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Phenomenology

Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation

Abstract

RATIONALE:
Accumulating evidence indicates that the mixed serotonin and dopamine receptor agonist lysergic acid diethylamide (LSD) induces an altered state of consciousness that resembles dreaming.
OBJECTIVES:
This study aimed to test the hypotheses that LSD produces dreamlike waking imagery and that this imagery depends on 5-HT2A receptor activation and is related to subjective drug effects.
METHODS:
Twenty-five healthy subjects performed an audiorecorded guided mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). Cognitive bizarreness of guided mental imagery reports was quantified as a standardised formal measure of dream mentation. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) questionnaire.
RESULTS:
LSD, compared with placebo, significantly increased cognitive bizarreness (p < 0.001). The LSD-induced increase in cognitive bizarreness was positively correlated with the LSD-induced loss of self-boundaries and cognitive control (p < 0.05). Both LSD-induced increases in cognitive bizarreness and changes in state of consciousness were fully blocked by ketanserin.
CONCLUSIONS:
LSD produced mental imagery similar to dreaming, primarily via activation of the 5-HT2A receptor and in relation to loss of self-boundaries and cognitive control. Future psychopharmacological studies should assess the differential contribution of the D2/D1 and 5-HT1A receptors to cognitive bizarreness.
Kraehenmann, R., Pokorny, D., Vollenweider, L., Preller, K. H., Pokorny, T., Seifritz, E., & Vollenweider, F. X. (2017). Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation. Psychopharmacology, 1-16. 10.1007/s00213-017-4610-0
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Disrupted integration of sensory stimuli with information about the movement of the body as a mechanism explaining LSD-induced experience

Abstract

LSD (lysergic acid diethylamide) is a model psychedelic drug used to study mechanism underlying the effects induced by hallucinogens. However, despite advanced knowledge about molecular mechanism responsible for the effects induced by LSD and other related substances acting at serotonergic 5-HT2a receptors, we still do not understand how these drugs trigger specific sensory experiences. LSD-induced experience is characterised by perception of movement in the environment and by presence of various bodily sensations such as floating in space, merging into surroundings and movement out of the physical body (the out-of-body experience). It means that a large part of the experience induced by the LSD can be simplified to the illusory movement that can be attributed to the self or to external objects. The phenomenology of the LSD-induced experience has been combined with the fact that serotonergic neurons provide all major parts of the brain with information about the level of tonic motor activity, occurrence of external stimuli and the execution of orienting responses. Therefore, it has been proposed that LSD-induced stimulation of 5-HT2a receptors disrupts the integration of the sensory stimuli with information about the movement of the body leading to perception of illusory movement.

Juszczak, G. R. (2017). Disrupted integration of sensory stimuli with information about the movement of the body as a mechanism explaining LSD-induced experience. Medical Hypotheses, 100, 94-97. 10.1016/j.mehy.2017.01.022
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Weak phantasy and visionary phantasy: the phenomenological significance of altered states of consciousness

Abstract

In this paper we discuss the definitional problems of altered states of consciousness and their potential relevance in phenomenological investigation. We suggest that visionary states or visionary phantasy working induced by psychedelics (VSs), as extraordinary types of altered states, are appropriate subjects for phenomenological analysis. Naturally, visionary states are not quite ordinary workings of the human mind, however certain cognitive psychological and evolutionary epistemological investigations show that they can give new insights into the nature of consciousness. Furthermore, we suggest that contemporary inquiries concerning altered states in consciousness studies give an opportunity to complete the contemporary phenomenological investigations of phantasy with the notion of visionary phantasy. Here we propose that the similarities and differences between Dieter Lohmar’s weak phantasy (which has a crucial role in empathy and typifying perception) and Benny Shanon’s concept of vision are precisely discernible, and, consequently, it may be possible that weak phantasy and visionary phantasy are situated on the two outermost poles of the colorful spectrum of phantasy activity.

Horváth, L., Szummer, C., & Szabo, A. (2017). Weak phantasy and visionary phantasy: the phenomenological significance of altered states of consciousness. Phenomenology and the Cognitive Sciences, 1-13. 10.1007/s11097-016-9497-4

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Phenomenology, Structure, and Dynamic of Psychedelic States

Abstract

Classic serotonergic hallucinogens or psychedelics produce an Altered States of Consciousness (ASC) that is characterized by profound alterations in sensory perception, mood, thought including the perception of reality, and the sense of self. Over the past years, there has been considerable progress in the search for invariant and common features of psychedelic states. In the first part of this review, we outline contemporary approaches to characterize the structure of ASCs by means of three primary etiology-independent dimensions including Oceanic Boundlessness, Anxious Ego Dissolution, and Visionary Restructuralization as well as by 11 lower order factors, all of which can be reliably measured by the Altered State of Consciousness questionnaire (APZ-OAV). The second part sheds light on the dynamic nature of psychedelic experiences. Frequently, psychedelic subjects progresses through different stages over time and levels of changes along a perception-hallucination continuum of increasing arousal and ego dissolution. We then review in detail the acute effects of psychedelics on sensory perception, emotion, cognition, creativity, and time perception along with possible neural mechanisms underlying them. The next part of this review outlines the influence of non-pharmacological factors (predictors) on the acute psychedelic experience, such as demographics, genetics, personality, mood, and setting, and also discusses some long-term effects succeeding the acute experience. The last part presents some recent concepts and models attempting to understand different facets of psychedelic states of consciousness from a neuroscientific perspective.

Preller, K. H., & Vollenweider, F. X. (2016). Phenomenology, Structure, and Dynamic of Psychedelic States. 10.1007/7854_2016_459

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Serotonergic Hallucinogen-Induced Visual Perceptual Alterations

Abstract

Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT), are famous for their capacity to temporally and profoundly alter an individual’s visual experiences. These visual alterations show consistent attributes despite large inter- and intra-individual variances. Many reports document a common perception of colors as more saturated, with increased brightness and contrast in the environment (“Visual Intensifications”). Environmental objects might be altered in size (“Visual illusions”) or take on a modified and special meaning for the subject (“Altered self-reference”). Subjects may perceive light flashes or geometrical figures containing recurrent patterns (“Elementary imagery and hallucinations”) influenced by auditory stimuli (“Audiovisual synesthesia”), or they may envision images of people, animals, or landscapes (“Complex imagery and hallucinations”) without any physical stimuli supporting their percepts. This wide assortment of visual phenomena suggests that one single neuropsychopharmacological mechanism is unlikely to explain such vast phenomenological diversity. Starting with mechanisms that act at the cellular level, the key role of 5-HT2A receptor activation and the subsequent increased cortical excitation will be considered. Next, it will be shown that area specific anatomical and dynamical features link increased excitation to the specific visual contents of hallucinations. The decrease of alpha oscillations by hallucinogens will then be introduced as a systemic mechanism for amplifying internal-driven excitation that overwhelms stimulus-induced excitations. Finally, the hallucinogen-induced parallel decrease of the N170 visual evoked potential and increased medial P1 potential will be discussed as key mechanisms for inducing a dysbalance between global integration and early visual gain that may explain several hallucinogen-induced visual experiences, including visual hallucinations, illusions, and intensifications.

Kometer, M., & Vollenweider, F. X. (2016). Serotonergic Hallucinogen-Induced Visual Perceptual Alterations. 10.1007/7854_2016_461
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Measuring the subjective: revisiting the psychometric properties of three rating scales that assess the acute effects of hallucinogens

Abstract

Objective: In the present study we explored the psychometric properties of three widely used questionnaires to assess the subjective effects of hallucinogens: the Hallucinogen Rating Scale (HRS), the Mystical Experience Questionnaire (MEQ), and the Addiction Research Center Inventory (ARCI).

Methods: These three questionnaires were administered to a sample of 158 subjects (100 men) after taking ayahuasca, a hallucinogen whose main active component is N,N-dimethyltryptamine (DMT). A confirmatory factorial study was conducted to check the adjustment of previous data obtained via theoretical proposals. When this was not possible, we used an exploratory factor analysis without restrictions, based on tetrachoric and polychoric matrices and correlations.

Results: Our results sparsely match the theoretical proposals of the authors, perhaps because previous studies have not always employed psychometric methods appropriate to the data obtained. However, these data should be considered preliminary, pending larger samples to confirm or reject the proposed structures obtained.

Conclusions: It is crucial that instruments of sufficiently precise measurement are utilized to make sense of the information obtained in the study of the subjective effects of psychedelic drugs.

Bouso, J. C., Pedrero‐Pérez, E. J., Gandy, S., & Alcázar‐Córcoles, M. Á. (2016). Measuring the subjective: revisiting the psychometric properties of three rating scales that assess the acute effects of hallucinogens. Human Psychopharmacology: Clinical and Experimental, 31(5), 356-372. 10.1002/hup.2545
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Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans

Abstract

Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants, Banisteriopsis caapi and Psychotria viridis. It contains the psychedelic 5-HT2A and sigma-1 agonist N,N-dimethyltryptamine (DMT) plus β-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties. Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor, the molecular target of classical psychedelics, this has not been tested experimentally. Here we wished to study the contribution of the 5-HT2A receptor to the neurophysiological and psychological effects of ayahuasca in humans. We measured drug-induced changes in spontaneous brain oscillations and subjective effects in a double-blind randomized placebo-controlled study involving the oral administration of ayahuasca (0.75mg DMT/kg body weight) and the 5-HT2A antagonist ketanserin (40mg). Twelve healthy, experienced psychedelic users (5 females) participated in four experimental sessions in which they received the following drug combinations: placebo+placebo, placebo+ayahuasca, ketanserin+placebo and ketanserin+ayahuasca. Ayahuasca induced EEG power decreases in the delta, theta and alpha frequency bands. Current density in alpha-band oscillations in parietal and occipital cortex was inversely correlated with the intensity of visual imagery induced by ayahuasca. Pretreatment with ketanserin inhibited neurophysiological modifications, reduced the correlation between alpha and visual effects, and attenuated the intensity of the subjective experience. These findings suggest that despite the chemical complexity of ayahuasca, 5-HT2A activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans.

Valle, M., Maqueda, A. E., Rabella, M., Rodríguez-Pujadas, A., Antonijoan, R. M., Romero, S., … & Feilding, A. (2016). Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans. European Neuropsychopharmacology. http://dx.doi.org/10.1016/j.euroneuro.2016.03.012

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The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity

Abstract

Stimulation of serotonergic neurotransmission by psilocybin has been shown to shift emotional biases away from negative towards positive stimuli. We have recently shown that reduced amygdala activity during threat processing might underlie psilocybin’s effect on emotional processing. However, it is still not known whether psilocybin modulates bottom-up or top-down connectivity within the visual-limbic-prefrontal network underlying threat processing. We therefore analyzed our previous fMRI data using dynamic causal modeling and used Bayesian model selection to infer how psilocybin modulated effective connectivity within the visual–limbic–prefrontal network during threat processing. First, both placebo and psilocybin data were best explained by a model in which threat affect modulated bidirectional connections between the primary visual cortex, amygdala, and lateral prefrontal cortex. Second, psilocybin decreased the threat-induced modulation of top-down connectivity from the amygdala to primary visual cortex, speaking to a neural mechanism that might underlie putative shifts towards positive affect states after psilocybin administration. These findings may have important implications for the treatment of mood and anxiety disorders.

Kraehenmann, R., Schmidt, A., Friston, K., Preller, K. H., Seifritz, E., & Vollenweider, F. X. (2015). The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity. NeuroImage: Clinical. https://dx.doi.org/10.1016/j.nicl.2015.08.009
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LSD: a new treatment emerging from the past

Introduction

Psychedelics fell from medical grace nearly half a century ago, but recent activity suggests that some researchers have “high hopes” for their return. 1,2 Over 60 years ago, Albert Hofmann at Sandoz Pharmaceutical Laboratories in Switzerland first synthesized lysergic acid diethylamide (LSD) and personally experienced its effects (later described as a voyage into madness or a chemically induced psychosis) in 1943. Hofmann’s drug opened up a new era of hallucinogenic research. Over the next 15 years, more than a thousand articles on the use of LSD appeared in medical and scientific publications. In 1957, that work gave rise to the term “psychedelic” to describe a mind-manifesting response, described by some as an experience that brought to light matters that had previously been part of the unconscious [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][…]

Dyck, E. (2015). LSD: a new treatment emerging from the past. CMAJ: Canadian Medical Association journal= journal de l’Association medicale canadienne. https://dx.doi.org/10.1503/cmaj.141358

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22 May - Delivering Effective Psychedelic Clinical Trials

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