Emerging data indicate that e-cig use may adversely affect the pulmonary and cardiovascular systems. Also, limited evidence exists on the potential of e-cigs to cause carcinogenic effects. To date, clinical studies have primarily investigated the acute effects of vaping. By design, epidemiologic studies have explored the “association” of e-cig use with disease outcomes. So, the “causal” relationship between vaping and disease pathology remains largely unknown. Currently, determining the long-term health consequences of vaping is a top research priority. Of utmost importance is the long-term effects of vaping, especially among adolescents whose developing brains are more susceptible to influences on learning, memory, and attention. Future well-defined controlled experimental studies are needed to establish the mechanisms by which chronic vaping may lead to adverse health consequences in humans. These investigations are expected to identify the constituent of e-cig vapor, which are of most relevance to disease development. Though it is generally accepted that e-cig use exposes the users to fewer and lower levels of toxicants and carcinogens as compared to smoking, the net public health effect of vaping continues to be debated. The scientific community, regulatory authorities, and the general public are faced with competing views on the health risks or benefits of vaping. On the one hand, proponents of e-cigs advocate for: “harm reduction” potential of vaping, especially for smokers who are unable/unwilling to quit; and utility of vaping for smoking cessation. On the other hand, opponents argue against the adoption of an alternative tobacco product whose long-term health effects are yet to be determined. To reach a consensus, more conclusive scientific evidence will be needed; the available data favor the stance that vaping is likely to be less harmful than smoking, with the caveat that it may still pose a health risk on users,dry racks for plants which would otherwise be eliminated if neither product were used.
On June 22, 2009, with broad bipartisan support from Congress, President Obama signed into law the Family Smoking Prevention and Tobacco Control Act , also known as “Tobacco Control Act”. The FSPTCA granted FDA immediate authority and unprecedented power to regulate cigarettes,cigarette tobacco, roll-your-own tobacco, smokeless tobacco, and any other tobacco products that the agency, by regulation, deems to be subject to the law . On August 8, 2016, when FDA’s “Deeming Rule” took effect, many of the regulatory and statutory requirements that had been in place for manufacturers of the originally regulated tobacco products since passage of the FSPTCA in 2009, became applicable to the deemed products, including e-cigs and all other electronic nicotine delivery systems , cigars, pipe tobacco, nicotine gels, hookah tobacco, and any future products meeting the statutory definition of “tobacco product.” The applicable statutory provisions include the requirement that deemed products that meet the definition of a new tobacco product must receive premarket authorization from the FDA to be legally marketed. The premarket authorization requires a Premarket Tobacco Product Application for any new tobacco product seeking an FDA marketing order. In the deeming rule and subsequent guidance documents, FDA stated that it intended to defer enforcing the premarket review requirements, for a period of time, with respect to “deemed” new tobacco products that were on the market as of the effective date of the deeming rule. This policy did not extend to deemed new tobacco products that entered the market after the rule’s effective date . Under a federal court order, manufacturers of deemed new tobacco products that were on the market as of the deeming rule’s effective date, were required to submit premarket review applications by September 9, 2020. Following the court order, FDA accelerated its planning and preparation to receive a large number of applications by the premarket application deadline. Accordingly, the agency received thousands of submissions, representing more than 6.5 million products by the set deadline.
Per the court order, products for which applications were submitted by the deadline of September 9, 2020, could generally remain on the market for up to a year from the date of the application—or until September 9, 2021, at the latest—pending FDA review, although FDA retains enforcement discretion. Over the last year, FDA has worked to review thousands of PMTAs, representing products from roughly 500 companies.The vast majority of the PMTAs are for ENDS products. Under the PMTA pathway, manufacturers or importers must demonstrate to the FDA that permitting the marketing of the new tobacco product would be “appropriate for the protection of the public health,” among other things. That statutory standard requires the FDA to consider the risks and benefits to the population as a whole, including users and non-users of tobacco products. The FDA’s review of PMTAs includes assessment of a tobacco product’s components, ingredients, additives, toxicological profile, and health effects, as well as its manufacturing, packaging, and labeling processes, and data from consumer perception research , and the applicant’s description of marketing plans for the product. When reviewing PMTAs for ENDS products, FDA’s task is to follow the direction Congress provided in the law by taking into account the increased or decreased likelihood that existing users of tobacco products will stop using such products, as well as the increased or decreased likelihood that those who do not use tobacco products will start using such products. In making this determination, the impact of such products on youth initiation and use is a critical consideration. So far, the FDA has issued ruling on over 96% of the PMTAs submitted on or before the September 9, 2020 deadline, including 295 marketing denial orders for more than 1,089,000 flavored ENDS products. Products subject to a MDO for a premarket application may not be introduced or delivered for introduction into interstate commerce. If the product is already on the market, the product must be removed from the market or risk enforcement. On October 12, 2021, the FDA granted permission to R.J. Reynolds to market its Vuse Solo closed ENDS device and two accompanying tobacco-flavored e-liquid pods with a nicotine strength of 4.8%, which approximates the nicotine content of a pack of cigarettes.
The FDA simultaneously issued MDOs for ten other flavors submitted under Vuse Solo but declined to state which ones. RJR is the second-largest tobacco company in the United States , and a wholly owned subsidiary of Reynolds American Inc., after merging with the U.S. operations of British American Tobacco in 2004 . In a statement announcing the decision, the FDA said that “The authorized products’ aerosols are significantly less toxic than combusted cigarettes based on available data.” The statement concluded that “For these products, the FDA determined that the potential benefit to smokers who switch completely or significantly reduce their cigarette use, would outweigh the risk to youth,4 x 8 grow tray provided the applicant follows postmarketing requirements aimed at reducing youth exposure and access to the products”. The FDA’s decision came on the heels of the 2021 NYTS report showing an estimated 2.06 million U.S. middle and high school students as current users of e-cigs, with Puff Bar, Vuse, and Juul among the most popular brands. In its decision, the FDA stated that it was aware that 10% of high school students who used e-cigs, named Vuse as their favorite brand in the 2021 NYTS. Vuse has become the fastest-growing e-cig brand, accounting for over 26% market share in the top five markets, being the market leader in Canada, the UK, France, and Germany . In the United States, Vuse continues to outperform other brands, becoming the second largest and fastest growing player in the market in 2021. Currently, Vuse owns 33% of the market share in the United States whereas Juul owns 40%. The FDA’s decision to grant marketing orders for Vuse Solo and accompanying e-liquid pods marks a milestone in vaping regulations as this is the first time ever that a set of vaping products gets clearance from the agency. The cleared products can now be mass marketed and sold legally in the United States. As expected, the watershed decision by the FDA to green light Vuse Solo vaping products has been praised by the industry as well as proponents of e-cigs for harm reduction. Simultaneously, there have been swift and harsh criticisms of the decision by many experts in public health and medicine and numerous healthcare advocacy groups. As the FDA continues its premarket reviewing of the remaining PMTAs for ENDS products, including major brands such as Juul, and while teens’ favorite products, specifically Puff Bars , are being ordered off the market , Vuse is expected to continue its growth momentum owing to its “first-mover” advantage and industry leading FEELM ceramic coil. Alcohol use disorder is a highly prevalent, chronic, relapsing condition characterized by an impaired ability to stop or control alcohol use despite clinically significant impairment, distress, or other adverse consequences. It is the most common substance use disorder: in 2016, 100.4 million people globally were estimated to have an AUD. This disorder represents a significant public health concern. The WHO estimates that alcohol consumption is responsible for 5.9% of all deaths and 5.1% of global disease burden. Alcohol use and misuse is thought to contribute to over 200 related diseases and health conditions globally, including cardiovascular disease, cancer, liver cirrhosis, and injuries. AUD is also often comorbid with other substance use disorders, major depressive disorder, bipolar disorder, and other psychiatric disorders. In the USA alone, AUD is estimated to contribute to about 88,000 deaths each year. An estimated 44.6 million adults per year in the USA suffer from AUD, and 93.4 million adults in the USA will meet or have met AUD criteria at some point in their life.
Furthermore, the economic burden of AUD is estimated to be approximately $250 billion across the USA. Although AUD is an important public health concern, the disorder remains severely under treated with only 7% of adults with AUD in the USA and less than 10% in Europe receiving pharmacotherapy and/or psychotherapy treatment. Furthermore, the lag between the age at which AUD onsets and the age of first AUD treatment has been estimated to be eight years on average. Pharmacotherapies have seen limited use in the treatment of AUD, partially due to lack of addiction treatment training for medical professionals, lack of awareness regarding medication options , reluctance to prescribe and take medications, perceived low efficacy of medication, and stigma surrounding treatment. Indeed, only three pharmacotherapies are approved by the US Food and Drug Administration for use in AUD treatment. These medications are disulfram , acamprosate, and naltrexone. The European Medicines Agency similarly recognizes only these same three medications, as well as nalmefene, as established pharmacotherapies for AUD. These medications are only modestly effective and are under-utilized in treatment. A study conducted in 2019 found that only 1.6% of adults in the USA with past-year AUD received evidence-based AUD pharmacotherapies. Treatment outcomes for AUD differ widely across patients and medications. While abstinence may be desirable, it is infrequently obtained, such that only 16% of individuals in treatment for AUD achieve abstinence. Furthermore, evidence does not support abstinence as the only approach in the treatment of AUD. Not all individuals with AUD consider abstinence to be a goal of their recovery; only 2–6% of goals set in patient-driven treatment center on attaining alcohol abstinence. Non-abstinent recovery, including reductions in drinking and heavy drinking in particular , has been recognized to have health and societal value and has gained traction as a treatment target. Indeed, non-abstinent AUD recovery has been shown to be sustainable for up to 10 years following treatment. Despite growing recognition of the benefits of harm reduction, however, the most commonly prescribed pharmacotherapy to treat AUD remains disulfram, a medication advised strictly for abstinence. Furthermore, the heterogeneity of AUD suggests that it will be unlikely that one single medication will be effective for all individuals with an AUD. Therefore, there is a pressing need for the development of novel, diverse, and effective pharmacological treatment options for AUD with the hopes of increasing utilization and improving care.Specifically, this review provides a brief overview of currently approved medications and identifies new and repurposed agents “on the horizon” for which evidence indicates a potentially effective application toward AUD treatment.The following sections examine pharmacotherapies approved or in-development for AUD. Medications were selected for this qualitative review by considering gaps in existing review articles and the expertise of all authors; information was gathered via qualitative PubMed literature searches.