Department of Psychiatry, University of California San Diego, La Jolla, CA, 2093, USA; VA Research Service, USA; VA Mental Illness Research, Education, and Clinical Center, VA San Diego Healthcare System, San Diego, CA, USA.
2 papers in the library · 46 citations · publishing 2008-2025
The psychoactive tea ayahuasca contains DMT, 5-MeO-DMT, and MAO inhibitors harmine and harmaline. In rats, 5-MeO-DMT alone decreased movement and exploration. When combined with a low dose of harmaline, 5-MeO-DMT produced an initial decrease in locomotion followed by a later increase. This shift depended on inhibition of MAO-A, not MAO-B. The late hyperactivity was blocked by a 5-HT2A receptor antagonist, indicating that 5-HT2A receptors mediate this effect, while a 5-HT1A antagonist had no effect. Thus, harmaline alters 5-MeO-DMT's behavioral effects through MAO-A inhibition, and 5-HT2A receptors drive the delayed hyperactivity.
In mice with reduced Sp4 expression, a gene linked to schizophrenia in humans, restoring Sp4 in young adults partially corrected two schizophrenia-related behavioral deficits—prepulse inhibition and hypersensitivity to ketamine—but did not improve context memory. The SP4 gene is strongly associated with schizophrenia risk; human studies show that loss of one copy increases odds of schizophrenia by about 9-fold. These results suggest that Sp4 restoration in adulthood may reverse some but not all behavioral abnormalities, supporting further investigation of SP4 as a potential drug target.