This body of evidence, however, has been criticized for not considering the potential counterfactual that, for reasons related to experimentation, the same youth who initiated e-cigarettes first may have been likely to try cigarettes had ANDS been unavailable, and that most e-cigarette-only youth vape infrequently and are not necessarily using devices containing nicotine. Few studies consider other pathways, most notably from cigarettes to ANDS, which is arguably a pathway of harm reduction should smoking be eventually reduced or stopped. Findings from a growing body of qualitative research suggest that the positioning of ANDS as a “gateway” into smoking cigarettes may not align with the reasons why some youth report vaping.For example, a study of 16 young adult vapers in New Zealand found that participants, who smoked and vaped, used ANDS to either recreate or replace rituals of smoking, and non-smoking vapers tended to dislike smoking and vaped to foster social connectedness. Another study of disadvantaged young adult smokers and ex-smokers in Scotland found that although most participants preferred smoking, the few who used e-cigarettes were motivated by health concerns and desires to quit smoking.Qualitative studies have also highlighted that vapers are not a homogenous group and that meanings of vaping vary across users,vertical farm companies which suggests a need for a more nuanced understanding of the role of vaping for youth with different NT initiation pathways, particularly in light of ‘gateway’ concerns that early ANDS initiation leads to cigarette smoking initiation.

In California, the overall prevalence of youth cigarette smoking continues to decline, even with the emergence of ANDS. We conducted in-depth qualitative interviews with 49 Californian youth between the ages of 15-25, who reported ever vaping nicotine, to consider whether and how the meanings and role of vaping varies by youth’s pathways of initiation of vaping and smoking. By understanding how youth, with various NT use pathways, make sense of their vaping practices, we can more fully understand youth’s motivations for vaping and identify innovative and responsive prevention, treatment, and policy efforts that may be better tailored to youth’s unique needs and experiences. This study is based on narrative data from in-depth interviews with youth. Volunteers were recruited using street-level outreach methods ,through Facebook advertising, and by referral to participate in a 2-hour openended interview designed to collect descriptive data on the participant’s background and everyday life; their NT use pathways and current use practices, the socio-cultural meanings of e-cigarettes and cigarettes in youths’ lives; and perceptions of NT control policies. In person or by phone, participants were screened for eligibility which included being between 15-25 years old, reporting ever vaping nicotine, and living in the San Francisco Bay area. Preceding the interview, a questionnaire was administered that included basic demographics and questions about NT use, including age of initiation and past 30-day use. We obtained parental consent from eligible volunteers under the age of 18.Study procedures were approved by our Institutional Review Board. Interviews were digitally recorded, professionally transcribed, and integrated with ATLAS.ti, a qualitative data management software program.

The first stage of analysis included coding all transcripts to isolate narratives by topic into manageable analytical segments. The codelist was developed by the authors, informed by existing literature and preliminary analysis of interviews. Codes were extensive and included perceptions of smoking and vaping, initiation stories, social motivations of use, pathways of use, cessation motivation, and future intentions of use. Using questionnaire data on age of initiation of both vaping and smoking, the lead author categorized each participant according to 3 pathways: vaping-to-smoking, smoking-to-vaping, and vaping only, and then grouped interview transcripts by pathways to structure analysis of the coded data and to compare whether participants’ perceived role of vaping varied by pathway of use. The lead and second author then conducted a second phase of thematic analysis to identify emergent themes from the narrative data.We also examined divergent and conflicting discourses within interviews to reduce threats to validity by challenging our a priori assumptions, including the use of ANDS for cessation. 33 Quotations from participants introduced below are identified by participant-selected pseudonyms to maintain anonymity. The most common pathway reported among participants was smoking-to-vaping, with 36 of 49 participants characterized into this pathway. Eight participants began vaping prior to smoking and five participants reported only vaping but never smoking . Though youth held different attitudes about vaping—many were indifferent, others regarded them as “lame”, and a few considered vaping “cool”—nevertheless, participants’ narratives about their initiation pathways revealed important insights into the role that vaping played in their lives. Overall, analysis illustrated that regardless of pathway, youth considered vaping to be a valuable alternative to smoking, often chosen in consideration of relative risk.

The ways in which participants across pathways described vaping as an alternative varied, yet their discussions collectively highlighted widespread acknowledgement of the risks associated with smoking and how they attempted to minimize those risks by vaping. This qualitative study sought to understand the perceived role of vaping among youth who initiated vaping according to different pathways of nicotine use. Overall, youth, regardless of initiation pathway, were fully aware of the health consequences of smoking, and their decisions to vape reflected considerations of relative risk where vaping was seen as a suitable alternative to smoking. Some studies suggest that vaping as an alternative to smoking does not suggest a rational process of risk reduction but instead illustrates the ways in which nicotine consumption can be maintained in settings where smoking is prohibited.However, narratives from our participants reflected the ways in which youth considered risk reduction whereby vaping was strategically used to replace or reduce smoking to minimize short and long-term health risks, as a less harmful form of nicotine for coping with stress, or to temporarily engage in the positive social aspects of youthful experimentation while reducing the personal risks smoking presented. The fact that youth consider relative risks and integrate ANDS as a transitional behavior towards smoking cessation highlights the need to acknowledge harm reduction in constructing public health messaging and policies. To date, studies have not sufficiently considered the practice of harm reduction among young people despite some qualitative research suggesting that they may very well be seeking out relatively less harmful nicotine products, like ANDS, either in lieu of or to reduce/quit smoking cigarettes. For example, in a qualitative study of 50 young e-cigarette users in Scotland and Northern England, McKeganey and colleagues found that decisions to continue vaping were often related to youth’s perceptions that e-cigarettes were less harmful than smoking. Likewise, Robertson and colleagues, found that though vaping was originally intended for smoking cessation among some of their participants, vaping “failed to meet their expectations” and therefore goals to eliminate smoking shifted into goals to reduce smoking. Participants in our study were generally more positive about vaping as a suitable replacement for smoking. But, like Robertson’s participants, they similarly perceived the reduction in smoking that vaping facilitated to be valuable on the pathway towards eventual smoking cessation. Tobacco harm reduction approaches emphasize the substitution of less harmful forms of nicotine for more harmful combustible tobacco products for smokers,vertical farming racks who are unable or unwilling to quit.Though some approaches to tobacco control may be considered harm reduction strategies ,most often abstinence is an explicitly-stated goal and discussions of reducing harm remain controversial, particularly when it comes to nicotine use by young people. This is largely due to concerns about the developmental risks associated with any nicotine consumption and the threat of long-term addiction,combined with beliefs that young people behave irrationally and are in need of protection.This study suggests, instead, that youth are applying a logic of risk reduction to negotiate their nicotine use. Though tobacco harm reduction is arguably viewed as a “source of one of the most divisive…debates in tobacco control history,”our study highlights that tobacco harm reduction may be gaining momentum not as an explicit tobacco control strategy but rather as a “consumer-led health initiative” due to youth’s use of vaping to reduce smoking-related harms.Our findings should be interpreted in light of the following limitations. First the sample is not a representative sample of young vapers in the San Francisco bay area nor can it suggest which pathway of NT use is most common. Qualitative research is well-suited for identifying under explored or unanticipated phenomena to inform hypotheses for future studies. Second, this study did not set out to compare perceptions across initiation pathways and, thus, did not have equal numbers of participants in each pathway. However, it is intriguing that the majority of ever vapers recruited into the study were classified in the smoking-to-vaping pathway, particularly in light of the invisibility of young people characterized by this pathway in the existing literature.

Notably, since this was a study of youth who reported ever vaping, none were characterized into a smoking-only pathway. Future research should consider meanings of vaping among never vaping youth, both who smoke and those who do not. Also, this study cannot predict to what extent vaping for harm reduction ultimately leads to smoking cessation. This issue should be examined in future studies with longitudinal designs. Finally, we included a broad range of youth, 15-25 years old. Because qualitative research concerned with identifying variation of experience, we focused broadly on youth, as a socially-constructed category defined less by chronology and more by its progression of stages.Repeated, heavy exposure to methamphetamine is associated with central nervous system dysfunction across multiple neurotransmitter systems, including dopamine , serotonin, GABA, and glutamate . METH exerts particularly potent effects on the dopaminergic system by acting on the vesicular monoamine transporter and DA transporter to stimulate release of DA from presynaptic vesicles and inhibit its reuptake, resulting in excessive levels of synaptic DA . DA is highly active in frontostriatal pathways and DAergic excess disrupts frontal cortical circuitry that regulates motivation, self-control, decision-making and executive function, thereby perpetuating the cycle of addiction . METH-dependence is linked to negative neurocognitive outcomes in domains supported by frontostriatal structures, including learning, memory, executive function, attention/working memory, and cognitive control . Cross-sectional brain imaging studies of METH exposure demonstrate lower gray matter volumes and greater white matter abnormalities in frontostriatal and limbic regions such as the striatum, amygdala, hippocampus, and the prefrontal cortex . Positron emission tomography studies, which have enabled in vivo and regionally-specific evaluation of DAergic activity, provide evidence of DAergic dysfunction in METH users across a number of molecular markers in both the striatum and PFC . Notably, this DAergic dysregulation correlates with markers of neurobehavioral dysfunction, including psychomotor and memory impairment, impulsivity, and psychiatric distress . While adverse neurocognitive findings are frequently observed in METH users, METH use is not always associated with neurocognitive impairment and the reasons for this heterogeneity are unknown . Therefore, a major area of research interest lies in determining what factors may attenuate or exacerbate risk for METH-related CNS dysfunction and associated neurocognitive deficits. Thus far, investigations of a dose dependent relationship with greater METH exposure leading to more severe neurocognitive deficits have resulted in null findings . Self-reported duration of METH use, frequency of use, length of abstinence, and cumulative lifetime exposure do not predict neurocognitive performance . While parameters of drug exposure show little predictive value, individual differences in genetic and environmental factors may account for considerable variability in risk for METH-related neurocognitive deficits . Identifying genetic variations that influence an individual’s vulnerability to METH effects can inform personalized approaches to mitigate METH-related neurocognitive impairment. The catechol-O-methyltransferase enzyme is implicated in DA neurotransmission in the PFC, and specifically assists in regulating clearance of DA from the synapse via metabolic degradation . Functional variation in the COMT gene occurs at a single nucleotide polymorphism resulting in a valine to methionine amino acid substitution . Compared to the Val allele, the Met allele is associated with reduced thermostability and enzymatic activity, leading to slower degradation of DA at the synapse and higher DA concentration in the PFC . In contrast, the Val allele is associated with more efficient DA catabolism and lower levels of synaptic DA. In healthy adults, Met-carriers outperform Val-carriers on tests of PFC-dependent neurocognition, including executive function and working memory .