Prenatal alcohol exposure (PAE) is an established cause of brain-based disability, though co-
exposure to other drugs, i.e., poly-substance use, can exacerbate adverse PAE-associated
infant outcomes. The practice of Simultaneous Alcohol and Cannabinoid (SAC) use, i.e., co-
ingestion, is an emerging trend among adolescents and adults of child-bearing age. SAC is
motivated and maintained because combined use of alcohol and cannabinoids amplifies each
drug’s psychological effect. Cannabinoids are known contributors to teratogenicity. However, we
know virtually nothing about potential consequences of SAC for birth outcomes.
The premise of the proposed studies is informed by the published literature, which indicates that
PAE effects are, in part, mediated by activation of cannabinoid receptor signaling pathways and
that PAE and prenatal cannabinoids engender similar fetal developmental outcomes. Moreover,
recently published data shows developmental synergy between sub-teratogenic doses of
cannabinoids and ethanol in non-mammalian vertebrate models. Based on these, as well as our
own preliminary data we plan to address two questions: Firstly, “is SAC more damaging to fetal
development than either alcohol or cannabinoids alone?”; Secondly, and importantly, “will
cannabinoid antagonists protect against effects of PAE & SAC?”. Our studies will focus on the
effects of SAC on neurogenesis and vasculogenesis, the complementary growth of vasculature
that supports fetal brain growth.
We plan to use in vivo and ex vivo mouse PAE models in combination with molecular assays and
behavioral assays for hyperactivity and conditioned place preference, as well as state-of-the-art
optical imaging (optical coherence tomography and light-sheet microscopy) and high-resolution
ultrasound imaging, to assess the effects of SAC on, (Aim #1) brain and behavior, and (Aim #2)
on vasculogenesis and cerebrovascular blood flow.
Our overarching goal, to identify and minimize the contribution of factors, including poly-drug use,
that contribute to increased risk for brain disabilities due to PAE, is consistent with the goals of
the Collaborative Research on Addiction at NIH (CRAN) initiative. The rapid spread of recreational
cannabis use means that SAC is an important emerging mode of drug consumption, and a
potential contributor to the severity of PAE effects. As an outcome of these studies, we will
acquire evidence to guide human studies on SAC birth outcomes, and to assess the efficacy of
novel pharmacological intervention strategies targeted to cannabinoid receptors as a means to
prevent or reverse effects of PAE.