18 



In terms of tolerance, a study design that Paul put together was 

 to repeatedly inject animals with nicotine over several days, and 

 then test to determine whether or not the animal was tolerant to 

 the disruptive effects of nicotine. 



When you inject nicotine in an animal and he is working on a 

 lever for food, the performance of the animal becomes impaired. 

 That performance impairment goes away as the animal has expo- 

 sure to nicotine. We also demonstrated in that experiment that 

 part of that tolerance was physiological and part of the tolerance 

 was behavioral, that is, a learned tolerance. 



In physical dependence, we conducted two large experiments in 

 which we chronically administered nicotine to rats over several 

 days, if not weeks. We challenged the nicotine in the animals with 

 an antagonist, mecamylamine. Or in another experiment we let 

 the — simply the nicotine, took it away from the animal. We did not 

 observe any withdrawal syndrome as evidenced by changes in food- 

 motivated behavior. 



Mr. Waxman. So of the three hallmarks of dependence, you did 

 find that there was self-administration and tolerance, but you did 

 not find that there was a physical dependence? 



Mr. DeNoble. That is correct. 



Mr. Waxman. OK. And did the studies that you did also indicate 

 that nicotine has a potential for drug liability? 



Mr. DeNoble. Yes. The self-administration study is a classical 

 hallmark to indicate that a solution or drug substance has a poten- 

 tial for abuse, yes. 



Mr. Waxman. And what does "drug liability" mean? 



Mr. DeNoble. It essentially means that if you find it in an ani- 

 mal, it has the potential to be a drug of abuse in humans. You need 

 to then go on to do other species, and other strains of animals, and 

 also go into the human to determine the final factor. 



Mr. Waxman. Now, on March 31, I released a version of your 

 self-administration study. On that same day Philip Morris issued 

 a statement, which I'd like entered into the record, without objec- 

 tion, as Exhibit 2, 



Response of Philip Morris U.S.A. to Congressman Waxman's Press 



Conference 



Dr. Victor DeNoble was employed by Philip Morris from April 1980 to March 1984 

 as a research scientist in the Research and Development Department. Dr. DeNoble 

 conducted nicotine-related research and concluded that nicotine is a reinforcer in 

 the class of nonaddictive chemical compounds such as saccharin, or water, and that 

 he did not believe nicotine fit the accepted criteria for drug dependence. He also con- 

 cluded that nicotine self-administration cannot be viewed as a form of drug "abuse" 

 or as an "addiction." 



Contrary to the suggestions that Dr. DeNoble's research has been somehow with- 

 held from the scientific community and the public, we find dozens of publications 

 authored by him, including five based on his nicotine-related research conducted 

 while at Philip Morris. 



At no time did Philip Morris seek an injunction, legal or otherwise, against the 

 publication of any of Dr. DeNoble's research. As with virtually all industries, publi- 

 cation of research done while an employee must be reviewed and approved prior to 

 such publication. We are aware of one instance when Dr. DeNoble failed to go 

 through the Philip Morris manuscript review process and thus was told not to pub- 

 lish Philip Morris research until completing the process. An abstract based on that 

 research was published. 



