Effect of Psilocybin and Ketamine on Brain Neurotransmitters, Glutamate Receptors, DNA and Rat Behavior

Wojtas, Adam; Bysiek, Agnieszka; Wawrzczak-Bargieła, Agnieszka; Szych, Zuzanna; Majcher-Maślanka, Iwona; Herian, Monika; Maćkowiak, Marzena; Gołembiowska, Krystyna

doi:10.3390/ijms23126713

Cited by 47 publications

(60 citation statements)

References 75 publications

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“…A recent study conducted by Wojtas et al indicated that both ketamine and psilocybin increase dopamine, serotonin, glutamate, and GABA extracellular levels in the frontal cortex in rats. These results may support the hypothesis of mTOR signaling and neurogenesis as crucial factors in depression and explain the common antidepressant mechanisms of esketamine and psilocybin [ 50 ].…”

Section: Discussionsupporting

confidence: 84%

Esketamine and Psilocybin—The Comparison of Two Mind-Altering Agents in Depression Treatment: Systematic Review

Psiuk

Nowak²,

Natalia³

et al. 2022

IJMS

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This publication discusses two compounds belonging to the psychoactive substances group which are studied in the context of depression treatment—psilocybin and esketamine. The former is a naturally occurring psychedelic. The latter was invented in the laboratory exactly 60 years ago. Although the substances were controversial in the past, recent studies indicate the potential of those substances as novel antidepressant agents. The PubMed/MEDLINE database was used to identify articles for systematic review, using the following search terms: (depression) AND (psilocybin) OR (ketamine). From 617 items, only 12 articles were obtained in the final analyses. Three articles were devoted to psilocybin in depression treatment and nine to esketamine. In most studies, esketamine showed a significant reduction in both depressive symptoms and suicidal ideation shortly after intake and after a month of treatment compared to baseline and to standard-of-care antidepressant agents. Psilocybin’s antidepressive effects occurred one day after intake and after 6–7 weeks of treatment and were maintained for up to 6 or 8 months of follow-up. One study indicated that psilocybin’s effects are comparable with and may be superior to escitalopram treatment. Both esketamine and psilocybin demonstrated rapid and long-term effects in reducing depression symptoms and, after overcoming some limitations, may be considered as novel antidepressant agents in future.

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Section: Discussionsupporting

confidence: 84%

Esketamine and Psilocybin—The Comparison of Two Mind-Altering Agents in Depression Treatment: Systematic Review

Psiuk

Nowak²,

Natalia³

et al. 2022

IJMS

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“…Previous studies indicate that spine density is proportional to the excitatory synaptic input to a given neuron (Hering and Sheng, 2001 ). Patients with major depression show low levels of glutamate in prefrontal cortex regions (Arnone et al, 2015 ) and antidepressants increase glutamate concentration in frontal areas (Stone et al, 2012 ; Wojtas et al, 2022 ). Hence, HF-rTMS might exert positive effects on depression-like behavior through the regulation of glutamatergic neurotransmission in mPFC and a consequent increase in spine density and dendritic complexity.…”

Section: Discussionmentioning

confidence: 99%

High-frequency rTMS modulates emotional behaviors and structural plasticity in layers II/III and V of the mPFC

Cambiaghi

Infortuna

Gualano

et al. 2022

Front. Cell. Neurosci.

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Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique, and it has been increasingly used as a nonpharmacological intervention for the treatment of various neurological and neuropsychiatric diseases, including depression. In humans, rTMS over the prefrontal cortex is used to induce modulation of the neural circuitry that regulates emotions, cognition, and depressive symptoms. However, the underlying mechanisms are still unknown. In this study, we investigated the effects of a short (5-day) treatment with high-frequency (HF) rTMS (15 Hz) on emotional behavior and prefrontal cortex morphological plasticity in mice. Mice that had undergone HF-rTMS showed an anti-depressant-like activity as evidenced by decreased immobility time in both the Tail Suspension Test and the Forced Swim Test along with increased spine density in both layer II/III and layer V apical and basal dendrites. Furthermore, dendritic complexity assessed by Sholl analysis revealed increased arborization in the apical portions of both layers, but no modifications in the basal dendrites branching. Overall, these results indicate that the antidepressant-like activity of HF-rTMS is paralleled by structural remodeling in the medial prefrontal cortex.

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“…Ketamine itself is a drug and a stimulant, and one of its main functions is to increase release of dopamine. Even though many studies reported about the mechanisms of ketamine as antidepressants, ranging from effects on NMDA receptors to effects on GABA receptors [ 22 , 23 ], the major reason for ketamine to exert its antidepressant effect is related to DA release, possibly by activating astrocytic Ca 2+ signaling and changing the bursting of neurons in the Habula nucleus [ 24 ]. Thus, raising brain dopamine is certainly a quick way to change the depressed mood [ 25 ].…”

Section: Monoamine Neurotransmitters Mediate Three Core Effectsmentioning

confidence: 99%

Monoamine Neurotransmitters Control Basic Emotions and Affect Major Depressive Disorders

Jiang

Zou

et al. 2022

Pharmaceuticals

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Major depressive disorder (MDD) is a common and complex mental disorder, that adversely impacts an individual’s quality of life, but its diagnosis and treatment are not accurately executed and a symptom-based approach is utilized in most cases, due to the lack of precise knowledge regarding the pathophysiology. So far, the first-line treatments are still based on monoamine neurotransmitters. Even though there is a lot of progress in this field, the mechanisms seem to get more and more confusing, and the treatment is also getting more and more controversial. In this study, we try to review the broad advances of monoamine neurotransmitters in the field of MDD, and update its effects in many advanced neuroscience studies. We still propose the monoamine hypothesis but paid special attention to their effects on the new pathways for MDD, such as inflammation, oxidative stress, neurotrophins, and neurogenesis, especially in the glial cells, which have recently been found to play an important role in many neurodegenerative disorders, including MDD. In addition, we will extend the monoamine hypothesis to basic emotions; as suggested in our previous reports, the three monoamine neurotransmitters play different roles in emotions: dopamine—joy, norepinephrine—fear (anger), serotonins—disgust (sadness). Above all, this paper tries to give a full picture of the relationship between the MDD and the monoamine neurotransmitters such as DA, NE, and 5-HT, as well as their contributions to the Three Primary Color Model of Basic Emotions (joy, fear, and disgust). This is done by explaining the contribution of the monoamine from many sides for MDD, such the digestive tract, astrocytes, microglial, and others, and very briefly addressing the potential of monoamine neurotransmitters as a therapeutic approach for MDD patients and also the reasons for its limited clinical efficacy, side effects, and delayed onset of action. We hope this review might offer new pharmacological management of MDD.

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Effect of Psilocybin and Ketamine on Brain Neurotransmitters, Glutamate Receptors, DNA and Rat Behavior

Cited by 47 publications

References 75 publications

Esketamine and Psilocybin—The Comparison of Two Mind-Altering Agents in Depression Treatment: Systematic Review

Esketamine and Psilocybin—The Comparison of Two Mind-Altering Agents in Depression Treatment: Systematic Review

High-frequency rTMS modulates emotional behaviors and structural plasticity in layers II/III and V of the mPFC

Monoamine Neurotransmitters Control Basic Emotions and Affect Major Depressive Disorders

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