Neurotoxicological profile of the hallucinogenic compound 25I-NBOMe.

The synthetic hallucinogen 25I-NBOMe crosses the blood-brain barrier easily and accumulates in the brain after repeated doses. In rats, chronic treatment caused DNA damage in brain tissue 72 hours later, but no signs of apoptosis. The number of glial cells decreased in the frontal and medial prefrontal cortex, while neural cells were unaffected. These findings suggest that oxidative DNA damage from 25I-NBOMe may lead to glial cell death, indicating potential brain toxicity from recreational use.

Study at a glance

Abstract

4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a new psychoactive substance with strong hallucinogenic properties. Our previous data reported increased release of dopamine, serotonin, and glutamate after acute injections and a tolerance development in the neurotransmitters release and rats' behavior after chronic treatment with 25I-NBOMe. The recreational use of 25I-NBOMe is associated with severe intoxication and deaths in humans. There is no data about 25I-NBOMe in vivo toxicity towards the brain tissue. In this article 25I-NBOMe-crossing through the blood-brain barrier (BBB), the impact on DNA damage, apoptosis induction, and changes in the number of cortical and hippocampal cells were studied. The presence of 25I-NBOMe in several brain regions shortly after the drug administration and its accumulation after multiple injections was found. The DNA damage was detected 72 h after the chronic treatment. On the contrary, at the same time point apoptotic signal was not identified. A decrease in the number of glial but not in neural cells in the frontal (FC) and medial prefrontal cortex (mPFC) was observed. The obtained data indicate that 25I-NBOMe passes easily across the BBB and accumulates in the brain tissue. Observed oxidative DNA damage may lead to the glial cells' death.