Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine

Dakic, Vanja; Nascimento, Juliana; Sartore, Rafaela C.; Maciel, Roseli Martins Tristão; Araújo, Dráulio Barros de; Ribeiro, Sidarta; Martins-de-Souza, Daniel; Rehen, Stevens

doi:10.1101/108159

Cited by 5 publications

(5 citation statements)

References 85 publications

(101 reference statements)

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“…The use of serotonergic psychedelics is associated with decreased psychological suffering and lower suicide rates (17). These substances have also been shown to induce neural plasticity and synaptogenesis both in vitro and in vivo (18)(19)(20), and are therefore likely to enhance learning capacity. Indeed, psychedelics have been shown to enhance memory consolidation when administered after fear learning or novel object exploration (21,22).…”

Section: Introductionmentioning

confidence: 99%

d-Lysergic acid diethylamide has major potential as a cognitive enhancer

Silva

Ornelas

Marcos

et al. 2019

Preprint

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Psychedelic agonists of serotonin receptors induce neural plasticity and synaptogenesis, but their potential to enhance learning remains uncharted. Here we show that a single dose of d-LSD, a potent serotonergic agonist, increased novel object preference in young and adult rats several days after treatment. d-LSD alone did not increase preference in old animals, but could rescue it to young levels when followed by a 6-day exposure to enriched environment (EE).Mass spectrometry-based proteomics in human brain organoids treated with d-LSD showed upregulation of proteins from the presynaptic active zone. A computational model of synaptic connectivity in the hippocampus and prefrontal cortex suggests that d-LSD enhances novelty preference by combining local synaptic changes in mnemonic and executive regions, with alterations of longrange synapses. Better pattern separation within EE explained its synergy with d-LSD in rescuing novelty preference in old animals. These results advance the use of d-LSD in cognitive enhancement.

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Section: Introductionmentioning

confidence: 99%

d-Lysergic acid diethylamide has major potential as a cognitive enhancer

Silva

Ornelas

Marcos

et al. 2019

Preprint

Self Cite

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“…These changes in neuronal structure are accompanied by changes in protein expression. Using human cerebral organoids, Rehen and co‐workers performed proteomic studies to demonstrate that 5‐MeO‐DMT modulates levels of proteins associated with microtubule dynamics and cytoskeleton rearrangement (Dakic et al, 2017).…”

Section: Effects Of Psychedelics On Neuronal Growth and Survival Sign...mentioning

confidence: 99%

“…Taken together, these studies support the role of 5-HT 2A receptors in both innate and adaptive immune responses. Alongside these studies, other research groups have demonstrated that the naturally occurring psychedelics DMT and 5-MeO-DMT produce immunomodulatory effects through inhibition and down-regulation of the NF-κB signaling pathway in human iPSC-derived cerebral organoids (Dakic et al, 2017), and inhibition of LPS-induced inflammation in cultured human monocyte-derived dendritic cells (Szabo et al, 2014).…”

Section: Effec Ts Of Psychedeli C S On the Immune Sys Temmentioning

confidence: 99%

Psychedelic‐inspired approaches for treating neurodegenerative disorders

Saeger

Olson

2021

Journal of Neurochemistry

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“…Moreover, TAARs have been associated with pathological neuroadaptations associated with prolonged exposure to addictive drugs (e.g., alcohol, heroin, cocaine, etc.). Consequently, this molecular target might partially explain 5-MeO-DMTs promising neurorestorative and neuroprotective effects (Dakic, 2017). Because 5-MeO-DMT is able to target these receptors it might be able to regulate the pathological neurological adaptions, for example those caused by various substance (and possibly behavioural) addictions (cf.…”

Section: -Meo-dmt: An Endogenous Catalyst For Creativitymentioning

confidence: 99%

5-Methoxy-N,N-dimethyltryptamine: An Ego-Dissolving Endogenous Neurochemical Catalyst of Creativity

Germann

2019

Act Nerv Super

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5-Methoxy-N,N-dimethyltryptamine (acronymized as 5-MeO-DMT) is sui generis among the numerous naturally-occurring psychoactive substances due to its unparalleled ego-dissolving effects which can culminate in a state of nondual consciousness (which is phenomenologically similar to transformative peak experiences described in various ancient contemplative traditions, e.g., Advaita Vedānta, Mahāyāna Buddhism). The enigmatic molecule is endogenous to the human brain and has profound psychological effects which are hitherto only very poorly understood due to the absence of scientifically controlled human experimental trials. Its exact neuronal receptor binding profile is a matter of ongoing scientific research, however, its remarkable psychoactivity is presumably mediated via agonism of the 5-HT2A (serotonin) receptor subtype. Anthropological/ethnopharmacological evidence indicates that various cultures utilized 5-MeO-DMT containing plants for medicinal, psychological, and spiritual purposes for millennia. In this paper we argue that this naturally occurring serotonergic compound could be fruitfully utilized as a neurochemical research tool which has the potential to significantly advance our understanding of the cognitive and neuronal processes which underpin cognition and creativity (downregulation of the default-mode network, increased neuronal functional connectivity, etc.). An eclectic interdisciplinary perspective is adopted, and we present converging evidence from a plurality of sources in support of this conjecture. Specifically, we suggest that 5-MeO-DMT has great potential in this respect due to its incommensurable capacity to completely disintegrate self-referential cognitive/neuronal processes (viz., "ego death"). The importance of unbiased systematic scientific research on naturally occurring endogenous psychoactive compounds is discussed from a Jamesian radical empiricism perspective and potential scenarios of abuse are discussed (particularly in the context of military torture).

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Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine

Cited by 5 publications

References 85 publications

d-Lysergic acid diethylamide has major potential as a cognitive enhancer

d-Lysergic acid diethylamide has major potential as a cognitive enhancer

Psychedelic‐inspired approaches for treating neurodegenerative disorders

5-Methoxy-N,N-dimethyltryptamine: An Ego-Dissolving Endogenous Neurochemical Catalyst of Creativity

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