Therapeutic Properties of Ayahuasca Components in Ischemia/Reperfusion Injury of the Eye

A study tested whether N’N-dimethyltryptamine (DMT), a psychedelic compound, could protect the retina from damage caused by ischemia (restricted blood flow) followed by reperfusion. Because DMT is rapidly broken down by monoamine oxidase A (MAO-A), it was given alongside harmaline (a MAO-A inhibitor found in the Amazonian brew ayahuasca). In rats whose eye blood flow was blocked for 60 minutes and then restored for 7 days, harmaline alone protected the retina from injury. Surprisingly, adding DMT counteracted that protection. The two drugs had opposing effects on proteins involved in cell death, inflammation, tissue breakdown, and oxidative stress. The results suggest harmaline may have therapeutic potential for ischemic eye diseases, while DMT's effects on eye ischemia warrant caution.

Study at a glance

Abstract

Ischemic eye diseases are major causes of vision impairment. Thus, potential retinoprotective effects of N’N-dimethyltryptamine (DMT) were investigated. To inhibit its rapid breakdown by monoamine-oxidase A (MAO-A) enzyme, DMT was co-administered with harmaline, a β-carboline in the Amazonian Ayahuasca brew. Using ligation, 60 min of ischemia was provoked in eyes of rats, followed by 7 days of reperfusion whilst animals received harmaline alone, DMT + harmaline, or vehicle treatment. After 1 week of reperfusion, electroretinographical (ERG) measurements, histological analysis, and Western blot were performed. Harmaline alone exhibited retinoprotection in ischemia–reperfusion (I/R) which was, surprisingly, counterbalanced by DMT in case of co-administration. As both MAO-A inhibition and DMT increase serotoninergic tone synergistically, communicated to be anti-ischemic, thus, involvement of other pathways was investigated. Based on our experiments, DMT and harmaline exert opposite effects on important ocular proteins such as PARP1, NFκB, MMP9, or HSP70, each having a critical role in a different mechanism of eye-ischemia-related pathologies, e.g., cell death, inflammation, tissue destruction, and oxidative stress. Since DMT is proclaimed to be a promising drug candidate, its potentially undesirable effect on eye-ischemia should be further investigated. Meanwhile, this experiment revealed the potential therapeutic effect of MAO-A inhibitor harmaline in I/R-related eye diseases.