Dr. Weeks’ Comment: Nicotine is indeed addictive, but more so if smoked or chewed than if taken as a patch. The following Harvard study does NOT assert nicotine is not addictive but simply that pyrazines contribute to addiction potential. Nicotine patches, which are helpful as potent anti-inflammatory agents and energy enhancement, don’t contain pyrazines as an ingredient. A patch contains:
- Pharmaceutical-grade nicotine, either highly purified from tobacco or made synthetically.
- An adhesive and drug-release matrix, such as acrylate copolymers, polyisobutylene or silicone, depending on the brand.
Cigarettes typically contain over 600 ingredients, and each brand may have a slightly different formula. Pyrazines in cigarettes are flavor and aroma compounds that give roasted coffee, cocoa and toasted bread their smell. In cigarette tobacco, they form during curing and burning, and manufacturers have also added them to cigarettes as flavorings. Some researchers argue that added pyrazines make smoking more appealing and possibly harder to quit, because they smooth the harshness of the smoke. That concern applies to combustible tobacco and some flavored products, not to medicinal patches. Patches have no flavor and nothing is heated or inhaled.
How it causes addiction. Nicotine binds to nicotinic acetylcholine receptors in the brain, especially the α4β2 subtype. This triggers dopamine release in the brain’s reward circuit, the same pathway involved in other addictions. With repeated exposure the brain adds more of these receptors and adapts to nicotine’s presence. Stopping then causes withdrawal: irritability, anxiety, poor concentration, low mood, increased appetite and cravings. Tolerance, withdrawal and compulsive use despite harm are the hallmarks of addiction, and nicotine produces all three.
Speed of delivery of nicotine is critically important. Nicotine is addictive on its own, but how addictive it is depends heavily on how fast it reaches the brain and what it’s delivered with. Any substance which is rapid acting and rapidly leaves the body can create addiction. One of the tips to lower addiction of anything is to be well hydrated because substances like nicotine, in the presence of adequate hydration, leave the body more slowly, and this lowers any addictive potential. The same can be said for balancing blood sugar. If something makes your blood sugar spike and crash, it is more addictive than if something which simply maintains your blood sugar at a steady state. To clarify this principle, think about driving a standard car with a stick shift. Anything that leaves the system quickly is like revving the engine and popping the clutch. Not good for the engine in the long-term. Inhaled nicotine from cigarettes or vapes reaches the brain very rapidly – within about 10 to 20 seconds – and this sharp spike contributes to its addictiveness. Patches deliver nicotine slowly and steadily through the skin with no spike. As a result they have very low abuse potential. People rarely become dependent on patches. In fact, research studies giving patches to non-smokers (for example, in arthritis or Parkinson’s or ulcerative colitis trials), the participants didn’t develop addiction. Gum and lozenges fall in between: faster than patches, slower than smoking and also contaminated by pyrazines.
THE HARVARD STUDY
https://tobaccocontrol.bmj.com/content/tobaccocontrol/25/4/444.full.pdf
A study of pyrazines in cigarettes and how additives might be used to enhance tobacco addiction
Hillel R Alpert, Israel T Agaku, Gregory N Connolly
ABSTRACT Background Nicotine is known as the drug that is responsible for the addicted behaviour of tobacco users, but it has poor reinforcing effects when administered alone. Tobacco product design features enhance abuse liability by (A) optimizing the dynamic delivery of nicotine to central nervous system receptors, and affecting smokers’ withdrawal symptoms, mood and behaviour; and (B) effecting conditioned learning, through sensory cues, including aroma, touch and visual stimulation, to create perceptions of pending nicotine reward. This study examines the use of additives called ‘pyrazines’, which may enhance abuse potential, their introduction in ‘lights’ and subsequently in the highly market successful Marlboro Lights (Gold) cigarettes and eventually many major brands.
Methods: We conducted internal tobacco industry research using online databases in conjunction with published scientific literature research, based on an iterative feedback process.
Results: Tobacco manufacturers developed the use of a range of compounds, including pyrazines, in order to enhance ‘light’ cigarette products’ acceptance and sales. Pyrazines with chemosensory and pharmacological effects were incorporated in the first ‘full-flavour, lowtar’ product achieving high market success. Such additives may enhance dependence by helping to optimize nicotine delivery and dosing and through cueing and learned behaviour.
Conclusions: Cigarette additives and ingredients with chemosensory effects that promote addiction by acting synergistically with nicotine, increasing product appeal, easing smoking initiation, discouraging cessation or promoting relapse should be regulated by the US Food and Drug Administration. Current models of tobacco abuse liability could be revised to include more explicit roles with regard to non-nicotine constituents that enhance abuse potential.