A Project CBD Special Report: Part 1 of a 2-part series by Adrian Devitt-Lee
A 19-year-old is rushed to the emergency room, having passed out at home. The kid can’t breathe. He’s clearly in respiratory failure. Doctors notice blood around his mouth, but there’s no discernible cause – no infection, no trauma, no other damaged organs. Except the lungs. The patient undergoes mechanical ventilation for roughly 60 hours as the medics try to diagnose and treat the stricken teenager.
Luckily the injured youth survived, thanks to the doctor’s quick response.
“[A] chest CT scan revealed patchy scattered ground glass opacities,” according to the physician who wrote up the case. The medics determined it was a case of diffuse alveolar hemorrhage – blood vessels had ruptured, filling parts of the lungs with blood and preventing oxygen exchange.
This patient’s brush with death due to respiratory failure was described in a 2011 report on the adverse consequences of inhaling synthetic cannabinoids (sCBs), a group of hard-to-detect research chemicals that powerfully influence the endocannabinoid system. 3 This would prove to be the first in a series of case reports, extending to the present, which highlight that sCBs can cause respiratory failure.
During the Summer of 2019, the same symptoms that can indicate sCB toxicity – ground glass opacities, ruptured blood vessels, oxygen deprivation as lungs fill with fluid – would surface repeatedly in what the Centers of Disease Control (CDC) has deemed an “outbreak of lung injury associated with vaping.” Such incidents became more frequent in July. As of November 8th, more than 2000 people had been hospitalized and 39 had died from vaping-related pulmonary failure, according to the CDC, which issues weekly updates on the vaping crisis with the latest alarming statistics.4
The CDC has yet to identify a single common factor in all cases beyond the use of vaporizers or electronic cigarettes. Thus far, reported cases have involved people vaping THC (tetrahydrocannabinol) oil and/or CBD (cannabidiol) oil, as well as users of nicotine e-cigarettes. Black market THC vape cartridges are particularly suspect, but legal cannabis oil vapes and nicotine-only products have also been implicated.
Curiously, the CDC makes no mention of synthetic cannabinoids in their weekly updates, even though the symptoms of sCB-induced toxicity match symptoms that figure prominently in the current, headline-generating vaping crisis. Since the start of the outbreak, health officials have been eyeing several possible culprits – chemical flavorings, vitamin E, polymer thinning agents, metals leached from vaporizer heating coils, and so on. But vape oil contamination by synthetic cannabinoids is one possibility that has flown under the radar.567
Project CBD maintains that synthetic cannabinoids deserve serious attention.
CDC criteria for vaping-related lung injury
Let’s step back for a moment and assess the situation. A “case” is considered part of the current lung injury outbreak, according to the CDC, if an individual presents in dire respiratory distress and:
- was vaping or dabbing sometime within 90 days of symptoms;
- has pulmonary infiltrates in a chest scan, which, on CT scans, typically appear as ground-glass opacities; and
- is absent of infection or another plausible cause of respiratory distress.
If the third condition is not satisfied, a patient can still be classified as a “probable” rather than a “confirmed” case.1
Since the CDC’s classification of a case is broadly inclusive, there are likely a multitude of factors that could contribute to vaping-related lung injuries. Many types of lung pathologies have been reported during the current outbreak. Lung problems that are implicated include lipoid pneumonia, acute eosinophilic pneumonia, alveolar damage, and diffuse alveolar hemorrhage.
Synthetic cannabinoids have not been shown to cause lipoid pneumonia. But in cases with alveolar hemorrhage, sCBs need be considered. Synthetic cannabinoids may also be relevant in patients with acute eosinophilic pneumonia and anyone with concurrent neurological or cognitive impairment.
A potpourri of poison
Inhaling vitamin E acetate, a thickening additive, can cause lipoid pneumonia, and this may be germane to some of the recently reported cases.8 But other patients were found not to have lipid buildup in the lungs,9 so it is not the sole cause of problems. It should be noted that vitamin E is legal in most vaping products, despite a lack of demonstrable safety when heated and inhaled. Vitamin E is Generally Recognized as Safe as a food additive by the FDA, giving rise to the unfounded sense that it is also safe to inhale.
Thinning agents, like propylene glycol and polyethylene glycol, can be carcinogenic when heated to high temperatures 1011. But there are no reports of acute respiratory distress from thinning agents, despite their use in nicotine e-cigarettes since roughly 2007. The potentially harmful long-term effects of thinning agents are overshadowed by nicotine, which has an established toxic profile of its own.12
Flavoring agents are problematic, in part because they make products even more addictive for consumers and more appealing to children. Some flavoring additives have been linked to pulmonary problems like popcorn lung.13 They are also legal in most vaping products, despite a lack of safety data for heating and inhaling these ingredients.
Little evidence demonstrates that thinning agents or flavoring agents are causing the recent crisis. Although we view these dodgy additives as unlikely culprits in the current lung injury outbreak, this is not to say they should be regarded as safe, or that the current regulations are sufficient for consumer protection.
Which brings us to synthetic cannabinoids.
Numerous case reports have demonstrated that sCBs can land someone in the emergency room for respiratory distress. According to various accounts, sCB adulterants have been found in some unregulated online CBD products, as well as in black market THC vapes. 1516171819 Despite these findings, reports about the current outbreak generally do not discuss synthetic cannabinoids.2 And no legal market in the United States requires testing to ensure the absence of sCBs in cannabis or CBD products.
In order to assess the role that sCBs may be playing in the outbreak of vaping injuries, it’s important to understand the complex pharmacology of synthetic cannabinoids and how they are fundamentally different from THC and other naturally occurring plant cannabinoids.
Adrian Devitt-Lee, Project CBD’s chief science writer, is pursuing a PhD in Mathematics at the University College of London.
Copyright, Project CBD. May not be reprinted without permission.
Footnotes and References
- See here for the definition of a “case” of vaping-associated respiratory distress. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/assets/2019-L…
- In one table in a CDC report they state that four people had confirmed use of synthetic cannabinoids while 289 had not.14 The CDC additionally suggests that clinicians ask patients if they had intentionally used sCBs. Synthetic cannabinoids have not been
- Loschner, Anthony, et al. “Diffuse Alveolar Hemorrhage: Add ‘Greenhouse Effect’ to the Growing List.” Chest, vol. 140, no. 4, Oct. 2011, doi:10.1378/chest.1119854.
- “Outbreak of Lung Injury Associated with the Use of E-Cigarette, or Vaping, Products.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 5 Nov. 2019, www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.h….
- Owermohle, Sarah. “Vitamin E Named as Primary Culprit in Vaping Illness, but Feds Urge Caution.” POLITICO, 5 Sept. 2019, www.politico.com/story/2019/09/05/vitamin-e-vaping-disease-cdc-1709200.
- Hotz, Robert Lee. “Researchers Say Vitamin E Likely Isn’t the Culprit in Vaping-Related Ailments.” The Wall Street Journal, Dow Jones & Company, 2 Oct. 2019, www.wsj.com/articles/researchers-say-vitamin-e-unlikely-culprit-in-vapin….
- Dickson, EJ. “What’s Causing Vaping’s Mystery Illnesses? New Study Might Offer Some Answers.” Rolling Stone, 13 Sept. 2019, www.rollingstone.com/culture/culture-news/vape-illness-cause-vitamin-e-l….
- Dicpinigaitis, P.V., Trachuk, P., Fakier, F. et al. Lung (2019). https://doi.org/10.1007/s00408-019-00277-6
- Larsen BT et al. “Pathology of Vaping-Associated Lung Injury,” N Engl J Med (2019) http://doi.org/10.1056/NEJMc1913069
- Marcu, Jahan. “How Safe Is Your Vape Pen?” Project CBD: Medical Marijuana & Cannabinoid Science, 14 July 2015, www.projectcbd.org/industry/how-safe-your-vape-pen.
- Devitt-Lee, Adrian. “Toxic Vape Oil Additives Endanger Patients.” Update, 4 Apr. 2017, https://www.projectcbd.org/update-toxic-marijuana-vape-oil-additives-end…
- Benowitz, Neal L., et al. “Cardiovascular toxicity of nicotine: Implications for electronic cigarette use.” Trends in Cardiovascular Medicine, 2016, doi:10.1016/j.tcm.2016.03.001
- Park, H., O’Sullivan, M., Vallarino, J. et al. Transcriptomic response of primary human airway epithelial cells to flavoring chemicals in electronic cigarettes. Sci Rep 9, 1400 (2019) doi:10.1038/s41598-018-37913-9
- “Characteristics of a Multistate Outbreak of Lung Injury Associated with E-Cigarette Use, or Vaping - United States, 2019.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 3 Oct. 2019, www.cdc.gov/mmwr/volumes/68/wr/mm6839e1.htm.
- Kuehn B. Synthetic Cannabidiol Poisoning. JAMA. 2018;319(22):2264. doi:10.1001/jama.2018.7219
- Justin L. Poklis, Haley A. Mulder, Michelle R. Peace, The unexpected identification of the cannabimimetic, 5F-ADB, and dextromethorphan in commercially available cannabidiol e-liquids, Forensic Science International, Volume 294, 2019, Pages e25-e27, ISSN 0379-0738, https://doi.org/10.1016/j.forsciint.2018.10.019.
- Tony Rianprakaisang, Roy Gerona & Robert G Hendrickson (2019) Commercial cannabidiol oil contaminated with the synthetic cannabinoid AB-FUBINACA given to a pediatric patient, Clinical Toxicology, DOI: 10.1080/15563650.2019.1619758
- Roberts, Chris. “With Dangerous Vapes and Killer Pills, Why Is the Surgeon General Worried About Weed?” Observer, Observer, 10 Sept. 2019, https://observer.com/2019/09/with-dangerous-vapes-and-killer-pills-why-i….
- “Health Warning Issued over Fake ‘THC Vape’ That in Fact Contains ‘Spice.’” NHS Choices, NHS, 16 July 2019, www.christie.nhs.uk/about-us/news/latest-news-stories/health-warning-iss….