Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents

Abstract

RationaleCannabis is the most commonly used illicit drug among pregnant women. Since the endocannabinoid system plays a crucial role in brain development, maternal exposure to cannabis derivatives might result in long-lasting neurobehavioral abnormalities in the exposed offspring. It is difficult to detect these effects, and their underlying neurobiological mechanisms, in clinical cohorts, because of their intrinsic methodological and interpretative issues.ObjectivesThe present paper reviews relevant rodent studies examining the long-term behavioral consequences of exposure to cannabinoid compounds during pregnancy and/or lactation.ResultsMaternal exposure to even low doses of cannabinoid compounds results in atypical locomotor activity, cognitive impairments, altered emotional behavior, and enhanced sensitivity to drugs of abuse in the adult rodent offspring. Some of the observed behavioral abnormalities might be related to alterations in stress hormone levels induced by maternal cannabis exposure.ConclusionsThere is increasing evidence from animal studies showing that cannabinoid drugs are neuroteratogens which induce enduring neurobehavioral abnormalities in the exposed offspring. Several preclinical findings reviewed in this paper are in line with clinical studies reporting hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis. Conversely, genetic, environmental and social factors could also influence the neurobiological effects of early cannabis exposure in humans.

Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood

“…Moreover, it has been suggested that exogenous cannabinoids during adolescent maturation may result in long-term effects on HPA function which might affect subsequent stress reactivity, cognitive functioning, and emotionally relevant behavior (Viveros et al 2005;Realini et al 2009Realini et al , 2011Rubino et al 2009;Buwalda et al 2011;Campolongo et al 2011;LlorenteBerzal et al 2011). Hence, the reversal effects observed during the late-adolescent period, but not during adolescence, could be the result of a developing CNS that is more sensitive to environmental influences, such as stress and drugs, than the adult CNS.…”

At the Tip of an Iceberg: Prenatal Marijuana and Its Possible Relation to Neuropsychiatric Outcome in the Offspring

“…alcohol, nicotine, morphine or cannabis) may pose severe threats -unrelated to miscarriage or placental deficits -to the foetus, providing the foundation of neurobehavioral teratology (12). CNS vulnerability is a leading fingerprint of harmful developmental drug effects, and predominantly manifest as functional impairments in early childhood or adolescence, much less so by birth (13).…”

THC Treatment Alters Glutamate Receptor Gene Expression in Human Stem Cell-Derived Neurons

“…Evidence from neuron subtype-specific deletions suggests that CB1R may have different functions and pharmacological properties in different cell types (reviewed in [17]) and that its subcellular localization may mediate distinct signaling [18,19]. Endocannabinoids play critical roles during fetal brain development, being involved in neuronal differentiation, survival and the regulation of neurotransmitter systems [20,21,22]. …”