HENNINGFIELD: On Increased Nicotine Levels

Author: Jack E. Henningfield, Ph.D.

Increased nicotine in cigarettes could help perpetuate and or increase nicotine addiction in the population without making the individual cigarette demonstrably more addictive

In considering the Massachusetts Report data suggesting increased nicotine levels of US cigarettes, some of the discussion had debated whether increased nicotine makes cigarettes more addictive. A perspective from other addictive drugs shows how abuse and addiction at the population level can be altered by drug dosing factors that do not necessarily make the drugs more addictive. The following observations pertain to most widely recognized addictive drugs, licit and illicit and key elements are based on animal and human studies

(1) Bigger doses are not necessarily more addictive nor smaller doses necessarily less addictive. For a given addictive drug, be it cocaine, morphine, alcohol, or nicotine, the dosage is a critical determinant of effects, desired and undesired, and individuals differ in their "ideal" dose

(2) If dosing is so limited or inflexible or costly as to constrain the ability to achieve desired dosing, then development and maintenance of addiction can be impeded, whether the drug is cocaine, alcohol or nicotine, in humans, rats or monkeys

(3) Similarly, for a person or animal that has developed addictive drug seeking ("self-administration") increasing the difficulty in maintaining addictive/desired dosing, whether by limiting access, reducing unit dose or by increasing cost per dose, eventually results in extinction ("giving up") of the addictive behavior (technically referred to as the "break point" in response-cost studies). Of course, people and animals vary in their break points and persistence in the face of difficulty in achieving desired dose levels

(4) Therefore, drug formulations that provide ready flexibility to adjust/calibrate/titrate dose are often more attractive to drug abusers and the importance of drug formulation as a determinant of drug abuse is increasingly the focus of drug regulatory and control efforts (e.g., smokable cocaine is an example among illicit substances; among licit drugs, the OxyContin formulation of oxycodone, and other prescription drugs that enable ready dose tampering and/or drug extraction are further examples)

(5) At the population level the prevalence of a given form of substance abuse and addiction is related to the ease of achieving and sustaining addictive/desired drug intake. Thus, cocaine abuse and addiction exploded in the US during the 1970s and early 1980s (before free-basing and crack were generally known) as supply increased, cost decreased, and it thus became easier to achieve addictive intake - the drug did not become "more addictive"

Implications for evaluating the Massachusetts data:

If the Massachusetts findings are valid, then the data suggest that by increasing available nicotine in cigarettes, it will be easier for tobacco users to sustain their addictions, as restrictions on smoking, and cost of the products increase, and number of cigarettes per day decrease. At the population level this could contribute to maintaining addiction. This conclusion is not based on the premise that such cigarettes are "more addictive" or that lower nicotine cigarettes are less addictive. Of course, with cigarettes as with illicit and prescription drugs of abuse many factors beyond dose and formulation also affect prevalence of use and attractiveness (even with crack-cocaine and heroin, creative "branding" and "marketing" are important, as well as health concerns about particular formulations and "brands")

For further reading see:

Griffiths, Bigelow, and Henningfield. Similarities in animal and human drug-taking behavior. In: Mello, N.K. (ed.) Advances in Substance Abuse, pp. 1-90, 1980

Expert Panel (Henningfield and Johanson, Rapporteurs; Sellers, Chair). Abuse liability assessment of CNS drugs: Conclusions, recommendations, and research priorities. Drug and Alcohol Dependence, 70(Supl.): S107-S114, 2003

Grudzinskas, Balster, Gorodetzky, Griffiths, Henningfield, Johanson, Mansbach, McCormick, Schnoll and Wright. Impact of formulation on the abuse liability, safety, and regulation of medications: the expert panel report. Drug and Alcohol Dependence, 83: S77-S82, 2006

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By way of disclosure, I consult to pharmaceutical companies on tobacco dependence treatments, on drug abuse liability and control related issues across stimulants, opioids, sedatives and other drugs, have testified on addictive drug control, and formerly headed the US National Institute on Drug Abuse Laboratory given the lead role in assessing abuse liability ("addictiveness") of substances with known or suspected potential for abuse and addiction.

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Jack E. Henningfield, Ph.D.

Vice President, Research and Health Policy

Pinney Associates

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and

Professor and Director

Innovators Awards Program

Dept. of Psychiatry and Behavioral Sciences

The Johns Hopkins University School of Medicine

Baltimore, Maryland

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