Effects of <i>N</i>,<i>N</i>-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression

Cameron, Lindsay P.; Benson, Charlie J; Dunlap, Lee E.; Olson, David E.

doi:10.1021/acschemneuro.8b00134

Cited by 130 publications

(171 citation statements)

References 79 publications

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“…First, psilocybin has cue-potentiated fear on the first extinction trial, and DMT has shown post-acute anxiogenic effects. However, both substances have been shown to generally facilitate the extinction of fear conditioned by a cue, but not by context, which may have been mediated by its action on the amygdala [60,61]. This two-way effect is consistent with the observation that the effects of psychedelics in humans are heavily dependent on the context in which they are used.…”

Section: Animal Studiessupporting

confidence: 78%

Natural Psychoplastogens As Antidepressant Agents

Vrankova

2020

Molecules

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Increasing prevalence and burden of major depressive disorder presents an unavoidable problem for psychiatry. Existing antidepressants exert their effect only after several weeks of continuous treatment. In addition, their serious side effects and ineffectiveness in one-third of patients call for urgent action. Recent advances have given rise to the concept of psychoplastogens. These compounds are capable of fast structural and functional rearrangement of neural networks by targeting mechanisms previously implicated in the development of depression. Furthermore, evidence shows that they exert a potent acute and long-term positive effects, reaching beyond the treatment of psychiatric diseases. Several of them are naturally occurring compounds, such as psilocybin, N,N-dimethyltryptamine, and 7,8-dihydroxyflavone. Their pharmacology and effects in animal and human studies were discussed in this article.

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Section: Animal Studiessupporting

confidence: 78%

Natural Psychoplastogens As Antidepressant Agents

Vrankova

2020

Molecules

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“…According to the published literature, the antidepressant potential of psilocin and psilocybin has not previously been investigated in an animal model of depression. Some studies have reported related effects of serotonergic psychedelics, such as normalisation of learning behaviour by lysergic acid diethylamide in the olfactory bulbectomy model of depression (Buchborn et al, 2014), antidepressant-like effects of N,N-dimethyltryptamine (DMT) (Cameron et al, 2018), and Ayahuasca (Amazonian brew that contains DMT) (Pic-Taylor et al, 2015) in the rodent FST. Other studies have investigated the therapeutic potential of psilocin or psilocybin in animal models of other psychiatric disorders such as anxiety (Horsley et al, 2018), OCD (Sard et al, 2005), and PTSD (Catlow et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat

Jefsen

Højgaard

Christiansen

et al. 2019

Acta Neuropsychiatr.

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Objective:Psilocybin is a serotonin receptor agonist with a therapeutic potential for treatment-resistant depression and other psychiatric illnesses. We investigated whether the administration of psilocybin had an antidepressant-like effect in a rat model of depression.Methods:Using the Flinders Sensitive Line (FSL) rat model of depression, we assessed the antidepressant-like effect of psilocin and psilocybin, measured as a reduction in immobility time in the forced swim test (FST). We measured locomotor activity in an open field test (OFT) to control for stimulant properties of the drugs. We performed a set of experiments to test different doses, treatment paradigms, and timing of the tests in relation to the drug administration.Results:Psilocin and psilocybin showed no effect on immobility, struggling, or swimming behaviour in the FST and no effect on locomotor activity in the OFT. FSL rats did show significantly more immobility than their control strain, the Flinders Resistant Line, as expected.Conclusion:Psilocin and psilocybin showed no antidepressant-like effect in the FSL rats, despite a positive effect in humans. This suggests that other animal models of depression and other behavioural tests may be more appropriate for translational studies in the effects of psilocybin.

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“…29,33,38 The action of DMT at 5-HT 1A receptors and TAARs affords a rationale for exploring the efficacy of DMT in treating anxiety and depression, and recent rat behavioral models support this hypothesis. 20,39 Moreover, neuroplastic effects linked to antidepressant drug activity (increases in dendritic spine formation, changes in spine morphology, increased synapse formation), as well as neuroprotective, immunosuppressive, anti-ischemic, and anti-inflammatory responses, have been associated with the action of DMT and its congener 5-MeO-DMT at sigma-1 receptors. [40][41][42][43] It has been suggested that cross-talk among serotonin receptors, sigma-1 receptors, and toll-like receptors may underlie common immunomodulatory effects of psychedelic agents.…”

Section: Pharmacologymentioning

confidence: 99%

“…The 13 C resonances are in close agreement with previously reported 13 C peak values. 37,39,53,65,75,76 Figure S5). 54…”

Section: Synthesesmentioning

confidence: 99%

Synthesis and characterization of high‐purity N,N‐dimethyltryptamine hemifumarate for human clinical trials

Cozzi

Daley²

2020

Drug Testing and Analysis

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Since 2006, there has been a resurgent interest in the pharmacology and therapeutics of psychedelic drugs. Psilocybin, the 4-phosphoryl ester of N,Ndimethyltryptamine (DMT), has been studied most often, but DMT itself is also appealing because of its brief but profound psychological effects and its presence as an endogenous substance in mammalian brain. Although there have been a few studies of ayahuasca, a DMT-containing water infusion, only one human study with pure DMT has been reported since the early 2000s. Newly planned clinical trials to assess the safety and efficacy of DMT in humans with major depressive disorders require high-purity water-soluble DMT for intravenous administration. Accordingly, we synthesized and characterized DMT hemifumarate for these upcoming studies. The synthetic approach of Speeter and Anthony was slightly modified to gain some efficiency in time. In particular, this is the first known report to use aluminum hydride, generated in situ from lithium aluminum hydride, to reduce the intermediate 2-(1Hindol-3-yl)-N,N-dimethyl-2-oxoacetamide to DMT. A quench protocol was developed to produce a good yield of exceptionally pure free base DMT upon workup, which was then converted to the hemifumarate salt. Analysis of the final product included differential scanning calorimetry, thermogravimetric analysis, gas chromatographymass spectrometry (GC-MS), 1 H and 13 C nuclear magnetic resonance spectroscopy, high-performance liquid chromatography, residual solvent analysis by GC headspace sampling, X-ray powder diffraction analysis, and residual lithium analysis by inductively coupled plasma-mass spectrometry. The DMT hemifumarate was minimally 99.9% pure, with no significant impurities or residual solvents, thus meeting regulatory standards for administration to humans.

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Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression

Cited by 130 publications

References 79 publications

Natural Psychoplastogens As Antidepressant Agents

Natural Psychoplastogens As Antidepressant Agents

Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat

Synthesis and characterization of high‐purity N,N‐dimethyltryptamine hemifumarate for human clinical trials

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