Cannabinoids exacerbate alcohol-induced eye and face malformations. (a) The incidence of defects in either the right or the left eye in fetal mice following GD 8 exposure to the CB vehicle (n = 103 fetuses/13 litters), Alcohol 1.4 g/kg alone (n = 62 fetuses/10 litters), Alcohol 2.8 g/kg alone (n = 85 fetuses/10 litters), CP 55,940 0.25 mg/kg alone (n = 101 fetuses/12 litters), simultaneous CP 55,940 0.25 mg/kg + Alcohol 1.4 g/kg (n = 133 fetuses/16 litters), or simultaneous CP 55,940 0.25 mg/kg + Alcohol 2.8 g/kg (n = 50 fetuses/7 litters). (b) The incidence of defects in either the right or the left eye in fetal mice following GD 8 exposure to the CB vehicle (n = 103 fetuses/13 litters), HU-210 0.03 mg/kg alone (n = 89 fetuses/11 litters), simultaneous HU-210 0.03 mg/kg + Alcohol 1.4 g/kg (n = 122 fetuses/15 litters), THC 0.56 mg/kg alone (n = 76 fetuses/9 litters), or simultaneous THC 0.56 + Alcohol 1.4 g/kg (n = 87 fetuses/11 litters). Data are expressed as the percent of mice with eye defects (number of affected mice/total number of mice *100), observed in a single experiment. **p < 0.01, ***p < 0.001, vs CB vehicle; ^p < 0.05, ^^^p < 0.001 vs. respective doses of CP 55,940 alone using a Chi-square test. (c–k) Craniofacial, palate, and brain malformations following simultaneous alcohol and cannabinoids. (c,f,i) A typical fetal mouse face as well as hematoxylin and eosin staining of coronal sections through the anterior palate and the brain at the level of the septal area, following the CB vehicle treatment. (d,g,j) Anophthalmia and philtrum deficiency, as well as cleft palate (indicated by black arrows), holoprosencephaly, and septal deficiency caused by alcohol 1.4 g/kg + CP 55,940 0.25 mg/kg. (e,h,k) Near anophthalmia, philtrum, and nostril deficiency, as well as cleft palate and widespread brain structural changes caused by alcohol 1.4 g/kg + HU-210 0.03 mg/kg. See also Supplementary Table 2 for data on eye defect severity, body weight and length, and the number of live offspring per litter. See Supplementary Fig. 2c–f for separate analysis of left and right eye defects.