Animal evidence considered in determination of cannabis smoke and Δ9‐tetrahydrocannabinol (Δ9‐THC) as causing reproductive toxicity (developmental endpoint); Part II. Neurodevelopmental effects. Issue 18 (16th September 2022)

• Record Type: Journal Article
• Authors: Iyer, Poorni; Niknam, Yassaman; Campbell, Marlissa; Moran, Francisco; Kaufman, Farla; Kim, Allegra; Sandy, Martha; Zeise, Lauren
• Other Names: Iyer Poorni guestEditor.; Watanabe Michiko guestEditor.; Artinger Kristin B guestEditor.
• Is Part Of: Birth defects research. Volume 114:Issue 18(2022)
• Page Start: 1155
• Page End: 1168
• Publication Date: 2022-09-16
• Subjects: cross generational -- developmental toxicity -- epigenetics -- neurodevelopment -- proposition 65 -- THC; Teratology -- Periodicals; Abnormalities, Human -- Periodicals; Congenital Abnormalities; Embryo, Mammalian -- abnormalities; Teratology; Abnormalities, Human; Teratology; Periodicals; Periodicals; 616.043
• DOI: 10.1002/bdr2.2084
• Languages: English
• ISSNs: 2472-1727

Abstract

Abstract: This review focuses on neurodevelopmental effects observed in animal studies of cannabis smoke and Δ 9 ‐THC. Effects in offspring after preconceptional, prenatal, or perinatal exposure to cannabis smoke or Δ 9 ‐THC were considered. Locomotor and exploratory behavior effects were noted in rats. Cognitive effects observed included impairment of memory and learning, attention deficits, time taken to complete tasks (rats) and alterations in response to visual stimuli (rats/monkeys). Emotionality was observed in rodents as an increase in separation‐induced ultrasonic vocalizations, reduced social interaction and play behavior, and increased generalized anxiety. Increased rate of acquisition of morphine self‐administration and/or enhanced sensitivity towards the rewarding effects of morphine or heroin were observed in adult rats prenatally exposed to Δ 9 ‐THC. Expression of cannabinoid receptors was examined in rodent studies along with behavioral parameters. Altered mRNA levels of genes relevant to synaptic plasticity in the nucleus accumbens (the brain region associated with compulsivity, addiction vulnerability, and reward sensitivity) were noted. Findings in zebrafish supported effects in mammalian models. Neurochemical effects on specific brain regions and neurotransmitter systems seen in these animal studies appear to impact cognitive function, motor activity, and drug sensitivity. Mechanistic studies provided evidence for the biological plausibility of effects observed. Observations from animal studies of changes in motor behavior, cognitive performance, emotionality and susceptibility to drug sensitivity later in life were among the findings from animal and human studies considered by California's Developmental and Reproductive Toxicant Identification Committee, in concluding that cannabis smoke and Δ 9 ‐THC are developmental toxicants.