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Depressive Disorders

Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics

July 25, 2016 / Ayahuasca, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Despite reports of apparent benefits, social and political pressure beginning in the late 1960s effectively banned scientific inquiry into psychedelic substances. Covert examination of psychedelics persisted through the 1990s; the turn of the century and especially the past 10 years, however, has seen a resurgent interest in psychedelic substances (eg, LSD, ayahuasca, psilocybin). This chapter outlines relevant EEG and brain imaging studies evaluating the effects of psychedelics on the brain. This chapter also reviews evidence of the use of psychedelics as adjunct therapy for a number of psychiatric and addictive disorders. In particular, psychedelics appear to have efficacy in treating depression and alcohol-use disorders.

Tófoli, L. F., & de Araujo, D. B. (2016). Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics. International Review of Neurobiology. 10.1016/bs.irn.2016.06.005
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Neurovascular Plasticity of the Hippocampus One Week after a Single Dose of Ketamine in Genetic Rat Model of Depression

July 21, 2016 / Depressive Disorders, Ketamine, Neuroscience, Papers, Publications / By / , , , ,

Abstract

Glutamatergic system and the structural plasticity hypothesis are principal components for rapid and sustained antidepressant effects of novel antidepressant therapeutics. This study represents the first investigation of the structural plasticity of the hippocampus as one of the main contributed mechanisms to the sustained anti-depressive effect of ketamine. Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats were given a single intraperitoneal injection of ketamine (15 mg/kg) or saline 7 days before perfusion-fixed. The optical fractionator method was used to estimate the total number of neurons in the granular cell layer. Microvessel length in the molecular layer of DG was evaluated with global spatial sampling method. By use of the physical disector method, the number of synapses was estimated. The volume of the hippocampus was larger in the FRL-vehicle rats compared with FSL-vehicle group and in FSL-ketamine versus FSL-vehicle rats (P < 0.05). The number of non-perforated synapses was significantly higher in the FSL-ketamine versus FSL-vehicle group, (P = 0.01). A significant effect of ketamine on enhancement of the number of neurons in DG in FSL rats was observed (P = 0.01). The total length of the microvessels 1 week after ketamine treatment in the FSL rats significantly increased (P  < 0.05). Our results indicate that neurovascular changes of hippocampus could be one of the possible mechanisms underlying the sustained antidepressant effect of ketamine by reversing alteration of the number of the excitatory synapses, neuronal number and length of the microvessels in the hippocampus.

Ardalan, M., Wegener, G., Polsinelli, B., Madsen, T. M., & Nyengaard, J. R. (2016). Neurovascular Plasticity of the Hippocampus One Week after a Single Dose of Ketamine in Genetic Rat Model of Depression. Hippocampus. http://dx.doi.org/10.1002/hipo.22617
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Efficacy and safety of ketamine in bipolar depression: A systematic review

July 4, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

The depression is the most prevalent state throughout the life of the bipolar patient. Ketamine has been shown to be an effective and rapid treatment for depression. The objective of the present work is to perform a systematic review on the efficacy and safety of ketamine as treatment of bipolar depression, as well as its different patterns of administration. The search found 10 relevant manuscripts that met the inclusion criteria: one clinical trial, 5 cohort studies, and 4 case reports. Intravenous infusion was used in 60% of the studies. According to data, ketamine seems to be an effective and safe treatment for bipolar depression, although the length of its effect is short. Adverse effects observed generally occurred at the time of infusion, and tended to completely disappear within 1-2h. Therefore, more studies are necessary to explore new patterns of administration, as well as on its safety and adverse effects.

Alberich, S., Martínez-Cengotitabengoa, M., López, P., Zorrilla, I., Núñez, N., Vieta, E., & González-Pinto, A. (2016). Efficacy and safety of ketamine in bipolar depression: A systematic review. Revista de psiquiatria y salud mental. 10.1016/j.rpsm.2016.05.005

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Major Depressive Disorder Induced by Chronic Ketamine Abuse: A Case Report

June 23, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

Ketamine, an NMDA (N-methyl-d-aspartate) glutamate antagonist, commonly used as an anesthetic agent, has emerged as a major substance of abuse particularly in Asia.1 Here, we present, to our knowledge, the first case of a patient who developed major depressive episodes after heavy and long-term ketamine use.

Chang, H., Huang, M. C., & Chen, L. Y. (2016). Major Depressive Disorder Induced by Chronic Ketamine Abuse: A Case Report. The Primary Care Companion for CNS Disorders, 18(3). 10.4088%2FPCC.15l01881
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Magic mushroom compound is a potential treatment for patients with major depression

June 8, 2016 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

A hallucinogenic compound derived from magic mushrooms could provide a new route for antidepressant research.

Carhart-Harris, R. L. Magic mushroom compound is a potential treatment for patients with major depression. http://dx.doi.org/10.7748/ns.30.41.15.s18
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Potential involvement of serotonergic signaling in ketamine’s antidepressant actions: A critical review

June 2, 2016 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , , ,

Abstract

A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine’s antidepressant effects.

The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms responsible for ketamine’s antidepressant activity do not appear to preclude the possibility that non-glutamate neurotransmitters are involved in the antidepressant effects. At multiple levels, the serotonergic and glutamatergic systems interact, and such crosstalk could support the notion that changes in serotonergic neurotransmission may impact ketamine’s antidepressant potential. In line with these prospects, ketamine may increase 5-HT levels in the prefrontal cortex of rats, plausibly via hippocampal NMDA receptor inhibition and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In addition, a number of preclinical studies suggest that the antidepressant-like effects of ketamine may depend on endogenous activation of 5-HT receptors. Recent imaging and behavioral data predominantly support a role for 5-HT1A or 5-HT1B receptors, but the full range of 5-HT receptors has currently not been systematically investigated in this context. Furthermore, the nature of any 5-HT dependent mechanism in ketamine’s antidepressant effect is currently not understood, and therefore, more studies are warranted to confirm this hypothesis and explore the specific pathways that might implicate 5-HT.

du Jardin, K. G., Müller, H. K., Elfving, B., Dale, E., Wegener, G., & Sanchez, C. (2016). Potential involvement of serotonergic signaling in ketamine’s antidepressant actions: A critical review. Progress in Neuro-Psychopharmacology and Biological Psychiatry. http://dx.doi.org/10.1016/j.pnpbp.2016.05.007
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Potential involvement of serotonergic signaling in ketamine's antidepressant actions: A critical review

June 2, 2016 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , , ,

Abstract

A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine’s antidepressant effects.

The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms responsible for ketamine’s antidepressant activity do not appear to preclude the possibility that non-glutamate neurotransmitters are involved in the antidepressant effects. At multiple levels, the serotonergic and glutamatergic systems interact, and such crosstalk could support the notion that changes in serotonergic neurotransmission may impact ketamine’s antidepressant potential. In line with these prospects, ketamine may increase 5-HT levels in the prefrontal cortex of rats, plausibly via hippocampal NMDA receptor inhibition and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In addition, a number of preclinical studies suggest that the antidepressant-like effects of ketamine may depend on endogenous activation of 5-HT receptors. Recent imaging and behavioral data predominantly support a role for 5-HT1A or 5-HT1B receptors, but the full range of 5-HT receptors has currently not been systematically investigated in this context. Furthermore, the nature of any 5-HT dependent mechanism in ketamine’s antidepressant effect is currently not understood, and therefore, more studies are warranted to confirm this hypothesis and explore the specific pathways that might implicate 5-HT.

du Jardin, K. G., Müller, H. K., Elfving, B., Dale, E., Wegener, G., & Sanchez, C. (2016). Potential involvement of serotonergic signaling in ketamine’s antidepressant actions: A critical review. Progress in Neuro-Psychopharmacology and Biological Psychiatry. http://dx.doi.org/10.1016/j.pnpbp.2016.05.007
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Efficacy and safety of oral ketamine versus diclofenac to alleviate mild to moderate depression in chronic pain patients: A double-blind, randomized, controlled trial

June 1, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Background: Ketamine is a glutamate N-methyl-d-aspartate receptor antagonist capable of exerting antidepressive effects in single or repeated intravenous infusions. The objective of this study was to investigate the safety and the efficacy of oral ketamine vs. diclofenac monotherapy in reducing symptoms of mild to moderate depression among patients with chronic pain.

Methods: This study is a 6-week, randomized, double-blind, controlled, parallel-group trial with two intervention arms (ketamine, fixed daily dosage of 150 mg vs. diclofenac, fixed daily dosage of 150 mg). Twenty participants in each arm completed the trial program all of whom had two post-baseline measurements at week 3 and week 6. Reduction in depression symptoms was assessed using the Hamilton Depression Rating Scale (HDRS) and the hospital anxiety and depression subscale for depression (HADSDepression) scores at baseline and week 3 and week 6 post-intervention.

Results: Significantly lower HDRS scores were observed in the ketamine treatment group as early as 6 weeks post-intervention (P=0.008). By comparison, mean (±standard deviation) HADS depression subscale scores were significantly lower for individuals receiving ketamine compared to diclofenac for both post-baseline measures at week 3 (6.95±1.47 vs. 8.40±1.6, P=0.005) and week 6 (6.20±1.15 vs. 7.35±1.18, p=0.003).

Limitations: The limitations of the present study were its small sample size and the short-term follow-up period.

Conclusions: Oral ketamine appears to be a safe and effective option in improving depressive symptoms of patients with chronic pain with mild-to-moderate depression.

Jafarinia, M., Afarideh, M., Tafakhori, A., Arbabi, M., Ghajar, A., Noorbala, A. A., … & Akhondzadeh, S. (2016). Efficacy and Safety of Oral Ketamine versus Diclofenac to Alleviate Mild to Moderate Depression in Chronic Pain Patients: A Double-Blind, Randomized, Controlled Trial. Journal of Affective Disorders. http://dx.doi.org/10.1016/j.jad.2016.05.076

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Psilocybin-assisted therapy shows promising results for treatment-resistant depression

December 6, 2021 / Depressive Disorders, Mushrooms / Psilocybin, Publications / By

psilocybin depression 2In a new study, the research team at the Imperial College London has tested the potential of psilocybin-assisted therapy to alleviate treatment-resistant depression. Statistics show that 20% of people suffering from major depression are unresponsive to conventional treatments like SSRI medication or cognitive behavioural therapy (Carhart-Harris et al., 2016).

Twelve subjects (six men and six women), all diagnosed with major depression, participated in the study. They received two oral doses of psilocybin – 10 mg and 25 mg – the former being the safety dose and the latter, administered seven days later, the treatment dose. The participants had been selected among 70 candidates; one of the main selection criteria was the absence of psychotic episodes in subjects themselves and in their immediate family members.

All participants, aged between 30 and 60, had a long history of major depression, with treatment attempts having had only minimal effects. Some of them had been suffering moderate to severe depression for about three decades. Previous treatment attempts included both chemical and psychological means: medication like serotonin or dopamine reuptake inhibitors (SSRI, NDRI, SNRI, etc.) and therapies like cognitive behavioural, group and counselling therapy.

The pharmacology of psilocybin is different from that of selective serotonin reuptake inhibitors (SSRIs), the most common medication for this kind of depression. SSRIs prevent the already released serotonin – one of the neurotransmitters involved in the regulation of emotion – from being taken back up by the same neurons that produced it, so that it can be taken up by serotonin receptors. Unlike SSRIs, psilocybin (converted in the body to psilocin) is structurally similar to serotonin, and causes the same effect as an overall increase in serotonin levels.

Over the course of the study, psychological support was provided before, during and after the psilocybin sessions. During the sessions, there was minimal intrusion into the patients´ experience. The patients were only asked the necessary questions to evaluate the effects of psilocybin on their physical and mental well-being. The most common adverse reactions reported included nausea, headaches, anxiety and confusion, all of which were transient. Only one patient reported transient paranoia that subsided after one hour.

The study demonstrated that the symptoms of depression were somewhat reduced in all of the twelve participants. The scores on the Quick Inventory of Depressive Symptoms (QIDS) showed that the depression level was reduced from 16-20 (severe depression) to 6-10 (mild depression). Five follow-up assessments took place between one week and three months after the treatment. The maximum positive effects were reached two weeks after the treatment. Eight subjects experienced complete remission in their depression one week after the treatment and in seven of them significant reduction in depression persisted after three months. One patient experienced an increase in depressive symptoms during the three months following the treatment.

This study was the first to explore the efficacy of psilocybin in treating major depression, and demonstrated the potential of psilocybin for reducing the symptoms of major treatment-resistant depression and the safety of the substance when administered under proper conditions. Previous research with psilocybin-assisted therapy has already showed that it can alleviate anxiety related to end-stage cancer (Grob C.S. et al., 2011).

Further research in more rigorous conditions (placebo-controlled and on a larger scale) is needed to confirm the potential of psilocybin in treating major depression. If this promise can be fulfilled, it could mean a new chance for millions of people struggling with severe depression.

References:

Carhart-Harris R.L., Bolstridge M., Rucker J., Day C.M.J., Erritzoe D., Kaelen M., Bloomfield M., Rickard J.A., Forbes B., Fielding A., Taylor D., Pilling S., Curran V.H., Nutt D.J. (2016) Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. http://dx.doi.org/10.1016/S2215-0366(16)30065-7

Grob C.S., Danforth A.L., Chopra G.S., Hagerty M., McKay C.R., Halberstadt A.L. and Greer G.R. (2011) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry, 68, pp. 71–78 http://dx.doi.org/10.1001/archgenpsychiatry.2010.116

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