Marijuana and the Unborn

(Reprinted from LISTEN Magazine, November 1984)

More research is documenting the serious and long lasting effects of smoking marijuana on the fertility o offspring of male and female users. In this LISTEN interview, Dr Susan L. Dalterio reveals just what those effects are. For the last 10 years, she’s been doing research with laboratory mice on the effects of marijuana on the reproductive system. Recently, she’s been looking at offspring whose parents have been exposed to marijuana.

Why did you choose mice as your research animals?

Mice are available in large numbers and are inexpensive. They are also very, very reproductive. You can look at generational effects in a fairly short time compared to what it would require of humans and monkeys or any other species which require years before you get one generation and an additional set of years before you get further generations.

Why did you choose to go into marijuana research?

At the time I began the research, there were reports coming out suggesting that there maybe some sexual and reproductive problems in young heavy users. I thought it important to determine if these effects are related to a drug life-style or nutrition or the marijuana itself.

Describe the type of procedure that you use.

I never use material directly from the marijuana plant itself. I use purified cannabinoids, the chemicals contained in marijuana, which have separated by the U.S. Government from the plant material that it grows under supervised conditions. I put the purified cannabinoids in sesame oil and place drops of the oil on the mice’s tongues. They readily take the cannabinoids without suffering stress from injections or the like.

I’ve looked at the effect of exposing mice to these cannabinoids on a single-dose basis in females during pregnancy or during the nursing period, and on a multiple dose basis in males. I’ve looked at the consequences on the adults and also on their offspring.

How do the animal doses compare to human doses?

It’s always difficult describing how doses are determined. You don’t just multiply or divide a human’s dose according to the relative weight of the animal. Because mice are little they metabolise or break down the drugs very rapidly. Their heartbeat is about 400 hundred beats per minute compared to 70 for humans. Thus the behavioural effects of marijuana on mice are gone within hours. Our doses are most closely equivalent to those taken by average/heavy marijuana users.

Compare the effects of marijuana that has been smoked and marijuana that has been injected or taken orally?

Marijuana taken orally is almost one third as potent as when it is smoked. This is one reason why the doses aren’t quite equivalent, but it eds up that the long-term effects on the reproductive system are about the same. Human beings do consume marijuana in some places by eating it. So it is not unrealistic for us to do so with these studies in animals.

In a typical case in your laboratory, do you give the cannabinoids to both the mother and father?

No, I haven’t in any yet given it to both the mother and father. I’ve always elected to give it to one or the other, because until you know what marijuana does to each other separately, there’s really no easy way to evaluate the contribution of each parent to the outcome of the offspring.

What effects do you see on the next generation when cabbaninoids are administered to the pregnant mother?

Fetuses are exposed to the various cannabinoids through the placenta, the organ that connects the fetal sac to the mother and through which nutrients flow to the fetus. We found two major effects of marijuana during mid-pregnancy. For one thing THC, the psycho-active or intoxicating agent in marijuana caused an abnormal number of fetal losses to the mother. There is evidence of a toxic effect on the fetus. The other thing is that both THC and CBN, a non-intoxicating chemical, reduce the amount of testosterone, the major male sex hormone, in male fetuses in the early period of development, when testosterone is critically important in all mammalian species during the prenatal period of time just as it is after puberty.

Do you know the reason for this effect?

It’s difficult when you are dealing with fetal development to pinpoint exactly what causes a critical effect. We’re still trying to find out what marijuana does, and then we will pick an effect and study it until we understand how it is produced. This is very difficult to do during the pregnancy phase.

Why did you choose to study THC and CBN?

All marijuana researchers have looked at THC first because that is the psycho-active or intoxicating part of marijuana. Without THC, marijuana would be of interest to no one.

What happens to offspring of THC exposed mice mothers?

I followed up through adulthood the pups I had given these drugs the day before they were delivered. The pups looked pretty normal in appearance and size when thy were born. It wasn’t until puberty that it was evident that they were underweight. We started to find hormonal imbalances that decreased testes weights, which started just before puberty but persisted up into the adult period of these animals who had only been exposed through their mother on the last day of her pregnancy or her through her milk the first six days of the nursing period.

Is THC through milk in purer form?

If the mother was given THC, it comes through the milk 90% pure. Milk is so very fatty that it’s a storage depot fro unmetabolised cannabinoids. It has been shown in monkeys, rats, sheep and mice that THC definitely gets through milk in largely unchanged form.

When giving the THC to the father, what effect does it have on conception or on the process of pregnancy?

When we treated the males with cannabinoids, some of them had significant problems in making the females pregnant.

And if those animals did make a pregnancy, many of the pups died as fetuses before the pregnancy went full term. In pups that survived birth, there was a significant increase in the number who died before they could eat on their own.

Once the THC-treated males impregnated the untreated females, the females had more difficulty maintaining the pregnancy and raising those pups to adulthood. We presume that the THC caused some defect in the father’s sperm, since that was the only way that these pups were exposed.

When we looked at the sons that did survive and grow up, they were as there fathers had been - less fertile and producing more losses in pregnancies which did occur. When we looked at chromosomes in the testes of both fathers and sons, we found abnormal chromosomes and birth defects in the third generation.

You are convinced that marijuana had an effect on testes and the production on male sperm which brings about abnormal chromosome development?

Yes, we certainly have evidence that the chromosomes are no longer normal, that there is a higher frequency of clumping of chromosomes so that when the cell divides, two equal cells are not produced. We know that in some condition in humans and in animals this is associated with severe defects, such as mongolism, in which an extra chromosome is present. I’m not saying that mongolism is related to marijuana use, but it is certainly known that if the chromosomes are not splitting properly, you get severe consequences. We know that in the testes of treated mice and of their untreated sons we are getting abnormalities.

What are the effects on the third generation?

I’m not going to say at this point that we have any kind of conclusive evidence of this, but we are speculating - based on the evidence - that there is some mutagenic effect - a change in genetic structure and sperm which is capable of being transmitted from generation to generations.

There are some other possibilities, such as the sons have an endocrine abnormality, which then affects their sperm. This is not genetic, but the interpretation is almost as serious either way. There is a transmissible defect which affects another generation, either directly (genetically) or indirectly (through endocrine hormonal imbalance).

You are convinced, then, that as far as your experimentation is concerned, marijuana does have a perceptible negative effect on pregnancy, from the standpoint of both the mother and father?

Yes. I think it is very clear that many drugs, marijuana included, can affect pregnancy. I think what is very important is that we’ve shown a reasonable amount of evidence to urge strongly that the father’s input be considered in terms of drug exposure. It may be that the consequences of the father’s drug involvement are even more serious than those of the mother’s.

What about applying these conclusions to humans?

Some of the research that we’ve already done in mice , some of the effects of marijuana on adult hormone levels, were actually found first in human users ten years ago. We know that some of the things that we find in mice have been found consistently in human users.

It’s a problem when you talk about offspring, because we don’t yet have any human third-generation offspring of marijuana users. But it’s very unlikely that we would be spared from what we consistently find in animals. Saying what will happen to the offspring of humans is a bit of a question, but having something similar to what we found in mice is very likely. This will finally be proved when we have third-generation offspring of marijuana users to test.

Do you feel your project is pretty well completed?

In some ways I wish it were completed; then I could say that I have the answers. But there are still two aspects of the issue that must be dealt with - 1) we have some questions about reversibility. How long and in how many generations will these results persist? And 2) which organs and in what order does marijuana hit to produce these effects? This might seem less relevant to the lay person, but it is extremely important when discussing therapeutic interventions. This may then be relevant to a number of other drugs and environmental hazards.

Do you have questions about reversibility?

The younger you are when you suffer damage, and that includes the fetus, the more likely the damage will be difficult to reverse. That is always a problem when young people ask why adults can use with less obvious effect some things that they can’t, including alcohol. It’s because once things are formed, it takes more to mess them up. But while they are forming, it takes relatively little to mess them up. The sensitivity to a variety of agents is very different in an adolescent from what it would be in a forty year old.

Susan L. Dalterio, Ph.D. 9114 Welles Way, San Antonio, TX 78240 (512) 692-9139