Effect of fasedienol (PH94B) pherine nasal spray and steroidal hormones on electrogram responses and autonomic nervous system activity in healthy adult volunteers

Objective

Fasedienol (PH94B) is a pherine compound formulated as a nasal spray that is hypothesized to regulate olfactory-amygdala circuits of fear and anxiety. Fasedienol's effect on the local electrogram of nasal chemosensory neurons (EGNR) and autonomic nervous system (ANS) responses versus steroidal hormones and controls in healthy adults is reported.

Methods

Eight males and 8 females randomly received aerosolized control (propylene glycol) and study drugs (fasedienol, 17β-estradiol, progesterone, cortisol, and testosterone, 0.4 μg each in propylene glycol) onto the nasal septum mucosal lining at 30-min intervals over 2 sessions. EGNR was continuously monitored; autonomic parameters were recorded before and after administration.

Results

Fasedienol significantly increased EGNR amplitude (males: 5.0 vs. 0.6 mV, p < 0.001; females:5.7 vs. 0.6 mV, p < 0.001), and rapidly reduced respiratory rate (p < 0.05), heart rate (p < 0.01), and electrodermal activity (p < 0.05) versus control. EGNR and ANS responses after steroidal hormone administration were similar to control. 81% reported feeling less tense/more relaxed after receiving fasedienol, but not after receiving either control or steroidal hormones.

Conclusions

Intranasal fasedienol, but not control or steroidal hormones, activated EGNR and rapidly reduced ANS responses, consistent with sympatholytic effects. Combined with subjective reports, results suggest fasedienol may provide acute relief in anxiety conditions.