Psilocybin-induced changes in brain network integrity and segregation correlate with plasma psilocin level and psychedelic experience

Madsen, Mogens; Stenbæk, Dea Siggaard; Arvidsson, Albin; Armand, Sophia; Marstrand-Joergensen, Maja Rou; Johansen, Sys Stybe; Línnet, Kristían; Ozenne, Brice; Knudsen, Gitte M.; Fisher, Patrick M.

doi:10.1016/j.euroneuro.2021.06.001

Cited by 63 publications

(69 citation statements)

References 69 publications

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“…Contrary to the MRI studies that report effects of using several distinct hallucinogenic drugs, the PET studies focused on the effects of the Psilocybin. These molecular studies reveal distinct 5-HT2AR receptor occupancy and density as a consequence of Psilocybin intake (Madsen et al, 2021). There was a decrease in receptor binding particularly in frontal regions.…”

Section: Resultsmentioning

confidence: 70%

“…In sum they assigned to the claustrum (dense in 5-HT 2A receptors ) a role in the psilocybin-induced disruption in both the DMN and taskpositive networks. Accordingly, Madsen et al (2021) found negative correlations between the DMN integrity and the plasma psilocin levels and subjective drug intensity. These results support the proposed theory of action for psychedelics to decrease the control of top-down structures and increase the excitability of areas involved in sensory, emotional and cognitive appraisal processes.…”

Section: Default Mode Networkmentioning

confidence: 87%

“…Furthermore, the review conducted by dos , suggested that hallucinogens increase introspection and positive mood by modulating brain activity in the fronto-temporo-parietooccipital cortices. Neuromodulatory changes induced by tryptamine psychedelics can give significant input to the study of neuropsychiatric conditions where similar patterns of activation or connectivity (Barrett et al, 2020b;Madsen et al, 2021) are found and to the implementation of new pharmacological or psychotherapeutic interventions taking advantage of this link between visual imagery, autobiographical memory and emotions (Barrett et al, 2020).…”

Section: Mental Imagerymentioning

confidence: 99%

“…In our analysis, a decreased connectivity within PCC/Precuneus, key components of the DMN, was observed. Regarding classic hallucinogens, studies revealed that psilocybin, LSD, and ayahuasca could decrease DMN functional integrity (Carhart-Harris et al, 2012, Carhart-Harris et al, 2016cPalhano-Fontes et al, 2015;Luppi et al, 2021;Madsen et al, 2021;Mason et al, 2021),. Barrett et al (2020b), recently proposed that Psilocybin alters default mode network integrity and fronto-parietal network modularity by reducing Claustrum functional connectivity with these circuits.…”

Section: Default Mode Networkmentioning

confidence: 99%

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The Effects of Tryptamine Psychedelics in the Brain: A meta-Analysis of Functional and Review of Molecular Imaging Studies

et al. 2021

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There is an increasing interest in the neural effects of psychoactive drugs, in particular tryptamine psychedelics, which has been incremented by the proposal that they have potential therapeutic benefits, based on their molecular mimicry of serotonin. It is widely believed that they act mainly through 5HT2A receptors but their effects on neural activation of distinct brain systems are not fully understood. We performed a quantitative meta-analysis of brain imaging studies to investigate the effects of substances within this class (e.g., LSD, Psilocybin, DMT, Ayahuasca) in the brain from a molecular and functional point of view. We investigated the question whether the changes in activation patterns and connectivity map into regions with larger 5HT1A/5HT2A receptor binding, as expected from indolaemine hallucinogens (in spite of the often reported emphasis only on 5HT2AR). We did indeed find that regions with changed connectivity and/or activation patterns match regions with high density of 5HT2A receptors, namely visual BA19, visual fusiform regions in BA37, dorsal anterior and posterior cingulate cortex, medial prefrontal cortex, and regions involved in theory of mind such as the surpramarginal gyrus, and temporal cortex (rich in 5HT1A receptors). However, we also found relevant patterns in other brain regions such as dorsolateral prefrontal cortex. Moreover, many of the above-mentioned regions also have a significant density of both 5HT1A/5HT2A receptors, and available PET studies on the effects of psychedelics on receptor occupancy are still quite scarce, precluding a metanalytic approach. Finally, we found a robust neuromodulatory effect in the right amygdala. In sum, the available evidence points towards strong neuromodulatory effects of tryptamine psychedelics in key brain regions involved in mental imagery, theory of mind and affective regulation, pointing to potential therapeutic applications of this class of substances.

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Section: Resultsmentioning

confidence: 70%

Section: Default Mode Networkmentioning

confidence: 87%

Section: Mental Imagerymentioning

confidence: 99%

Section: Default Mode Networkmentioning

confidence: 99%

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The Effects of Tryptamine Psychedelics in the Brain: A meta-Analysis of Functional and Review of Molecular Imaging Studies

et al. 2021

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“…Psychedelic stimulation of 5-HT 2A receptors increases excitability of neocortical pyramidal neurons, augmenting extracellular glutamate release in the prefrontal cortex, and thereby disrupting cortical rhythmicity and large-scale brain networks (Carhart-Harris et al, 2014;Varley et al, 2020;Vollenweider and Preller, 2020). This alteration of distributed neural processes manifests as increased synaptic plasticity and entropy, as well as reduced integrity of discrete brain networks (e.g., functional disintegration of the default-mode network [DMN]) and reduced segregation between networks (e.g., increased functional connectivity between the DMN and dorsal attention network) (De Gregorio et al, 2018;Preller et al, , 2020Madsen et al, 2021). Such changes in brain activity and connectivity lead to a flexible, functionally more connected brain during the psychedelic state (Petri et al, 2014;Tagliazucchi et al, 2016;Mason et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Psychedelics, Sociality, and Human Evolution

Arce¹,

Winkelman

2021

Front. Psychol.

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Our hominin ancestors inevitably encountered and likely ingested psychedelic mushrooms throughout their evolutionary history. This assertion is supported by current understanding of: early hominins’ paleodiet and paleoecology; primate phylogeny of mycophagical and self-medicative behaviors; and the biogeography of psilocybin-containing fungi. These lines of evidence indicate mushrooms (including bioactive species) have been a relevant resource since the Pliocene, when hominins intensified exploitation of forest floor foods. Psilocybin and similar psychedelics that primarily target the serotonin 2A receptor subtype stimulate an active coping strategy response that may provide an enhanced capacity for adaptive changes through a flexible and associative mode of cognition. Such psychedelics also alter emotional processing, self-regulation, and social behavior, often having enduring effects on individual and group well-being and sociality. A homeostatic and drug instrumentalization perspective suggests that incidental inclusion of psychedelics in the diet of hominins, and their eventual addition to rituals and institutions of early humans could have conferred selective advantages. Hominin evolution occurred in an ever-changing, and at times quickly changing, environmental landscape and entailed advancement into a socio-cognitive niche, i.e., the development of a socially interdependent lifeway based on reasoning, cooperative communication, and social learning. In this context, psychedelics’ effects in enhancing sociality, imagination, eloquence, and suggestibility may have increased adaptability and fitness. We present interdisciplinary evidence for a model of psychedelic instrumentalization focused on four interrelated instrumentalization goals: management of psychological distress and treatment of health problems; enhanced social interaction and interpersonal relations; facilitation of collective ritual and religious activities; and enhanced group decision-making. The socio-cognitive niche was simultaneously a selection pressure and an adaptive response, and was partially constructed by hominins through their activities and their choices. Therefore, the evolutionary scenario put forward suggests that integration of psilocybin into ancient diet, communal practice, and proto-religious activity may have enhanced hominin response to the socio-cognitive niche, while also aiding in its creation. In particular, the interpersonal and prosocial effects of psilocybin may have mediated the expansion of social bonding mechanisms such as laughter, music, storytelling, and religion, imposing a systematic bias on the selective environment that favored selection for prosociality in our lineage.

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The functional connectome of 3,4‐methyldioxymethamphetamine‐related declarative memory impairments

Coray,

Zimmermann,

Haugg

et al. 2023

Human Brain Mapping

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The chronic intake of 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) bears a strong risk for sustained declarative memory impairments. Although such memory deficits have been repeatedly reported, their neurofunctional origin remains elusive. Therefore, we here investigate the neuronal basis of altered declarative memory in recurrent MDMA users at the level of brain connectivity. We examined a group of 44 chronic MDMA users and 41 demographically matched controls. Declarative memory performance was assessed by the Rey Auditory Verbal Learning Test and a visual associative learning test. To uncover alterations in the whole brain connectome between groups, we employed a data‐driven multi‐voxel pattern analysis (MVPA) approach on participants' resting‐state functional magnetic resonance imaging data. Recent MDMA use was confirmed by hair analyses. MDMA users showed lower performance in delayed recall across tasks compared to well‐matched controls with moderate‐to‐strong effect sizes. MVPA revealed a large cluster located in the left postcentral gyrus of global connectivity differences between groups. Post hoc seed‐based connectivity analyses with this cluster unraveled hypoconnectivity to temporal areas belonging to the auditory network and hyperconnectivity to dorsal parietal regions belonging to the dorsal attention network in MDMA users. Seed‐based connectivity strength was associated with verbal memory performance in the whole sample as well as with MDMA intake patterns in the user group. Our findings suggest that functional underpinnings of MDMA‐related memory impairments encompass altered patterns of multimodal sensory integration within auditory processing regions to a functional heteromodal connector hub, the left postcentral gyrus. In addition, hyperconnectivity in regions of a cognitive control network might indicate compensation for degraded sensory processing.

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Psilocybin-induced changes in brain network integrity and segregation correlate with plasma psilocin level and psychedelic experience

Cited by 63 publications

References 69 publications

The Effects of Tryptamine Psychedelics in the Brain: A meta-Analysis of Functional and Review of Molecular Imaging Studies

The Effects of Tryptamine Psychedelics in the Brain: A meta-Analysis of Functional and Review of Molecular Imaging Studies

Psychedelics, Sociality, and Human Evolution

The functional connectome of 3,4‐methyldioxymethamphetamine‐related declarative memory impairments

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