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Neuroscience of nicotine addiction and treatment

Advance innovative research that addresses the continuum of nicotine addiction and treatment, with a goal of understanding and reducing tobacco use in populations that consistently have the highest smoking rates.

The starting point along the continuum of nicotine addiction and treatment is the underlying biology of the addiction itself. Nicotine dependence is the most common form of chemical dependence in the U.S., and studies have shown nicotine to be as addictive as heroin, cocaine and methamphetamine. Many smokers find it nearly impossible to quit, despite the well-known link between cigarette smoking and devastating diseases such as cardiovascular disease respiratory disease and cancer.

Nicotine replacement therapies (NRTs) have proven useful for reducing cravings and blunting withdrawal symptoms in many smokers who try to quit, but only 30 to 40 percent successfully quit using these therapies.  Although some of the variability in quit rates among smokers can be attributed to variable adherence to treatment, it is still unclear if there is a biological basis underlying the variability. Why can some smokers quit cold turkey while others are unable to quit even when combining multiple NRTs and complying with behavior-modifying strategies? Is there a genetic difference between individuals that determines how nicotine and NRTs affect the brain’s biochemistry? Do some individuals have baseline neurochemical differences due to their exposure to nicotine and/or other addictive substances in their developmental years?

Understanding the biological differences between highly-addicted and less-addicted smokers can lead to more effective cessation therapies that are tailored to the individual smoker. It may also help to identify links between smoking and tobacco-related disorders such as cardiovascular disease, obesity, diabetes and cerebrovascular disease.

Another space along the continuum is the harm potential of nicotine and other constituents of new tobacco products. Because of the emergence of new nicotine delivery products, such as e-cigarettes and “heat-not-burn" tobacco products (e.g. iQOS) that are particularly popular among youth and young adult, key research is needed understand the long term effect of nicotine, flavorings and other components of these products on the developing human brain. Research that can inform FDA regulations on new tobacco products are of particular interest.

Further along the continuum, is translating new cessation strategies to the clinic. New strategies using novel biologics, behavior modification techniques or a combination of both are needed combat the persistent cigarette consumption among Californians. One key area of translational research that has yet to be studied definitively among in California is the potential of various nicotine delivery products as cessation aids. E-cigarettes, in particular, have been pushed as potential cessation aids.  Definitive human studies, however, are needed to confirm these assertions and establish the methods of administration for effective cessation. With the advent of other purported harm-reduction products on the market, definitive studies on the role they may play in reducing smoking rates are essential.

Although tangential to the nicotine continuum, the co-use of nicotine with other substances such as alcohol and cannabis is another key area of research due to the recent legalization of cannabis in California. Adolescents are particularly susceptible to addictions because of the formative stage of their brain development, and they often experiment with multiple addictive substances such as nicotine, alcohol and cannabis. New nicotine delivery devices often are used to deliver combinations of these substances, as well as flavorings and other constituents. It is important, therefore, that we understand the biological and behavioral aspects of co-use of nicotine and other addictive substances among adolescents.

Sub-focus areas

  • Biological mechanisms of nicotine dependence
  • Harm potential of new products
  • Treatment and cessation
  • Co-use with addictive substances

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Examples of potential research topics include

  • Multi-parametric risk factors of nicotine addiction and response to treatment
  • Biological and behavioral characterization of individual smokers, personalized treatment for smoking disorders
  • Neuroimaging or other clinical studies of the acute effects of nicotine alone or co-use with other substances on human brain structure and function
  • Studies of brain connectivity and interaction between neural pathways utilized by different agonists (e.g., glutamatergic, cholinergic, dopaminergic, etc.)
  • Addictive potential of flavorings and other constituents of e-cigarette aerosol
  • Randomized controlled trial of e-cigarettes as cessation aids among African American young adults
  • Testing the efficacy and side effects of existing cessation drugs in racial/ethnic minority, LGBT and low socioeconomic status groups — sectors typically not fully represented in clinical trials

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