Finding common ground in addiction
The U.S. Food and Drug Administration (FDA) has put the fight against addiction to combustible cigarettes at the focus of its tobacco control strategy. The idea is that if the amount of nicotine is lowered to minimally or nonaddictive levels, it will become harder for future generations to become addicted in the first place and will allow more currently addicted smokers to quit or switch to potentially less harmful products.
Yet, is it justified to speak of “addiction” in the context of nicotine? The second breakout session of the 2018 Global Tobacco & Nicotine Forum looked at current definitions of addiction and to what extent nicotine users fit those definitions. Addiction is commonly defined as a chronic, relapsing disorder that is characterized by a compulsion to seek and take a drug or stimulus; loss of control in limiting intake; and emergence of a negative emotional state, such as dysphoria, anxiety or irritability when access to the drug or stimulus is prevented. Some scientists even consider addiction a brain disease because drugs can change the structure of the brain and how it works. According to their definition, the brain changes involved can be long-lasting and may lead to many harmful, often self-destructive behaviors.
While acknowledging that there are pharmacological and behavioral aspects to addiction, these definitions, however, neglect the fact that there are also non-pharmacological dependencies. With nicotine products, scientists agree that on the behavioral side there is also a psychological and emotional dependence. The relief smokers get from smoking a cigarette does not come solely from the nicotine, one panelist contended, but also from the behavior the smoker had engaged in to smoke the cigarette. Addiction to cigarettes, he pointed out, was increased by product-specific features: Smoking requires a lot of behavioral action. The time from inhalation to impact of the nicotine is very short if compared to the time a nicotine patch takes to develop this effect.
Studies on never-smoking Parkinson patients who received high doses of up to 100 milligrams of nicotine a day—three or four times the dose of a normal smoker—through a nicotine patch did not show any withdrawal symptoms when they stopped taking in nicotine. Among the pharmacological effects of nicotine is the increased availability of dopamine, which is thought to intensify the reward from nicotine.
A representative Swedish study looked into the various degrees of addiction caused by snus, cigarette, nicotine-replacement therapy (NRT) and coffee use. The results showed that snus and cigarettes were equally dependence-forming, whereas the potential of NRTs in this respect was lower. Coffee, interestingly, reached the same levels as NRTs. With regard to various nicotine products, the study suggests, there might be a continuum of dependence.
While nicotine brings about some positive reinforcement, such as mild euphoria, stress reduction, mood regulation or cognitive enhancement, it also negatively impacts the brain stress system. Abstinence will lead to irritability, anxiety, cognitive deficits, insomnia and craving—which is in line with current definitions of addiction. A trial on addictive-like behavior in rats showed that the animals escalated their nicotine intake when given extended and intermittent access, similar to any other drug of abuse. After exposure to nicotine, stress or nicotine cues, the rats would relapse their nicotine seeking. In another study with nonhuman primates, nicotine withdrawal was found to increase the cortisol-releasing factor (CFR) in the amygdala, the part of the brain involved with the experiencing of emotions, while it decreased dopamine activity in another area of the brain. The process is part of the nicotine addiction cycle. As a consequence of withdrawal, anxiety, stress and dysphoria are experienced. They lead to craving, relapse and once more to nicotine uptake.
Although addiction is a well-researched field, there are still research gaps, for example, insights on how to tackle addiction, how to deal with smokers and information about what smokers really want. In addition, the 1 billion smokers in the world are very heterogenic. At least two-thirds of them live in low- and middle-income countries (LMIC). So far, they have rarely been looked at by researchers. To reach these smokers and bring tobacco harm reduction closer to them remains a challenge. Hence, capacity of researchers in LMIC regions needs to be increased—according to research, the primary researchers are mostly based in the U.S. and the U.K.; very few are in Asia, and almost none are in Africa.
While tobacco control efforts focus on smokers in high-income countries, the harm reduction debate becomes very critical to people living in LMICs. The Foundation for a Smoke-Free World (FSFW) has therefore developed an approach that looks at how these smokers can be helped to quit, to switch or to continue using safer products. Based on its findings, the foundation’s research agenda will concentrate on indigenous people, people with mental disorders, prisoners and populations that are normally not reached by the normal health or cessation services, such as people living in slums.
The challenge behind introducing a reduced-risk product (RRP) to these target groups is how to make it cost-effective and how to get it to the majority of people who are not as well-educated and well-off as smokers in the developed world. According to the FSFW, innovation is key to bringing RRPs to those populations. More information on the individual priorities of smokers in LMICs is needed to define what they understand as addiction. The way to go in tobacco harm reduction is to develop the right policies and environments for this.