Given that pharmacotherapies for addiction can alter other appetitive responses, we hypothesized that IBUD would reduce tonic levels of high-fat/high-sugar food craving as well as reduce high fat/high-sugar food craving following alcohol infusion and stress. Understanding generaland domain-specific effects of IBUD will further medication development. A neuroimmune modulator such as IBUD may uniquely impact high-fat/high-sugar food craving because pro-inflammatory signaling may be associated with increased or decreased motivations to eat . Indeed, contrary to our hypothesis, IBUD increased high-fat/high-sugar food craving during psychological stress. It is uncertain why this effect emerged, although one might speculate that because IBUD inhibits pro-inflammatory signaling it reduces “sickness behavior” thereby increasing motivation to eat . Indeed, IBUD effects on high-fat/high-sugar food craving only emerged during a psychological stress task and psychological stressors acutely stimulate eating of high-fat/high-sugar food and production of pro-inflammatory cytokines , which could make modulation by IBUD more salient. Nevertheless, chronic peripheral levels of pro-inflammatory cytokines are associated with depression and increased comfort eating . In accordance with this, depressive symptomatology moderated the effects of IBUD versus PLAC on high-fat/high-sugar food craving during psychological stress reactivity: for those scoring higher in depressive symptoms,mobile vertical system grow high-fat/high-sugar food craving remained higher regardless of IBUD. For those scoring lower in depressive symptoms, IBUD increased high-fat/high-sugar food craving to a level comparable to the level experienced by those scoring higher in depressive symptoms.
These findings should be interpreted while considering that the overall mean of depressive symptoms in this study sample [M = 7.68] was below the clinical depression cutoff. Thus, effects may reflect differences in sub-clinical mood dysphoria. The associations among mood dysphoria, depression, acute and chronic neuroinflammation, and comfort eating are complex and future research is needed to tease apart inflammation mechanisms that drive changes in eating. On the other hand, IBUD did not alter high-fat/high-sugar food craving following alcohol infusion. This could be because alcohol did not generally increase high-fat/high-sugar food craving and had a non-linear effect on craving across target BrAC levels. In detail, a small amount of alcohol increased highest urge for high-fat/high-sugar food , yet more alcohol decreased this urge , and even more alcohol diminished effects . Although there is a substantial literature documenting that small alcohol doses stimulate eating , this is observed less in studies where individuals drink larger doses . The present study is the first to use a within-subjects design wherein food craving was measured at target BrAC levels.Alcohol was intravenously administered; this rules out expectancy effects and suggests that the observed nonlinear effect was mediated by pharmacological or physiological mechanisms. Intravenously administering alcohol comes with the drawback of reduced real-world validity but prior research indicates that participants who drink placebos eat similarly to those in control conditions rather than those who drink alcohol , again suggesting that the stimulatory eating effect of small alcohol doses is pharmacological or physiological. It is important to note that there was some variability across the two craving items in the results for high-fat/high-sugar food craving following psychological stress and alcohol administration. The reason for the different findings between items is uncertain. It could be that asking about highest urge felt during the tasks rather than urge felt right after the task increased response variance and improved statistical precision.
Finally—and critical to the development of IBUD for addiction indications—IBUD did not alter daily urge for high-fat/high-sugar food. This effect remained across all days of each condition in the trial. Although not what we hypothesized, in terms of medication development, this suggests that the effects of IBUD are domain-specific. The trial showed that IBUD reduced tonic levels of alcohol craving . Other research on IBUD has demonstrated its safety and initial efficacy for methamphetamine use disorder and opioid use disorder . IBUD, however, did not reduce tonic levels of high-fat/high-sugar food craving. IBUD seems to be influencing drug-specific mechanisms rather than general appetitive mechanisms. This is in contrast to other addiction medications such as naltrexone and naloxone, which have been shown to have a notable effect on food cravings and eating . The results alternatively highlight that multiple pathways regulate eating including inflammation, satiety, and reward signaling . Although some of these pathways may overlap with drug use, others may not. The present study findings should be interpreted while considering limitations. The sample was moderately sized and only powered to detect large effect sizes . Also, the sample comprised individuals with AUD. This sampling is typical when studies test if pharmacotherapies for addiction alter eating , yet a trial examining IBUD effects in a sample with obesity or eating disorders may yield different results. In addition, the items measuring high-fat/high-sugar food craving may have been too vague. Providing a clear definition of high-fat/high-sugar food with examples may have improved measurement precision. The present study nonetheless had several methodological strengths. Foremost, IBUD is a novel medication for addictions with support from theoretical rationale and strong preclinical data. The randomized, placebo-control, crossover design reduced study bias and error variance because participants served as their own controls. The design additionally included observation of medication adherence and a standardized meal prior to alcohol administration.
Another strength of the design is measurement of the effect of IBUD on tonic food craving as well as food craving following stress and alcohol administration. Calls in the medical field have emphasized that studying multiple behavior intersections in treatment may increase health benefits, maximize health promotion, and reduce health care costs . Understanding intersections between eating and alcohol use—and intersections in the context of medication effects—may be important to promoting overall health in addiction treatment. Tobacco industry has continuously used product modifications, such as manipulating smoke pH with various chemical additives, to make combustible cigarettes more appealing to novice users. For decades, Philip Morris and other tobacco companies have used ammonia as a relatively innocuous additive for a variety of purposes, including augmenting certain flavors, cutting costs by expanding or “puffing up” the volume of cured tobacco leaves, preparing reconstituted tobacco sheet , denicotinizing tobacco , and even lowering/removing tobacco smoke carcinogens. In the early 1960s, while evaluating the impact of ammoniated recons used in Marlboro cigarettes, Philip Morris discovered that freebase or unbound nicotine, as opposed to nicotine bound to other molecules , is more volatile and vaporizable,movable vertical grow rack system thus being highly bio-available. This led to the development of low-yield cigarettes that still had the nicotine kick necessary to keep customers “satisfied”. The freebased low-yield version of Marlboro cigarettes became the world’s most popular cigarette; Marlboro has remained the top selling cigarette brand in the world since 1972. The commercial success of Marlboro persuaded the rest of the tobacco industry to utilize ammonia to convert nicotine to its freebase form, as part of a new process for manufacturing cigarettes. However, this was achieved only after competitors uncovered Philip Morris’ “secret” of freebasing nicotine in cigarettes by reverse engineering the chemistry of Marlboro cigarettes. More than half a century later, a relatively unknown vape company, Juul Labs Inc., recognized the utility of salt-based nicotine for a novel electronic cigarette device, called JUUL. Started in 2017, Juul Inc. is a spin off company from Pax Labs, which was a manufacturer of vaporizing devices for cannabis and loose-leaf tobacco; Pax Labs was preceded by Ploom as the original company for e-cig development. Remarkably, JUUL’s use of salt-based nicotine, which is significantly less aversive than freebase nicotine, made it very quickly popular among naïve users, particularly adolescents and youth. The high content of nicotine in JUUL, which was claimed to be equivalent to nicotine content of a pack of 20 cigarettes, also made JUUL highly appealing to adult smokers, seeking a putatively less-harmful alternative to combustible cigarettes. Shortly after its launch, JUUL became the preeminent vaping product on the market and a dominant player in the vaping industry. In December 2018, Altria, one of the world’s largest cigarette manufacturers and the parent company of Philip Morris USA, acquired a 35% stake in JUUL. This made Altria a major force in both the tobacco and vaping markets. Nearly 1 year later, the US Surgeon General declared “youth vaping” an “epidemic” in the United States, and the US Food and Drug Administration called JUUL a particular cause for concern. Not long after, in August 2019, the Centers for Disease Control and Prevention , the FDA, state and local health departments, and other clinical and public health partners reported a nation-wide outbreak of vaping related severe lung illnesses and deaths, also referred to as “ecig, or vaping, product use-associated lung injury ”. Most EVALI cases reported using e-cig products containing vitamin E acetate and tetrahydrocannabinol , the principal psychoactive component of cannabis. However, the CDC did not rule out the etiologic involvement of other substances present in non-THC containing e-cig products. The EVALI outbreak lasted for several months, but declined considerably by February 2020. Worldwide, there are around 1.1 billion current cigarette smokers aged 15 or older, of whom 942 million are males and 175 million are females.
In 2019, there were an estimated 155 million smokers aged between 15 and 24 years – equivalent to 20.1% of young men and 5.0% of young women, globally. Two-thirds of all current smokers began smoking by age 20, and 89% of smokers began by age 25, highlighting a critical age window during which individuals develop nicotine addiction and transition to become established smokers. Globally, 7.4 trillion cigarette-equivalents of tobacco were consumed in 2019, amounting to 20.3 billion each day. Countries with the highest consumption per person were mostly in Europe. One in three male and one in five female smokers consumed 20 or more cigarette-equivalents per day, worldwide. The 10 countries with the largest number of tobacco smokers, which together comprised nearly two-thirds of the global tobacco smoking population in 2019, were China, India, Indonesia, the United States, Russia, Bangladesh, Japan, Turkey, Vietnam, and the Philippines—one in three current tobacco smokers lived in China. In many countries, progress in reducing the prevalence of smoking did not keep a pace with population growth, resulting in significant rises in the number of young smokers. India, Egypt, and Indonesia had the largest absolute increases in number of young male smokers. Turkey, Jordan, and Zambia had the largest increases in number of young female smokers. Over half of countries, worldwide, showed no progress in reducing smoking among 15–24 years old. Youth vaping is an evolving public health problem in the United States and around the world. Results from the 2020 National Youth Tobacco Survey and Monitoringthe Future survey showed that nearly 3.6 million American teens were current users of e-cigs, of whom 80% reported using flavored products, such as fruit, mint, menthol, and candy, desserts, or other sweet-flavored eliquids. Specifically, one in five U.S. high school students and one in ten middle school students reported current use of e-cigs in 2020. The CDC and FDA analysis of the 2021 NYTS, conducted during January 18 – May 21, 2021, showed an estimated 2.06 million U.S. middle and high school students reporting current use of e-cigs. The authors, however, cautioned that because the 2021 NYTS was fully conducted amid the COVID-19 pandemic through mostly online data collection, estimates from this year’s survey should not be compared to previous NYTS survey waves that were primarily conducted on school campuses. Following a same trend, the percentage of college-age youth who vape nicotine, has risen dramatically in recent years. Between 2017 and 2019, the 30-day prevalence of e-cig use increased from 6 to 22% among college students, and from 8 to 18% among 19 to 22 year-olds not in college. Together, these data indicate a continued and dynamic evolution of the global tobacco epidemic and youth vaping epidemic. Tobacco smoking-related diseases, including cardiovascular disease, pulmonary disease, stroke, and cancer in multiple organ sites, such as the lung, mouth , throat, nose and sinuses, esophagus, bladder, kidney, and ureter, pancreas, stomach, liver, cervix and ovary, the bowel , and white blood cells , are the leading causes of preventable death, worldwide. In 2019, smoking was associated with 1.7 million deaths from ischemic heart disease, 1.6 million deaths from chronic obstructive pulmonary disease, 1.3 million deaths from tracheal, bronchus, and lung cancer, and nearly 1 million deaths from stroke.