Medical cannabis became legal in California in 1996 under Proposition 215–the Compassionate Use Act (CUA). In November 2016, 57% of voters passed Proposition 64–the Adult Use of Marijuana Act (AUMA), leading to recreational cannabis sales in California. Since then, cannabis products are expanding into many innovative forms consumed by both medical patients and recreational cannabis users. A variety of cannabis products are available in California including joints, beverages (in different flavors), concentrates/distillate, vape cartridges (in different flavors), topicals, oral supplements, tinctures, capsules, and various infused edibles such as candies/chocolates, mint/chews, dried meat, crackers, dairy product, and baked goods. Among these cannabis products, vape oil cartridges are particularly popular as they share the electronic nicotine delivery systems (ENDS). This method of consumption and delivery of tetrahydrocannabinol (THC) is claimed to be safer and more efficient than other products. However, ENDS use is not without short or long-term adverse effects due to additional chemicals generated in the system and the strength of active contents.

ENDS was first invented by Lik Hon in Hong Kong in 2003 and was entered in Europe and the United States in 2006. It became popular in 2012 after tobacco manufacturers joined the market. There are many terms used to describe ENDS such as vapes, vaporizers, vape pens, hookah pens, electronic cigarettes, etc. It consists of an atomizer as the heating element, a wick, a battery power source, and a cartridge or tank container. Instead of containing nicotine, cannabis vape cartridges typically contain a mixture of cannabinoids, terpenes, various solvents used as thinning agents, and flavoring additives. By pressing the power button, the vape oil is heated to create an aerosol that the user inhales. Overall, e-liquid aerosol contains fewer types and lower levels of toxicants than smoke from combustible tobacco cigarettes  H, however, the recent outbreak of EVALI has triggered health concerns in the vaping community.

The EVALI outbreak was first identified in August 2019 and peaked in September 2019 followed by a gradual, but persistent decline of February 18, 2020, a total of 2,807 hospitalized EVALI cases or deaths have been reported to CDC from all 50 states. National and state data from patient reports show THC-containing e-cigarette or vaping products, particularly from informal sources, online dealers, and the illicit market are linked to most EVALI cases. Vitamin E acetate has been found in these product samples tested by FDA and state laboratories. It was also found in patient lung fluid samples collected from various states and tested by CDC. The surge of the EVALI outbreak strongly shows the need for routine investigation of cannabis products on the markets and in-depth research for the safe use of e-cigarettes or vaping products.

Numerous studies have been conducted on e-liquids containing nicotine using propylene glycol (PG) and Vegetable Glycerin (VG) as solvent thinning agents (also called cutting agents for the ease of vaporizing) with added flavonoids. These studies revealed the concerns of Harmful and Potentially Harmful Constituents (HPHCs) formation during heating and aerosolization of the e-liquids. Such studies cannot be directly applied to cannabis products as they have different major constituents such as THC (50–80% concentration) and terpenes. From limited studies on cannabis vape cartridges, ketene as an exceptionally toxic gas may be a potential byproduct in the aerosol of vape cartridges containing Vitamin E acetate. Polis and Peace et al. also found synthetic cannabinoids in vape liquids. In addition, residual solvents, pesticides, heavy metals, and other toxic chemicals can be concentrated during the cannabis extraction process and remain in the vape oil. Many vape pens have poor temperature control and the vape cartridge content may be heated to beyond the optimum temperatures, or even to the point of combustion. Consequentially, users may inhale cannabis smoke containing carbon-monoxide, tar, ammonia, heavy metals, and other by-products that are harmful to the lungs and respiratory health. Therefore, to expand the understanding and collect more knowledge to ensure product safety for consumers, the National Academies of Sciences research group suggested studies focus on cannabis products containing cannabis, cannabinoids, or THC.

In the current study, we investigated twelve cannabis cartridge samples obtained from various dispensaries in California from September 2018 to December 2019. Among these twelve samples, two were before the EVALI outbreak and ten were during the EVALI outbreak. We analyzed the composition of the vape oils focusing on volatile and semivolatile chemicals. By using a non-targeted gas chromatography-mass spectrometry (GC-MS) screen method, we were able to detect and identify unknown and suspicious compounds in addition to cannabinoids, terpenes, and other known major additives. We hypothesized there were different constituents in the cartridges collected before and during the EVALI outbreak. As manufacturers drive to improve profits, they may alter product formulations by using cheaper ingredients in their products, and these new ingredients may pose health risks to consumers. The new ingredients should have a safety assessment by following U.S. Department of Health and Human Services, Food and Drug Administration (USFDA) guidance before adding them into the products /. A nonclinical toxicity assessment can also help to address the potential toxicity of chemicals, especially novel chemicals and impurities generated from heating in product delivery systems.

In this study, we also tested vape oil composition in its vapor and aerosol phases using headspace heating and solid-phase microextraction (SPME) GC-MS analyses. We hypothesized that there were some differences among original vape oil liquid, vapor, and aerosol. By heating and aerosolizing the vape oil, we simulated the battery-powered vape pen conditions used by consumers. This may help to determine the major constituents and the amount of vapor or aerosol that gets into the user’s lungs. To the best of our knowledge, this is the first study that compared the major constituents in unused vape oil to those of its vaporized and aerosolized forms.

Method and Materials

Cannabis Vape Cartridge Samples

In this study, we investigated twelve cannabis vape cartridges obtained through the California state surveillance program from September 2018 to December 2019. Sample details are listed below. Each of the twelve cannabis vape cartridges went through analyses in its oil liquid, vapor, and aerosol phases for the determination of the major constituents.