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Reviews in the Neurosciences

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Volume 28, Issue 1


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

Gábor Kapócs
  • Social Home for Psychiatric Patients, H-9970, Szentgotthard, Hungary
  • Institute of Behavioral Sciences, Semmelweis University, H-1089, Budapest, Hungary
  • Other articles by this author:
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/ Felix Scholkmann
  • Biomedical Optics Research Laboratory, Department of Neonatology, University Hospital Zurich, University of Zurich, CH-8091 Zurich, Switzerland
  • Research Office for Complex Physical and Biological Systems (ROCoS), CH-8038 Zurich, Switzerland
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/ Vahid Salari
  • Department of Physics, Isfahan University of Technology, Isfahan 84156-83111, Iran (Islamic Republic of)
  • School of Physics, Institute for Research in Fundamental Sciences (IPM), Tehran 19395-5531, Iran (Islamic Republic of)
  • Other articles by this author:
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/ Noémi Császár
  • Psychoszomatic OutPatient Department, H-1037, Budapest, Hungary
  • Gaspar Karoly University Psychological Institute, H-1091 Budapest, Hungary
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/ Henrik Szőke / István Bókkon
  • Corresponding author
  • Psychoszomatic OutPatient Department, H-1037, Budapest, Hungary
  • Social Home for Psychiatric Patients, H-9970, Szentgotthard, Hungary
  • Vision Research Institute, Neuroscience and Consciousness Research Department, Lowell, MA 01854, United States of America
  • Email
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Published Online: 2016-10-12 | DOI: https://doi.org/10.1515/revneuro-2016-0047


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.

Keywords: LSD; ultra-weak photon emission; visual hallucinations/phosphenes; visual system


  • Abi-Saab, W.M., Bubser, M., Roth, R.H., and Deutch, A.Y. (1999). 5-HT2 receptor regulation of extracellular GABA levels in the prefrontal cortex. Neuropsychopharmacology 20, 92–96.Google Scholar

  • Alema, G. (1952). Allucinazioni da acido lisergico in cieco sen a bulbi ocular. Riv. Neurol. 22, 720–733.Google Scholar

  • Alvermann, M., Srivastava, Y.N., Swain, J., and Widom, A. (2015). Biological electric fields and rate equations for biophotons. Eur. Biophys. J. 44, 165–170.Google Scholar

  • Arshavsky, V.Y. and Burns, M.E. (2014). Current understanding of signal amplification in phototransduction. Cell. Logistics 4, e28680.Google Scholar

  • Ashtari, M., Cyckowski, L., Yazdi, A., Marshal, K., Viands, A., Bókkon, I., Maguire, A., and Bennett, J. (2014). fMRI of retinal originated phosphenes experienced by patients with Leber congenital amaurosis. PLoS ONE 9, e86068.Google Scholar

  • Axelrod, J., Brady, R.O., Witkop, B., and Evarts, E.V. (1957). The distribution and metabolism of LSD. Ann. N. Y. Acad. Sci. 66, 435–444.Google Scholar

  • Baeken, C., De Raedt, R., Bossuyt, A., Van Hove, C., Mertens, J., Dobbeleir, A., Blanckaert, P., and Goethals, I. (2011). The impact of HF-rTMS treatment on serotonin (2A) receptors in unipolar melancholic depression. Brain Stimul. 4, 104–111.Google Scholar

  • Blake, T., Dotta, B.T., Buckner, C.A., Cameron, D., Lafrenie, R.M., and Persinger, M.A. (2011). Biophoton emissions from cell cultures: biochemical evidence for the plasma membrane as the primary source. Gen. Physiol. Biophys. 30, 301–309.Google Scholar

  • Bókkon, I. (2008). Phosphene phenomenon: a new concept. Biosystems 92, 168–174.Google Scholar

  • Bókkon, I. and Vimal, R.L.P. (2009). Retinal phosphenes and discrete dark noises in rods: a new biophysical framework. J. Photochem. Photobiol. B Biol. 96, 255–259.Google Scholar

  • Bókkon, I., Salari, V., Tuszynski, J., and Antal, I. (2010). Estimation of the number of biophotons involved in the visual perception of a single-object image: biophoton intensity can be considerably higher inside cells than outside. J. Photochem. Photobiol. B Biol. 100, 160–166.Google Scholar

  • Bókkon, I., Vimal, R.L.P., Wang, C., Dai, J., Salari, V., Grass, F., and Antal, I. (2011). Visible light induced ocular delayed bioluminescence as a possible origin of negative afterimage. J. Photochem. Photobiol. B Biol. 103, 192–199.Google Scholar

  • Borroto-Escuela, D.O., Romero-Fernandez, W., Narvaez, M., Oflijan, J., Agnati, L.F., and Fuxe, K. (2014). Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes. Biochem. Biophys. Res. Commun. 443, 278–284.Google Scholar

  • Braitenberg, V. and Schüz, A. (1998). Cortex: Statistics and Geometry of Neuronal Connectivity. 2nd ed. Berlin: Springer.Google Scholar

  • Brigatti, L. and Maguluri, S. (2005). Reproducibility of self-measured intraocular pressure with the phosphene tonometer in patients with ocular hypertension and early to advanced glaucoma. J. Glaucoma 14, 36–39.Google Scholar

  • Brust, J.C.M. (2004). Neurological Aspects of Substance Abuse. 2nd ed. USA: Elsevier, Inc. p. 260.Google Scholar

  • Carhart-Harris, R.L., Muthukumaraswamy, S., Roseman, L., Kaelen, M., Droog, W., Murphy, K., Tagliazucchi, E., Schenberg, E.E., Nest, T., Orban, C., et al. (2016). Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proc. Natl. Acad. Sci. U. S. A. 113, 4853–4858.Google Scholar

  • Cattaneo, Z. and Vecchi, T. (2011). Blind Vision: The Neuroscience of Visual Impairment. (Cambridge, MA: MIT Press), p. 98.Google Scholar

  • Cliento, G. (1988). Photobiochemistry without light. Experientia 44, 572–576.Google Scholar

  • Cohen, S. and Popp, F.A. (1997). Biophoton emission of the human body. J. Photochem. Photobiol. B Biol. 40, 187–189.Google Scholar

  • Császár, N., Scholkmann, F., Salari, V., Szőke, H., and Bókkon, I. (2016). Phosphene perception is due to the ultra-weak photon emission produced in various parts of the visual system: glutamate in the focus. Rev. Neurosci. 27, 291–299.Google Scholar

  • Das, S., Barnwal, P., Ramasamy, A., Sen, S., and Mondal, S. (2016). Lysergic acid diethylamide: a drug of ‘use’? Ther. Adv. Psychopharmacol. 6, 214–228.Google Scholar

  • Devaraj, B., Scott, R.Q., Roschger, P., and Inaba, H. (1991). Ultraweak light emission from rat liver nuclei. Photochem. Photobiol. 54, 289–293.Google Scholar

  • Fuglesang, C., Narici, L., Picozza, P., and Sannita, W.G. (2006). Phosphenes in low earth orbit: survey responses from 59 astronauts. Aviat. Space Environ. Med. 77, 449–452.Google Scholar

  • Gomes, M.M., Dörr, F.A., Catalani, L.H., and Campa, A. (2012). Oxidation of lysergic acid diethylamide (LSD) by peroxidases: a new metabolic pathway. Forensic Toxicol. 30, 87–97.Google Scholar

  • Green, P.S., Mendez, A.J., Jacob, J.S., Crowley, J.R., Growdon, W., Hyman, B.T., and Heinecke, J.W. (2004). Neuronal expression of myeloperoxidase is increased in Alzheimer’s disease. J. Neurochem. 90, 724–733.Google Scholar

  • Gur, E., Lerer, B., Dremencov, E., and Newman, M.E. (2000). Chronic repetitive transcranial magnetic stimulation induces subsensitivity of presynaptic serotonergic autoreceptor activity in rat brain. NeuroReport 11, 925–929.Google Scholar

  • Hecht, S., Schlaer, S., and Pirenne, M.H. (1942). Energy, quanta and vision. J. Opt. Soc. Am. 38, 196–208.Google Scholar

  • Hofmann, A. (1980). LSD: My Problem Child. New York, NY: McGraw-Hill.Google Scholar

  • Hubel, D.H. and Wiesel, T.N. (1965). Binocular interaction in striate cortex of kittens reared with artificial squint. J. Neurophysiol. 28, 1041–1059.Google Scholar

  • Imaizumi, S., Kayama, T., and Suzuki, J. (1984). Chemiluminescence in hypoxic brain – the first report. Correlation between energy metabolism and free radical reaction. Stroke 15, 1061–1065.Google Scholar

  • Isojima, Y., Isoshima, T., Nagai, K., Kikuchi, K., and Nakagawa, H. (1995). Ultraweak biochemiluminescence detected from rat hippocampal slices. NeuroReport 6, 658–660.Google Scholar

  • Johansen, P.Ø. and Krebs, T.S. (2015). Psychedelics not linked to mental health problems or suicidal behavior: a population study. J. Psychopharmacol. 29, 270–279.Google Scholar

  • Kamal, A.H. and Komatsu, S. (2015). involvement of reactive oxygen species and mitochondrial proteins in biophoton emission in roots of soybean plants under flooding stress. J. Proteome Res. 14, 2219–2236.Google Scholar

  • Kamal, A.H. and Komatsu, S. (2016). Proteins involved in biophoton emission and flooding-stress responses in soybean under light and dark conditions. Mol. Biol. Rep. 43, 73–89.Google Scholar

  • Karu, T. (1999). Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J. Photochem. Photobiol. B 49, 1–17.Google Scholar

  • Kataoka, Y., Cui, Y., Yamagata, A., Niigaki, M., Hirohata, T., Oishi, N., and Watanabe, Y. (2001). Activity-dependent neural tissue oxidation emits intrinsic ultraweak photons. Biochem. Biophys. Res. Commun. 285, 1007–1011.Google Scholar

  • Kato, M., Shinzawa, K., and Yoshikawa, S. (1981). Cytochrome oxidase is a possible photoreceptor in mitochondria. J. Photochem. Photobiol. 2, 263–269.Google Scholar

  • Kharazia, V.N. and Weinberg, R.J. (1994). Glutamate in thalamic fibers terminating in layer IV of primary sensory cortex. J. Neurosci. 14, 6021–6032.Google Scholar

  • Knoll, M., Kugler, J., Höfer, O., and Lawder, S.D. (1963). Effects of chemical stimulation of electrically-induced phosphenes on their bandwidth, shape, number and intensity. Confin. Neurol. 23, 201–226.Google Scholar

  • Kobayashi, M. (2014). Highly sensitive imaging for ultra-weak photon emission from living organisms. J. Photochem. Photobiol. B. 139, 34–38.Google Scholar

  • Kobayashi, M., Takeda, M., Ito, K., Kato, H., and Inaba, H. (1999a). Two-dimensional photon counting imaging and spatiotemporal characterization of ultraweak photon emission from a rat’s brain in vivo. J. Neurosci. Methods 93, 163–168.Google Scholar

  • Kobayashi, M., Takeda, M., Sato, T., Yamazaki, Y., Kaneko, K., Ito, K., Kato H., and Inaba, H. (1999b). In vivo imaging of spontaneous ultraweak photon emission from a rat’s brain correlated with cerebral energy metabolism and oxidative stress. Neurosci. Res. 34, 103–113.Google Scholar

  • Kobayashi, K., Okabe, H., Kawano, S., Hidaka, Y., and Hara, K. (2014). Biophoton emission induced by heat shock. PLoS ONE 9, e105700.Google Scholar

  • Kobayashi, M., Iwasa, T., and Tada, M. (2016). Polychromatic spectral pattern analysis of ultra-weak photon emissions from a human body. J. Photochem. Photobiol. B. 159, 186–190.Google Scholar

  • Krill, A.E., Alpert, H.J., and Ostfeld, A.M. (1963). Effects of a hallucinogenic agent in totally blind subjects. Arch. Ophthalmol. 69, 180–185.Google Scholar

  • Kruk, I., Lichszteld, K., Michalska, T., Wronska, J., and Bounias, M. (1989). The formation of singlet oxygen during oxidation of catechol amines as detected by infrared chemiluminescence and spectrophotometric method. Z. Naturforsch. C 44, 895–900.Google Scholar

  • Kumar, S., Boone, K., Tuszynski, J., Barclay, P.E., and Simon, C. (2016). Possible existence of optical communication channels in the brain. arXiv:1607.02969.

  • Laager, F. (2015). Light based cellular interactions: hypotheses and perspectives. Front. Phys. http://dx.doi.org/10.3389/fphy.2015.00055.Crossref

  • Lefkowitz, D. and Lefkowitz, S. (2008). Microglia and myeloperoxidase: a deadly partnership in neurodegenerative disease. Free Radic. Biol. Med. 45, 726–731.Google Scholar

  • Li, Z. and Dai, J. (2016). Biophotons contribute to retinal dark noise. Neurosci. Bull. 32, 246–252.Google Scholar

  • Lindenblatt, G. and Silny, J. (2002). Electrical phosphenes: on the influence of conductivity inhomogeneities and small-scale structures of the orbita on the current density threshold of excitation. Med. Biol. Eng. Comput. 40, 354–359.Google Scholar

  • Liu, R., Jolas, T., and Aghajanian, G. (2000). Serotonin 5-HT(2) receptors activate local GABA inhibitory inputs to serotonergic neurons of the dorsal raphe nucleus. Brain Res. 73, 34–45.Google Scholar

  • Malle, E., Furtmuller, P., Sattler, W., and Obinger, C. (2007). Myeloperoxidase: a target for new drug development? Br. J. Pharmacol. 152, 838–854.Google Scholar

  • Mazhul’, V.M. and Shcherbin, D.G. (1999). Phosphorescent analysis of lipid peroxidation products in liposomes. Biofizika 44, 676–681.Google Scholar

  • Merabet, L.B., Theoret, H., and Pascual-Leone, A. (2003). Transcranial magnetic stimulation as an investigative tool in the study of visual function. Am. J. Optom. Physiol. Opt. 80, 356–368.Google Scholar

  • Miniussi, C., Paulus, W., and Rossini P.M. (2013). Transcranial Brain Stimulation. (London: CRC Press, Taylor & Francis Group).Google Scholar

  • Moreno, J.L., Holloway, T., Albizu, L., Sealfon, S.C., and González-Maeso, J. (2011). Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neurosci. Lett. 493, 76–79.Google Scholar

  • Muschamp, J.W., Regina, M.J., Hull, E.M., Winter, J.C., and Rabin, R.A. (2004). Lysergic acid diethylamide and [-]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex. Brain Res. 1023, 134 –140.Google Scholar

  • Nakano, M. (1989). Low-level chemiluminescence during lipid peroxidations and enzymatic reactions. J. Biolumin. Chemilum. 4, 231–240.Google Scholar

  • Narici, L., De Martino, A., Brunetti, V., Rinaldi, A., Sannita, W.G., and Paci, M. (2009). Radicals excess in the retina: a model for light flashes in space. Radiat. Meas. 44, 203–205.Google Scholar

  • Narici, L., Paci, M., Brunetti, V., Rinaldi, A., Sannita, W.G., and De Martino, A. (2012). Bovine rod rhodopsin. 1. Bleaching by luminescence in vitro by recombination of radicals from polyunsaturated fatty acids. Free Radic. Biol. Med. 53, 482–487.Google Scholar

  • Narici, L., Paci, M., Brunetti, V., Rinaldi, A., Sannita, W.G., Carozzo, S., and Demartino, A. (2013). Bovine rod rhodopsin: 2. Bleaching in vitro upon 12C ions irradiation as source of effects as light flash for patients and for humans in space. Int. J. Radiat. Biol. 89, 765–769.Google Scholar

  • Nichols, D.E. (2004). Hallucinogens. Pharmacol. Ther. 101, 131–181.Google Scholar

  • Oliveri, M. and Caltagirone, C. (2006). Suppression of extinction with TMS in humans: from healthy controls to patients. Behav. Neurol. 17, 163–167.Google Scholar

  • Passie, T., Halpern, J.H., Stichtenoth, D.O., Emrich, H.M., and Hintzen, A. (2008). The pharmacology of lysergic acid diethylamide: a review. CNS Neurosci. Ther. 14, 295 –314.Google Scholar

  • Pospisil, P., Prassad, A., and Rac, M. (2014). Role of reactive oxygen species in ultra-weak photon emission in biological systems. J. Photochem. Photobiol. B Biol. 139, 11–23.Google Scholar

  • Reznikov, I.u.E. (1981). Mechanophosphene in optic nerve changes [in Russian]. Oftalmol. Z. 36, 218–220.Google Scholar

  • Roseman, L., Sereno, M.I., Leech, R., Kaelen, M., Orban, C., McGonigle, J., Feilding, A., Nutt, D.J., and Carhart-Harris, R.L. (2016). LSD alters eyes-closed functional connectivity within the early visual cortex in a retinotopic fashion. Hum. Brain Mapp. DOI: 10.1002/hbm.23224.CrossrefGoogle Scholar

  • Salari, V., Valian, H., Bassereh, H., Bókkon, I., and Barkhordari, A. (2015). Ultraweak photon emission in the brain. J. Integr. Neurosci. 14, 419 –429.Google Scholar

  • Salari, V., Scholkmann, F., Bókkon, I., Shahbazi, F., and Tuszynski, J. (2016). The physical mechanism for retinal discrete dark noise: thermal activation or cellular ultraweak photon emission? PLoS ONE 11, e0148336.Google Scholar

  • Salminen-Vaparanta, N., Vanni, S., Noreika, V., Valiulis, V., Móró, L., Revonsuo, A., Oliverim, M., and Caltagironem, C. (2014). Suppression of extinction with TMS in humans: from healthy controls to subjective characteristics of TMS-induced phosphenes originating in human V1 and V2. Cereb. Cortex 24, 2751–2760.Google Scholar

  • Scholkmann, F., Kleiser, S., Metz, A.J., Zimmermann, R., Mata Pavia, J., Wolf, U., and Wolf, M. (2014). A review on continuous wave functional near-infrared spectroscopy and imaging instrumentation and methodology. Neuroimage 85, 6–27.Google Scholar

  • Scott, R.Q., Roschger, P., Devaraj, B., and Inaba, H. (1991). Monitoring a mammalian nuclear membrane phase transition by intrinsic ultraweak light emission. FEBS Lett. 285, 97–98.Google Scholar

  • Scruggs, J.L., Schmidt, D., and Deutch, A.Y. (2003). The hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) increases cortical extracellular glutamate levels in rats. Neurosci. Lett. 346, 137–140.Google Scholar

  • Sczesny-Kaiser, M., Beckhaus, K., Dinse, H.R., Schwenkreis, P., Tegenthoff, M., and Höffken, O. (2016). Repetitive transcranial direct current stimulation induced excitability changes of primary visual cortex and visual learning effects – a pilot study. Front. Behav. Neurosci. 10, 116.Google Scholar

  • Slawinski, J. (1988). Luminescence research and its relation to ultraweak cell radiation. Experientia 44, 559–571.Google Scholar

  • Snyder, S.H. and Reivich, M. (1966). Regional localization of LSD in monkey brain. Nature 209, 1093–1095.Google Scholar

  • Steele, R.H. (2003). Electromagnetic field generation by ATP-induced reverse electron transfer. Arch. Biochem. Biophys. 411, 1–18.Google Scholar

  • Sun, Y., Wang, C., and Dai, J. (2010). Biophotons as neural communication signals demonstrated by in situ biophoton autography. Photochem. Photobiol. Sci. 9, 315–322.Google Scholar

  • Takeda, M., Tanno, Y., Kobayashi, M., Usa, M., Ohuchi, N., Satomi, S., and Inaba, H. (1998). A novel method of assessing carcinoma cell proliferation by biophoton emission. Cancer Lett. 127, 155–160.Google Scholar

  • Tang, R. and Dai, J. (2014a). Biophoton signal transmission and processing in the brain. J. Photochem. Photobiol. B. 139, 71–75.Google Scholar

  • Tang, R. and Dai, J. (2014b). Spatiotemporal imaging of glutamate-induced biophotonic activities and transmission in neural circuits. PLoS ONE 9, e85643.Google Scholar

  • Tehovnik, E.J. and Slocum, W.M. (2007). Phosphene induction by microstimulation of macaque V1. Brain Res. Rev. 53, 337–343.Google Scholar

  • Tehovnik, E.J., Slocum, W.M., Smirnakis, S.M., and Tolias, A.S. (2009). Microstimulation of visual cortex to restore vision. Prog. Brain Res. 175, 347–375.Google Scholar

  • Tinsley, J.N., Molodtsov, M.I., Prevedel, R., Wartmann, D., Espigulé-Pons, J., Lauwers, M., and Vaziri, A. (2016). Direct detection of a single photon by humans. Nat. Commun. 7, 12172.Google Scholar

  • Vladimirov, IuA., L’vova, O.F., and Cheremisina, Z.P. (1966). Ultra-weak luminescence of mitochondria and its relation to enzymic oxidation of lipids. Biokhimiia 31, 507–515.Google Scholar

  • Wang, C., Bókkon, I., Dai, J., and Antal, I. (2011). Spontaneous and visible light-induced ultra-weak photon emission from rat eyes. Brain Res. 1369, 1–9.Google Scholar

  • Watts, B.P., Barnard, M., and Turrens, J.F. (1995). Peroxynitrite-dependent chemiluminescence of amino acids, proteins, and intact cells. Arch. Biochem. Biophys. 317, 324–330.Google Scholar

About the article

Received: 2016-08-03

Accepted: 2016-09-03

Published Online: 2016-10-12

Published in Print: 2017-01-01

Conflict of interest statement: The authors declare no conflicts of interest. The authors alone are responsible for the content.

Citation Information: Reviews in the Neurosciences, Volume 28, Issue 1, Pages 77–86, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2016-0047.

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