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Engineering Safer Psychedelics for Treating Addiction.

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TLDR
Tabernanthalog (TBG) appears to have long-lasting therapeutic effects in preclinical models relevant to alcohol and opioid addiction, and the implications of these results for the development of addiction treatments, as well as the next steps for advancing TBG and related non-hallucinogenic psychoplastogens as addiction therapeutics as discussed by the authors.
Abstract
Addiction is best described as a disorder of maladaptive neuroplasticity involving the simultaneous strengthening of reward circuitry that drives compulsive drug seeking and weakening of circuits involved in executive control over harmful behaviors. Psychedelics have shown great promise for treating addiction, with many people attributing their therapeutic effects to insights gained while under the influence of the drug. However, psychedelics are also potent psychoplastogens-molecules capable of rapidly re-wiring the adult brain. The advent of non-hallucinogenic psychoplastogens with anti-addictive properties raises the intriguing possibility that hallucinations might not be necessary for all therapeutic effects of psychedelic-based medicines, so long as the underlying pathological neural circuitry can be remedied. One of these non-hallucinogenic psychoplastogens, tabernanthalog (TBG), appears to have long-lasting therapeutic effects in preclinical models relevant to alcohol and opioid addiction. Here, we discuss the implications of these results for the development of addiction treatments, as well as the next steps for advancing TBG and related non-hallucinogenic psychoplastogens as addiction therapeutics.

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Journal ArticleDOI

Biochemical Mechanisms Underlying Psychedelic-Induced Neuroplasticity.

David P. Olson
- 21 Jan 2022 - 
TL;DR: A review of the biochemical signaling pathways activated by psychedelics and related neuroplasticity-promoting molecules, with an emphasis on key unanswered questions can be found in this paper .
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Rearing behaviour in the mouse behavioural pattern monitor distinguishes the effects of psychedelics from those of lisuride and TBG

TL;DR: This article examined the effects of phenylalkylamine and indoleamine psychedelics on locomotor activity and exploratory behavior using the mouse Behavioural Pattern Monitor (BPM).
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Psilocybin in neuropsychiatry: a review of its pharmacology, safety, and efficacy

TL;DR: The potential for use of psilocybin and psilocin as a treatment agent in neuropsychiatry has been investigated in this article , where the potential for harm is also assessed.
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Psilocybin in Neuropsychiatry: a review of its pharmacology, safety and efficacy.

TL;DR: The potential for use of psilocybin and psilocin as a treatment agent in neuropsychiatry has been investigated in this article and the potential for harm is also assessed.
Journal ArticleDOI

Psychotherapeutic and neurobiological processes associated with ayahuasca: A proposed model and implications for therapeutic use

TL;DR: In this paper, a model of psychotherapeutic processes associated with the consumption of ayahuasca is proposed, which is based on qualitative data from a large cross-sectional study of drinkers.
References
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Journal ArticleDOI

Identification of Psychoplastogenic N,N-Dimethylaminoisotryptamine (isoDMT) Analogues through Structure-Activity Relationship Studies.

TL;DR: This work has discovered several key features of the psychoplastogenic pharmacophore and used this information to develop N,N-dimethylaminoisotryptamine (isoDMT) Psychoplastogens that are easier to synthesize, have improved physicochemical properties, and possess reduced hallucinogenic potential as compared to their DMT counterparts.
Journal ArticleDOI

The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs

TL;DR: This review will cover recent advances in both the biosynthesis and chemical synthesis of iboga alkaloids as well as their use as next-generation neurotherapeutics and historical context for the discoveries of the past decade is provided.
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An analog of psychedelics restores functional neural circuits disrupted by unpredictable stress.

TL;DR: In this article, the effects of mild stress on cortical neuronal circuit activity patterns and demonstrate that TBG combats the detrimental effects of stress by modulating basal and stimulus-dependent neural activity in cortical networks.
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