Potential Of Ketamine Research Articles

Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm.

Traditional treatments for post-traumatic stress disorder (PTSD) often show limited success with high dropout. Ketamine, an N-methyl-D-aspartate antagonist known for rapid antidepressant effects, has decreased PTSD symptoms in some studies but not in others. Administering ketamine in ways that parallel psychedelic-assisted treatments-including preparatory, integration, sensory immersion, and psychotherapy sessions-could decrease PTSD symptoms meaningfully. A retrospective sample of 117 screened outpatients with elevated PTSD Checklist for DSM-5 (PCL-5) scores received intravenous ketamine in supportive environments. The protocol included preparation, intention-setting, and integration sessions accompanying at least six administrations. Administration sessions included eye shades and evocative music paralleling typical psychedelic therapy trials. Mean PCL scores decreased from 52.54 (SD = 12.01) to 28.78 (SD = 16.61), d = 1.64. Patients tolerated treatment well, with no serious adverse events. Covariates, including age, gender, days between PCL assessments, number of psychiatric medications, and suicidal ideation were not significant moderators; concomitant psychotherapy did reach significance, d = 0.51. Of the 117 patients' final PCL scores, 88 (75.21%) measures suggested clinically meaningful improvement and 72 (61.54%) suggested remission of PTSD symptoms. Intravenous ketamine in supportive environments, with hallmarks of psychedelic therapy, preceded large reductions in PTSD symptoms. These results highlight ketamine's potential when delivered in this manner, suggesting environmental factors might account for some variation seen in previous work. Given the molecule's cost, minimal interaction with other psychiatric medications, and legal status, intravenous ketamine in a psychedelic paradigm may be a promising option for PTSD unresponsive to other treatments.

Ketamine in Substance Use Disorder Treatment: A Narrative Review.

Substance use disorder (SUD) continues to pose a significant global health challenge, necessitating innovative and effective therapeutic interventions. Ketamine, traditionally recognized for its anesthetic properties, has emerged as a novel and promising avenue for the treatment of SUD. This narrative review critically examines the current body of literature surrounding the use of ketamine in various forms and settings for individuals grappling with substance abuse. The review explores the neurobiological underpinnings of ketamine's potential therapeutic effects in SUD, shedding light on its impact on glutamatergic neurotransmission, neuroplasticity, and reward pathways. Special attention is given to the psychotropic and dissociative properties of ketamine, exploring their implications for both therapeutic outcomes and patient experience. Ultimately, this review aims to provide a comprehensive overview of the current state of knowledge regarding ketamine's role in the treatment of SUD, emphasizing the need for further research and clinical exploration. As we navigate the complex terrain of addiction medicine, understanding the nuances of ketamine's potential in SUD holds promise for the development of more effective and personalized therapeutic strategies.

Empowering understanding: navigating consent to ketamine treatment in adolescent mental health.

The rising prevalence of mental health disorders in adolescents, compounded by treatment resistance, underscores the need for innovative interventions. Ketamine, recognized for its rapid antidepressant and anti-suicidal effects in adults, has recently emerged as a potential treatment for adolescents with treatment-resistant depression and suicidality. This paper aims to highlight key elements of the informed consent process, including obtaining parental consent and adolescent assent, and discussing the nature of ketamine treatment, its benefits, and potential risks. Obtaining informed consent for ketamine treatment in this demographic poses unique challenges. During the informed consent process, clinicians should balance an adolescent's growing autonomy with parental consent and address the distinct features of treatment, including ketamine's potential to induce psychedelic-like effects. Additionally, clinicians should highlight the "off-label" use in this population and the uncertainty inherent to treatment at this time, including the lack of data on repeated ketamine exposure on the developing brain. This paper also addresses challenging scenarios related to informed consent for this treatment, such as instances when parents are willing to consent but the adolescent refuses. Alternative treatment strategies such as transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) are also considered. In conclusion, while an emerging body of evidence suggests that ketamine shows potential for the acute treatment of adolescents with severe depression and suicidality, adherence to informed consent principles is paramount to ensure best clinical practices and uphold ethical standards amidst the current landscape of ongoing research.

P.0382 Evaluation of the antidepressant-like potential of ketamine in aged rats

P.0382 Evaluation of the antidepressant-like potential of ketamine in aged rats

Augmentation effect of ketamine by guanosine in the novelty-suppressed feeding test is dependent on mTOR signaling pathway

The ketamine's potential for the treatment of refractory depression and anxiety has been considered one the most important discoveries in the last years, however, repeated use of ketamine is limited due to its side/adverse effects. Therefore, the search for effective augmentation strategies that may reduce ketamine doses is welcome. Therefore, this study sought to augment the effect of ketamine by guanosine in the novelty-suppressed feeding (NSF) test, a behavioral paradigm able to detect depression/anxiety-related behavior. Acute administration of guanosine (0.05 mg/kg, p.o.), similar to ketamine (1 mg/kg, i.p.), produced a rapid behavioral response in mice submitted to NSF test. Moreover, the coadministration of sub-effective doses of guanosine (0.01 mg/kg, p.o.) and ketamine (0.1 mg/kg, i.p.) was effective in mice submitted to NSF test. Subsequently, the intracellular mechanism underpinning the augmentation effect of ketamine by guanosine was investigated. Our results suggest that augmentation response of ketamine by guanosine in the NSF test probably involves the activation of mTOR signaling, since the treatment with rapamycin (0.2 nmol/site, i.c.v., a selective mTOR inhibitor) completely abolished this effect. This augmentation strategy also increased mTOR phosphorylation (Ser2448) in the hippocampus, reinforcing the role of mTOR in this augmentation response. However, no changes in the p70S6K, PSD-95, GluA1, and synapsin immunocontents were found in the hippocampus of ketamine plus guanosine-treated mice. Overall, results provide evidence that guanosine is able to augment the effect of ketamine in the NSF test via mTOR activation, a finding that might have therapeutic implications for the management of depression/anxiety.

Should ketamine be used for the clinical treatment of depression?

There has been widespread interest from the public and media in the potential of ketamine as a novel treatment for depression. This paper reviews whether current evidence supports the use of ketamine for the clinical treatment of depression. Clinical trials have investigated the use of intravenous ketamine for the treatment of depressive symptoms over the past 15 years. However, there remain many unanswered questions regarding its effectiveness, safety, and the route, dose and regimen for repeated administration. Experts have also raised concerns regarding ketamine's adverse effects, abuse potential and the risk of addiction. At this stage, the use of ketamine in the treatment of depression remains in the realm of research settings.

Ketamine for depression: evidence, challenges and promise.

Major depressive disorder and bipolar depression are among the most prevalent and disabling mental disorders worldwide. Real-world effectiveness trials in major depressive disorder have underscored that most pharmacological options target monoamines, which are involved in a minority (15-20%) of synaptic contacts in the mammalian brain. Most synapses (∼50%) use the amino acid glutamate as their primary neurotransmitter, and preclinical models of depression have implicated aberrant glutamatergic neurotransmission for 25 years (1). More recently, the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine was shown to produce rapid and robust antidepressant effects in patients with treatment-resistant major depressive disorder and bipolar depression (2–7).

Ketamine

This review describes the medical, research and recreational uses of ketamine, an anaesthetic derivative of phencyclidine that has dissociative, analgesic and psychedelic properties. Ketamine has a complex mechanism of action that is further complicated by stereoselectivity; however, antagonism of glutamate NDMA receptors is thought to underlie its analgesic, dissociative and neuroprotective effects. While ketamine use in medical and veterinary settings is well documented and has a good safety record, the increase in its unregulated use outside of such controlled environments is a cause for concern. The impact on higher centres in the brain, particularly altered perception of auditory, visual and painful stimuli, results in a general lack of responsive awareness that puts the recreational user at (often unrecognised) risk of personal harm. The perceptual and mood changes observed in those who have consumed ketamine are highly sensitive to age, dose, route of administration, previous experience and setting. At low doses, stimulant effects predominate and the effect of environmental conditions are significant; with higher doses, psychedelic effects predominate and the effect of the environment diminishes. The potential of ketamine as a novel clinical and research tool is matched by its abuse potential outside medical settings.

Potential of ketamine and midazolam, individually or in combination, to induce apoptotic neurodegeneration in the infant mouse brain

Recently, it was reported that anesthetizing infant rats for 6 h with a combination of anesthetic drugs (midazolam, nitrous oxide, isoflurane) caused widespread apoptotic neurodegeneration in the developing brain, followed by lifelong cognitive deficits. It has also been reported that ketamine triggers neuroapoptosis in the infant rat brain if administered repeatedly over a period of 9 h. The question arises whether less extreme exposure to anesthetic drugs can also trigger neuroapoptosis in the developing brain. To address this question we administered ketamine, midazolam or ketamine plus midazolam subcutaneously at various doses to infant mice and evaluated the rate of neuroapoptosis in various brain regions following either saline or these various drug treatments. Each drug was administered as a single one-time injection in a dose range that would be considered subanesthetic, and the brains were evaluated by unbiased stereology methods 5 h following drug treatment. Neuroapoptosis was detected by immunohistochemical staining for activated caspase-3. It was found that either ketamine or midazolam caused a dose-dependent, statistically significant increase in the rate of neuroapoptosis, and the two drugs combined caused a greater increase than either drug alone. The apoptotic nature of the neurodegenerative reaction was confirmed by electron microscopy. We conclude that relatively mild exposure to ketamine, midazolam or a combination of these drugs can trigger apoptotic neurodegeneration in the developing mouse brain.