When mice are socially isolated, their levels of pregnenolone decrease, a shift that also occurs in lonely humans. In a 2013 study of 31 healthy people, another research team found that giving people oral doses of a compound called allopregnanolone – derived from pregnenolone – had a calming effect on the participants’ amygdala and insula, which are the regions of the brain responsible for threat detection, emotional recall, and the anticipation of unpleasant reactions.
The Cacioppos started focusing on pregnenolone and allopregnanolone after preclinical trials showed that the compound could counteract some of the loneliness-related biological changes in brain and was well-tolerated in humans. Some antidepressants provide a similar effect but come with undesirable side effects, like drowsiness, nausea, and insomnia.
“If we could successfully reduce the alarm system in the minds of lonely individuals, then we could have them reconnect, rather than withdraw from others,” Stephanie says.