Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity.

Cannabidiol (CBD), a non-euphoric component of cannabis, reduces seizures in multiple forms of pediatric epilepsies, but the mechanism(s) of anti-seizure action remain unclear. In one leading model, CBD acts at glutamatergic axon terminals, blocking the pro-excitatory actions of an endogenous membrane phospholipid, lysophosphatidylinositol (LPI), at the G-protein-coupled receptor GPR55. However, the impact of LPI-GPR55 signaling at inhibitory synapses and in epileptogenesis remains underexplored. We found that LPI transiently increased hippocampal CA3-CA1 excitatory presynaptic release probability and evoked synaptic strength in WT mice, while attenuating inhibitory postsynaptic strength by decreasing GABAARγ2 and gephyrin puncta. LPI effects at excitatory and inhibitory synapses were eliminated by CBD pre-treatment and absent after GPR55 deletion. Acute pentylenetrazole-induced seizures elevated GPR55 and LPI levels, and chronic lithium-pilocarpine-induced epileptogenesis potentiated LPI's pro-excitatory effects. We propose that CBD exerts potential anti-seizure effects by blocking LPI's synaptic effects and dampening hyperexcitability.

Using a Psychopharmacogenetic Approach To Identify the Pathways Through Which-and the People for Whom-Testosterone Promotes Aggression.

Little is known about the neurobiological pathways through which testosterone promotes aggression or about the people in whom this effect is observed. Using a psychopharmacogenetic approach, we found that testosterone increases aggression in men ( N = 308) with select personality profiles and that these effects are further enhanced among those with fewer cytosine-adenine-guanine (CAG) repeats in exon 1 of the androgen receptor (AR) gene, a polymorphism associated with increased AR efficiency. Testosterone's effects were rapid (~30 min after administration) and mediated, in part, by subjective reward associated with aggression. Testosterone thus appears to promote human aggression through an AR-related mechanism and to have stronger effects in men with the select personality profiles because it more strongly upregulates the subjective pleasure they derive from aggression. Given other evidence that testosterone regulates reward through dopaminergic pathways, and that the sensitivity of such pathways is enhanced among individuals with the personality profiles we identified, our findings may also implicate dopaminergic processes in testosterone's heterogeneous effects on aggression.

The Facial Width-to-Height Ratio Predicts Sex Drive, Sociosexuality, and Intended Infidelity.

Previous research has linked the facial width-to-height ratio (FWHR) to a host of psychological and behavioral characteristics, primarily in men. In two studies, we examined novel links between FWHR and sex drive. In Study 1, a sample of 145 undergraduate students revealed that FWHR positively predicted sex drive. There were no significant FWHR × sex interactions, suggesting that FWHR is linked to sexuality among both men and women. Study 2 replicated and extended these findings in a sample of 314 students collected from a different Canadian city, which again demonstrated links between the FWHR and sex drive (also in both men and women), as well as sociosexuality and intended infidelity (men only). Internal meta-analytic results confirm the link between FWHR and sex drive among both men and women. These results suggest that FWHR may be an important morphological index of human sexuality.