Novel harmala-ocudelic tuning (HOT) for ocular disorders.

The eye contains serotonin and its receptors, and drugs that bind to these receptors may affect vision. Selective serotonin reuptake inhibitors (SSRIs) can impair ocular function, while other serotonin-binding drugs might improve it. Harmine, a naturally occurring alkaloid found in plants such as Passiflora, Peganum, and Banisteriopsis, is proposed as a candidate for improving vision. At individualized low doses, these plants are minimally hallucinogenic and well tolerated, with potential long-lasting benefits from one or few administrations. The hypothesized mechanism involves tuning serotonergic receptors in the eye. Blinded research with harmala alkaloid-containing plants, using psychedelic therapy methods, could assess visual acuity in presbyopia.

Study at a glance

Abstract

The eye contains serotonin, and possesses serotonergic receptors and modulators. Selective serotonin reuptake inhibitors (SSRIs) may impair ocular function, while other serotonin receptor-binding drugs might improve it. A putative vision-improving drug must be safe at therapeutic doses, most preferably with long-lasting benefits from a single or very few administration(s). One drug potentially satisfying these criteria is the common, botanically-occurring indole alkaloid and "major hallucinogen," harmine. Harmine is prominent in the leaves of the Generally Recognized as Safe (GRAS) Passiflora, and in Peganum and Banisteriopsis, the two preeminent "sacred" medicinal plants of India/pre-Islamic Persia/modern Iran and the Amazon respectively. Though the possibility of drug-drug or herb-drug interactions exists, especially with SSRIs, at correct patient-individualized dosages, these plants, used alone, are minimally hallucinogenic, well tolerated, potentially exerting profound therapeutic effects on vision from a single or few administration(s) lasting months or years. The hypothesized mechanism for this extraordinary action is tuning of the serotonergic receptors in the eye in their binding affinity for serotonin, a putative neurochemical "ocudelic" homologue to the psychedelic phenomenon, likely potentiated, according to clinical experience with classical hallucinogens, by therapeutic music, positive psychological "set," and conducive environmental "setting." Blinded research with harmala alkaloid-containing plants in ocular patients using psychedelic therapy accoutrements, viz. eyeshades, high fidelity classical music, headphones, two guides, pre-dosing preparation, and post-dosing integration, could non-invasively assess visual acuity in presbyopia. Significant results would stimulate further exploration of this novel approach to ocular disorders. Deeper benefit, particularly when the retina is compromised, might follow co-ingestion of the harmala alkaloid-containing plants with plants containing dimethyltryptamine.