N,N-dimethyltryptamine reduces infarct size and improves functional recovery following transient focal brain ischemia in rats

Nardai, Sándor; László, Marcell; Szabó, Attila; Alpár, Alán; Hanics, János; Zahola, Péter; Merkely, Béla; Frecska, Ede; Nagy, Zoltán

doi:10.1016/j.expneurol.2020.113245

Cited by 52 publications

(48 citation statements)

References 22 publications

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“…Four studies (out of 16) investigated the relationship between biological effects of psychedelics (5-MeO-DMT, DMT, ayahuasca, LSD, and psilocybin), and behavioral changes (41,46,62,63). While the acute effects of a single dose of a psychedelic on biological markers and behavior were not assessed, the longterm effects of a single dose of psilocybin were investigated (62).…”

Section: Behaviormentioning

confidence: 99%

“…Moreover, a well-established in vivo technique to identify neurogenesis is immunostaining ["immunohistochemistry" (IHC)] with the mitotic marker 5bromo-2 ′ -deoxyuridine (BrdU) or Ki-67 to determine progenitor cell growth and division (proliferation) (45). These techniques can be used in healthy, intact animals or after surgical damage to the brain using suturing of an internal carotid artery to test neuroplasticity changes after drug administration and brain damage (46).…”

Section: Introductionmentioning

confidence: 99%

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Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics

2021

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Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies (n = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.

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Section: Behaviormentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics

2021

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“…DMT has been shown to reduce ischemic brain injury after middle cerebral artery occlusion (MCAO) through S1R dependent activity in murine models ( 27 ). Nardai et al ( 27 ) documented a significant reduction of the infarct core volume in rats at 24 h post MCAO with administration of DMT, as well as enhanced functional regeneration of the affected limb at 30 days post MCAO ( 27 ). These results are consistent with other in vitro studies showing cytoprotective effects of DMT against reperfusion injury ( 28 ).…”

Section: Neuroinflammationmentioning

confidence: 99%

Psychedelics for Brain Injury: A Mini-Review

Khan

Carter²,

Aggarwal

et al. 2021

Front. Neurol.

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Objective: Stroke and traumatic brain injury (TBI) are among the leading causes of disability. Even after engaging in rehabilitation, nearly half of patients with severe TBI requiring hospitalization are left with major disability. Despite decades of investigation, pharmacologic treatment of brain injury is still a field in its infancy. Recent clinical trials have begun into the use of psychedelic therapeutics for treatment of brain injury. This brief review aims to summarize the current state of the science's relevance to neurorehabilitation, and may act as a resource for those seeking to understand the precedence for these ongoing clinical trials.Methods: Narrative mini-review of studies published related to psychedelic therapeutics and brain injury.Results: Recent in vitro, in vivo, and case report studies suggest psychedelic pharmacotherapies may influence the future of brain injury treatment through modulation of neuroinflammation, hippocampal neurogenesis, neuroplasticity, and brain complexity.Conclusions: Historical data on the safety of some of these substances could serve in effect as phase 0 and phase I studies. Further phase II trials will illuminate how these drugs may treat brain injury, particularly TBI and reperfusion injury from stroke.

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“…DMT ( 9 ) also showed an interaction with moderate affinity at sigma receptors [ 54 ]. Indeed, the activity of DMT ( 9 ) at sigma-1 receptors mediates cytoprotective properties against hypoxic neuron injury in vitro, and in the reperfusion injury model in vivo [ 55 ].…”

Section: Binding Sites Of Hallucinogens In Vitromentioning

confidence: 99%

Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans

et al. 2021

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Hallucinogens are a loosely defined group of compounds including LSD, N,N-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with N1-([11C]-methyl)-2-bromo-LSD ([11C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [11C]-MBL specific binding was to serotonin 5-HT2A receptors. However, interactions at serotonin 5HT1A and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood–brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT2A/2C agonist N-(2[11CH3O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([11C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([15O]-water) or metabolism ([18F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research.

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N,N-dimethyltryptamine reduces infarct size and improves functional recovery following transient focal brain ischemia in rats

Cited by 52 publications

References 22 publications

Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics

Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics

Psychedelics for Brain Injury: A Mini-Review

Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans

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