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Depressive Disorders

Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder

December 6, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

OBJECTIVE: Insomnia and disrupted sleep are associated with increased risk of suicide. The N-methyl-D-aspartate antagonist ketamine has been associated with reduced suicidal thoughts, but the mechanism of action is unknown. This study sought to evaluate differences in nocturnal wakefulness in depressed individuals who did and did not have an antisuicidal response to ketamine.

METHODS: Thirty-four participants with baseline suicidal ideation diagnosed with either DSM-IV major depressive disorder (n = 23) or bipolar depression (n = 11) between 2006 and 2013 completed nighttime electroencephalography (EEG) the night before and the night after a single ketamine infusion (0.5 mg/kg over 40 minutes). Suicidal ideation was assessed at baseline and the morning after ketamine infusion via several measures, including the Hamilton Depression Rating Scale suicide item, the suicide item of the Montgomery-Asberg Depression Rating Scale, and the first 5 items of the Scale for Suicide Ideation. A generalized linear mixed model evaluated differences in nocturnal wakefulness, as verified by EEG, between those who had an antisuicidal response to ketamine and those who did not, controlling for baseline nocturnal wakefulness. Results were also compared to the sleep of healthy controls (n = 22).

RESULTS: After analyses adjusted for baseline sleep, participants with an antisuicidal response to ketamine showed significantly reduced nocturnal wakefulness the night after ketamine infusion compared to those without an antisuicidal response (F₁,₂₂ = 5.04, P = .04). Level of nocturnal wakefulness after antisuicidal response to ketamine did not differ significantly from nocturnal wakefulness in the control sample but did differ at a trend level (F₁,₄₀ = 3.15, P = .08).

CONCLUSIONS: Reductions in wakefulness following ketamine may point to a biological mechanism underlying the effect of ketamine on suicidal ideation.

Vande Voort, J. L., Ballard, E. D., Luckenbaugh, D. A., Bernert, R. A., Richards, E. M., Niciu, M. J., … & Zarate, C. A. (2016). Antisuicidal response following ketamine infusion is associated with decreased nighttime wakefulness in major depressive disorder and bipolar disorder. Journal of clinical psychiatry. 10.4088/JCP.15m10440
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Harmine stimulates proliferation of human neural progenitors

December 6, 2016 / Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / By / , , , , ,

Abstract

Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY), and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

Dakic, V., de Moraes Maciel, R., Drummond, H., Nascimento, J. M., Trindade, P., & Rehen, S. K. (2016). Harmine stimulates proliferation of human neural progenitors. PeerJ, 4, e2727. 10.7717/peerj.2727
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Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

December 1, 2016 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.

Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., … & Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology, 30(12), 1181-1197. 10.1177/0269881116675513
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Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial

December 1, 2016 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.

Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., … & Su, Z. (2016). Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology, 30(12), 1165-1180. 10.1177/0269881116675513
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The Therapeutic Potential of Ayahuasca

December 1, 2016 / Anxiety Disorders / PTSD, Ayahuasca, Biology & Ethnobotany, Depressive Disorders, Papers, Psychology, Publications / By / ,

Abstract

Ayahuasca is a plant-based psychoactive decoction traditionally utilized by cultural groups throughout parts of Brazil, Peru, Colombia, Bolivia, Venezuela, and Ecuador during rites of passage, divination, warfare, magico-religious practices, and for healing in ethnomedical contexts. Over the last 150 years, ayahuasca has entered the global sphere and become a focus of scientific inquiry due to its reported use as an effective medicine to diagnose and treat illness. As a result, the use of ayahuasca within a healing context has become widespread and prompted researchers to investigate its putative therapeutic potential. In this chapter, the authors discuss current therapeutic applications of ayahuasca to treat addiction, depression, and anxiety. In this context, we highlight several studies to help facilitate a greater understanding of the therapeutic potential of ayahuasca.

Coe, M. A., & McKenna, D. J. (2017). The Therapeutic Potential of Ayahuasca. In Evidence-Based Herbal and Nutritional Treatments for Anxiety in Psychiatric Disorders (pp. 123-137). Springer International Publishing. 10.1007/978-3-319-42307-4_7

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Ketamine’s Mechanisms of Rapid Antidepressant Activity: Evidence from Preclinical Studies

November 30, 2016 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

Enthusiasm over the growing series of reports describing ketamine’s rapid onset of robust antidepressant activity in clinical trials has ignited a large number of back-translational efforts attempting to employ rodent models to better characterize the antidepressant properties of the drug and to improve our understanding of its underlying mechanisms of antidepressant action. On balance, these preclinical studies have yielded fairly consistent findings demonstrating that ketamine has a broad range of behavioral effects consistent with antidepressant activity in a variety of rodent models. Many of these studies further suggest that ketamine’s effects are unique from other classic antidepressant drugs in producing more durable effects in some models and more rapidly reversing the behavioral effects of chronic stressor exposure in other models. The preclinical studies are also beginning to elucidate the drug’s mechanisms of antidepressant activity, with the majority of recent studies suggesting that increased levels of regional alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptor activation and brain-derived neurotrophic factor (BDNF) expression, as well as enhanced synaptic plasticity, are critical components of the response. However, there remain several points of disagreement and inconsistency in the preclinical literature that require additional investigation, including the effectiveness of other NMDA receptor-targeting drugs and the specific targets of ketamine’s proximal effects. This chapter provides an overview and critical review of this preclinical literature. It is anticipated that a more complete understanding of ketamine’s mechanisms of antidepressant action will allow for a safer and more efficient use of ketamine in the clinical setting and afford us new opportunities for novel drug development.

Hermes, G., & Sanacora, G. (2016). Ketamine’s Mechanisms of Rapid Antidepressant Activity: Evidence from Preclinical Studies. In Ketamine for Treatment-Resistant Depression (pp. 73-98). Springer International Publishing. 10.1007/978-3-319-42925-0_6

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