Dream over life : Psychedelic terphenyl derivative induce hallucination via cannabinoid receptor 1

F.A. Fauzi, M.S. Goh, S.A.T.T. Johari, F. Hashim, M.F.N. Hassim

The International Fundamentum Sciences Symposium 2018 IOP Publishing
IOP Conf. Series: Materials Science and Engineering 440 (2018) 012045

doi:10.1088/1757-899X/440/1/012045

 

Abstract.

For ages, natural psychedelic resources have been used by ancient tribes for religious inspiration. In modern medicine, these compounds were prescribed to relieve severe distress and depression on cancer patients. Despite medical benefit, abuse of these compounds have become prevalent in our modern society. These compounds usually interacted withcannabinoid receptor 1 (CNR1) on neuron cell causing hallucination, and on other cell-types. In this study, chemically synthesized terphenyl derivative, 1,4-di(phenyl)benzene (13-BPB) interaction with human and its animal model were assessed. This derivative is an analogue found in fungi although their functional molecular mechanism is unknown. Terphenyl derivative known to have pharmacological activities – antifungal, anti-cancer, anticoagulant. Our study designed includes in-vitro assessment and in-silico model of 13-BPB interaction to the molecular mechanism in human and its animal model, mice. Cytotoxicity assessment using MTT has shown that treatment of 13BPB on NIH-3T3 and RAW 264.7 have significant reduction in cell viability at 0.016mM and 0.08mM, respectively. Virtual database screening based on homologous compounds identified possible interaction with 15 different proteins from receptors, enzymes and transcription factors, in human and mice. Further docking analysis shows terphenyl derivatives binding affinities (pKd/pKi) are the highest with CNR1 and oestrogen receptors (ESRs).

1. Introduction

For ages, psychedelic plants and fungi were used by shamans of ancient tribe during religious ritual.
They believe that these plants assist their ascension to the spiritual dimension [1]. Psychedelic plants have psilocybin that can alter the states of consciousness or hallucination. In modern medicine, psilocybin was prescribed by the cancer patients as it can relieve severe distress and depression [2].
Depression is synonym with cancer patients due to prolonged hospital admission and having a limited day of being alive. Psilocybin which can be found in Psilocybe cubensis, magic mushroom can alter the emotions and perceptions of the patients by causing hyperactivity of frontal regions of brain followed by other hallucinogenic effects such as euphoria. Other effect includes increase body temperature and blood pressure as well as having difficulty in thinking. This due to hypermetabolism on right hemisphere of brain caused by the consumption of psilocybin [3,4]. At the molecular level, the hallucination is caused by psilocybin interaction with cannabinoid receptors (CNRs) of neuronal cells [5]. Hallucination also can be caused by terphenyl derivatives which mainly found in fungi. In this study, pharmaceutical potential of a terphenyl analogue found in fungi, 1,4- di(phenyl)benzene (13-BPB) was assessed. Terphenyl derivative, 13-BPB is chemically synthesised which is more eco- friendly that mimic the characteristics of natural terphenyl. Our study designed included in-vitro assessment and in-silico model of 13-BPB interaction to the molecular mechanism in human.

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