Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation

Raut, Sanket B; Marathe, Padmaja A; Eijk, Liza van; Eri, Rajaraman; Ravindran, Manoj; Benedek, David M.; Ursano, Robert J.; Canales, Juan J.; Johnson, Luke R.

doi:10.1016/j.pharmthera.2022.108195

Cited by 38 publications

(45 citation statements)

References 457 publications

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“…Central serotonergic pathways, which originate from the raphe nuclei, are spread to most brain structures, especially the cortex, modulating the activity of a wide range of neurons (e.g., glutamatergic and dopaminergic) and many mood-related processes (155). Among the plethora of 5-HT receptor subtypes, 5-HT 2A is the main subtype attributed to be responsible for such effects, as it has been shown to be involved in reconsolidation of contextual fear, object recognition and conditioned food aversion memories, which are processes affected in psychiatric disorders such as depression, PTSD, anxiety and even drug (156,157) as reviews]. Thereby, psychedelics may help with neurocircuitry rewiring addressing negative emotional processing and negativity bias, which can lead to more rumination, a common symptom of MDD (158).…”

Section: Psychedelicsmentioning

confidence: 99%

“…Among the plethora of 5-HT receptor subtypes, 5-HT 2 A is the main subtype attributed to be responsible for such effects, as it has been shown to be involved in reconsolidation of contextual fear, object recognition and conditioned food aversion memories, which are processes affected in psychiatric disorders such as depression, PTSD, anxiety and even drug addiction [see refs. ( 156 , 157 ) as reviews]. Thereby, psychedelics may help with neurocircuitry rewiring addressing negative emotional processing and negativity bias, which can lead to more rumination, a common symptom of MDD ( 158 ).…”

Section: Psychedelicsmentioning

confidence: 99%

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3,4-Methylenedioxy methamphetamine, synthetic cathinones and psychedelics: From recreational to novel psychotherapeutic drugs

et al. 2022

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The utility of classical drugs used to treat psychiatric disorders (e.g., antidepressants, anxiolytics) is often limited by issues of lack of efficacy, delayed onset of action or side effects. Psychoactive substances have a long history of being used as tools to alter consciousness and as a gateway to approach the unknown and the divinities. These substances were initially obtained from plants and animals and more recently by chemical synthesis, and its consumption evolved toward a more recreational use, leading to drug abuse-related disorders, trafficking, and subsequent banning by the authorities. However, these substances, by modulation of certain neurochemical pathways, have been proven to have a beneficial effect on some psychiatric disorders. This evidence obtained under medically controlled conditions and often associated with psychotherapy, makes these substances an alternative to conventional medicines, to which in many cases the patient does not respond properly. Such disorders include post-traumatic stress disease and treatment-resistant depression, for which classical drugs such as MDMA, ketamine, psilocybin and LSD, among others, have already been clinically tested, reporting successful outcomes. The irruption of new psychoactive substances (NPS), especially during the last decade and despite their recreational and illicit uses, has enlarged the library of substances with potential utility on these disorders. In fact, many of them were synthetized with therapeutic purposes and were withdrawn for concrete reasons (e.g., adverse effects, improper pharmacological profile). In this review we focus on the basis, existing evidence and possible use of synthetic cathinones and psychedelics (specially tryptamines) for the treatment of mental illnesses and the properties that should be found in NPS to obtain new therapeutic compounds.

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Section: Psychedelicsmentioning

confidence: 99%

Section: Psychedelicsmentioning

confidence: 99%

3,4-Methylenedioxy methamphetamine, synthetic cathinones and psychedelics: From recreational to novel psychotherapeutic drugs

et al. 2022

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“…In fear learning, the new engram consisting of a fear-provoking unconditioned stimulus (e.g., an explosion) and the conditioned context (e.g., the place where it happened and the people around the explosion) form a new active engram that consolidates into an allocated inactive engram via amygdala-hippocampal-cortical interactions [19,29,34,53]. During retrieval, the engram is destabilized, and there is a chance to modify it, for example, by extinction or reconstructing the content [54,55].…”

Section: Reconsolidation Of Fear Memories: a Potential Mechanism Of A...mentioning

confidence: 99%

“…From a theoretical and clinical point of view, it is indispensable to understand how psychedelics and other similar substances modify the reconsolidation of engrams at the intracellular level [53,71]. MDMA is a potent monoamine reuptake inhibitor.…”

Section: Reconsolidation Of Engrams and The Cellular Mechanism Of Psy...mentioning

confidence: 99%

“…In addition to blocking the serotonin, norepinephrine, and dopamine transporter in the presynaptic terminal, MDMA also inhibits type 2 vesicular monoamine transporter (VMAT-2), resulting in a marked increase of monoamine concentration in the synaptic cleft. In the postsynaptic membrane, MDMA activates type 1A and 2A serotonin receptors (5-HT1A, 5-HT2A) [53,72,73]. 5-HT2A agonism is a common mechanism of serotonergic psychedelics, including psilocybin ("magic mushroom", 4-phosphoryloxy-N, N-dimethyltryptamine) and Ayahuasca (N,N-dimethyltryptamine, DMT) [60].…”

Section: Reconsolidation Of Engrams and The Cellular Mechanism Of Psy...mentioning

confidence: 99%

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Trauma and Remembering: From Neuronal Circuits to Molecules

Kéri

2022

Life

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Individuals with posttraumatic stress disorder (PTSD) experience intrusions of vivid traumatic memories, heightened arousal, and display avoidance behavior. Disorders in identity, emotion regulation, and interpersonal relationships are also common. The cornerstone of PTSD is altered learning, memory, and remembering, regulated by a complex neuronal and molecular network. We propose that the essential feature of successful treatment is the modification of engrams in their unstable state during retrieval. During psychedelic psychotherapy, engrams may show a pronounced instability, which enhances modification. In this narrative review, we outline the clinical characteristics of PTSD, its multifaceted neuroanatomy, and the molecular pathways that regulate memory destabilization and reconsolidation. We propose that psychedelics, acting by serotonin-glutamate interactions, destabilize trauma-related engrams and open the door to change them during psychotherapy.

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