Possible role of biochemiluminescent photons for lysergic acid diethylamide (LSD)-induced phosphenes and visual hallucinations

This review (2016) appraises the role of bioluminescent photons in LSD-induced visual hallucinations/phosphenes. LSD induced visual hallucinations may be due to the transient enhancement of bioluminescent photons in the early retinotopic visual system in blinds as well as in healthy people.

Abstract

Today, there is an increased interest in research on lysergic acid diethylamide (LSD) because it may offer new opportunities in psychotherapy under controlled settings. The more we know about how a drug works in the brain, the more opportunities there will be to exploit it in medicine. Here, based on our previously published papers and investigations, we suggest that LSD-induced visual hallucinations/phosphenes may be due to the transient enhancement of bioluminescent photons in the early retinotopic visual system in blind as well as healthy people.

Authors: Gábor Kapócs, Felix Scholkmann, Vahid Salari, Noémi Császár, Henrik Szőke & István Bókkon

Summary

Possible role of biochemiluminescent photons for lysergic acid diethylamide (LSD) – induced phosphenes and visual hallucinations

Today, there is increased interest in research with LSD because it may offer new opportunities in psychotherapy under controlled settings. Here, we suggest that LSD may induce visual hallucinations/phosphenes.

Introduction

Lysergic acid is a natural substance from the parasitic rye fungus Claviceps purpurea. It was first synthesized by Albert Hofmann in 1938 and has been used for psychotherapy in the US and western Europe for several decades.

LSD causes visual hallucinations involving phosphenes, which are brief sensations of light. We propose that phosphenes may be due to the transient enhancement of bioluminescent photons in the visual system, and that early visual experience is essential to maintain any level of residual visual function.

Ultra-weak photon emission

Numerous experiments have shown that living cells continuously emit ultra-weak light without any excitation during natural metabolic processes. This ultra-weak light is mainly produced by several chemical reactions, mostly through bioluminescent radical reactions of reactive oxygen species and reactive nitrogen species. Ultra-weak photon emission (UPE) occurs in the range of 200-800 nm and is mainly produced by naturally occurring oxidation processes on the surface of the biological object (skin, cellular membranes). However, the real intensity of UPE can be basically higher inside cells.

The brain can generate electronically excited states through metabolic processes, blood flow, oxidative processes, and electrical activity, which implies that there can be neural activity-dependent UPE in the brain.

A new biopsychophysical idea was suggested about the phosphene phenomenon, which is thought to be caused by endogenous free-radical reactions causing bioluminescent biophotons. When this excess biophoton emission exceeds a distinct threshold, it then can become a conscious light sensation. In the case of retinal phosphenes, the phototransduction enzyme cascade provides enormous signal amplification. However, in the case of retinotopic visual areas, a different mechanism regarding phosphene generation would require UPE among synchronized neurons.

Regarding the prediction by Bókkon (2008), phosphene phenomena during space travel were found to follow this prediction. Ionizing radiation (cosmic rays) induced free radicals that elicited reactions producing photon emission through retinal lipid peroxidation.

We first suggested that phosphenes and discrete dark noise of retinal rods can be due to bioluminescent photons of lipid peroxidation, which were later fundamentally supported by experiments and calculations.

Metabolism and distribution of LSD

LSD is well absorbed from the gastrointestinal tract and is further distributed to different body tissues. It can easily pass the blood-brain barrier and enter the brain where it is metabolized to inactive 2-oxy-LSD and 2-oxo-3-hydroxy LSD.

LSD pharmacology: a short review

LSD can bind to various monoamine receptors, including 5-HT2A/2C, 5-HT5A, 5-HT6, and 5-HT7, D1 and D2 dopamine receptors, and 1- and 2-adrenergic receptors, and can enhance glutamatergic transmission, activate dopamine pathways, and activate noradrenaline neurons in the locus coeruleus.

We agree with Nichols’ notion that hallucinogens enhance sensitivity/excitability of the cortical processing while at the same time causing glutamate to be released from thalamic afferents that normally signal incoming sensory information to be processed.

Although retinal as well as cortical processes can contribute to LSD-induced visual hallucinations, they can also occur without a functioning retina. Thirteen of 24 subjects reported LSD-induced visual hallucinations, and these visual experiences did not seem to differ from the hallucinations reported by normal subjects after LSD.

Carhart-Harris et al. (2016) used functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) to visualize the effects of LSD on the human brain. They found that the visual cortex increased its communication with other brain areas and that there was a decreased connectivity between the parahippocampus and retrosplenial cortex.

Roseman et al. (2016) investigated whether the early visual system works as if it were seeing spatially localized external visual inputs under LSD.

LSD is metabolized to O-H-LSD and nor-LSD by cytochrome P450 complex liver enzymes, but it can also be metabolized by horseradish peroxidase (HRP) and myeloperoxidase (MPO) peroxidases. The reactions are chemiluminescent and sensitive to inhibition by reactive oxygen scavengers.

MPO is expressed in immune cells as neutrophils and monocytes, as well as by neurons and microglia, which represent roughly 5 – 10% of the cells found in normal brain.

Summary

LSD induces visual phosphenes and hallucinations that can occur without a functioning retina, as well as in blind subjects that had some kind of prior visual experience. These visual experiences do not seem to differ from the hallucinations reported by normal subjects after LSD. LSD causes chemiluminescent reactions with peroxidases, which are expressed in immune cells, neurons, and microglia. This leads to increased release of glutamate from cortical neurons, which is a common mechanism in the action of hallucinogens.

There are some studies that support the conclusion that cortical phosphenes are due to glutamate related excess biophoton emission in the retinotopic early visual parts. LSD may also generate biochemiluminescent photons in the visual regions of the brain via MPO.

One could argue that adding LSD to cells would enhance the production rate of biochemiluminescent photons to a negligible degree, but the experimental setup prevented the detection of weak photon emission, thus the real photon production rate might be underestimated.

The authors conclude that transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can induce visual phosphenes only in blind that had prior visual experiences. The authors also suggest that both methods can induce nonspecific effects on serotonin system and 5-HT2A receptors similar to LSD.

Knoll et al. (1963) induced phosphenes by simultaneous electrical and chemical stimulation. The phosphenes were enhanced by hallucigenic chemical stimulation.

One could argue that environmental light (sunlight or light from lamps) may cause phosphenes as well, but we are of the opinion that endogenously produced light (UPE) has specific features that prevent the triggering of phosphenes under normal environmental light conditions.

LSD can induce visual hallucinations by enhancing bioluminescent photons in the early retinotopic visual system in blinds as well as in healthy people. This specific effect may offer opportunities for psychotherapy under controlled settings.

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