Medications for treating the core symptoms of autism spectrum disorder (ASD) continue to be an unmet need. The only medications approved by the U.S. Food and Drug Administration (FDA) for the treatment of individuals with ASD are effective in treating irritability and associated aggressive behaviors, but these medications can also cause severe long-term side effects such as diabetes and involuntary motor movements. Effective medications with more tolerable side effect profiles are highly desirable.

Antonio Hardan and his colleagues at Stanford University are planning to examine the effectiveness of pregnenolone in the treatment of adolescents with ASD. Pregnenolone belongs to a new class of hormones known as neurosteroids, which have been shown to be effective in treating various psychiatric conditions, including bipolar depression and schizophrenia. Compared with current FDA-approved medications, preliminary data from Hardan’s group in a small open-label study of pregnenolone suggests that this compound represents a potentially effective and well-tolerated agent for treating irritability in individuals with ASD¹. In addition, preliminary evidence suggests that pregnenolone may be helpful in improving select core ASD symptoms, such as social deficits and sensory abnormalities.

Hardan’s team aims to extend their work by performing a 12-week randomized, double-blind, placebo-controlled pilot trial to examine the effectiveness of orally administered pregnenolone in reducing irritability and associated behaviors in adolescents with ASD. As ASD is a heterogeneous disorder, the team also plans to examine the usefulness of biomeasures (including blood levels of neurosteroids, eye-tracking and brain wave recording) in predicting treatment response and assessing biological changes with pregnenolone treatment. The use of biomeasures may help identify whether a select subgroup of ASD individuals are responsive to pregnenolone. The results of this pilot trial will further clarify the potential utility of pregnenolone as a medical treatment for ASD.