THE RELATIONSHIP BETWEEN QEEG AND PSYCHOPATHOLOGY DURING PSILOCYBIN INTOXICATION Filip Tylš, Tomáš Páleníček, Jakub Korčák, Michaela Viktorinová, Peter Zach, Dominika Prokopcová, Renata Androvičová, Martin Brunovský National Institute of Mental Health (Czech Republic), Czech Psychedelic Society, 3rd Medical Faculty (Charles University in Prague)
[email protected]
INTRODUCTION The serotonergic hallucinogen psilocybin has profound effects on the human mind, which can be characterized by alteration in perception, thinking disorder and strong emotional salience. The mechanism of action of psilocybin in the brain can be characterized by agonism of serotonergic receptors on three structural levels of the brain (Fig. 1), leading to complex changes in the interaction of neuronal networks. The character of the altered state of consciousness induced by hallucinogens is hardly predictable; ; however, the environment in which psilocybin is administered (the setting) plays a very important role. Recent works have shown that psilocybin-induced altered states of consciousness have a potential in the treatment of some psychiatric disorders. The purpose of this study is to characterize the psychopathology and brain activity during psilocybin intoxication in human volunteers by QEEG. Fig.1: The mechanism of psilocybin action in the brain
In a double-blind placebo-controlled design, 20 healthy volunteers were administered an oral dose of psilocybin (0.26 mg/kg, average dose 18.7 mg) in a comfortable decorated living room-like setting (Fig. 2). We asessed the pharmacokinetics and the effects on several physiological measures. Furthermore, the phenomenology of intoxication was assesed by observers (Brief Psychiatric Rating Scale - BPRS) and subjectively by volunteers themselves (Altered state of consciousness Scale - ASCS). All subjects underwent resting-state EEG recordings at baseline and after 50-60, 90-100, 180-190 minutes after intoxication. The effect of intoxication was evaluated on EEG power spectra and on current density using sLORETA (standardized low-resolution brain electromagnetic tomography).
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Dread of ego dissolution (AIA) = ego desintegration, loss of autonomy and self-control, excitement, anxiety, paranoia, feelings of danger.
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Oceanic boundlessness (OSE) = loss of boundaries, ecstatic feelings, happiness, cosmic experineces, blissfull and mystic states
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Fig.4: Phenomenology of intoxication: BPRS
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Fig.5: Phenomenology of intoxication: ASCS
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Fig.3: Pharmacokinetics of psilocin after peroral psilocybin
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RESULTS I - phenomenology and physiology The effects of psilocybin peaked in 60 minutes and subsided after 6 hours (Fig.3). A significant increase of psychopathology was documented by BPRS (Fig 4) and ASCS (Fig. 5) . Total BPRS score (r = 0.526, p = 0.044) and „thought disturbance“ (r = 0.598, p = 0.018) correlated positively with psilocin serum concentration (not shown). Psilocybin induced mydriasis, increase in both systolic and diastolic blood pressure and heart rate (Fig. 6).
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Fig.2: Experimental setting for present study in our laboratory
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RESULTS II - quantitative electroecephalography
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Fig.6: Psilocybin - heart rate and blood pressure
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Psilocybin induced a decrement in absolute theta, alpha and low beta spectral power and strong increase in gamma power compared to placebo (Fig. 7). The LORETA analysis revealed the source of decreased alpha in midline parietal structures and occipital lobes; however, the increase in higher frequencies was pronounced in large temporal areas (Fig. 8). The decrement of theta to alpha in the these structures correlated positively with ASCS score OSE (Fig. 9).
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Fig.7: Absolute mean spectral power 50-60 (A) , 80-90 (B) and 180-190 after administration of psilocybin 0.26 mg / kg p.o. vs placebo Fig.9: LORETA activtity correlation with ASCS subscale OSE
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delta 1-4 Hz theta 4-8 Hz alpha 8-12 Hz beta 12-25 Hz high beta 25-30 Hz low gamma 30-40 Hz high gamma 40-50 Hz
We confirmed the safety and beneficial effects of psilocybin administration under controlled experimental conditions. The decrement of EEG theta/alpha activity was observed mainly in brain structures involved in the default mode network (DMN), which is thought to represent introspective processes. We found negative correlation between LORETA activity and subjectively perceived loss of boundaries - positively experienced ego-dissolution. Strong activation of large association brain areas (increase in gamma) may be an underlying process of perceptual and cognitive changes. These findings will help facilitate future clinical trials using psychedelics in patients. The transformative experience of ego dissolution is an important part of psychedelic therapy, therefore the decrement of basic activity in DMN may be used as a biomarker of treatment efficacy.
Fig.8: LORETA source localization 50-60 after administration of psilocybin 0.26 mg / kg p.o. versus placebo This study was supported by the projects IGA MHCR NT/13897, “National Institute of Mental Health (NIMH–CZ)”, grant number ED2.1.00/03.0078, and by the European Regional Development Fund.
