Effects of Prenatal Exposure to Cannabinoids

Abstract

Marijuana is among the most widely used psychoactive substances in the Western world. In the United States, about 255 of Americans 18 to 25 years of age use it to some degree (U.S. Department of Health, Education, and Welfare 1980). Considerable marijuana use also appears to be occurring among pregnant women (Sokol et al. 1980; Hingson et al. 1982; Linn et al. 1983; Fried et al. 1984; Gibson et al. 1983). It is only in the last few years, however, that critical attention has been focused on the possibility that these substances can cause birth defects and postnatal behavioral aberrations, although delta-9-tetrahydrocannabinol (6 9-THC), the principal psychoactive ingredient in marijuana, is known to cross the placenta (Abel 1983). Before examining the data relevant to this issue, the first part of this review will examine some of the general methodological considerations which should be kept in mind in evaluating research in this area. CLINICAL AND EPIDEMIOLOGICAL STUDIES Since experimental administration of drugs to pregnant women is unethical, evaluation of potential teratogens is limited to clinical observations or epidemiological investigations. Although clinical reports can be of considerable importance in alerting physicians and health care providers to possible agents causing abnormal development, they are often difficult to evaluate. For example, two early clinical reports of malformations in children born to marijuana users (Hecht et al. 1968; Carakushansky et al. 1969) were inconclusive since the mothers of these children were users of other drugs as well. When clinical reports are followed by epidemiological studies involving larger numbers of patients, a better appreciation of incidence and causation is possible. Such epidemiological studies can be divided into two types, retrospective and prospective, each of which has its own strengths and shortcomings.

Marihuana

“…Resorption rates increased in mice but not rats following in utero exposure. A decrease in maternal food and water consumption occurred and led to decreased maternal weight gain, which may be the cause of various effects associated with prenatal exposure (ABEL 1985b). Prenatal exposure to cannabinoids led to a decrease in pup birth weight, which may be the only postnatal effect on offspring reliably demonstrated.…”

“…Investigations of minor physical abnormalities indicated that there was no correlation between the number of anomalies present in an individual and marihuana use, though two anomalies (true ocular hypertelorism and severe epicanthus) were found only among children of heavy users of cannabis (O'CONNELL and FRIED 1984). However, a survery of the literature indicates that prenatal exposure to cannabinoids does not produce malformations in humans and only does so in mice following exposure to high doses administered by the intraperitoneal route (ABEL 1985b). Long-term studies on postnatal effects have produced generally inconsistent results, which may be due to methodological flaws in experimental design (ABEL 1985b).…”

“…However, a survery of the literature indicates that prenatal exposure to cannabinoids does not produce malformations in humans and only does so in mice following exposure to high doses administered by the intraperitoneal route (ABEL 1985b). Long-term studies on postnatal effects have produced generally inconsistent results, which may be due to methodological flaws in experimental design (ABEL 1985b). Experiments that do not consider the confounding influences of maternal toxicity (prenatal and postnatal) are likely to yield a high rate of false-positive results, which has been observed in studies of cannabis that preceded current concerns for pair-feeding and surrogate fostering (ABEL 1985b;HUTCHINGS and Dow-EDWARDS 1991).…”

“…Long-term studies on postnatal effects have produced generally inconsistent results, which may be due to methodological flaws in experimental design (ABEL 1985b). Experiments that do not consider the confounding influences of maternal toxicity (prenatal and postnatal) are likely to yield a high rate of false-positive results, which has been observed in studies of cannabis that preceded current concerns for pair-feeding and surrogate fostering (ABEL 1985b;HUTCHINGS and Dow-EDWARDS 1991). Nearly all such studies found neurobehavioral effects that included changes in activity as well as impairments in learning and memory (HUTCHINGS and Dow-EDWARDS 1991).…”

Developmental and behavioral effects in neonatal and adult mice following prenatal activation of endocannabinoid receptors by capsaicin

“…Therefore it is tempting to speculate that an interaction or cross talk exists between the G-protein-coupled CBR system and the vanilloid system as demonstrated previously [8]. Prenatal exposure to cannabinoids has been shown to produce a reliable decrease in birth weight in animals [9], but this is the only postnatal effect on offspring that has been reliably documented. Studies examining long-term postnatal effects have generally been inconsistent.…”