A UNIFIED ALTERNATIVE HYPOTHESIS ON THE MECHANISMS OF ACTION OF IBOGAINE, PSYCHO ACTIVE PLANTS AND ENTHEOGENS
Umit SAYIN, M.D., Ph.D., Institute of Forensic Sciences, İstanbul University, Aksaray-İstanbul, ASEHERT
Levent KARTAL, ASEHERT
İpek Zeynep YILMAZ, ASEHERT
Background: Most of the psychedelic chemicals have been proposed to exert their actions through serotonin (5-HT) receptors; particularly, 5-HT2A and 5-HT2c. In the case of LSD, psilocybin, psilocin, DMT and mescaline mostly serotonin receptors have been reported to be the targets for most of the effects of Hallucinogen Induced Altered States of Consciousness (H-ASCs) (Hintzen, 2010; Passie, 2008). Although ibogaine, ketamine and PCP (phencyclidine) have some similar psychoactive effects or induce similar hallucinations, they act on NMDA receptors, and have no substantial binding on 5-HT receptors, while some hallucinogens work on sigma receptors and/or kappa opioid receptors, whereas opium does not have noticeable hallucinogenic effects. THC has no effects on 5-HT receptors, but binds on CB1 and CB2 cannabinoid receptors. Thus, “serotonin receptor theory” and its correlation with the psychedelic drugs and H-ASCs is not yet a completed theory to explain the main mechanisms of H-ASCs. More importantly, SSRI’s (serotonin re-uptake inhibitors, used in depression) that increase the serotonin in many parts of the brain, do not have any hallucinogenic effects, even in very high doses; otherwise all the people treated with SSRI’s would be hallucinating if they overdosed themselves.
An Alternative Unified Hypothesis on the Mechanism of H-ASCs: The effects of hallucinogens can also be explained by an alternative hypothesis, such as “Gate-way Hypothesis”. It may be possible that certain circuitries and loops in the brain may have a capacity to experience psychedelic consciousness, however it is normally under the control of and inhibited by other hypothetical areas and circuits in the brain during normal daily life; some hallucinogens may be disinhibiting this gating mechanism, through an action which has not yet been discovered. Thus, some hallucinogens may trigger an innate mechanism in the brain, which already exists but becomes explicit during hyper-excitation states (probably, of a couple different receptor systems and different pathways), to experience H-ASCs (Sayin, 2014).
Hintzen A, Passie T. The pharmacology of LSD: a critical review. Oxford: Oxford University Press, 2010.
Passie T, Halpern JH, Stichtenoth O, Emrich HM and Hintzen A. Pharmacology of lysergic acid diethylaminde: A review. CNS Neuroscience & Therapeutics 2008; 14:295-314.
Sayin HÜ. Does the Nervous System Have an Intrinsic Archaic Language? Entoptic Images and Phosphenes (Research and Review). NeuroQuantology 12 (3): 427-445, 2014.