UNITED STATES DISTRICT COURT FOR THE DISTRICT OF COLUMBIA ____________________________________ ) UNITED STATES OF AMERICA, ) ) Plaintiff, ) ) v. ) Civil Action ) No. 99-CV-02496 (GK) PHILIP MORRIS USA INC., ) f/k/a PHILIP MORRIS INC., et al., ) Next Scheduled Court Appearance: ) Trial (ongoing) Defendants. ) ____________________________________) WRITTEN DIRECT EXAMINATION OF JACK E. HENNINGFIELD, Ph.D. SUBMITTED BY THE UNITED STATES PURSUANT TO ORDER #471 1 Q: Please state your full name for the record. 2 A: Jack Edward Henningfield. 3 Q: Where do you currently work? 4 A: I currently work for Pinney Associates in Bethesda, Maryland, as well as The Johns 5 Hopkins University School of Medicine in Baltimore, Maryland. 6 Q: You have been shown U.S. Ex. 78,534. Do you recognize this to be a copy of your 7 curriculum vitae as of December 9, 2003? 8 A: Yes. 9 Q: Let’s briefly review your educational background. Where did you go to college? 10 A: I received my undergraduate degree from the University of Minnesota’s College of 11 Liberal Arts. 12 Q: What year did you graduate? 13 A: I graduated in 1974. 14 Q: What was your major and degree? 15 A: I graduated with a Bachelor of Arts degree with a major in psychology and a strong 16 supporting program in biological sciences. 17 Q: Did you graduate with honors? 18 A: Yes, summa cum laude. 19 Q: Did you go on to graduate school after graduation? 20 A: Yes, I did. 21 Q: Where did you go to graduate school? 22 A: I attended the University of Minnesota. 23 Q: Did you receive any type of fellowship? Written Direct: Jack E. Henningfield, Ph.D., US v. PM, 99-cv-02496 (GK) (D.D.C.) Page 1 1 A: Yes. 2 Q: What was the nature of the fellowship? 3 A: I was awarded a United States Public Health Service Predoctoral Fellowship established 4 to train scientists to specialize in drug addiction through the Psychopharmacology Training 5 Program at the University of Minnesota. 6 Q: What was the focus of your Ph.D. program? 7 A: It was an Experimental Psychology in the Psychopharmacology Training Program. 8 Q: What is Experimental Psychology in Psychopharmacology? 9 A: The training program was a Ph.D.-only program to train scientists specializing in drug 10 addiction. The program combined the departments of Experimental Psychology, or “research 11 psychology,” from the Graduate School, with Pharmacology from the Medical School, to provide 12 training for the relatively new field of “psychopharmacology.” 13 Q: What is psychopharmacology? 14 A: Psychopharmacology is essentially the study of drugs that affect the brain and hence 15 mood and behavior. The major category of these “psychoactive” drugs in which I specialize in 16 my work are the addictive drugs, including nicotine. 17 Q: Is there any other name for the field of psychopharmacology? 18 A: Yes, there is. The field is increasingly called “behavioral pharmacology,” emphasizing 19 the interaction between drugs and behavior and the behavior-modifying effects of the drugs. Of 20 course, the brain is the physiological target of the drugs, but behavior change, including addictive 21 behavior in some cases, is the main consequence. 22 Q: What types of training have you received to become a psychopharmacologist? 23 A: I was trained in psychology, pharmacology, research design and evaluation, drug Written Direct: Jack E. Henningfield, Ph.D., US v. PM, 99-cv-02496 (GK) (D.D.C.) Page 2 1 formulation and dosing factors, psychiatric diagnosis, and many other aspects relevant to 2 understanding the effects of drugs, including alcohol, amphetamines, cocaine, morphine, 3 nicotine, and sedatives. 4 Q: Did you perform any research while in this program? 5 A: Yes, I did. 6 Q: What type of research did you perform? 7 A: I performed research on the behavioral and pharmacological factors involved with the 8 self-administration of addictive drugs by rats and monkeys 9 Q: What do you mean by “self-administration” and “behavioral and pharmacological 10 factors”? 11 A: Self-administration refers to the behavior of an animal to give itself a dose of drug. For 12 example, in the laboratory, it can be arranged so that pressing a lever will result in an intravenous 13 injection of nicotine or cocaine. Alcohol studies more typically involve pressing levers to 14 provide tiny drinks of alcohol solutions. 15 Pharmacological factors include the comparison of the physiological effects of different 16 drugs or chemical entities, and the dose, or amount, of the drug administered. Behavioral factors 17 include how the accessibility of the drug – e.g., 1 hour per day versus 3 hours per day versus 24 18 hours per day – affects the animal’s behavior; and how the cost of the drug – e.g., “paying” by 19 pressing a lever ten, one hundred, or a thousand times per dose – influences behavior. Other 20 factors included physiological state such as whether the animals were hungry or had eaten their 21 fill. 22 Q: Did you focus your research on any particular substances? 23 A: Yes. It was focused primarily on alcohol and barbiturate sedatives. However, I also Written Direct: Jack E. Henningfield, Ph.D., US v. PM, 99-cv-02496 (GK) (D.D.C.) Page 3 1 assisted in the conduct of research involving cocaine, amphetamines, morphine-like opioids, 2 marijuana, and other drugs. 3 Q: When did you complete this Ph.D. program? 4 A: I completed it in 1977. 5 Q: What did you do upon completion of your Ph.D. program? 6 A: I was awarded a fellowship by the National Council on Alcoholism to continue my 7 research on the development and evaluation of animal models of alcoholism. 8 Q: What is the National Council on Alcoholism? 9 A: It is a nongovernmental, non-profit organization that supports research, clinical practice, 10 and policy to prevent alcoholism and alcohol abuse, as well as to find more effective treatments 11 for those afflicted. 12 Q: Did you receive this fellowship after a selective process? 13 A: Yes. I submitted a research proposal to continue work to develop an animal model of 14 alcoholism involving rhesus monkeys as an extension of my thesis work. I do not know how 15 many proposals were submitted, but I believe I was the only awardee and was told that it had 16 been highly competitive. It was a great honor. 17 Q: What were duties in that position? 18 A: I conducted research to extend and validate the monkey model of alcoholism and 19 participated in graduate and postdoctoral seminars on drug addiction and addiction research. I 20 also conducted studies of the importance of the dose of alcohol; the frequency of access; the 21 “cost” of the alcohol to the animals, that is, how hard animals will work to get alcohol; and 22 potentially interactive alterations in diet. I also conducted research on pentobarbital, a 23 barbiturate sedative. Written Direct: Jack E. Henningfield, Ph.D., US v. PM, 99-cv-02496 (GK) (D.D.C.) Page 4 1 Q: What type of research did you do on pentobarbital? 2 A: I studied the sedative’s potential similarities and differences with alcohol, including the 3 effects of drug dose and cost per dose on self-administration patterns. 4 Q: What did the studies show about the effects of drug dose and cost per dose on self- 5 administration patterns? 6 A: Essentially, we found that self-administration of drugs in animals is similar, in key 7 respects, to how humans behave when there are changes in drug dose, as well as the cost to attain 8 the drug. For example, the behavior of self-administration is generally inversely proportional to 9 the amount or dose of the substance given. As alcohol dose or concentration is decreased, the 10 animals take more drinks, and vice versa. This is similar to findings with food studied in other 11 laboratories and reflects the biological effects of drugs and food to modulate the behavior. 12 Q: Do you mean that the animal or person will maintain a constant intake of drug by 13 compensating for changes in the dose? 14 A: In actuality, compensation is rarely perfect because as the dose increases, the number of 15 units taken tends to decrease but not in perfect proportion. Therefore, the user generally ends up 16 taking in somewhat more drug, or food if caloric value or meal size is increased. Conversely, as 17 the dose decreases, the number of units taken tends to increase, but compensation is generally not 18 complete and the total intake is less. 19 Q: Is there a minimum dose required? 20 A: At very low doses, it may be physically very difficult if not impossible to maintain 21 desired intake or the intake necessary to sustain addiction. For example, in prior studies in which 22 I was involved, when we decreased the alcohol concentration to .5%, the animals were not able 23 to consume enough liquid to sustain reliable behavior and for the observance of the behavioral Written Direct: Jack E. Henningfield, Ph.D., US v. PM, 99-cv-02496 (GK) (D.D.C.) Page 5 1 effects of alcohol. 2 Q: Was any of your compensation research published? 3 A: Yes. My first journal-published paper, which investigated the effects of changing the 4 amounts of alcohol provided to rats by variation of miniature “cups” used to “serve” the alcohol, 5 was accepted with minimal revision by the journal Pharmacology, Biochemistry and Behavior. 6 My other studies on the subject were also accepted, published in major international journals and 7 presented at national and international meetings including the College on Problems of Drug 8 Dependence, the International Council on Alcoholism and Addictions, and the International 9 Society Investigating Drugs as Reinforcers.