported as a complication of EVALI in an immunocompetent adolescent (15). However, as this is only a recent phenomenon, there is very little published research available.

Cannabis plants

Marijuana is the most commonly used illegal drug in the world (1). Prepared from the leaves, flowers, and stem of the Cannabis plant, it can be smoked, vaporised, added as an ingredient to food or brewed as a tea. In addition to recreational use, the use of medicinal cannabis has increased over the last decade, due to FDA approval for its use in HIV-1 and cancer patients. It has been recommended for the alleviation of pain, and for nausea and vomiting in those undergoing chemotherapy (2).

Since the 1970s there have been a small but significant number of case reports describing a link between marijuana use and invasive aspergillosis. This is thought to be due to the direct inhalation of fungal spores that are present on the surface of the plant. The heating of cannabis buds may not be sufficient for sterilization and so users (particularly those with compromised immune systems) are potentially exposed to life threatening pulmonary infection. Conditions of storage during shipment or aging processes may also contribute to the presence of mould in marijuana (3).

In a 1981 study, 11 out of 12 marijuana samples tested contained aspergillus organisms and found that the spores could easily be inhaled through contaminated cigarettes (4). In a more recent study, both marijuana and cigarettes were found to be heavily contaminated by fungal spores (5).

Marijuana inhalation may generate a serological response to Aspergillus in healthy participants, though there is only weak evidence for this. In 28 marijuana smokers, 13 had precipitins to Aspergillus antigens (significantly higher than a non-marijuana smoking control group) (4). The presence of precipitins demonstrated exposure to Aspergillus, but there was no correlation between the presence of precipitins and the total estimated marijuana exposure. One smoker had systemic aspergillosis, despite an active cellular immune response. The author suggests that a defect in the patient’s innate immune capabilities, combined with the exposure to Aspergillus through marijuana, may have led to the development of the disease, in the one patient. More research is required to examine the risk to healthy participants further. A longitudinal study could be useful in determining whether healthy people who take up smoking marijuana develop infectious lung disorders over time. Cases of invasive aspergillosis from marijuana have been studied in the following immunocompromised groups:

Cancer patients on chemotherapy (6,7)

Leukaemia patients (2,8,9)

A renal transplant patient (10)

AIDS patients (11)

The association is not limited to invasive aspergillosis – marijuana has been implicated in several other forms of the disease. A case of allergic bronchopulmonary aspergillosis (ABPA) in an asthma patient has been linked to marijuana contaminated with A. fumigatus, A. niger and A. flavus (3). The report suggests that Atopy, with or without asthma may offer a bronchial environment favourable to the growth of aspergillus and so the use of marijuana may be particularly hazardous for the atopic asthmatic subject. An atypical presentation of aspergillosis was found in a patient with Chronic Granulomatous Disease (12), and more recently, two cases of chronic pulmonary aspergillosis (CPA) have been associated with extensive medical use of marijuana (13). Overall however, the risk of developing any form of aspergillosis appears to be low, given the numbers of marijuana smokers, with the likely exception of invasive aspergillosis in highly immunocompromised patients.

Helen Le Sueur, National Aspergillosis Centre


Sources and Further Reading

References

  1. United Nations International Drug Control Programme., United Nations Office for Drug Control and Crime Prevention., & United Nations Office on Drugs and Crime. (1997). World drug report. Oxford: Oxford University Press.
  2. Ruchlemer, R., Amit-Kohn, M., Raveh, D., & Hanuš, L. (2015). Inhaled medicinal cannabis and the immunocompromised patient. Supportive Care in Cancer, 23(3), 819-822.
  3. Llamas, R., Hart, D. R., & Schneider, N. S. (1978). Allergic bronchopulmonary aspergillosis associated with smoking moldy marihuana. Chest, 73(6), 871-872.
  4. Kagen, S. L., Kurup, V. P., Sohnle, P. G., & Fink, J. N. (1983). Marijuana smoking and fungal sensitization. Journal of allergy and clinical immunology,71(4), 389-393.
  5. Verweij PE, Kerremans JJ, Voss A, Meis JF (2000) Fungal contamination of tobacco and marijuana. JAMA 284:2875
  6. Cescon, D. W., Page, A. V., Richardson, S., Moore, M. J., Boerner, S., & Gold, W. L. (2008). Invasive pulmonary aspergillosis associated with marijuana use in a man with colorectal cancer. Journal of Clinical Oncology,26(13), 2214-2215.
  7. Sutton S, Lum BL, Torti FM. Possible risk of invasive aspergillosis with marijuana use during chemotherapy for small cell lung cancer. Drug Intell Clinical Pharm 1986; 20: 289-91.
  8. Hamadeh, R., Ardehali, A., Locksley, R. M., & York, M. K. (1988). Fatal aspergillosis associated with smoking contaminated marijuana, in a marrow transplant recipient. CHEST Journal, 94(2), 432-433.
  9. Szyper-Kravitz M, Lang R, Manor Y, Lahav M. Early Invasive Pulmonary Aspergillosis in a Leukemia Patient Linked to Aspergillus Contaminated Marijuana Smoking. Leuk Lymphoma 2001; 42: 1433-7.
  10. Marks, W. H., Florence, L., Lieberman, J., Chapman, P., Howard, D., Roberts, P., & Perkinson, D. (1996). Successfully treated invasive pulmonary aspergillosis associated with smoking marijuana in a renal transplant recipient. Transplantation, 61(12), 1771-1774.
  11. Denning DW, Follansbee SE, Scolaro M, Norris S, Edelstein H, Stevens DA. Pulmonary aspergillosis in the acquired immunodeficiency syndrome. NEJM 1991; 324: 654-62.
  12. Chusid, M. J., Gelfand, J. A., Nutter, C. & Fauci, A. S., 1975. Pulmonary aspergillosis, inhalation of contaminated marijuana smoke, chronic granulomatous disease. Ann. Intern. Med. 82:682 683.
  13. Gargani, Y., Bishop, P., & Denning, D. (2011). Too many mouldy joints–marijuana and chronic pulmonary aspergillosis. Mediterranean journal of hematology and infectious diseases, 3(1), 2011005.
  14. Mathews-King, A. (2019). E-cigarette fluids contain ‘bacteria and fungi toxins’, study finds. The Independent [24th April]. Available at: https://www.independent.co.uk/news/health/vaping-e-cigarette-bacteria-fungus-cigarette-smoking-health-risk-a8882481.html
  15. Kupelian C, Kim A, Vijayan V. (2021). E-cigarette or Vaping Product Use-Associated Lung Injury Complicated by Pulmonary Aspergillosis. Cureus, 13(12):e20075 [doi: 10.7759/cureus.20075]

Further reading

  1. Kurup, V. P., Resnick, A., Kagen, S. L., Cohen, S. H., & Fink, J. N. (1983). Allergenic fungi and actinomycetes in smoking materials and their health implications. Mycopathologia, 82(1), 61-64.
  2. Sipsas, N. V., & Kontoyiannis, D. P. (2008). Occupation, lifestyle, diet, and invasive fungal infections. Infection, 36(6), 515-525.
  3. Llewellyn, G. C., & O’Rear, C. E. (1977). Examination of fungal growth and aflatoxin production on marihuana. Mycopathologia, 62(2), 109-112.
  4. McKernan, K., Spangler, J., Zhang, L., Tadigotla, V., Helbert, Y., Foss, T., & Smith, D. (2015). Cannabis microbiome sequencing reveals several mycotoxic fungi native to dispensary grade cannabis flowers.F1000Research, 4.
  5. Schwartz IS (1985) Marijuana and fungal infection. Am J Clin Pathol 84:256
  6. Weinrieb RM, Lucey MR (2007) Treatment of addictive behaviors in liver transplant patients. Liver Transpl 13:S79–82

Marijuana: collected papers