Biological Psychiatry
April 26, 2014
Rainer Kraehenmann, Katrin H. Preller, Milan Scheidegger et al.
325 citations
A double-blind, randomized, crossover study in 25 healthy volunteers found that a single dose of psilocybin (0.16 mg/kg) reduced amygdala reactivity to negative and neutral stimuli, measured with functional magnetic resonance imaging, compared with placebo. The reduction in right amygdala reactivity to negative stimuli was linked to an increase in positive mood, assessed with the Positive and Negative Affect Schedule and the State-Trait Anxiety Inventory. These findings suggest psilocybin may dampen neural responses to negative emotional cues and improve mood, which could be relevant for treating conditions like major depression where amygdala hyperactivity and negative mood states are common.
Proceedings of the National Academy of Sciences
April 18, 2016
Katrin H. Preller, Thomas Pokorny, Andreas Hock et al.
175 citations
Social ties are crucial for health, but psychiatric patients often face social rejection, and heightened reactivity to exclusion affects disorder development and treatment. The neuromodulatory substrates of rejection are largely unknown. Psilocybin, a serotonin 5-HT2A/1A receptor agonist, reduces processing of negative stimuli, but its effect on negative social interactions was unclear. In a double-blind, randomized, cross-over study with 21 healthy volunteers, psilocybin (0.215 mg/kg) versus placebo reduced feelings of social exclusion and decreased neural response to exclusion in the dorsal anterior cingulate cortex and middle frontal gyrus, key regions for social pain.
European Neuropsychopharmacology
January 22, 2016
Thomas Pokorny, Katrin H. Preller, Rainer Kraehenmann et al.
148 citations
Psilocybin dose-dependently induces an altered state of consciousness with changes in perception, mood, thought, and self-awareness, mainly through 5-HT2A receptor activation. In a double-blind, within-subject study with 36 healthy participants, the partial 5-HT1A agonist buspirone (20 mg) significantly reduced psilocybin-induced (170 µg/kg) visual hallucinations and, at a trend level, feelings of oceanic boundlessness, derealization, and depersonalization. The non-hallucinogenic 5-HT2A/1A agonist ergotamine (3 mg) had no effect. These results suggest that modulating 5-HT1A receptor activity may help treat visual hallucinations in psychiatric and neurological disorders.
Frontiers in Pharmacology
November 8, 2017
Rainer Kraehenmann, Dan Pokorný, Helena Aicher et al.
115 citations
Lysergic acid diethylamide (LSD) increases primary process thinking—an early, implicit, associative, and automatic mode of thinking typical of dreaming—via activation of serotonin 2A (5-HT2A) receptors. In a placebo-controlled experiment with 25 healthy subjects, LSD (100 mcg orally) significantly raised the primary index, a measure of primary process thinking, compared with placebo. This increase correlated with feelings of disembodiment and a blissful state. Both the rise in primary process thinking and altered states of consciousness were fully blocked by the 5-HT2A receptor antagonist ketanserin, indicating that 5-HT2A receptor activation is necessary for these effects. Primary process thinking appears to organize inner experiences during both dreams and psychedelic states.
NeuroImage Clinical
August 22, 2015
Rainer Kraehenmann, André Schmidt, Karl Friston et al.
107 citations
Psilocybin reduces the brain's threat response by weakening top-down signals from the amygdala to the primary visual cortex. Using dynamic causal modeling of fMRI data, researchers found that psilocybin decreased the threat-induced modulation of this specific connection within the visual-limbic-prefrontal network. This neural mechanism may help explain how psilocybin shifts emotional processing away from negative toward positive stimuli, which could be relevant for treating mood and anxiety disorders.
NeuroImage
July 12, 2017
Candace R. Lewis, Katrin H. Preller, Rainer Kraehenmann et al.
105 citations
Psilocybin, the active compound in psychedelic mushrooms, acts on serotonin receptors. In a placebo-controlled, double-blind study with 58 healthy participants, two oral doses of psilocybin (0.160 mg/kg and 0.215 mg/kg) were given. After adjusting for global brain perfusion, psilocybin increased relative perfusion in right frontal and temporal regions and the anterior insula, while decreasing it in left parietal and temporal cortices and left subcortical regions. However, absolute perfusion was reduced across frontal, temporal, parietal, and occipital lobes, and in bilateral amygdalae, anterior cingulate, insula, striatal regions, and hippocampi. The findings show consistency with both the hyperfrontal hypothesis and recent studies showing decreased perfusion, depending on analysis method.
European Neuropsychopharmacology
April 25, 2018
O. Grimm, Rainer Kraehenmann, Katrin H. Preller et al.
94 citations
Psilocybin, a psychedelic 5-HT2A receptor agonist, modulates emotion processing networks in the brain. In a double-blind crossover study with 18 healthy volunteers, psilocybin increased reaction time to emotional faces and decreased connectivity between the amygdala and the striatum during angry face discrimination, and between the amygdala and the frontal pole during happy face discrimination. No effect was seen during fearful face discrimination. These findings suggest psilocybin alters connectivity in key emotion-processing hubs, which may underlie its antidepressant effects, though further research is needed to link connectivity changes to therapeutic outcomes.
Current Neuropharmacology
June 19, 2017
Rainer Kraehenmann
90 citations
The overlap between dreaming and psychedelic states suggests that psychedelics temporarily produce dreamlike subjective experiences, which may lead to lasting improvements in psychosocial functioning and well-being. Future clinical research should investigate how the acute dreamlike effects of psychedelics relate to therapeutic outcomes.
Human Brain Mapping
February 25, 2016
Milan Scheidegger, A Henning, Martin Walter et al.
78 citations
Ketamine, an NMDA receptor antagonist, reduced neural reactivity in the bilateral amygdalo-hippocampal complex during emotional stimulation in 23 healthy subjects. Reduced amygdala reactivity to negative pictures correlated with resting-state connectivity to the pregenual anterior cingulate cortex. The intensity of psychedelic alterations of consciousness during ketamine infusion predicted the reduction in neural responsivity to negative but not to positive or neutral stimuli. These findings suggest that modulation of glutamate-responsive circuits, associated with a shift in emotional bias and reduced amygdalo-hippocampal reactivity, may represent an early mechanism to restore disrupted neurobehavioral homeostasis in major depressive disorder.
European Neuropsychopharmacology
March 8, 2017
Oliver G. Bosch, Michael M. Havranek, A Baumberger et al.
22 citations
Gamma-hydroxybutyrate (GHB), a drug used for narcolepsy and abused recreationally, has prosexual effects in healthy men. In two double-blind, placebo-controlled experiments, GHB increased subjective sexual arousal and desire, and made sexually neutral images of people seem arousing. Brain scans showed that GHB boosted activity in reward regions like the nucleus accumbens when viewing erotic pictures, and increased connectivity between the nucleus accumbens and the ventromedial prefrontal cortex. The findings indicate GHB enhances hedonic sexual functioning and lowers the threshold for perceiving erotic cues by sensitizing mesolimbic reward pathways.
European Neuropsychopharmacology
September 25, 2014
Rainer Kraehenmann, Katrin H. Preller, Erich Seifritz et al.
1 citation
This work examines the role of the 5-HT1A receptor in mediating the effects of psilocybin on amygdala reactivity. Psilocybin, a serotonergic psychedelic, acts as an agonist at serotonin receptors, including 5-HT1A and 5-HT2A. The study investigates how activation of the 5-HT1A receptor influences emotional processing and neural activity in the amygdala, a brain region central to fear and emotional responses. Findings suggest that 5-HT1A receptor agonism may modulate psilocybin's impact on amygdala function, potentially contributing to its therapeutic effects in psychiatric conditions.
Psychopharmacology
July 1, 2017
Rainer Kraehenmann, Dan Pokorný, Leonie Vollenweider et al.
Lysergic acid diethylamide (LSD) produces waking mental imagery that resembles dreaming, an effect driven by activation of the 5-HT2A receptor. In a study with 25 healthy subjects, LSD (100 mcg orally) significantly increased cognitive bizarreness in guided mental imagery reports compared with placebo, and this increase correlated with a loss of self-boundaries and cognitive control. Both the imagery changes and altered state of consciousness were fully blocked by the 5-HT2A antagonist ketanserin (40 mg orally). The findings suggest that LSD-induced dreamlike imagery depends specifically on 5-HT2A receptor activation.