do cbd oils have dicetyl for vaping

What are the mechanisms underlying vaping-induced lung injury?

1 Pulmonary and Critical Care Section, VA San Diego Healthcare System, La Jolla, California, USA.

2 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, UCSD, La Jolla, California, USA.

3 Division of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Find articles by Alexander, L. in: JCI | PubMed | Google Scholar |

1 Pulmonary and Critical Care Section, VA San Diego Healthcare System, La Jolla, California, USA.

2 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, UCSD, La Jolla, California, USA.

3 Division of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Find articles by Bellinghausen, A. in: JCI | PubMed | Google Scholar

1 Pulmonary and Critical Care Section, VA San Diego Healthcare System, La Jolla, California, USA.

2 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, UCSD, La Jolla, California, USA.

3 Division of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Published May 11, 2020 – More info

Electronic cigarette (e-cigarette) use and vaping have dramatically increased in recent years, particularly among teenagers and young adults, with an estimated 7.6% reporting current, everyday e-cigarette use and 27.5% reporting use in the past 30 days ( 1 , 2 ). The exact numbers of nicotine vapers who also vape marijuana are unknown, but there is significant overlap, with young adults who use e-cigarettes having an adjusted odds ratio of concurrent marijuana use of 3.47 ( 3 ).

In 2019, e-cigarette or vaping product use–associated lung injury (EVALI) was recognized as a unique disease entity, and rapid escalation of the numbers of those affected was such that it has been labeled a public health crisis, with over 2800 cases of hospitalizations and 68 deaths as of March 2020. Individuals affected are predominantly males (66%) who use tetrahydrocannabinol-containing (THC-containing) vapes (82%). However, many EVALI patients report using both nicotine and THC products (43%) ( 4 ). Interestingly, there is significant clinical overlap between the EVALI epidemic and the COVID-19 pandemic. Both of these diseases have substantial gastrointestinal symptoms, bilateral lung infiltrates, and significant numbers of those affected progressing to hypoxic respiratory failure and acute respiratory distress syndrome (ARDS). But whereas EVALI is mainly a disease of the young, with a median age of 24 years, severe COVID-19 is primarily a disease of the elderly. Although smoking has been linked to increased COVID-19 severity ( 5 ), it is as yet unknown whether vaping increases the susceptibility to or severity of this novel viral illness.

At the core of EVALI and COVID-19 is the clinical syndrome of acute lung injury (ALI), which is defined by injury to both alveolar epithelial cells and pulmonary vascular endothelial cells throughout both lungs. The damage to epithelial and endothelial cells leads to destruction of alveolar-capillary membrane integrity, with fluid filling the alveoli, migration of neutrophils into the lungs, and release of both proinflammatory and cytotoxic factors ( 6 ). The exact mechanism behind the lung injuries seen in EVALI is unknown, but we propose two possibilities (Figure 1A): (a) a chemical inhaled within the aerosol created by vaping or dabbing is directly cytotoxic to certain lung cells, leading to cellular necrosis, neutrophilic inflammation, and collateral damage, or, alternatively, (b) a two-hit phenomenon occurs, in which inhalation of the base ingredients of e-liquids (propylene glycol and glycerin) within e-device–derived aerosols leads to alterations in the homeostatic state of lung immune cells, such that when a normally well-tolerated inhalant hits the lungs, it tips the balance and triggers massive inflammation. This JCI Viewpoint article discusses these potential mechanistic pathways in the context of how other lung inhalation injuries occur and pinpoints important research needs moving forward.

Mechanisms underlying lung injury in EVALI. (A) In the panel on the left, cells of the lung are damaged by one chemical inhaled within e-cigarette aerosols. This cell damage leads to epithelial and endothelial cell necrosis (indicated by a yellow “X”). An alternative hypothesis is depicted on the right, in which inhalation of chemicals common in e-cigarette aerosols (propylene glycol, glycerin, nicotine, or THC) alters the inflammatory state of the lungs, including changing alveolar macrophages to a proinflammatory phenotype with the release of inflammatory cytokines (indicated by yellow circles), such that a second hit causes a pathologic inflammatory response. (B) The immune state of the lungs is known to be altered by the chronic, daily inhalation of e-cigarette aerosols. It is likely that vitamin E is directly cytotoxic to lung cells (indicated by a yellow “X”), leading to necrosis, neutrophil recruitment and activation resulting in collateral damage, and noncardiac pulmonary edema. Illustration credit: Rachel Davidowitz. H&E-stained lung tissues are from the UCSD Liebow Collection, 1974.

As the popularity of vaping has risen, there has been a profusion of novel flavor additives, particularly fruit and candy flavors. Nontobacco flavors appeal more to younger e-cigarette users ( 7 ) and are associated with a greater likelihood of initiation and continued use over time ( 8 , 9 ). Many of the chemicals used to create particular flavors contain known toxins, including diacetyl and 2,3-pentanedione ( 10 ). Complex chemical reactions occur during heating of the e-liquid, generating additional bioactive compounds that may be damaging to the lungs.

In addition to flavored nicotine solutions, cannabis products are frequently used in e-devices. Up to 61% of cannabis users report vaping a THC product at some time in their life ( 11 ). This includes vaping THC liquids, vaping cannabidiol (CBD) oils added to regular e-liquids, and dabbing highly concentrated THC substances. Unfortunately, exact statistics on cannabinoid vaping and dabbing are not available, making accurate assessments of their incidence impossible.

To support our direct toxicity hypothesis (Figure 1), there are multiple chemicals known to cause inflammation when inhaled. Diacetyl, a chemical added to e-liquids to give a buttery flavor, is known to cause bronchiolitis obliterans (popcorn lung), an obstructive disease of the small airways ( 12 ). The mechanism of this disease is not fully understood but is believed to be due to direct damage to the respiratory epithelium, with disorganized fibrotic repair ( 13 ). Nicotine itself is believed to be the causal agent in acute eosinophilic pneumonia, seen in both cigarette smokers and e-cigarette vapers, but the mechanism remains unknown ( 14 , 15 ). In EVALI, the neutrophil, not the eosinophil, is the predominant inflammatory cell recruited to the lungs, which makes the disease more pathologically similar to ALI ( 16 ). EVALI is also similar to acute interstitial pneumonia (AIP), in that neutrophils are the main cells driving inflammation and AIP rapidly responds to steroid treatment.

Chlorine is another well-known chemical cause of ALI and ARDS ( 17 ), and its pattern of lung damage may best parallel that seen in EVALI. In chlorine pulmonary toxicity, chloride gas (Cl2) combines with water in the airway mucosa to form hydrochloric acid (HCl) and hypochlorous acid (HOCl), both of which directly damage the airway epithelial surface. Reactive nitrogen compounds are also formed by increased activity in the inducible nitric oxide synthase (iNOS) pathway. Furthermore, neutrophil recruitment and mitochondrial dysfunction lead to additional oxygen radical formation. This results in diffuse lung damage and ARDS, similar to what is observed in EVALI. Phosgene gas (carbonyl dichloride), used as a bioweapon during World War I, similarly causes ARDS by direct cellular toxicity and increased free radical generation ( 18 ). The decreased water solubility of phosgene (compared to chlorine) results in a delay of symptom onset, which may be a factor in the inconsistent time course of EVALI.

Currently, the prime suspect molecule in EVALI is vitamin E, which has been identified in many e-liquids and bronchoalveolar lavage (BAL) samples from affected individuals ( 19 ). Little is known about the nondermatologic and nongastrointestinal ingestion effects of vitamin E. It is possible that the inhalation of this large molecule leads to direct cytotoxicity of particular lung cell types, versus an attempted clearance of this molecule by alveolar macrophages that leads to accumulation within the vacuoles due to an inability of these cells to break it down, followed by macrophage cell death or promotion of a proinflammatory macrophage phenotype that drives ALI (Figure 1B).

In order to prevent the considerable harms linked to EVALI and ongoing e-cigarette use, it is important to consider public health policies to both prevent the use of e-cigarettes by young people and identify evidence-based interventions to help e-cigarette users quit. Given the heterogenous potential mechanisms for EVALI, any intervention to decrease vaping-associated lung injury will need to be sufficiently flexible to cover the spectrum of possible causative agents. Although legislation to ban flavor additives in prefilled cartridges except for tobacco and menthol has been passed, this does not address either non–flavor-related lung toxicity or the flavored e-liquids used in refillable or disposable vaping devices. Given that EVALI has been observed in individuals who do not use flavors other than tobacco or menthol, it is likely that this intervention will not eliminate EVALI. Additionally, the current pod-based partial flavor ban policy is unsatisfactory, since it leaves menthol products and other flavorings available for other vaping products that have been shown to appeal to youth.

If a flavor ban is not the solution to EVALI, what is the alternative? We propose that increased labeling of e-liquid contents based on mass spectrographic analysis is an important first step. Improved characterization of chemical components in e-liquid will allow researchers to better identify possible pulmonary toxins in future cases of EVALI. Furthermore, it will empower consumers of e-liquids to limit their exposure to potentially harmful additives by increasing awareness of what they are inhaling. A drawback to this approach is that it is time consuming and costly, meaning that legislation would likely be necessary to motivate manufacturers of e-liquid to increase labeling.

Tobacco control policies, such as raising the minimum age to purchase tobacco products to 21, which was recently passed in the US, are critical to reduce youth access. Another target for public policy intervention would be to limit the nicotine content of e-liquid, with the aim of reducing the addictiveness of vaping. It has been hypothesized that the limit of nicotine to less than 20 mg/mL in the United Kingdom is the main reason that vaping is not as prominent in their youth. Additionally, legislation prohibiting e-cigarette marketing to adolescents and young adults should be strengthened to prevent future generations of youth from acquiring the habit. If vaping and e-cigarette use can be reduced, not only will we reduce the incidence of EVALI, but we will hopefully prevent the (as-yet unknown) long-term health consequences of vaping.

There are currently no evidence-based interventions to help individuals stop using e-cigarettes. Interventions that are currently being promoted or recommended have been modified from existing counseling interventions for helping individuals quit combustible tobacco use and have not been directly evaluated in e-cigarette users or validated in children or teenagers, a population that is now in need of treatment for nicotine addiction. There is a critical need for increased funding for research to identify evidence-based interventions that are tailored for e-cigarette cessation across age groups.

The potential mechanisms for EVALI are diverse (Figure 1). Investigators have identified vitamin E acetate as a possible causative agent of EVALI, however, it is likely that additional damaging compounds will be identified as the research continues. Exploration of other toxic inhalation syndromes as well as utilization of animal models to assess the cytotoxic and inflammatory effects of various chemicals in THC vaping and dabbing devices may serve to better elucidate the mechanisms of lung injury in vaping-associated lung disease.

There is a critical need for a broad research agenda to address the public health epidemic of EVALI ( 20 ). The CDC and FDA have been working with researchers to track cases and identify possible mechanisms or exposures linked to the development of this disorder. Further research is needed to more directly clarify the precise mechanism of action to both treat and prevent EVALI as well as vaping-induced lung diseases in general. In particular, it is critical that biomedical researchers be allowed to study all THC and nicotine products being used by the general public. Finally, there is a need for broad tobacco control policies to prevent access to these products and identify evidence-based interventions to support cessation.

LECA’s salary was supported in part by the VA San Diego Healthcare System and by grants from the NIH (R01HL147326, to LECA) and the Tobacco-Related Disease Research Program (TRDRP T30IP0965 and 26IP-0040, to LECA). ALB is supported by a training grant from the National Heart, Lung, and Blood Institute of the NIH (T32HL134632).

LECA’s salary was supported in part by the VA San Diego Healthcare System and by grants from the NIH (R01HL147326, to LECA) and the Tobacco-Related Disease Research Program (TRDRP T30IP0965 and 26IP-0040, to LECA). ALB is supported by a training grant from the National Heart, Lung, and Blood Institute of the NIH (T32HL134632).

Corresponding Author: Laura E. Crotty Alexander; 9500 Gilman Drive, MC 9111J, San Diego, California 92093, USA. Phone: 619.438.4207; Email: [email protected]

Conflict of interest: The authors have declared that no conflict of interest exists.

THE CLINICAL ASSESSMENT OF VAPING EXPOSURE

Vaping, the inhalation of a nicotine or tetra hydrocannabinol (THC), cannabidiol (CBD), or non-drug infused solution delivered by vaping devices, is a growing phenomenon across many segments of the US population. Complications associated with vaping are newly emerging and relatively unstudied; little guidance exists on how clinicians may best elicit information related to vaping practices and associated medical problems. This publication, therefore, provides physicians and other treatment clinicians with direction for obtaining the medical history that can guide clinical decision-making for patients at risk for adverse effects associated with vaping.

Introduction

Vaping, the inhalation of a nicotine or tetrahydrocannabinol (THC), cannabidiol (CBD), or non-drug infused solution delivered by vaping devices, is a growing phenomenon across many segments of the US population. 1,2 Vaping has been marketed as a safer alternative than smoking cigarettes, but safety data are lacking. The new phenomenon of vaping is changing the culture of nicotine and marijuana use. Because vaping devices do not combust plant matter and therefore lack the characteristic odor of burning tobacco or marijuana, discrete or surreptitious use can occur in almost any location, promoting use and making indoor smoking bans and other health-promoting restrictions challenging to enforce. 3 The popularity of vaping has eclipsed that of cigarette smoking; adolescents have been particularly affected by the epidemic, with 3.6 million middle and high school students reporting e-cigarette use in 2018. 1 Complications associated with vaping are newly emerging and not yet well studied. 4 Respiratory manifestations range from mild respiratory symptoms to fulminant respiratory failure culminating in death. 5 Other complications include patterns of behavioral dysregulation related to high delivered concentration of nicotine and THC similar to other addictive substances. 6,7 Despite striking increases in the incidence of vaping in the US and the number of adverse events associated with it, little guidance exists on how to best adapt history-taking during the clinical encounter to elicit information related to vaping practices. Accurate recording of the quantity, frequency, dosage, type and duration of vaping exposure can help develop treatment plans and has the potential to help allied fields such as pathology and epidemiology in understanding acute toxicities as well as in assessing potential cumulative effects. The clinical process of assessing vaping use can also support vaping cessation efforts. Accordingly, we propose a coherent approach to obtaining the patient history component to help clinicians assess the breadth, frequency, and severity of vaping in patients.

Definitions

Vaping devices consist of a power source, an electronic heating element, and a reservoir containing a liquid to be aerosolized. These devices use heat to aerosolize nicotine or THC solutions (called an “e-liquid”) in a process referred to as “heat not burn”. 3

Cartridges (or ‘pods’) are purchased with premade liquids that typically contain substances such as nicotine, stabilizing compounds, flavorings, and other chemicals. Empty cartridges can also be to be filled with homemade, custom blends of chemicals. These are often referred to as vaping solutions, e-juice, or juice.

JUUL is a vaping device for the delivery of nicotine. When introduced in 2015, JUUL (San Francisco, CA, USA) revolutionized the vaping industry by commercializing a vaping liquid that contained twice the nicotine concentration (5%) of previous 1–2% nicotine formulations. 3 Addiction is central to the JUUL business model. 3 Accordingly, high nicotine devices such as JUUL deliver nicotine at far higher concentrations than combustible cigarettes. 3

Nicotine or nicotine salt is used in vaping solutions to deliver nicotine to the brain, resulting in the characteristic rewarding experience. Compared to combustible cigarettes, nicotine concentrations are higher in these solutions. Nicotine salts used in newer vaping devices such as JUUL are much less noxious to airways than cigarettes and allow more vaping as well as delivery of much higher concentrations of nicotine. 3 The use of nicotine salts therefore alters the pharmacokinetic profile of inhaled nicotine; individuals can inhale larger amounts of the drug more rapidly than combustible cigarettes, achieve higher blood and brain concentrations of nicotine and, presumably, develop nicotine dependence more rapidly. 3

Dab pens are small easily concealable vaping devices that are used with highly concentrated THC-containing oil-based solutions. Dab pens are designed to deliver more highly concentrated THC than most other forms of THC delivery.

Tricks are acts that involve the inhalation and release of vapor that are intended to entertain and impress. Successfully performed tricks (eg, Ghost inhale, French inhale, Dragon, Waterfall, among others) are touted by online influencers as conveying social capital upon the performer. 8

Mod builds are modifications made to commercial vaping devices to alter their performance characteristics. Information about ways to perform tricks and mod builds are available online, particularly YouTube. 9

E-cigarette or Vaping Associated Lung Injury (EVALI)—Lung injury associated with vaping in which the patient had 1) a history of vaping or dabbing (inhalation of vaporized marijuana concentrates) within 90 days before symptom onset; 2) imaging studies demonstrating lung injury; 3) absence of evidence of infection or infection not thought to be the sole cause of lung injury, or infectious testing not performed; and 4) absence of alternative plausible diagnoses. 2

Additives are materials added to vaping solution that vary by product and manufacturer. 10 Many vaping solutions contain chemicals with pronounced toxicity such as flavoring agents (e.g., diacetyl), volatile organic compounds (e.g., benzene), heavy metals (e.g., nickel, tin, lead), vitamin E acetate, polyethylene glycol, and medium chain triglycerides. 10 Homemade solutions or modified commercial products can contain any soluble drug or chemical. 10

Vaping nicotine

The delivery of nicotine using vaping devices is distinct from that of combustible cigarettes.

Adolescents may not understand what vaping devices are intended to do: administer drugs through pulmonary routes of delivery. 11 Whereas recognition that cigarettes deliver nicotine is broad, over 60% of adolescents do not understand that JUUL devices are nicotine delivery devices. 11,12 Whereas the size, nicotine content, rate of combustion, and amount of daily use of traditional cigarettes are established, comparable standardization of products has not occurred in the vaping industry where each puff from a vaping device delivers a variable dose of nicotine and other materials. The common metric to assess traditional cigarette smoking exposure is pack-years, the number of packs/day multiplied by the number of exposure years. This lifetime exposure estimate is highly relevant for two reasons; first, the low concentration of nicotine delivered by cigarette smoking makes acute poisoning unlikely; second, the main harms from smoking combustible tobacco are dose related and accumulate over time. Unfortunately, no measure of cumulative exposure that parallels the pack/day metric has been developed for vaping. Furthermore, unlike smoking tobacco or marijuana cigarettes, vaping both nicotine and THC can result in acute toxicity (e.g., hallucinations and psychosis from vaping marijuana, gastrointestinal symptoms of nausea and vomiting from nicotine inhalation) due to the very high concentrations of drugs that can be delivered. 13,14 Finally, because vaping can cause fulminant lung disease due to chemicals in the vaping fluid, specific information about the source of the vaping fluid is critical, particularly among patients presenting with respiratory symptoms. 4 When assessing vaping, therefore, lifetime measures alone are insufficient to generate a complete understanding of health risks associated with the behavior.

The clinical evaluation of vaping nicotine mimics the assessment for tobacco use; the general approach is presented in Table 1 . While nearly all individuals addicted to nicotine ingest larger amounts of nicotine than intended, develop tolerance, and exhibit abstinence symptoms upon cessation of use, a notable difference is that many individuals who vape, particularly adolescents, present with behavioral dysregulation characterized by stealing, lying, increased aggression and irritability. While social factors may exacerbate nicotine use and confound attributing behavioral dysregulation to vaping, these derangements often culminate in a functional decline in scholastic performance that is unusual among cigarette users. 14 These symptoms are believed to be related to the direct impact of high-dose nicotine on the central nervous system. 3,14 Changes in behavior including more frequent and severe arguments, disinhibition, disturbed psychosocial functioning, irrational behavior, and declining school performance are measures of behavioral dysregulation consistent with nicotine use disorder from vaping.

Table 1.

Summary of Vaping Evaluation Recommendations (Content in italics may be appropriate for focused assessment)

Vaping Use History (Ask parent to leave the room and assure confidentiality)
  • Type of substance:
    ▪ THC
    ▪ CBD
    ▪ Nicotine
      - 20mg/mL
      - 70mg/mL
      - 2%
      - 7%
    ▪ E juice/liquid only
    ▪ Modified products
    ▪ Home made products including components used, source of products, source of directions for mixing, websites from which information was obtained
  • Specific products including brand, name and manufacturer, flavorings used
  • Product source
      - Vape shop, convenience store, online, friend, adult
  • Age at initiation
      - Reason for initiation
  • Duration of use
  • Frequency of use
  • Number of pods or volume used in typical day
  • Time of last use
  • Product delivery system
      - E-cigarette
      - Juul
      - Pod Vape
      - Vape Pen
      - Box Mod Kit
      - Dab pen
  • Method of use including tricks
  • Additional use of other nicotine and THC products
      - Cigarettes
      - Cigars
      - Pipes
      - Bongs
      - Other inhalants
Assess for other substance use
Assess for interest in change in habits/quitting
Respiratory Symptom History (If any positive symptoms perform further pulmonary evaluation)
  -Acute symptoms
     • Cough, sputum production, chest pain, shortness of breath, dyspnea on exertion, hemoptysis
     • Note duration and if any of these symptoms correlate with initiation of vaping or change in vaping practices
  -Chronic symptoms and any underlying respiratory past medical history
     • Pneumonia
     • Bronchitis
     • Pneumothorax
     • Hemoptysis
Screen for Gastroenterology Symptoms
   • Abdominal Pain, nausea, vomiting, diarrhea
Screen for Systemic Symptoms
   • Fever, chills, weight loss, malaise
Screen for Neuro-behavioral Complications of Vaping
   • Changes in mood, aggression, irritability, sleep disturbance, anxiety, fighting, seizure activity
   • Disinhibition, psychosis, hallucinations
   • Withdrawal symptoms upon cessation of use
   • Need to use more to produce desired effects
   • Use of more product or more frequently than intended
   • Increasing amount of money spent on vaping products
   • Changes in activities, physical activity, peer interactions or scholastic performance
   • Interpersonal relationship changes
   • Risk taking behaviors (e.g. stealing, lying, hiding use, use in school)
   • Quit attempts
Screen for Mental Health History
   • ADHD/ADD, Anxiety, Depression, other

In the initial stages of an assessment, we recommend that clinicians focus on objective information. Particularly among patients presenting for evaluation of acute respiratory illness, learning the sources of vaping liquid including the name of the manufacturer and product, the addition of substances by the user of the end product and whether the commercial product or delivery system was altered provides important information. Queries about the experience of acute toxicity (e.g., hallucinations and psychosis from vaping marijuana, gastrointestinal symptoms of nausea and vomiting from nicotine inhalation) are a useful component of the clinical assessment. 14 To make an estimate of lifetime exposure, we recommend asking age of initiation, frequency of use, number of pods used per day, and associated symptoms such as signs of nicotine toxicity. The DSM-5 criteria can establish a diagnosis of nicotine use disorder. 15 Withdrawal symptoms, including the development of depressed mood, sleep disturbance, irritability, anxiety, and increased hunger, are common upon abstinence from nicotine. Assessing whether patients have used vaping devices to a greater extent than was intended, impact on physical activity, quit attempts, as well as the motivation for them all point to a detrimental impact on day-to-day functioning while exploring ambivalence. Generally, adolescents can report accurately whether more frequent vaping is needed to achieve desired effects; determining the number of cartridges or pods used over time can help identify the presence of the neuroadaptive phenomenon of tolerance. 16 We also recommend identifying the frequency and intensity of cravings. Asking about the extent to which e-cigarette users also smoke traditional cigarettes or use other tobacco products can be particularly important for making decisions regarding initiating nicotine replacement therapy.

Clinicians should be aware of potential differences in responses from adults or adolescents in the assessment of vaping. For example, adolescents may not recognize the impact of nicotine on their behavior and, instead attribute recurrent, severe behavioral dysregulation to interpersonal or interfamilial conflict that characterize adolescence instead of their drug use. To distinguish between typical adolescence and the impact of nicotine use disorder, clinical assessment of adolescent vaping should therefore focus on increased frequency of use and include surrogate measures such as amount of money and resources directed toward obtaining vaping solutions, devices, and cartridges. Furthermore, vaping devices carry less stigma than cigarettes, adolescents recognize that parental discomfort with vaping often makes use of e-cigarettes a stigmatized behavior. Understanding the extent to which adolescents use these products outside of the house, including in school, or try to hide their vaping, is therefore important in understanding the problems, and in particular the interpersonal conflict, associated with nicotine use. Whereas adult patients may recognize a need to decrease cigarette use, adolescents, with limitations in executive function and greater impulsivity typical of the age group, may not register that nicotine use has become problematic.

Vaping cannabis

The use of THC is not new; what is new is the scale, scope, and variety of new and more concentrated cannabis products fostered by commercialization of marijuana. 17,18 Because vaping avoids the characteristic smell of burning marijuana, inhalation of THC by vaping can be highly discreet; as the social contexts surrounding THC use have made it more overt and less stigmatized, use of the drug, particularly by vaping, has grown. 19 The amount of THC that some users vape can be dramatic, reaching up 50 mg THC inhaled in a single session, with a total consumption of up to 700mg per day; in comparison, a typical “joint” of marijuana delivers approximately 12mg inhaled THC (Monte A, personal communication, 2019). As with nicotine, the more rapidly delivery of THC to the brain by vaping compared to combustible and edible products dramatically alters the clinical presentation, such as increased incidence of hallucinosis or psychotic reactions. 17

Assessment of behaviors related to the vaping of cannabis is complex, not only because of the large number of THC-containing products manufactured by an industry that remains largely unregulated, but also because of the growth of ‘grey market’ cannabis vaping products coupled with homemade vaping liquids of unknown and variable chemical compositions. Even the method individuals can use to inhale THC is complex; in addition to e-cigarette and “dab pens”, vaporizers can deliver THC from cannabis flower, shatter (a hard, translucent concentrate of THC similar in texture to glass), or wax (a sticky, highly viscous concentrate of cannabis oils that holds its form after cooling). Some users increase the concentration of THC delivered by “dripping” where THC solutions are applied directly to heating coil to produce a vapor to be inhaled. 20 As the frequency of use and dose of inhaled THC have increased, so too have the incidence of clinical conditions associated with problematic cannabis use such as cannabis hyperemesis syndrome as well as mental health and behavioral disorders. 21

As with the assessment of nicotine vaping, identifying where THC vaping products were purchased, the product name, and the manufacturer, if available, can provide useful information, particularly for patients who present to an emergency department of evaluation of acute respiratory symptoms. 2 When evaluating users who experiment with custom or homemade vaping solutions, clinicians should obtain sources of information about methods used to make these products; review of online tutorials, for example, can help define method of preparation, identify the chemicals used in vaping solutions (e.g., extraction solvents, heating, distillation, flavorings), and reveal other individualized aspects of cannabis vaping.

The age of initiation, frequency of use, and change in cannabis use over time can help identify lifetime exposure; change in cannabis use over time can help identify development of tolerance. 22 Other questions that can be useful for both assessing severity of illness as well as optimizing the effectiveness of interventions include identifying problems related to marijuana use, changes in school or work function, loss of interest in other activities, interpersonal problems with parent, teachers, coaches, or friends, or dangerous use (particularly while driving). 22 Questions about quit attempts can help uncover ambivalence about ongoing THC use and readiness to change. A brief assessment followed by psychoeducation to correct misinformation about THC use, addiction, and adverse effects of use, coupled with advice that choosing not to use is the healthiest option for all adolescents, can serve as an initial brief intervention. 22

Special considerations: Focused assessments

Certain clinical environments demand more focused assessments of vaping. In particular, emergency department clinicians, with their emphasis on efficient disposition of patients, do not have the time to complete comprehensive evaluations and may reasonably limit their assessments to discriminating between a medical and behavioral workup. Accordingly, the italicized content presented in Table 1 , which focuses on the relationship between substance use and respiratory outcomes, may be more realistic for use in emergency settings.

Conclusion

Our understanding of acute and chronic effects of vaping is limited by variations in use patterns (especially since adolescents share vaping products) and extensive overlap of nicotine and THC vaping, particularly in combination with other drug use behaviors. Further complexity comes from rapid changes in the vaping landscape arising from introduction of new vaping brands, vaping liquids, and “knock-off” products; banning of vaping products; expanding THC legalization; and use of “black market” or homemade vaping materials. Finally, proprietary vaping liquid compositions can contain potentially thousands of flavorants, additives, and other chemicals designed to alter the vaping experience; assigning causation of lung injury to a specific chemical is therefore difficult. Our recommendations presented here can help clinicians obtain a detailed history of drug exposure and outcomes from nicotine and THC vaping that can serve as useful guidance until estimates of both lifetime and acute exposure to these drugs can be rigorously established.

Acknowledgments

Sources of Support that Require Acknowledgement/Conflicts of Interest and Sources of Funding:

“Authors must state all possible conflicts of interest in the manuscript, including financial, consultant, institutional and other relationships that might lead to bias or a conflict of interest. If there is no conflict of interest, this should also be explicitly stated as none declared. All sources of funding should be acknowledged in the manuscript.”

Health Canada to start testing cannabis vape emissions from products already on market

Agency tells CBC News it's 'expanding' its 'laboratory capability'

Health Canada says it's preparing to test the health effects of inhaling substances emitted from cannabis vaping products that are already legally for sale in Canada.

Agency spokesperson Eric Morrissette said in a statement this week it has "research underway" on the emissions of nicotine e-cigarettes and is now "expanding" its "laboratory capability" to include the testing of cannabis vapes as well.

The statement comes after CBC News reported the federal health agency does not conduct emissions testing on cannabis vapes and one company pre-emptively pulled its product over health and safety concerns.

Cannabis vapes are among a series of new products — including edibles, extracts and topicals such as lotions — that can be legally sold in Canada as of Tuesday.

The products have not yet appeared in legal cannabis stores or websites in Canada, but Health Minister Patty Hajdu said Tuesday they can now be legally sold by authorized retailers under "strict rules."

Cannabis vaping product for sale despite lack of Health Canada testing

"Licensed processors are responsible for ensuring that all their products meet safety requirements, and that none of their products contain anything that may cause injury to the health of the user," Hajdu said in a separate statement.

"Given the recent cases of vaping-associated lung illnesses, Health Canada requested additional information from licensed processors on the ingredients and product formulation of certain vaping products they intend to sell in Canada's legal market."

As of Dec. 10, 2,409 cases, including 52 deaths, have been reported to the U.S. Centers for Disease Control and Prevention (CDC) in all 50 states this year.

There have been 14 cases of vaping-associated lung illness reported to the Public Health Agency of Canada, as of Dec. 10. Three occurred in British Columbia, two in New Brunswick, four in Ontario and five in Quebec.

The majority of the cases of vaping illness are linked to illicit cannabis vapes. The CDC has not singled out any one brand but recommends that people not use the devices at all.

On Nov. 28, Health Canada sent out a request for "further information" on the 359 notices of intent to sell that it received from 34 licence holders or processors that had requested to sell the products and found two that may have already violated regulatory requirements.

That information request was not emissions-related, but instead asked for detailed measurements of each individual ingredient, their classification and composition and the name of the supplier.

"The department has had subsequent communications with two licence holders, where examination of the additional information identified potential non-compliance with regulatory requirements," Morrissette said in the statement.

"In all these instances, the licensed processor in question has stated that they have chosen to voluntarily not introduce these products to the market at this time."

Morrissette said ethyl alcohol and medium chain triglycerides (MCT oil), a common extract from coconut oil, may have been found in the products but did not identify the licence holders in question.

Canadian cannabis companies Canopy Growth, Aphria, Aurora Cannabis and Organigram said that they do not test the emissions of their devices, as it is not required by the federal government.

HEXO, a Canadian cannabis company that made headlines after it announced in October it would sell cannabis cheaper for $4.49 a gram, said last week it will not yet release cannabis vapes because of concerns about their safety.

Similar to the rules for nicotine e-cigarettes, banned ingredients for cannabis vape oils include added vitamins or minerals, nicotine or alcohol, caffeine and added sugars, sweeteners or colours.

That includes vitamin E acetate, which has been identified as a "chemical of concern" by the CDC in the vaping-related illness outbreak across North America but has not officially been confirmed as the culprit.

But Health Canada will allow flavours, the use of which has been discouraged by the Canadian Paediatric Society in nicotine-based vaping products because of a fear that they will make the products more attractive to young users.

Flavouring chemicals, such as diacetyl (found in buttery flavours), are also associated with conditions, such as "popcorn lung," and pulegone (found in menthol) can have toxic effects when vaped at high levels.

Health Canada said it requires those licensed to sell cannabis vaping products to test vaping liquids for contaminants and to maintain records of the test results, which it can verify during inspections. The agency can also take samples for independent testing, it said.

In a previous statement, Morrissette said that diacetyl and vitamin E acetate have not been found in the ingredients of licensed processors to date, but did not provide details on other flavouring chemicals that may be present.