The Domino Effect: Ed Domino’s early studies of Psychoactive Drugs

Denomme, Nicholas

doi:10.1080/02791072.2018.1506599

Cited by 45 publications

(12 citation statements)

References 13 publications

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“…Despite the considerable progress in this area, one key remaining question is the link between ketamine’s side effects and its antidepressant effects. In initial testing in the 1960s, individuals receiving ketamine described feeling “spaced out” or “dreaming” when administered subanesthetic doses 23 . Ed Domino, who was largely responsible for introducing ketamine into clinical practice as an anesthetic, described individuals who received ketamine patients as “disconnected from their environment somehow” 23 , prompting the coining of the phrase “dissociative anesthetic” 23 .…”

Section: Introductionmentioning

confidence: 99%

“…In initial testing in the 1960s, individuals receiving ketamine described feeling “spaced out” or “dreaming” when administered subanesthetic doses 23 . Ed Domino, who was largely responsible for introducing ketamine into clinical practice as an anesthetic, described individuals who received ketamine patients as “disconnected from their environment somehow” 23 , prompting the coining of the phrase “dissociative anesthetic” 23 . Ketamine thus has a longstanding association with dissociation, broadly defined as altered consciousness and awareness of the self, environment, and reality.…”

Section: Introductionmentioning

confidence: 99%

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The role of dissociation in ketamine’s antidepressant effects

2020

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Ketamine produces immediate antidepressant effects and has inspired research into next-generation treatments. Ketamine also has short term dissociative effects, in which individuals report altered consciousness and perceptions of themselves and their environment. However, whether ketamine’s dissociative side effects are necessary for its antidepressant effects remains unclear. This perspective examines the relationship between dissociative effects and acute and longer-lasting antidepressant response to ketamine and other N-methyl-D-aspartate (NMDA) receptor antagonists. Presently, the literature does not support the conclusion that dissociation is necessary for antidepressant response to ketamine. However, further work is needed to explore the relationship between dissociation and antidepressant response at the molecular, biomarker, and psychological levels.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of dissociation in ketamine’s antidepressant effects

2020

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“…Ketamine is an anesthetic drug first synthesized in 1962 at the Parke-Davis pharmaceutical company following the discovery of phencyclidine (PCP), another anesthetic belonging to the arylcyclohexylamine chemical class [13]. At that time, several different drugs sharing a similar structure were screened in search of an optimal candidate for further development-preferably one that lacked the unwanted psychotropic effects of PCP.…”

Section: What Is Ketamine?mentioning

confidence: 99%

Ketamine—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms

Kohtala

2021

Pharmacol. Rep

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Over the past 50 years, ketamine has solidified its position in both human and veterinary medicine as an important anesthetic with many uses. More recently, ketamine has been studied and used for several new indications, ranging from chronic pain to drug addiction and post-traumatic stress disorder. The discovery of the rapid-acting antidepressant effects of ketamine has resulted in a surge of interest towards understanding the precise mechanisms driving its effects. Indeed, ketamine may have had the largest impact for advancements in the research and treatment of psychiatric disorders in the past few decades. While intense research efforts have been aimed towards uncovering the molecular targets underlying ketamine’s effects in treating depression, the underlying neurobiological mechanisms remain elusive. These efforts are made more difficult by ketamine’s complex dose-dependent effects on molecular mechanisms, multiple pharmacologically active metabolites, and a mechanism of action associated with the facilitation of synaptic plasticity. This review aims to provide a brief overview of the different uses of ketamine, with an emphasis on examining ketamine’s rapid antidepressant effects spanning molecular, cellular, and network levels. Another focus of the review is to offer a perspective on studies related to the different doses of ketamine used in antidepressant research. Finally, the review discusses some of the latest hypotheses concerning ketamine’s action.

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“…Dissociation is characterized by disruptions in and fragmentation of the usually integrated functions of consciousness, memory, identity, body awareness, and perception of the self and the environment (American Psychiatric Association 2013). A well-established pharmacological manipulation of dissociation is intravenous infusion of ketamine, a non-competitive N-methyl-Daspartate glutamate receptor (NMDAR) antagonist often coined as "dissociative drug" (Denomme 2018;Ballard and Zarate 2020). After initial observations of altered consciousness and awareness of the self and environment during administration of subanesthetic doses of ketamine in the 1960s (Denomme 2018), many studies in healthy and clinical populations have replicated ketamine's dissociative effects (e.g., Krystal 1994; Short et al 2018;Duek et al 2019;Dehestani et al 2022).…”

Section: Introductionmentioning

confidence: 99%

Effects of a Dissociative Drug on Fronto-Limbic Resting-State Functional Connectivity in Individuals with Posttraumatic Stress Disorder: A Randomized Controlled Pilot Study

Danböck¹,

Duek²,

Ben‐Zion³

et al. 2023

Preprint

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Rationale. A subanesthetic dose of ketamine, a non-competitive N-methyl-D-aspartate glutamate receptor (NMDAR) antagonist, elicits dissociation in individuals with posttraumatic stress disorder (PTSD), who also often suffer from chronic dissociative symptoms in daily life. Theses debilitating symptoms have not only been linked to worse PTSD trajectories, but also to increased resting-state functional connectivity (RSFC) between medial prefrontal cortex (mPFC) and amygdala, supporting the conceptualization of dissociation as emotion overmodulation. Yet, as studies were observational, causal evidence is lacking. Objectives. To examine the effect of ketamine, a dissociative drug, on RSFC between mPFC subregions and amygdala in individuals with PTSD.Methods. Twenty-six individuals with PTSD received either ketamine (0.5mg/kg; n = 12) or the control drug midazolam (0.045mg/kg; n = 14) during functional magnetic resonance imaging (fMRI). RSFC between amygdala and mPFC subregions, i.e., ventromedial PFC (vmPFC), dorsomedial PFC (dmPFC) and anterior-medial PFC (amPFC), was assessed at baseline and during intravenous drug infusion.Results. Contrary to pre-registered predictions, ketamine did not promote a greater increase in RSFC between amygdala and mPFC subregions from baseline to infusion compared to midazolam. Instead, ketamine elicited a stronger transient decrease in vmPFC-amygdala RSFC compared to midazolam. Conclusions. Experimental findings expand previous observational work on the association between dissociation and fronto-limbic RSFC in individuals with PTSD and call for further research, and potentially, a more differentiated view on the neurobiological underpinning of dissociative phenomena in PTSD.

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The Domino Effect: Ed Domino’s early studies of Psychoactive Drugs

Cited by 45 publications

References 13 publications

The role of dissociation in ketamine’s antidepressant effects

The role of dissociation in ketamine’s antidepressant effects

Ketamine—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms

Effects of a Dissociative Drug on Fronto-Limbic Resting-State Functional Connectivity in Individuals with Posttraumatic Stress Disorder: A Randomized Controlled Pilot Study

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