Much concern about possible effects on the unborn generations has arisen because of marihuana's use by persons in their reproductive years. Presently, most studies are preliminary.

There are three isolated case reports in man (Gelehrter, 1970; Carakiishansky et al., 1969; Heelit et al., 1968) of birth defects in mail in the offspring of parents who had used marihuana and LSD. However, due to their complex gestational histories and the high level of birth defects seen in a "normal" population, a causal relationship cannot be attributed to cannabis or anything else. At present, there is no substantial evidence indicating that marihuana at the dose commonly used is a teratogen in man.

Marihuana has been implicated as a teratogen in animals by several groups at high doses. One study (Miras, 1965) showed reduced fertility in rats impregnated after being fed a diet containing marihuana extract for several months. However, the offspring were normal. The reduced fertility may be related to the finding of marked decrease rate of cellular division, but without chromosomal damage, -when Delta 9 or All THC is added to white blood cell cultures (Neu et al., 1969 Martin, 1969).

Dorrance et al. (1970) and Gilmore et al. (1970) detected no significant difference in lymphocyte chromosomes in groups of users and nonusers. No significant differences were, found in lymphocyte chromosomes between heavy, long-term. Jamaican ganja users and matched nonusers. (Rubin and Comitas, 1972)

Pregnant mice injected with cannabis resin on day six of gestation caused stunted but not malformed offspring. Fetal reabsorption occurred when the dose was given on days one to six (Persand and Ellington, 1967). A second experiment using rats injected on days one to six produced a high frequency of malformed progeny. Another investigator (Geber, 1969; Geber and Schramm, 1969) demonstrated congenital malformations in fetal hamsters and rabbits after large multiple doses of cannabis extract.

Another group (Pace et al., 1971) have administered a wide range of dosages of Delta 8 and Delta 9 THC and marihuana extract by subcutaneous, intraperitoneal and intravenous routes at varying intervals pre- and post-conception to rats, hamsters and rabbits. Delta 9 THC up to 200 mg/kg in variety of dose schedules produced reduced average litter size and stunted pups at high doses but no birth defects. A low incidence of abnormalities occurred in rats and rabbits with marihuana extract, but a high incidence of neonatal deaths was observed apparently due to inadequate material lactation.

Studies with radioactive labeled THC (Idanpaaiini-Heikkila et al., 1969) indicated that it did cross the placenta in high concentrations early in gestation during the developmentally labile phase.

These studies suggest that Delta 9 THC itself is not a teratogen. Instead, perhaps some unidentified substance or substances in the plant extract may be causing the teratogenic effect noted by this group and others when injected. It is uncertain whether this theoretical substance(s) volatilizes during smoking or enters the pulmonary vasculature (Pace et al., 1971).

Consequently, the following FDA label required of many currently prescribed psychoactive drugs warning about use in Pregnant women and women of childbearing age, appeals indicated. "Safe use of the drug during pregnancy and lactation has not been established; therefore, in administering the drug to Pregnant patients, nursing mothers, or women of childbearing potential, the potential benefits must be weighed against the possible hazards. Animal reproduction studies have yielded inconclusive results. . . . There have been clinical reports of congenital malformation associated with the use of this drug, but a causal relationship has not been confirmed."