You gave up marihuana because of its possible physical effect, or at least that was one reason you gave.

Dr. DUPONT. Yes, sir.

Senator HUGHES. Would not the same reason apply to alcohol with abundantly more evidence?

Dr. DUPONT. I think, Senator, that my own view of alcohol is that my use is moderate and is not a substantial risk to my health at this time.

Senator HUGHES. Would that not apply to marihuana on the basis of the way you used it, three or four times in 5 years? That is certainly moderation, is it not?

Dr. DUPONT. Yes, it is. But there are some differences in the substances in terms of at least the potential problems

Senator HUGHES. One is illegal and the other one is legal. Is that not the main reason?

Dr. DUPONT. That is one big difference. In addition there are some pharmacological differences. Alcohol is cleared out of the body very quickly and does not appear to affect basic biochemical functions to the same extent that marihuana does.

Senator HUGHES. Does not alcohol affect the brain on a permanent basis with continued usage, Doctor?

Dr. DUPONT. At very high levels of daily use, yes, Senator. I do not believe that there is any evidence that alcohol affects the brain in intermittent use at moderate levels.

Senator HUGHES. Has there ever been any research done on that? Dr. DUPONT. Yes; there has, and you are probably more expert on that subject than I am. I would defer to you on that, but it is my understanding that I am not risking brain damage with the level of consumption of alcohol that I maintain at this point in my life.

Senator HUGHES. Have you ever known a death attributable to marihuana use?

Dr. DUPONT. No; but such a possibility exists. The substance can produce death in high doses, and I think that part of the problemSenator HUGHES. Could anyone smoke enough marihuana in 24 hours to kill himself?

Dr. DUPONT. Yes. It depends on the concentration of the substance. Senator HUGHES. I am not talking about hashish. I am talking about marihuana.

Dr. DUPONT. Then probably not.

Senator HUGHES. Could they drink enough alcohol in 24 hours to kill themselves?

Dr. DUPONT. Yes; I think you could probably do it in half an hour or less.

Senator HUGHES. If you took it in extreme doses, it would bring death?

Dr. DUPONT. Yes.

Senator HUGHES. There are deaths resulting from both alcohol and nicotine, are there not?

Dr. DUPONT. Many, yes.

Senator HUGHES. We have really no evidence of death from marihuana use?

Dr. DUPONT. I think that is a fair statement.

Senator HUGHES. Not that I am aware of at least.

Dr. DUPONT. Part of the problem in terms of death, is that when you talk about alcohol deaths, you are often talking about alcohol-related deaths due to accidents, particularly traffic accidents. We just do not know enough about the effect of

Senator HUGHES. Let us rule out accidents and talk about physiological death caused by the drug.

Dr. DUPONT. Again, I think that part of the problem is that the medical examiners of the country do not now have the capability of testing for marihuana in the tissues, and I think there is much yet to be learned on the subject of marihuana and death.

I am not saying that I think there is any large number of marihuana-related deaths, but the technology is not there now to definitively answer that question.

Senator HUGHES. Thank you. I am sorry to belabor you on that point. I do think the perspective is important.

You drink and I smoke nicotine, and we are talking about a third substance that other people use for the same reasons that you drink and I smoke. Ours is legal and theirs is not. We are talking about the question of which is more dangerous to society, the most effective and most moderate and reasonable way to control those substancesall three of them are our responsibility.

Dr. DUPONT. Absolutely.

Senator HUGHES. I think we should give equal attention to all of them, certainly with the same sense of responsibility to the public. I know you feel the same way. That was the perspective of my questioning only.

As you know, and as a matter of public record, I smoked marihuana once in my life, and that has been over 30 years now. It was during World War II when I did so, it created almost a sensation, as if I were an addict as a result of it.

When I said I gave it up because there was not anything to it, I immediately got letters from users all over the country saying I should continue the use of it and I would eventually get it. [Laughter.] I did not follow their advice because I had no more interest in it. Dr. DUPONT. Senator, I might add that I was quite anxious about how my admission of use would be reported in the press. At least the initial reactions I have had convince me that we have come a long way in this country in terms of the press managing of this issue. The articles I have seen and the television clips about my "confession," if you will, of yesterday, have been a lot more moderate and reasonable than was the treatment of similar confessions in the past.

Senator HUGHES. You will get some letters, Doctor, that would indicate that they would rather you had lied about it than to have stated publicly that you had experimented with it.

Unfortunately, that is the attitude, the questioning of the integrity of every public official today. And I am glad you were honest about the experimentation and brought it out. I think if we all were as truthful, we could get a better perspective and a reasoned approach to what we are doing.

I would like to get down to some of the other questions, if I could. You mentioned the research that has been done since the Marihuana Commission report 2 years ago and the additional evidence. Though we all uniformly agree that we do not have enough evidence yet, is there not an abundance of it?

Are you satisfied with the quality of the research projects which have suggested danger in marihuana use? I am referring to the studies which led you to revise your fourth annual report.

Dr. DUPONT. Yes, I think the quality of most of the studies is quite high. Let me put this in a little perspective.

Four or five years ago, the research community was in a great struggle with the law enforcement community with regard to research on marihuana and other illegal drugs. I am sure you remember those bad old days. Researchers were unable to get authorization to pursue research and were unable to find a standardized substance to carry out research.

One of the measures of the changes in the last few years has been that this is no longer the case.

As a matter of fact, the Federal Government now funds a marihuana plantation in Mississippi and produces a very high quality standardized marihuana cigarette for research activities. I think that this is one of the factors that has helped our research become more sophisticated.

On the other hand, these more sophisticated research activities are still quite new and most of the results are still preliminary. I am not satisfied that we have yet seen the full fruition of a more reasonable and a more highly supported research activity. But I think the studies are good, and getting better.

Let me give you an example of one kind of study that has been of concern. That has been the impact of marihuana use on testosterone levels. That study by Dr. Kolodny in St. Louis has been criticized because he studied individuals who were smoking an unknown substance, that is street users, and not using a standard substance in a laboratory setting. The Kolodny study has now been replicated in a controlled laboratory setting, and the results from the two different laboratories are contradictory. We are pursuing that now to understand why the difference exists.

One difference appears to be the time that the blood samples are taken in relationship to the last use of marihuana. But the sophistication in the field is shown by the fact that we are asking these questions in a perfectly open way in the scientific community and coming up with very sound answers.

Senator HUGHES. Of course, as to street users, you would not have any control over the use of multiple substances.

Dr. DUPONT. That is another great concern, absolutely.

Senator HUGHES. Would that not be a real concern? Because, frequently, in street users you do have multiple use. Marihuana is sort of a bridge to substances which are considered more dangerous.

Dr. DUPONT. Yes, that is a very real concern in terms of attributing effects to a special agent, to-wit, marihuana. That is why many studies have to be carried out in a laboratory setting where the individual subjects are carefully monitored in terms of their use of other drugs, with regular urine tests being taken to be sure that they are not also using something else.

Senator HUGHES. Were any of these projects supported financially by the Special Action Office or the National Institute on Drug Abuse? Dr. DUPONT. Yes. The initial Kolodny study was not, but the followup testing is being supported by the Federal Government.

Senator HUGHES. I am sure you are aware of the criticisms some of the studies have encountered.

Just to refresh your memory, such as the use of very massive doses of cannabis beyond the level which humans would or could ingest, and reliance upon the subjective reporting of the use of marihuana by subjects of research.

Dr. DUPONT. Yes, sir, I am well aware of that. Some of the studies have indeed suffered from this kind of a problem.

I recently was reviewing the Nobel Prize winner, Julius Axelrod's comments before a Senate subcommittee. He made this point specifically with respect to the research of Dr. Robert Heath.

Senator HUGHES. Are efforts by other scientists being made to replicate the studies?

Dr. DUPONT. Yes, absolutely. Not all the studies by any means are based on use of very high levels of marihuana.

One of the more convincing of the studies to me, at least, is the study referred to in Switzerland. These researchers expose tissue cultures to smoke from tobacco and marihuana cigarettes, and to a combination of the two in doses that are relatively small. In other words, they do not use high levels but relatively modest physiologic levels of both tobacco smoke and marihuana smoke. They found major cell pathology from both marihuana and tobacco smoke, but the cells were more affected by marihuana smoke.

On the other hand, I must emphasize with respect to this study that they are exposing tissue cultures to the smoke and not the whole organism. The body has many mechanisms for dealing with toxic substances that are not available to tissue culture. The whole respiratory system is designed to help prevent the kind of problems that are seen more vividly in tissue cultures.

Nevertheless, I was impressed by that data. And although it is not finally convincing in terms of the effect of marihuana smoke on man, it certainly is a cause for considerable concern.

Another fact which there is just no quarrel about, is that chronic bronchitis is indeed a common consequence of regular marihuana use. Some investigators have found early development of emphysema. as well. It does indeed appear that marihuana smoke, quite independent of tobacco smoke, is an irritant to the lungs and can have serious health consequences just on that basis.

Senator HUGHES. Senator Schweiker.

Senator SCHWEIKER. Thank you, Mr. Chairman.

Doctor, you mentioned that one of the studies that you are trying to replicate has to do with the absorption in the fatty tissue of one of the key ingredients. You do not say in your statement how long a period of time you are talking about here.

What does the study indicate?

Dr. DUPONT. Something in the nature of a week. The metabolic breakdown products can be recovered in the urine until a week after use. The presumption is that it is present at even lower levels for longer periods of time. The closest analogy to this would be DDT, which also accumulates in the fatty tissues.

The body is designed to rid itself of substances which are water soluble. They are flushed out through the blood and urine quite fre

quently. But when a substance is highly fat soluble and not soluble in water, then it tends to accumulate in fatty tissues.

Senator SCHWEIKER. You also say in your statement that if this study is borne out, there would be a significant difference between this and other kinds of drugs, because of the residual nature of it. Dr. DUPONT. Yes, sir, absolutely.

Senator SCHWEIKER. A study was done, I guess it was the Columbia study you are referring to

Dr. DUPONT. The study at Columbia which I referred to was the Nahas study about the immune response of the white cells.

Senator SCHWEIKER. You referred to the Columbia study in terms of the capacity of cells to divide and reproduce normally. There you talk about attempting to replicate this finding.

When do you expect to have a definitive outcome or determination on usual replication efforts? How long a program is that?

Dr. DUPONT. This is Dr. Szara.

Dr. SZARA. There are several grants and contracts that are designed to follow up the Columbia studies by systematic, well-controlled fashion. Dr. L. Harris and his coworkers in the Department of Pharmacology of the Medical College of Virginia are studying the effects of THC on RNA and DNA replication in animals. These studies are still ongoing and we have only preliminary abstracts essentially confirming the effects of high doses of THC on nucleic acid metabolism in certain cell types. Other studies are following up the immunological and chromosomal implications of the Columbia study. One of these studies done by Silverstein and Lessin on chronic marihuana users has just been published, and the results are essentially negative. The study was done by a different technique which is used clinically to detect gross cellular immune defects. I have a copy of the article and, if you permit me, I would like to submit it for the record.

Senator SCHWEIKER. Yes, we would like to have it. I would like to put it in the record, Mr. Chairman.

Senator HUGHES. Without objection, so ordered.

[The document referred to follows:]