In cynomolgus monkeys, noribogaine—a drug being developed for opioid dependence—did not cause seizures or EEG signals that warn of increased seizure risk, even at the highest dose tested (320 mg/kg). Monkeys showed mild behavioral effects such as reduced activity, scratching, licking, chewing, and some poor coordination. One monkey had brief myoclonic movements at the high dose, but these did not spread or link to EEG abnormalities. In contrast, the positive control pentylenetetrazol consistently triggered seizure-related EEG patterns and generalized seizures. The study establishes 320 mg/kg as the EEG no observed adverse effect level for noribogaine in this model.
5-MeO-DMT, a serotonin receptor agonist being developed for major depression, was tested for seizure risk in beagle dogs. Eight dogs received intranasal doses of 0.5, 1.0, and 1.5 mg/kg/day for nine days. Continuous EEG monitoring showed no seizures or epileptiform discharges at any dose, despite dose-dependent behavioral signs of serotonergic stimulation such as head shaking, tremors, and dilated pupils. These signs correlated with peak plasma levels and resolved within an hour. In a canine model sensitive to serotonergic drug-induced seizures, 5-MeO-DMT did not induce seizures, indicating low seizure liability.