However, regarding resting-state blood oxygenation level-dependent (BOLD) responses and global brain connectivity during acute ketamine administration, studies consistently show an attenuation by lamotrigine pretreatment [26,27,28]. Since lamotrigine pretreatment had no effect on resting brain perfusion [15], it was proposed that the attenuation of ketamine’s acute effects by lamotrigine might not be due to changes in neurovascular responsivity but rather to reduced glutamate release. A recent post-hoc analysis investigates whether a lifetime history of psychosis influences patients’ response to a single infusion of ketamine in clinical trials for depression. The authors merged the results of three randomized, placebo-controlled crossover trials with depressed patients. Of the 69 patients evaluated, two were diagnosed with MDD with psychotic features and ten with bipolar disorder with psychotic features in the past. This study reveals that a single infusion of ketamine produces antidepressant effects in people with a history of psychosis without generating psychotic symptoms [21].

1. While preclinical studies provide a framework to investigate mechanisms of ketamine action, clinical studies have also provided mechanistic insight.
2. Despite the effort in defining clear-cut criteria of substance-induced psychosis, the results of the present review shows a picture of the complex relationship between psychotic symptoms and the use and abuse of illicit drugs.
3. Regarding pharmacodynamics, SCs mimic the action of Δ9-tetrahydrocannabinol (Δ9-THC), activating thus CB-1 receptors, resulting in psychotomimetic effects.
4. They also found, however, that post-stimulus and after ketamine administration, the amplitude of the rats’ beta and gamma oscillations decreased, which is linked to impaired perception.
5. The figure depicts an alternative basic synaptic circuit where an excitatory pyramidal neuron receives inputs from other excitatory neurons, where inhibitory inputs regulate the extent of glutamate release from primary excitatory neurons.

He has assigned his rights on the patent to the U.S. government but will share a percentage of any royalties that may be received by the government. All other authors report no biomedical financial interests or potential conflicts of interest.

Studies Retrieved

Even psychiatric comorbidities were proven to be a risk factor, especially regarding ADHD (86), previous psychotic episodes (95), and various personality disorders (96), amongst which the most common are antisocial and borderline personality disorders. Interestingly, Radhakrishnan et al. (43) tested the hypothesis that inducing a GABA deficit in healthy crack withdrawal timeline subjects might increase cannabis psychotomimetic properties. In fact, pre-treatment with iomazenil (an antagonist of benzodiazepines on GABA receptors), followed by THC administration, exacerbated subjective and psychophysiological effects of THC in healthy subjects and induced a significantly more severe psychotic episode when compared to THC alone.

Moreover, through an fMRI, they found that changes of global brain connectivity in certain region-specific areas predicted the occurrence of psychotic symptoms. Accordingly, in their clinical trial, Hoflich et al. (152) found an increased PANSS score after i.v. Ketamine administration compared to placebo in healthy volunteers and a significant increase of cortico-thalamic connectivity of the somatosensory and temporal cortex. Interestingly, these alterations of thalamic connectivity in healthy volunteers are similar to those reported for patients with schizophrenia (CIT).

Firstly, it helps individuals who have experienced ketamine-induced psychosis to have a better understanding of their condition and what to expect during the recovery process. Secondly, it enables healthcare professionals to provide appropriate treatment and support to those affected. Lastly, it contributes to the overall body of knowledge surrounding ketamine use and its potential consequences. There is significant evidence that an increase in synaptic neuroplasticity is essential for the antidepressant effect of ketamine.

Even though the clinical impact in humans remains unknown, ketamine has shown dopamine-enhancing effects in vitro. The dopamine D2 receptor antagonist haloperidol might therefore interact with ketamine’s effects. In addition, haloperidol reduced the anxiogenic effects and increased the sedative and prolactin responses to ketamine.

“Ketamine showed good antidepressant effects and, in some cases, the comorbid symptoms even improved or disappeared after ketamine treatment,” Veraart summarized. However, the effect size of ketamine might be lower in those with a history of psychosis, she added. Early intervention is crucial in managing ketamine-induced psychosis and reducing its duration. Seeking professional help as soon as symptoms arise can lead to more effective treatment and a faster recovery.

Additionally, lower frequency cannabis users showed a reduction in symptoms following CBD administration alone, compared to placebo. A similar finding was reported by Kleinloog et al. (37) in a randomized, placebo-controlled, clinical trial on male mild cannabis-users. Specifically, transient positive symptoms were seen after THC administration, as measured by the Positive and Negative Symptoms Scale (PANSS).

Co-occurring Mental Health Conditions

Spinogenesis is well studied in early development, however these initial spines are not functional and undergo synapse maturation to become functional. The ketamine mediated structural effect on spinogenesis requires intracellular signaling, which may involve MeCP2 processes, in order to produce functional changes on neurotransmission that mediate the sustained action. Collectively, taken together these data strongly support further investigation into the intracellular signaling of MeCP2 and its links to mTOR and spinogenesis in order to elucidate potential points for therapeutic drug discovery. While preclinical studies provide a framework to investigate mechanisms of ketamine action, clinical studies have also provided mechanistic insight. As stated above, recent findings demonstrated a causal link between initial homeostatic neuroplasticity events elicited by ketamine and subsequent transcriptional mechanism that sustains ketamine’s behavioral effects.

Neuregulin signaling mediates the acute and sustained antidepressant effects of subanesthetic ketamine

The study by Xu et al. (2015) investigated 0.5 mg/kg IV ketamine in 36 patients with bipolar TRD that were maintained on a therapeutic dose of lithium (plasma target level of 0.6–1.2 mEq/L) or valproate. Depressive symptoms improved significantly after ketamine in both the lithium and valproate group, and there were no significant differences between the 2 mood stabilizers. Taken together, lithium did not seem to potentiate ketamine’s antidepressant effect in patients with depression (Table 1). Since 2000 the rapid and robust antidepressant effects of ketamine have been reported repeatedly (Han et al., 2016; Kishimoto et al., 2016).

Ketamine-induced psychosis is a condition that can occur as a result of using ketamine, a dissociative anesthetic drug. It is important to understand the factors that can influence the duration of this condition in order to provide appropriate support and treatment to individuals experiencing it. Research has shown that the symptoms of ketamine-induced psychosis can persist for varying lengths of time. Some individuals may experience symptoms for a few days or weeks, while others may experience symptoms for months or even years.

Currently, no biomarker/biosignature has been well validated for clinical use, although some seem intriguing [34]. The research suggests that there was no psychotic exacerbation among the participants in the included studies on this topic. In several cases, comorbid psychotic symptoms improved or completely disappeared after the administration of ketamine or esketamine for depression, consistent with the theoretical notions underlying the treatment of TRD with the novel pharmacological approaches [27].

Three patients exhibited considerable improvement or complete remission of both depressed and psychotic symptoms 24 h after esketamine injection and after two and four weeks of follow-up examination. The administration of esketamine to these four patients did not aggravate their psychotic https://rehabliving.net/ symptoms. The structured Montgomery–Asberg depression rating scale interview was used to evaluate the severity of depression symptoms (MADRS-Sigma). Before infusions, on days 1, 8, 14, and 21, as well as one week afterwards, outcome measurements were collected (day 35).