Pharmacological strategies for post-traumatic stress disorder (PTSD): From animal to clinical studies

Gasparyan, Ani; Navarro, Daniela; Navarrete, Francisco

doi:10.1016/j.neuropharm.2022.109211

Cited by 19 publications

(12 citation statements)

References 235 publications

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“…Methylone is a structurally similar, beta-ketone analog of MDMA, so the similarities and differences between the two compounds should be considered when putting our new data into context. MDMA-assisted psychotherapy significantly alleviates symptoms of PTSD ( 7 ), a condition for which antidepressants (sertraline and paroxetine) are the only approved treatments ( 33 ). In contrast to methylone, MDMA has been well-studied using both binge-dosing paradigms and lower therapeutic doses in preclinical species.…”

Section: Discussionmentioning

confidence: 99%

Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity

et al. 2023

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IntroductionSelective serotonin reuptake inhibitor (SSRI) antidepressants represent first-line pharmacological treatment for a variety of neuropsychiatric illnesses, including major depressive disorder (MDD), anxiety, and post-traumatic stress disorder (PTSD), which show high rates of comorbidity. SSRIs have a delayed onset of action. Most patients do not show significant effects until 4–8 weeks of continuous treatment, have impairing side effects and as many as 40% of patients do not respond. Methylone (3,4-methylenedioxy-N-methylcathinone; MDMC, βk-MDMA, M1) is a rapid-acting entactogen that showed significant benefit in a clinical case series of PTSD patients and was well-tolerated in two Phase 1 studies of healthy volunteers. Based on these early observations in humans, in the current study we tested the hypothesis that methylone has antidepressant-like and anxiolytic effects in preclinical tests.MethodsFor all studies, 6–8-week-old male Sprague Dawley rats (N = 6–16) were used. We employed the Forced Swim Test (FST), a classic and widely used screen for antidepressants, to explore the effects of methylone and to probe dose-response relationships, durability of effect, and potential interactions with combined SSRI treatment. We compared the effect of methylone with the prototypical SSRI fluoxetine.ResultsThree doses of fluoxetine (10 mg/kg) given within 24 h before FST testing caused a 50% reduction in immobility compared with controls that lasted less than 24 h. In contrast, a single dose of methylone (5–30 mg/kg) administered 30 min prior to testing produced a rapid, robust, and durable antidepressant-like response in the FST, greater in magnitude than fluoxetine. Immobility was reduced by nearly 95% vs. controls and effects persisted for at least 72 h after a single dose (15 mg/kg). Effects on swimming and climbing behavior in the FST, which reflect serotonergic and noradrenergic activity, respectively, were consistent with studies showing that methylone is less serotoninergic than MDMA. Fluoxetine pretreatment did not change methylone’s antidepressant-like effect in the FST, suggesting the possibility that the two may be co-administered. In addition, methylone (5–30 mg/kg) exhibited anxiolytic effects measured as increased time spent in the center of an open field.DiscussionTaken together, and consistent with initial clinical findings, our study suggests that methylone may have potential for treating depression and anxiety.

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Section: Discussionmentioning

confidence: 99%

Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity

et al. 2023

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“…There are currently no approved pharmacotherapies for cocaine, amphetamine, cannabis, or benzodiazepine use disorders. Sertraline and paroxetine, the only two approved medications for PTSD, have shown only modest effects in PTSD (18). Similarly, while multiple behavioral therapies for combined PTSD and substance use disorders have been explored (i.e., cognitive behavioral therapy, mindfulness based therapies, and prolonged exposure therapy), treatment outcomes remain limited (19).…”

Section: Open Access Edited Bymentioning

confidence: 99%

Perspectives on the therapeutic potential of MDMA: A nation-wide exploratory survey among substance users

Jones

2023

Front. Psychiatry

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BackgroundAlcohol and other substance use disorders are commonly associated with post-traumatic stress disorder (PTSD), and the presence of these comorbidities is associated with worse treatment outcomes. Additionally, disparities in substance and PTSD prevalence have been associated with minority races and ethnicities, and minorities have been shown to be less likely to engage in treatment. Psychedelic-assisted treatments, including 3,4-methylenedioxymethamphetamine (MDMA), have shown preliminary trans-diagnostic effectiveness, however it is unknown how individuals with substance use disorders view the therapeutic potential of MDMA therapy. Previous studies have also shown that minority races and ethnicities are under-represented in the MDMA trials, leading to concerns about inequitable access to clinical treatment.MethodsTo explore demographic characteristics related to patient-level perspectives on the therapeutic potential of MDMA-assisted therapy, this study describes data from a nationwide, cross-sectional survey of 918 individuals self-reporting criteria consistent with alcohol or substance use disorders.ResultsOverall, a majority of individuals reported support for medical research of MDMA (68.1%), belief that MDMA-assisted therapy might be a useful treatment (70.1%), and willingness to try MDMA-assisted therapy if it were determined to be an appropriate treatment for them (58.8%). No race or ethnicity differences were found in support for further research or belief in effectiveness, however there were small disparities in terms of willingness to try MDMA-assisted therapy and concerns related to use of this treatment approach.ConclusionThese results provide insights and future directions as the field of psychedelic-assisted therapy seeks to provide equitable access to clinical care and to diversify research participation.

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“…Effective drugs for the treatment of these disorders are tricyclic antidepressants (TCAs; Zohar and Westenberg, 2007 ; Puetz et al, 2015 ), reversible and irreversible monoamine oxidase inhibitors (MAOIs; Liebowitz et al, 1990 ; Chamberlain and Baldwin, 2021 ), benzodiazepines (Steenen et al, 2016 ), selective serotonin reuptake inhibitor (SSRIs; Zohar and Westenberg, 2007 ), and antiepileptic drugs (Berlin, 2007 ; Gasparyan et al, 2022 ). TCAs and MAOIs are effective for treatment but have high side effects, thus limiting their use.…”

Section: Perspective On the Treatment Of Trauma And Fear-related Diso...mentioning

confidence: 99%

Update on neurobiological mechanisms of fear: illuminating the direction of mechanism exploration and treatment development of trauma and fear-related disorders

Liu

Zhi

et al. 2023

Front. Behav. Neurosci.

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Fear refers to an adaptive response in the face of danger, and the formed fear memory acts as a warning when the individual faces a dangerous situation again, which is of great significance to the survival of humans and animals. Excessive fear response caused by abnormal fear memory can lead to neuropsychiatric disorders. Fear memory has been studied for a long time, which is of a certain guiding effect on the treatment of fear-related disorders. With continuous technological innovations, the study of fear has gradually shifted from the level of brain regions to deeper neural (micro) circuits between brain regions and even within single brain regions, as well as molecular mechanisms. This article briefly outlines the basic knowledge of fear memory and reviews the neurobiological mechanisms of fear extinction and relapse, which aims to provide new insights for future basic research on fear emotions and new ideas for treating trauma and fear-related disorders.

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Pharmacological strategies for post-traumatic stress disorder (PTSD): From animal to clinical studies

Cited by 19 publications

References 235 publications

Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity

Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity

Perspectives on the therapeutic potential of MDMA: A nation-wide exploratory survey among substance users

Update on neurobiological mechanisms of fear: illuminating the direction of mechanism exploration and treatment development of trauma and fear-related disorders

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