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Marijuana as a Teratogen

 

 

What is Marijuana?  

 

 Marijuana is a recreational drug that comes from the hemp plant called Cannabis Sativa and Cannabis Indica. Marijuana is classified as a Schedule I Narcotic in the United States. This means that according to the Drug Enforcement Administration, it has no recognized use medically and has potentially easily abused. The leaves of the plant are dried and then can either be smoked or eaten. People who use marijuana report a feeling of relaxation and elevated mood. Sometimes feelings of stimulation and tranquility occur. Sometimes, people may feel scared or anxious. (Kuhn, 2003)

 
 Delta-9-tetrahydrocannabinol or THC is the main psychoactive ingredient in marijuana. When marijuana is smoked, the THC reaches the blood vessels through the lungs and then makes its way to the brain. Once in the brain, the THC activates the cannabanoid receptor, which is responsible for controlling pain and stress. One area of the brain, the hippocampus, has a large number of cannabinoid receptors. The hippocampus is responsible for memory formation and one of the most well known side of effects of marijuana is that it makes it difficult to store new memories. This is the same for marijuana that is eaten; except less THC reaches the brain. Marijuana also builds up in other areas; spleen, kidneys, liver, testes, and for women who are pregnant, can marijuana can build in the placenta and travel to the fetus. It can take as long as three weeks for THC to leave the body. (Kuhn,2003)    
 
It is basically impossible to have a lethal overdose of marijuana. Physical dependence on marijuana is rare, however psychological dependence is more likely. There are little to no withdrawal effects from chronic users of marijuana. (Kuhn, 2003) 
 
Image courtesy of Kevin Bonsor 2007.  

 

 

 

Marijuana and Fertility

 

Long term use of marijuana does affect fertility in both men and women. For men, marijuana causes a lower sperm count and smaller volume of seminal fluid, that is about half of the normal amount. However, Marijuana also causes abnormalities in the existing sperm. The problem comes from timing. In normal sperm, hyperactivation occurs when the sperm is in the cervix, close to the egg. In the sperm affected by THC, hyperactivation occurs too early, and the sperm “burn themselves out”. (DeNoon, 2003) The sperm is only able to stay hyperactivated for a few hours, to push through the egg. When this occurs to early, the sperm are not able to break through the egg and therefore unable to fertilize the egg. At the same time, men that smoke marijuana are able to get women pregnant. It is thought that the effects of marijuana use are most clearly seen among males who already are borderline- infertile. The problem is that many men do not know if they are borderline infertile or not, and the general consensus is that if marijuana does contribute to infertility in general. (DeNoon, 2003) Marijuana use can also lead to erectile dysfunction due to its ability to suppress hormones that important to the male reproductive system. (Kuhn, 2003)

 

There has been much less research done on women’s use of marijuana and fertility. However, it has been found that even traces of THC in the women’s vaginal fluids can affect the sperm negatively. When sperm comes into contact with the vaginal fluid it can then absorb the THC and show the same sort of effects that come from the man using marijuana. (DeNoon, 2003) There is also evidence that large amounts of marijuana after awhile can create an irregular menstrual cycle. (Kuhn, 2003)

 

There is still the question of the ability to reverse the effects of marijuana over time. It seems as if things will go back to normal but it may take a long time. (Otis, 2007)THC is stored in fat deposits and the process to which it leaves can be very slow. (About, 2003)

 

 

 

 Marijuana and Breastfeeding

 

    Though a child might already by born, if it is breastfeeding, it still has a significant connection to the mother, and to her body. When a mother is exposed to marijuana, her breastmilk is also exposed. Some studies have shown that it actually concentrates in breastmilk, and the infant is exposed to a higher level than the mother(Perez-Reyes & Wall, 1982). Others suggest a more moderate exposure (Committee, 1991). Either way, an infant who does not yet have all their brain functions fully developed is exposed to a mind-altering drug. In animal studies it has been shown that marijuana use by breastfeeding mothers can decrease the productivity of milk in the mammary glands(Perez-Reyes & Wall, 1982).

 

    Another study suggests that exposure to marijuana through a mother's breastmilk within the first month of life can cause a delayed motor response at one year (Astley & Little, 1990). Babies who are exposed to marijuana through breastfeeding are also more oftern lethargic, feed less and feed for shorter period of times. Exposure to marijuana during the first few months of life is partiuclarly concerning because a baby's brain has not fully developed until much later in development, and exposure to a mind-altering drug could have a significant effect on that development.

 

 

Longterm Effects of Prenatal Exposure to Marijuana

 

    Upon birth, many children who were exposed to marijuana prenatally have lowered response to light stimuli, lowered habituation to the same, less "self-quieting" behavior (thumb-sucking, etc.), more tremors are startled more easily, and they also have more high-pitched cries. These symptoms of exposure to marijuana gradually even out as the infant gets older, however there are a few long term effects of prenatal marijuana exposure that continue on into the child's life.

 

    One of the major effects is a smaller head circumference. The smaller head circumference is usually noted at birth, though it becomes much more concerning when the child reaches adolescence and the head circumference difference does not correct itself (Fried, Waatkinson, & Gray, 1999). Though there are some physical longterm effects, the behavioral longterm effects seem to be more lasting. A study done by Goldschmidt, Day, & Richardson (2000) found that prenatal marijuana exposure led to increased hyperactivity, impulsivity, and increased delinquency.

 

    Cognitive skills may also be effected by prenatal exposure to martijuana. A study found that women who exposed themselves to marijuana in their first and second trimesters had children who scored much lower on intelligence tests at age three (Day et al., 1994). The tests did improve greatly however with the attendence at day-care or preschool. These children are put at a disadvantage from birth because of a possible difference in development and physiology caused by their early exposure to marijuana.

 

 

Teratogenic and Neurological Effects

 

   There is some evidence that marijuana can have teratogenic and neurological effects at various dosings, based on experimental animal studies and corellational studies of humans.

 

   Marijuana is evidenced to cause reproductive abnormalities at several different junctures. Though not all of its effects are strictly teratogenic, in the sense that they cause developmental abnormalities directly by marijuana's interaction with the unborn child, they nevertheless result in unpleasant consequences.

 

   Even before conception, marijuana has the potential to affect the pregnancy-- in several ways. In men, chronic marijuana use has been corellated with lower sperm quantity and quality (Bloch, 1983, National Academy of Science, 1982; Wenger et al, 1992). While this may not technically count as a teratogenic effect, a mutant sperm might contribute mutant DNA to the child and cause deformities or other abnormalities in that way. Interestingly, this effect seems to be a result of a dual action on the part of THC (the active ingredient in marijuana): on the testes themselves, which produce the sperm, and on hypothalamic secretions that interact with the testes (Wenger et al, 1992). These effects are especially pronounced for younger users of cannabis, and heavy chronic users with existing reproductive problems (Hollister, 1986). Bloch (1983) is of the opinion that a similar phenomenon occurs in women, also due to hypothalamic effects, resulting in overall lower reproductive function.

 

   The second way in which marijuana may affect future pregnancies is a mugagenic effect. Cannabis smoke "has been ... associated with chromosomal aberrations ... such as hypoploidy, mutagenicity in the Ames test ... " (Bloch, 1983, p413). Smoking marijuana is in fact probably the most common means of consumption; THC must be "activated" by heat before it is in its effective form, and so it is typically smoked. These genetic changes brought on by the smoke may be permanent, and so could be passed on to the sperm, and then to the egg, and so on, resulting in a abnormalities in the early stages of development, which may not be significant to the already developed adult, but very significant for the still-developing conceived child.

 

   Actual teratogenic effects of marijuana are "resorption, growth retardation, and malformations" in mice, rats, rabbits, and hamsters (Bloch, 1983, p406), with resorption and retardation more consistently reported than malformations (Abel, 1985). However, these effects have typically necessitated very large doses of crude marijuana extract. Marijuana has also been found to produce lower birth weights in mammals. This effect however, may not be direct. There are studies with mammals that have shown that this could be mediated by a reduction in appetite of the animals involved. Furthermore, this effect was found to decrease the closer in the evolutionary tree the animals were to humans, primates being the most human.

 

   Undesirable neonatal effects of marijuana that are not mechanically teratogenic include: lowered response to light stimuli, lowered habituation to the same, less "self-quieting" behavior (thumb-sucking, etc.), more tremors and increased startling, and more "cri du chat" (high-pitched cries).

 

 

Marijuana and Tubal Pregnancy

The Vanderbilt University Medical Center has experimented with mice and has found that excessive cannabis intake can result in less pregnancies; specifically, these mice had an increased number of tubal pregnancies. CB1 is a cannaboid-receptor which assists muscle contractions that moves the embryo down to the uterus, and when this receptor is blocked, over-stimulated, or not present, tubal pregnancies occur more often in mice (Snyder, 2004). It has not been concluded if these results would occur in humans, but it is advised that women who are trying to become pregnant should avoid marijuana usage. There is also an anti-obesity drug which seems to have the same effect in mice (Snyder, 2004).

 

 

How Marijuana Crosses the Placenta

 

How Drugs Cross the Placenta

Courtesy of Michael R. Foley, M.D. (2007) http://www.merck.com/mmhe/sec22/ch259/ch259a.html

 

Refer to the diagram above to understand the pathway of marijuana from the mother's blood to the fetus' blood. Some of the fetus' blood vessels are located in the villi of the placenta, and they extend into the wall of the mother's uterus. The mother's blood is traveling through the intervillous space which is separated from the villi by a thin placental membrane. Chemicals from marijuana are able to travel from the mother's blood through the placental membrane into the villi which contain fetal blood vessels. Once the chemicals enter, they travel from the umbilical cord to the fetus (Foley, 2007).

 

 

Challenges to Research

 

A lot of debate exists on whether or not marijuana should be considered a teratogen since it can not ultimately be concluded that marijuana causes birth defects. Anywhere between 5 to 30 percent of mothers reported marijuana use during their pregnancies (Plumbo, n.d.). It is difficult to determine whether developmental abnormalities that occur in infants whose mothers used marijuana are actually caused by the marijuana or by other factors. Researchers cannot separate the use of marijuana from other maternal factors such as lifestyle, previous or multiple drug use, nutrition, and lack of prenatal care (Gurnee & Sylvestri, n.d.). It has also been argued that only excessive marijuana abuse leads to complications in the exposed fetus, and this may not be because of the actual marijuana itself, but rather because of the side effects of the drug on the mother such as malnutrition (Johnson, 1998). In addition, it is possible that mothers who purchase marijuana may not have the resources to provide their baby with proper care because of their socioeconomic status.

 

Like any other social drug that may be considered a teratogen, there are certain factors that influence how marijuana effects the fetus. These factors include the amount of marijuana that is used, at which point in development the marijuana is used, the duration of usage, other environmental influences, and the fetus' susceptibility to the drug (Gurnee & Sylvestri, n.d.). It has been claimed that marijuana has minimal effects on a fetus if the mother smokes less than three grams of marijuana per day, which is an extremely high dosage (Johnson, 1998). There are critical periods of prenatal development in which certain aspects of development may be affected more. According to Dr. Richard S. Abram, author of Will It Hurt the Baby?, marijuana usage during the first trimester of pregnancy probably will not lead to defects (Marijuana Passion, n.d.). If a mother is exposed to other teratogens, then it is hard to conclude that marijuana usage is what caused birth defects.

 

There are other cultural and medical implications involving marijuana usage among pregnant mothers. A medical anthropoligist from the University of Massachusetts, Melanie Dreher, and colleagues conducted research in Jamaica during the 1980s and 1990s and found that many Jamaican pregnant mothers smoked marijuana to relieve nausea associated with morning sickness, to treat depression, to help fatigue, and to promote appetites (1994). Among these women, there were no reports of longitudinal birth defects or behaviorial problems.

 

Although studies on the effects of marijuana usage during human pregnancy conclude that there are minimal effects, animal studies have had different findings. Studies performed on mice, rats, rabbits, and hamsters indicate that marijuana usage can result in resorption, growth retardation, and malformations in these animals (Johnson, 1998). Although these are reliable findings in animals, no human studies have found similar results. On the other hand, studies have been done specifically on THC and its effects on human genes; it has been found that THC may reduce the body's response to infection. In addition, since THC can pass into the placenta and through breastmilk, it is advised not to use marijuana while pregnant or nursing (Kassuba, 1982). Most studies on this topic are performed on animals since it would be unethical to do human experimental-type studies using a potential teratogen.

 

 

 

 


Citations 

 

Abel, E.L. (1985). Effects of prenatal exposure to cannabinoids.
In T.M. Pinkert (ed) Current Research on the Consequences of Maternal Drug Abuse.
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About. (2003). Marijuana May Impair Male Fertility. Retrieved September 26, 2007, from http://alcoholism.about.com/cs/pot/a/blub031013.htm.
 

Astley S, Little RE. (1990). Maternal marijuana use during lactation and infant development at one year. Neurotoxicology and Teratology. 12, 161–168.

 
Bloch, E. (1983). Effects of marijuana and cannabinoids on reproduction, endocrine function,
development and chromosomes. In K.O. Fehr and H. Kalant (eds)
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Bonsor, K. (2007) How Marijuana Works. How Stuff Works. Retrieved September, 30, 2007, from http://static.howstuffworks.com/gif/marijuana-leaf.jpg.
 

Committee on Nutritional Status During Pregnancy and Lactation, Institute of Medicine. Illegal drugs. Washington, DC: National Academy Press; 1991.

 

 

Day NL, Richardson GA, Goldschmidt L, Robles N, Taylor PM, Stoffer DS, Cornelius MD, Geva D. (1994) Effect of prenatal marijuana exposure on the cognitive development of

 

              offspring at age three. Neurotoxicology and Teratology 16 (2), 169-175.

 

DeNoon, D. (2003, October) Smoking Marijuana Lowers Fertility. Mens Health. Retrieved September, 25, 2007, from WebMD.
 
Dreher, M., Hudgins, R., & Nugent, K. (1994). Prenatal Marijuana Exposure
and Neonatal Outcomes in Jamaica: An Ethnographic Study. Pediatrics, 93:2.

Retrieved September 27, 2007, from http://www.druglibrary.org/SCHAFFER/hemp/medical/can-babies.htm

 
Foley, M. R. (2007). Drug Use During Pregnancy.
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Fried PA, Watkinson B, Gray A. (1999). Growth from birth to early adolescence in offspring prenatally exposed to cigarettes and marijuana. Neurotoxicology and Teratology.       

            21(5):513-25.

 

 

Goldschmidt L, Day NL, Richardson GA.(2000) Effects of prenatal marijuana exposure on child behavior problems at age 10. Neurotoxicology and Teratology. 22,(3),325-36.

 

Gurnee, M.C., & Sylvestri, M.F. (n.d.). Teratogenicity of Drugs. U.S. Pharmacist, 23:9.
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Hollister, L.E. (1986). Health aspects of cannabis. Pharmacological Reviews, 38, 1-20.
 
Johnson, L. (1998). The Effects of Marijuana on the Fetus. Health
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Kassuba, S. L. (1982). Environmental Causes of Birth Defects. Human Fetal Development, VII.
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Kuhn, C. (2003) Buzzed. New York: W.W. Norton & Company, Inc.

 
Marijuana Passion. (n.d.) The Debate on the Effects of Marijuana Use During Pregnancy.
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Perez-Reyes M, Wall ME. (1982). Presence of delta-9-tetrahydrocannabinol in human milk. New England Journal of Medicine. 307, 819–820

 

Plumbo, P. (n.d.). Marijuana use: Dangerous to baby-to-be?
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Snyder, B. (2004). Pot smoking could increase tubal pregnancies. The Reporter.
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Wenger, T., Croix, D., Tramu, G., & Leonardeli, J. (1992). Effects of delta-9-
tetrahydrocannabinol on pregnancy, puberty and the neuroendocrine system.
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