Marijuana enhances social interactions (or so I've heard). But how does this work on the molecular level? And what's it tell us about the normal chemistry of the brain?

Well, cannabinoid receptors are present in brain regions involved in social and emotional things. The endocannabinoids that activate (and justify the existence of) these receptors are known to be involved in social reward and anxiety. And social reward—i.e., fun—is known to be mediated and reinforced by a hormone called oxytocin.

Is it possible that oxytocin mediates social reward by harnessing endocannabinoids? Recent work suggests that that is exactly how it happens—at least in mice.

Oxytocin has kind of a touchy-feely reputation, often being portrayed in the press as the hormone responsible for bonding and trust. But a more nuanced view holds that it's a bit more mixed. It actually functions to intensify whatever emotional state we already inhabit or enhance social ties within a clique to the detriment of anyone outside.

Much of the work delineating oxytocin's effects has been behavioral, relying on people's answers to mood questionnaires or choices in simulated morality tests; since this study used mice, these weren't options. But the researchers could, and did, expose the mice to different social environments and look at oxytocin levels in different brain regions. They either let mice socialize or kept them isolated and then “removed and snap-froze their brains” (which clearly brought the socializing to an end) to see where and how oxytocin might be working.

First, they showed that social contact increases the endocannabinoid anandamide specifically in a region of the brain called the nucleus accumbens, but not in other brain regions. The nucleus accumbens is a key region in the brain's reward circuit.

Next they showed that oxytocin also increases anandamide specifically in the nucleus accumbens, just like social contact does. To connect the dots, they showed that anandamide can recapitulate oxytocin's effects—mice with extra anandamide don't need oxytocin to enjoy social rewards. So socializing elicits oxytocin, which elicits anandamide, which binds to the endocannabinoid receptors in the nucleus accumbens to make socializing feel good.

About those mice with extra anandamide: due to a genetic mutation, they lack an enzyme that degrades the chemical. And they just love to socialize—all that stimulation of their endocannabinoid receptors really heightens the reward they get from it. This phenotype can be mimicked by inhibiting the enzyme with other drugs.

The authors of this study suggest that a drug that inhibits this anandamide-degrading enzyme might be a treatment for people with social impairment disorders. Conveniently, they have patented just such a drug.

PNAS, 2015. DOI: 10.1073/pnas.1509795112 (About DOIs).