Psychopharmacology
November 1, 2008
Adam L Halberstadt, Mahalah R Buell, Virginia L Masten et al.
46 citations
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.
Journal of psychiatric research
July 1, 2025
Joris Kamp, Megan E Sikkink, Mahalah R Buell et al.
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.
Psychopharmacology
April 1, 2016
Adam L Halberstadt, Natalia Slepak, James Hyun et al.
Methoxetamine (MXE), a ketamine analog sold online, produces behavioral effects in rats that closely resemble those of other dissociative anesthetics like phencyclidine (PCP) and ketamine. In Sprague-Dawley rats, MXE disrupted prepulse inhibition (PPI) of acoustic startle at doses of 3 and 10 mg/kg, with a potency ranking (PCP > MXE > S-(+)-ketamine > NANM > R-(-)-ketamine) that matches their affinities for the PCP binding site on NMDA receptors. In the behavioral pattern monitor, 10 mg/kg MXE caused locomotor hyperactivity, reduced rearing, increased path roughness, and perseverative locomotion—effects similar to those of PCP. These findings indicate MXE acts as a dissociative drug with abuse potential comparable to PCP and ketamine.