Toxicological Profile of 25I-NBOMe: Brain Distribution, DNA Damage, Apoptotic Signal and Glial Abnormalities

The hallucinogenic drug 25I-NBOMe crosses the blood-brain barrier easily and accumulates in brain tissue after repeated doses. In rats, chronic treatment caused DNA damage but no apoptosis 72 hours later, and reduced the number of glial cells in the frontal and medial prefrontal cortex without affecting neural cells. These findings suggest that oxidative DNA damage may underlie glial cell death, indicating potential brain toxicity from recreational use.

Study at a glance

Abstract

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 multiply injections was found. The DNA damage but no apoptotic signal was detected 72 h after the chronic treatment. 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 BBB and accumulates in the brain tissue. Observed oxidative DNA damage may lead to the glial cells’ death.