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K. Preller

Effect of psilocybin on empathy and moral decision-making

June 16, 2017 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Background:

Impaired empathic abilities lead to severe negative social consequences and influence the development and treatment of several psychiatric disorders. Furthermore, empathy has been shown to play a crucial role in moral and prosocial behaviour. Although the serotonin (5-HT) system has been implicated in modulating empathy and moral behaviour, the relative contribution of the various 5-HT receptor subtypes is still unknown.

Methods:

We investigated the acute effect of psilocybin (0.215mg/kg p.o.) in healthy human subjects on different facets of empathy and hypothetical moral decision-making using the Multifaceted Empathy Test (MET) (n=32) and the Moral Dilemma Task (MDT) (n=24).

Results:

Psilocybin significantly increased emotional, but not cognitive empathy compared to placebo, and the increase in implicit emotional empathy was significantly associated with psilocybin-induced changed meaning of percepts. In contrast, moral decision-making remained unaffected by psilocybin.

Conclusions:

These findings provide first evidence that psilocybin has distinct effects on social cognition by enhancing emotional empathy but not moral behaviour. Furthermore, together with previous findings psilocybin appears to promote emotional empathy presumably via activation of 5-HT2A/1A receptors suggesting that targeting 5-HT2A/1A receptors has implications for potential treatment of dysfunctional social cognition.

Pokorny, T., Preller, K. H., Kometer, M., Dziobek, I., & Vollenweider, F. X. (2017). Effect of psilocybin on empathy and moral decision-making. International Journal of Neuropsychopharmacology. 10.1093/ijnp/pyx047

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Changes in Resting-State Global Brain Connectivity in LSD-Induced Altered States of Consciousness are Attributable to the 5-HT2A Receptor

April 29, 2017 / LSD, Neuroscience, Papers, Psychology, Publications / By / , , , , ,

Preller, K., Schleifer, C., Stämpfli, P., Krystal, J., Vollenweider, F., & Anticevic, A. (2017). 951-Changes in Resting-State Global Brain Connectivity in LSD-Induced Altered States of Consciousness are Attributable to the 5-HT2A Receptor. Biological Psychiatry, 81(10), S385. 10.1016/j.biopsych.2017.02.677
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Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation

April 7, 2017 / LSD, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

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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The Fabric of Meaning and Subjective Effects in LSD-Induced States Depend on Serotonin 2A Receptor Activation

January 26, 2017 / LSD, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / By / , , , , , ,

Abstract

A core aspect of the human self is the attribution of personal relevance to everyday stimuli enabling us to experience our environment as meaningful [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”][1]. However, abnormalities in the attribution of personal relevance to sensory experiences are also critical features of many psychiatric disorders [2 and 3]. Despite their clinical relevance, the neurochemical and anatomical substrates enabling meaningful experiences are largely unknown. Therefore, we investigated the neuropharmacology of personal relevance processing in humans by combining fMRI and the administration of the mixed serotonin (5-HT) and dopamine receptor (R) agonist lysergic acid diethylamide (LSD), well known to alter the subjective meaning of percepts, with and without pretreatment with the 5-HT2AR antagonist ketanserin. General subjective LSD effects were fully blocked by ketanserin. In addition, ketanserin inhibited the LSD-induced attribution of personal relevance to previously meaningless stimuli and modulated the processing of meaningful stimuli in cortical midline structures. These findings point to the crucial role of the 5-HT2AR subtype and cortical midline regions in the generation and attribution of personal relevance. Our results thus increase our mechanistic understanding of personal relevance processing and reveal potential targets for the treatment of psychiatric illnesses characterized by alterations in personal relevance attribution.

Preller, K. H., Herdener, M., Pokorny, T., Planzer, A., Kraehenmann, R., Stämpfli, P., … & Vollenweider, F. X. (2017). The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation. Current Biology, 27(3), 451-457. 10.1016/j.cub.2016.12.030
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Phenomenology, Structure, and Dynamic of Psychedelic States

December 27, 2016 / Papers, Psychology, Publications / By / ,

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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Effects of serotonin 2A/1A receptor stimulation on social exclusion processing

April 18, 2016 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Social ties are crucial for physical and mental health. However, psychiatric patients frequently encounter social rejection. Moreover, an increased reactivity to social exclusion influences the development, progression, and treatment of various psychiatric disorders. Nevertheless, the neuromodulatory substrates of rejection experiences are largely unknown. The preferential serotonin (5-HT) 2A/1A receptor agonist, psilocybin (Psi), reduces the processing of negative stimuli, but whether 5-HT2A/1A receptor stimulation modulates the processing of negative social interactions remains unclear. Therefore, this double-blind, randomized, counterbalanced, cross-over study assessed the neural response to social exclusion after the acute administration of Psi (0.215 mg/kg) or placebo (Pla) in 21 healthy volunteers by using functional magnetic resonance imaging (fMRI) and resting-state magnetic resonance spectroscopy (MRS). Participants reported a reduced feeling of social exclusion after Psi vs. Pla administration, and the neural response to social exclusion was decreased in the dorsal anterior cingulate cortex (dACC) and the middle frontal gyrus, key regions for social pain processing. The reduced neural response in the dACC was significantly correlated with Psi-induced changes in self-processing and decreased aspartate (Asp) content. In conclusion, 5-HT2A/1A receptor stimulation with psilocybin seems to reduce social pain processing in association with changes in self-experience. These findings may be relevant to the normalization of negative social interaction processing in psychiatric disorders characterized by increased rejection sensitivity. The current results also emphasize the importance of 5-HT2A/1A receptor subtypes and the Asp system in the control of social functioning, and as prospective targets in the treatment of sociocognitive impairments in psychiatric illnesses.

Preller, K. H., Pokorny, T., Hock, A., Kraehenmann, R., Stämpfli, P., Seifritz, E., … & Vollenweider, F. X. (2016). Effects of serotonin 2A/1A receptor stimulation on social exclusion processing. Proceedings of the National Academy of Sciences, 201524187. http://dx.doi.org/10.1073/pnas.1524187113

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Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience

January 22, 2016 / Mushrooms / Psilocybin, Neuroscience, Papers, Publications / By / , , ,

Abstract

The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20 mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3 mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (p<0.001), which was mostly driven by a reduction of the VR item cluster scores for elementary and complex visual hallucinations. Further, buspirone also reduced the main scale score for Oceanic Boundlessness including derealisation and depersonalisation phenomena at a trend level (p=0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases.

Pokorny, T., Preller, K. H., Kraehenmann, R., & Vollenweider, F. X. (2016). Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience. European Neuropsychopharmacology. http://dx.doi.org/10.1016/j.euroneuro.2016.01.005
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The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity

August 22, 2015 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , , ,

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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The Effect of 5-HT2A/1a Agonist Treatment On Social Cognition, Empathy, and Social Decision-making

March 28, 2015 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , ,

Abstract

Social cognition is a crucial factor influencing development, progress, and treatment of psychiatric disorders. However, social cognition skills are insufficiently targeted by current treatment approaches. In particular, patients suffering from depression show an increased negative reaction to social exclusion and deficits in empathy. The 5HT-1A/2A receptor agonist psilocybin has previously been shown to reduce the neural response to negative emotional stimuli. However, it is not known if this extends to negative social interaction and whether 5HT-1A/2A receptor stimulation induces changes in empathy. Given the clear need for improved treatment of socio-cognitive functioning in psychiatric disorders, it is important to better understand the neuronal and neuromodulatory substrates of social cognition.

In a double-blind, randomized, cross-over design we therefore investigated the neural response to ostracism after the acute administration of psilocybin (0.215mg/kg) and placebo in healthy volunteers using fMRI. Furthermore, we assessed cognitive and emotional empathy using the Multifaceted Empathy Test.

The neural response to social exclusion in the ACC – a brain region associated with ‘social pain”- was reduced after psilocybin administration compared to placebo. Furthermore, emotional empathy was enhanced after treatment with psilocybin while no significant differences were found in cognitive empathy.

These results show that the 5HT-1A/2A receptor subtypes play an important role in the modulation of socio-cognitive functioning and therefore may be relevant for the treatment of social cognition deficits in psychiatric disorders. In particular, they may be important for the normalization of empathy deficits and increased negative reaction to social exclusion in depressed patients.

Preller, K. H., Pokorny, T., Krähenmann, R., Dziobek, I., Stämpfli, P., & Vollenweider, F. X. (2015). The Effect of 5-HT2A/1a Agonist Treatment On Social Cognition, Empathy, and Social Decision-making. European Psychiatry, 30, 22. http://dx.doi.org/10.1016/S0924-9338(15)30017-1
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Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

November 29, 2014 / LSD, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / By / , , , , , ,

Abstract

Background

After no research in humans for >40 years, there is renewed interest in using lysergic acid diethylamide (LSD) in clinical psychiatric research and practice. There are no modern studies on the subjective and autonomic effects of LSD, and its endocrine effects are unknown. In animals, LSD disrupts prepulse inhibition (PPI) of the acoustic startle response, and patients with schizophrenia exhibit similar impairments in PPI. However, no data are available on the effects of LSD on PPI in humans.

Methods

In a double-blind, randomized, placebo-controlled, crossover study, LSD (200 μg) and placebo were administered to 16 healthy subjects (8 women, 8 men). Outcome measures included psychometric scales; investigator ratings; PPI of the acoustic startle response; and autonomic, endocrine, and adverse effects.

Results

Administration of LSD to healthy subjects produced pronounced alterations in waking consciousness that lasted 12 hours. The predominant effects induced by LSD included visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization phenomena. Subjective well-being, happiness, closeness to others, openness, and trust were increased by LSD. Compared with placebo, LSD decreased PPI. LSD significantly increased blood pressure, heart rate, body temperature, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine. Adverse effects produced by LSD completely subsided within 72 hours. No severe acute adverse effects were observed.

Conclusions

In addition to marked hallucinogenic effects, LSD exerts methylenedioxymethamphetamine-like empathogenic mood effects that may be useful in psychotherapy. LSD altered sensorimotor gating in a human model of psychosis, supporting the use of LSD in translational psychiatric research. In a controlled clinical setting, LSD can be used safely, but it produces significant sympathomimetic stimulation.

Schmid, Y., Enzler, F., Gasser, P., Grouzmann, E., Preller, K. H., Vollenweider, F. X., … & Liechti, M. E. (2014). Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects. Biological psychiatry. https://dx.doi.org/doi:10.1016/j.biopsych.2014.11.015
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