3. Umbruch 4.4..2005 - Online Pot

72 M. Maccarrone
FAAH and human reproduction
Human reproductive fluids, such as seminal plasma, mid-cycle oviductal fluid,
follicular fluid, amniotic fluid and milk have been reported to contain AEA,
N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA) in the low
nanomolar range, from 3 nM for AEA in the follicular fluid to 67 nM for OEA
in human milk [26]. This suggests that endocannabinoids might regulate multiple
physiological and pathological reproductive functions in humans, implying
that exogenous cannabinoids delivered by marijuana smoke could threaten
these processes. Consistently, Table 1 shows that blood AEA levels in women
experiencing miscarriage are approximately 4-fold higher than the levels
found in women with normal gestation [4]. Since the human reproductive tissues
are only sparsely accessible to experimenters, we took advantage of the
critical role of peripheral lymphocytes in embryo implantation and successful
pregnancy [27] to investigate in these cells how the endocannabinoid system
might affect human reproduction.
Table 1. The endocannabinoid system in human gestation. The endogenous levels of AEA were
assayed in the blood of healthy women and of women who had miscarried. The binding to CB 1 receptors,
and the activity of FAAH and AMT, were assayed in peripheral lymphocytes from the same subjects
Parameter Women with normal gestation Women who miscarried
AEA content (pmol/ml) 0.9 ± 1.0 (100%) 4.0 ± 2.2 (444%) *
CB1 binding (cpm/mg protein) 20380 ± 1930 (100%) 20400 ± 1795 (100%)
FAAH activity (pmol/min/mg protein) 133 ± 9 (100%) 48 ± 5 (36%) *
AMT activity (pmol/min/mg protein) 50 ± 4 (100%) 49 ± 4 (98%)
* P < 0.01 versus normal gestation (P>0.05 in all other cases).
The pathophysiological effects of AEA, and possibly of several congeners,
are under control of FAAH. Indeed, FAAH-knockout mice have been shown
to have 15-fold higher levels of AEA than wild-type littermates, suggesting
that the hydrolase controls the in vivo levels of this endocannabinoid [28]. In
particular, lymphocyte FAAH might be involved in controlling pregnancy
failure by regulating the level of AEA at the feto–maternal interface, thus
interfering with the lymphocyte-dependent cytokine networks around the
mother and the fetus [27]. In this line, we have recently demonstrated that
decreased activity and expression of FAAH in maternal lymphocytes is an
early (