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Neuroscience of nicotine addiction and treatment

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

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, but only 30 to 40 percent of those who use these therapies successfully quit. 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 youth? 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. In addition, new approaches using novel biologics or behavior modification techniques are needed to combat persistent cigarette consumption among Californians. New and emerging tobacco products, especially e-cigarettes, are being promoted as potential cessation aids, but studies are needed to confirm these assertions and establish potential mechanisms by which novel products and approaches support effective cessation.

An important area of interest is the harm potential of nicotine, flavorants and other constituents in new and emerging tobacco products, such as e-cigarettes and “heat-not-burn” (e.g. iQOS). Because use of these devices is particularly popular among youth and young adults, key research is needed to understand the long-term effects of various inhaled constituents on the developing brain. Research that can inform FDA regulations on new and emerging tobacco products is of particular interest.

The effects of co-use of nicotine with other substances such as alcohol and cannabinoids is another key area of research, especially in light of the recent legalization of recreational cannabis in California. Adolescents are particularly susceptible to addictions because of the formative stage of their brain development, and they often experiment with multiple substances of abuse, consumed separately or combined in new nicotine delivery devices. It is important, therefore, that we understand the biology and behavioral aspects of co-use of nicotine with other substances of abuse among adolescents.

TRDRP has a strong interest in supporting research that aims to understand and reduce health disparities and requests studies that focus on one or more groups that are disproportionately affected by tobacco use (see a list of priority groups under Appendix B, Research Award).

Sub-focus areas and examples of relevant research topics

Sub-focus areas and examples of relevent research topics

Biology and behavior of nicotine dependence

  • Multi-parametric risk factors of nicotine addiction and response to treatment in vulnerable populations
  • Studies of brain connectivity and interaction between neural pathways utilized by different agonists (e.g., glutamatergic, cholinergic, dopaminergic, etc.) in response to nicotine
  • The neurological effects of complete switching from combusted to e-cigarettes in veterans
  • Effects of flavorants and other constituents of e-cigarette aerosol on nicotine addiction
  • Neuroimaging or other clinical studies of the acute effects of nicotine or flavorants, alone or combined, on human brain structure and function

Biology and behavior of cessation Treatments for nicotine addiction – conventional cigarettes and new tobacco products

  • The mechanistic characterization of biological and behavioral differences between female and male e-cigarette users during withdrawal
  • Studies of the side effects of existing cessation drugs in priority populations such as various racial/ethnic, sexual or socioeconomic sectors that are often not fully represented in clinical trials

Harm potential of new and emerging tobacco products on the developing brain

  • The molecular, cellular and behavioral effects of nicotine, with and without flavorants, on the developing brain

Biology and behavior of co-use of nicotine with other substances of abuse

  • The study of the impact of other substances of abuse on the molecular, cellular and behavioral effects of nicotine on the developing brain
  • Addictive potential of combined nicotine and cannabinoid use in African American youth

NOTE: While submission of projects focused on co-use of tobacco with other substances of abuse are welcome, studies in “Neuroscience of nicotine addiction and treatment“ that address non-tobacco substances (e.g. cannabinoids) only are not eligible under this Call.

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