Ecstasy

Name: ECSTASY
Class: Central Stimulant
Risk Factor: C

Fetal Risk Summary

In the United States, ecstasy (“Adam”), a central stimulant, is an illicit substance of abuse that is used for its mind-altering properties. It has been associated with dance events known as “raves.” (1) Chemically, ecstasy is a member of the amphetamine (3,4-methylenedioxymethamphetamine; MDMA) class of drugs (see also Amphetamines) (1,2).
A brief 2000 publication reported the results of a chemical analysis of 107 pills of ecstasy that were voluntarily and anonymously donated to the authors for analysis after a nationwide solicitation (1). However, because the donors were required to pay a fee for the analysis, the findings may not represent what is actually available. Of the total, only 67 pills (63%) contained some MDMA or a closely related analogue (either 3,4-methylenedioxy-ethyl-amphetamine or 3,4-methylenedioxyamphetamine) (1). Forty (37%) contained no MDMA or related amphetamine. Of these, 23 (58%) contained the antitussive dextromethorphan (see also Dextromethorphan) and 9 (23%) contained no identifiable drug. Other substances identified were caffeine, ephedrine, pseudoephedrine, and salicylates (1).
MDMA was not teratogenic in pregnant rats at oral doses of 2.5 or 10 mg/kg/day administered on alternate days from gestational day 6 to day 18 (3). The drug had no effect on gestational duration, litter sizes, or birth weights. Although most pup neurobehavior parameters were unaffected, olfactory discrimination was enhanced in both males and females, and negative geotaxis was delayed in females. However, the density of brain serotonin uptake sites and levels of brain serotonin and 5-hydroxyindoleacetic acid (5-HIAA; metabolite of serotonin) were not affected. There was a significant reduction of maternal weight and a dose-dependent decrease in maternal brain serotonin (5-HT) (3).
In another study with pregnant rats, MDMA 20 mg/kg SC was administered twice daily on days 14–17 of gestation (4). Marked, long-lasting maternal hyperthermia was observed after the first dose, but the response was attenuated with further doses. The body weight of the dams decreased during treatment and there was a 20% decrease in litter size. There was a slight reduction in pup weights on postnatal day 7, but the difference was not statistically significant compared with controls. In the dams, a significant decrease in the concentration of 5-HT and 5-HIAA in the hippocampus, striatum, and cortex of the brain were measured 1 week after parturition (i.e., nearly 2 weeks after the last dose). In contrast, neither the 5-HT or 5-HIAA level in the dorsal telencephalon of the pups was different from that of controls. The lack of MDMA-induced toxicity in the fetal brains suggested that either MDMA was not being metabolized to free radical-producing entities or the fetal brains were more efficient than adult brains in eliminating the toxic free radical metabolites (4).
Although there is no information on the placental passage of MDMA, other amphetamines rapidly cross the human placenta (see Amphetamines). Moreover, the relatively low molecular weight of MDMA (about 179, compared with about 135 for amphetamine), suggests that it also rapidly crosses to the fetus.
An abstract published in 1998 described the pregnancy outcomes of 49 women who had called a Teratology Information Service (TIS) in Holland concerning their exposure to pure MDMA or to closely related amphetamines (methylene dioxyamphetamine, MDA; methylene dioxyethylamphetamine, MDEA; or other) (5). In 47 cases the exposure occurred during the 1st trimester; the other 2 were in the 2nd trimester. The mean age of the women was 26 (range 17–44). Other abuse drugs, usually cocaine or marijuana, were taken by 43%, 34% drank alcohol, and 63% smoked cigarettes. Eleven pregnancies were still ongoing. The outcomes of the remaining 38 pregnancies were 2 spontaneous abortions, 2 elective abortions (1 fetus with a defect suggestive of an omphalocele), and 36 live-born infants (6 premature including 1 set of triplets). One term newborn, exposed in utero to ecstasy alone, had a congenital heart defect and died a few hours after birth (5).
A 1999 report from the United Kingdom National TIS cited 302 inquiries from pregnant women concerning ecstasy from January, 1989, to June, 1998 (6). Of the total, 31 pregnancies were ongoing and 135 were lost to follow-up. Outcome data were available for 136 pregnancies (1 set of twins). Among this group, 74 women took only ecstasy, and 62 took ecstasy with other drugs, including amphetamines (N=37), cocaine (N=20), marijuana (N=16), alcohol (N=13), and/or lysergic acid diethylamide (LSD) (N=9). Exposure to ecstasy was limited to the 1st trimester in 127 pregnancies (71 to ecstasy alone, 56 to ecstasy plus other drugs of abuse), to the 1st and 2nd trimesters in 2, to the 2nd trimester in 2, to the 3rd trimester in 1, and throughout gestation in 4. Thus, 133 of the pregnancies (98%) were exposed to ecstasy in the 1st trimester. The outcomes included 11 spontaneous abortions (8%) and 48 elective abortions (35%). One elective abortion occurred at 22 weeks' gestation because of a fetus with absent upper limbs, left scapula, and clavicles, and hypoplasticity of the first rib pair. The mother said she had taken only ecstasy during the 1st trimester. No data were available on the other aborted fetuses. There were 12 infants with congenital defects among the 78 born live infants (15.4%, 95% confidence interval [CI] 8.2–25.4). One newborn (without apparent birth defects) who was exposed in utero to ecstasy, heroin, and methadone throughout pregnancy died from an unknown cause. The birth defects and drug exposures (all in the 1st trimester except one case) were ecstasy only (6 cases): left 4th toe underlying 3rd toe; right-sided plagiocephaly; 2 with unilateral talipes; bilateral talipes; pyloric stenosis; ecstasy and amphetamine (2 cases): clicking hips; intrauterine growth retardation, ambiguous sex (1 of twins born at 25 weeks'); ecstasy, amphetamine, and gamma hydroxybutyric acid (1 case): ventricular septal defect (VSD) (possibly atrial and ventricular), bilateral hydronephrosis, bilateral clinodactyly; ecstasy and alcohol (3 cases): VSD; pigmentation of the right thigh; ptosis of left eye (exposed in 2nd trimester). There were 3 female infants with talipes (3.8%, 95% CI 8–109) compared with the expected rate of 0.1% (6). In addition, in Great Britain, there is a 3 to 1 male predominance of idiopathic talipes equinovarus (6). Neither the sex ratio nor birth weights of term infants (specific data not provided) were adversely affected by the exposures (6).
In summary, the use of amphetamines under controlled conditions, such as MDMA in the animal studies above and as amphetamines in the treatment of human disease (see Amphetamines), suggests that these agents are not teratogenic when used alone and do not cause clinically significant fetal toxicity. Other abuse drugs (e.g., LSD and marijuana) are also not teratogenic (see Lysergic Acid Diethylamide and Marijuana), but alcohol and cocaine are well-known teratogens and/or fetal toxins (see Cocaine and Ethanol). However, ecstasy is not used under controlled conditions. Neither the dosage nor the actual chemical consumed is usually known and, in many cases, the product is taken with other abuse drugs. Because both human studies involved voluntary reporting, a true incidence of major congenital defects cannot be determined, but there does not appear to be a clustering of similar anomalies.

Breast Feeding Summary

No reports describing the use of ecstasy or MDMA during human lactation have been located. The molecular weight (about 179) is low enough, however, that excretion into milk should be expected. The closely related drug amphetamine is concentrated in breast milk with milk:plasma ratios ranging from 2.8 to 7.5 (see Amphetamine). The American Academy of Pediatrics considers amphetamines to be contraindicated during breast feeding (7).

References

1. Baggott M, Heifets B, Jones RT, Mendelson J, Sferios E, Zehnder J. Chemical analysis of ecstasy pills. JAMA 2000;284:2190.
2. Plessinger MA. Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy. Obstet Gynecol Clin North Am 1998;25:119–38.
3. St.Omer VEV, Ali SF, Holson RR, Duhart HM, Scalzo FM, Slikker W Jr. Behavioral and neurochemical effects of prenatal methylenedioxymethamphetamine (MDMA) exposure in rats. Neurotoxicol Teratol 1991;13:13–20.
4. Colado MI, O'Shea E, Granados R, Misra A, Murray TK, Green AR. A study of the neurotoxic effect of MDMA (`ecstasy') on 5-HT neurones in the brains of mothers and neonates following administration of the drug during pregnancy. Br J Pharmacol 1997;121:827–33.
5. van Tonningen MR, Garbis H, Reuvers M. Ecstasy exposure during pregnancy (abstract). Teratology 1998;58:33A.
6. McElhatton PR, Bateman DN, Evans C, Pughe KR, Thomas SHL. Congenital anomalies after prenatal ecstasy exposure. Lancet 1999;354:1441–2.
7. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.

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