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Psychology

Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series

August 1, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , ,

Abstract

PURPOSE:
The aim of the study was to assess the effectiveness, tolerability, and safety of oral ketamine as an antidepressant treatment in adults with treatment-resistant depression.
METHODS:
We reviewed retrospective data on 22 patients with treatment-resistant depression, who failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation; subsequently, they received open-label treatment with oral ketamine, commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days, according to response and tolerability. The primary outcome measure was the Beck Depression Inventory II, which was used to rate subjective mood improvement at baseline and then at each follow-up visit. Data about adverse effects related to ketamine and a self-harm risk assessment were also obtained.
FINDINGS:
Over the course of treatment, 18% of the patients showed greater than 50% reduction in the Beck Depression Inventory II scores, 14% reported partial improvement in mood symptoms, while 45% had no response to ketamine and 23% showed a mild worsening in their depressive symptoms. The most frequent adverse effects were acute dissociation, dizziness, blurred vision, numbness and sedation. Neither serious adverse effects, nor any cases of abuse or dependence were observed.
CONCLUSIONS:
Although this case series found oral ketamine to be safe and well tolerated, the findings also showed rather modest effectiveness of oral ketamine in treatment-resistant depression, with only approximately 30% reporting some benefit and approximately 70% reporting no change or worsening of mood. However, bearing in mind the limitations of this small, open-label case series, further exploration of the effectiveness of oral ketamine is warranted.
Al Shirawi, M. I., Kennedy, S. H., Ho, K. T., Byrne, R., & Downar, J. (2017). Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series. Journal of Clinical Psychopharmacology, 37(4), 464. 10.1097/JCP.0000000000000717
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A Systematic Review Of Research On N,N-Dimethyltryptamine

August 1, 2017 / DMT, Neuroscience, Papers, Psychology / By / ,

Abstract

Introduction: The effects of the endogenous hallucinogen N,N-dimethyltryptamine are poorly understood and its medical significance is widely unknown. A small number of  studies regarding its biochemical, pharmaceutical and physiological role have been conducted and the efficacy of its therapeutic potential is presently disregarded. How can scientists proceed in gaining insight into DMT and discovering possible medical uses of this substance?
Materials and Methods: Published articles from  1964 to the present year have been reviewed and the outcome of the studies summarized. The results of drug action,  therapeutic use and potential were investigated . Studies that appeared to have little medical purpose or those, which focus on the use of  Ayahuasca, a South American ritual drink containing N,N-dimethyltryptamine and a monoamine oxidase (MAO)  inhibitor of plant origin, have been excluded.
Results: The research conducted between 1964 and 1987 seems to be an approach to understanding general chemical and biochemical properties of the substance (e.g. metabolites, tolerance, distribution, toxicity, etc.). Rick Strassman, who conducted a broad study from 1990 till 1994 has initiated a recurring interest in the field of psychopharmacology towards DMT. Thus, in the following years, the research was focused on the therapeutic gain of N,N-dimethyltryptamine but resulted mostly inconclusively leading to suggestions of further research. The findings have shown contradictions of already established knowledge, especially for receptors like the sigma-1 receptor, the only direct agonist of which is found to be N,N-dimethyltryptamie.
Conclusion: The studies that now need to be conducted should analyze the correlations between psychiatric diseases (e.g. schizophrenia), purpose of the normal endogenous production and exact action, and the already suggested in various studies therapeutic importance. The low amount of knowledge about the drug action (in case of pharmaceutical use), its targets and drug effect should motivate researchers to gain more insight.
Hristova, D., & Zhelyazkova-Savova, M. (2017). A SYSTEMATIC REVIEW OF RESEARCH ON N, N-DIMETHYLTRYPTAMINE. Scripta Scientifica Vox Studentium, 1(1).
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Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series

August 1, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , ,

Abstract

Purpose The aim of the study was to assess the effectiveness, tolerability, and safety of oral ketamine as an antidepressant treatment in adults with treatment-resistant depression.
Methods We reviewed retrospective data on 22 patients with treatment-resistant depression, who failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation; subsequently, they received open-label treatment with oral ketamine, commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days, according to response and tolerability. The primary outcome measure was the Beck Depression Inventory II, which was used to rate subjective mood improvement at baseline and then at each follow-up visit. Data about adverse effects related to ketamine and a self-harm risk assessment were also obtained.
Findings Over the course of treatment, 18% of the patients showed greater than 50% reduction in the Beck Depression Inventory II scores, 14% reported partial improvement in mood symptoms, while 45% had no response to ketamine and 23% showed a mild worsening in their depressive symptoms. The most frequent adverse effects were acute dissociation, dizziness, blurred vision, numbness and sedation. Neither serious adverse effects, nor any cases of abuse or dependence were observed.
Conclusions Although this case series found oral ketamine to be safe and well tolerated, the findings also showed rather modest effectiveness of oral ketamine in treatment-resistant depression, with only approximately 30% reporting some benefit and approximately 70% reporting no change or worsening of mood. However, bearing in mind the limitations of this small, open-label case series, further exploration of the effectiveness of oral ketamine is warranted.
Al Shirawi, M. I., Kennedy, S. H., Ho, K. T., Byrne, R., & Downar, J. (2017). Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series. Journal of clinical psychopharmacology, 37(4), 464. 10.1097/JCP.0000000000000717
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Behavioral Changes Over Time Following Ayahuasca Exposure in Zebrafish

July 28, 2017 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Papers, Psychology / By / , , , , , ,

Abstract

The combined infusion of Banisteriopsis caapi stem and Psychotria viridis leaves, known as ayahuasca, has been used for centuries by indigenous tribes. The infusion is rich in N, N-dimethyltryptamine (DMT) and monoamine oxidase inhibitors, with properties similar to those of serotonin. Despite substantial progress in the development of new drugs to treat anxiety and depression, current treatments have several limitations. Alternative drugs, such as ayahuasca, may shed light on these disorders. Here, we present time-course behavioral changes induced by ayahuasca in zebrafish, as first step toward establishing an ideal concentration for pre-clinical evaluations. We exposed adult zebrafish to five concentrations of the ayahuasca infusion: 0 (control), 0.1, 0.5, 1, and 3 ml/L (n = 14 each group), and behavior was recorded for 60 min. We evaluated swimming speed, distance traveled, freezing and bottom dwelling every min for 60 min. Swimming speed and distance traveled decreased with an increase in ayahuasca concentration while freezing increased with 1 and 3 ml/L. Bottom dwelling increased with 1 and 3 ml/L, but declined with 0.1 ml/L. Our data suggest that small amounts of ayahuasca do not affect locomotion and reduce anxiety-like behavior in zebrafish, while increased doses of the drug lead to crescent anxiogenic effects. We conclude that the temporal analysis of zebrafish behavior is a sensitive method for the study of ayahuasca-induced functional changes in the vertebrate brain.
Savoldi, R., Polari, D., Pinheiro-da-Silva, J., Silva, P. F., Lobao-Soares, B., Yonamine, M., … & Luchiari, A. C. (2017). Behavioral changes over time following ayahuasca exposure in zebrafish. Frontiers in behavioral neuroscience, 11. 10.3389/fnbeh.2017.00139
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Side-effects associated with ketamine use in depression: a systematic review

July 27, 2017 / Depressive Disorders, Ketamine, Papers, Psychology / By / , , , ,

Abstract

This is the first systematic review of the safety of ketamine in the treatment of depression after single and repeated doses. We searched MEDLINE, PubMed, PsycINFO, and Cochrane Databases and identified 288 articles, 60 of which met the inclusion criteria. After acute dosing, psychiatric, psychotomimetic, cardiovascular, neurological, and other side-effects were more frequently reported after ketamine treatment than after placebo in patients with depression. Our findings suggest a selective reporting bias with limited assessment of long-term use and safety and after repeated dosing, despite these being reported in other patient groups exposed to ketamine (eg, those with chronic pain) and in recreational users. We recommend large-scale clinical trials that include multiple doses of ketamine and long-term follow up to assess the safety of long-term regular use.
Short, B., Fong, J., Galvez, V., Shelker, W., & Loo, C. K. (2017). Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry. 10.1016/S2215-0366(17)30272-9
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The 2017 Ayahuasca Technical Report

July 26, 2017 / Anthropology & Sociology, Anxiety Disorders / PTSD, Ayahuasca, Biology & Ethnobotany, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications, Substance Use Disorder / By

ICEERS has just released the 2017 edition of the Ayahuasca Technical Report. Signed by ten of the world’s leading ayahuasca researchers, this report is an important document that summarizes the most relevant scientific findings from the past few decades, as well as key information about the history, legality, pharmacology, and potential therapeutic or adverse effects of ayahuasca. Our intention with this report is to provide objective and up-to-date information to policy makers, judges, lawyers and other officials in charge of developing policies, programs, legislation or involved in legal cases relating to ayahuasca.
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Psychedelic drug use in healthy individuals: A review of benefits, costs, and implications for drug policy

July 26, 2017 / Ayahuasca, DMT, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

The potential of psychedelic drugs in the treatment of mental health problems is increasingly being recognized. However, relatively little thrust has been given to the suggestion that individuals without any mental health problems may benefit from using psychedelic drugs, and that they may have a right to do so. This review considers contemporary research into the use of psychedelic drugs in healthy individuals, including neurobiological and subjective effects. In line with findings suggesting positive effects in the treatment of mental health problems, such research highlights the potential of psychedelic drugs for the enhancement of wellbeing even in healthy individuals. The relatively low risk associated with usage does not appear to align with stringent drug laws that impose heavy penalties for their use. Some policy implications, and suggestions for future research, are considered.
Elsey, J. W. (2017). Psychedelic drug use in healthy individuals: A review of benefits, costs, and implications for drug policy. Drug Science, Policy and Law, 3, 2050324517723232.
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Qualitative and Quantitative Features of Music Reported to Support Peak Mystical Experiences during Psychedelic Therapy Sessions

July 25, 2017 / Mushrooms / Psilocybin, Papers, Psychology / By / , , , ,

Abstract

Psilocybin is a classic (serotonergic) hallucinogen (“psychedelic” drug) that may occasion mystical experiences (characterized by a profound feeling of oneness or unity) during acute effects. Such experiences may have therapeutic value. Research and clinical applications of psychedelics usually include music listening during acute drug effects, based on the expectation that music will provide psychological support during the acute effects of psychedelic drugs, and may even facilitate the occurrence of mystical experiences. However, the features of music chosen to support the different phases of drug effects are not well-specified. As a result, there is currently neither real guidance for the selection of music nor standardization of the music used to support clinical trials with psychedelic drugs across various research groups or therapists. A description of the features of music found to be supportive of mystical experience will allow for the standardization and optimization of the delivery of psychedelic drugs in both research trials and therapeutic contexts. To this end, we conducted an anonymous survey of individuals with extensive experience administering psilocybin or psilocybin-containing mushrooms under research or therapeutic conditions, in order to identify the features of commonly used musical selections that have been found by therapists and research staff to be supportive of mystical experiences within a psilocybin session. Ten respondents yielded 24 unique recommendations of musical stimuli supportive of peak effects with psilocybin, and 24 unique recommendations of musical stimuli supportive of the period leading up to a peak experience. Qualitative analysis (expert rating of musical and music-theoretic features of the recommended stimuli) and quantitative analysis (using signal processing and music-information retrieval methods) of 22 of these stimuli yielded a description of peak period music that was characterized by regular, predictable, formulaic phrase structure and orchestration, a feeling of continuous movement and forward motion that slowly builds over time, and lower perceptual brightness when compared to pre peak music. These results provide a description of music that may be optimally supportive of peak psychedelic experiences. This description can be used to guide the selection and composition of music for future psychedelic research and therapy sessions.
Barrett, F. S., Robbins, H., Smooke, D., Brown, J. L., & Griffiths, R. R. (2017). Qualitative and quantitative features of music reported to support peak mystical experiences during psychedelic therapy sessions. Frontiers in psychology, 8. 10.3389/fpsyg.2017.01238
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Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA)

July 24, 2017 / Anxiety Disorders / PTSD, MDMA, Neuroscience, Papers, Psychology / By / , , , , , ,

Abstract

Rationale

3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD, particularly in treatment-resistant patients. However, given MDMA’s broad pharmacological profile, further investigation is warranted before moving to a complex clinical population.

Objectives

We aimed to inform clinical research by providing a translational model of MDMA’s effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction.

Methods

We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training.

Results

MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA’s effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA’s effect by 5-HTT inhibition also downregulated 5-HT2A-mediated behavior, and 5-HT2A antagonism disrupted MDMA’s effect on extinction.

Conclusions

We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.

Young, M. B., Norrholm, S. D., Khoury, L. M., Jovanovic, T., Rauch, S. A., Reiff, C. M., … & Howell, L. L. (2017). Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3, 4-methylenedioxymethamphetamine (MDMA). Psychopharmacology, 234(19), 2883-2895. 10.1007/s00213-017-4684-8
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MDMA-induced indifference to negative sounds is mediated by the 5-HT2A receptor

July 22, 2017 / MDMA, Papers, Psychology / By / , , , ,

Abstract

BACKGROUND:
MDMA has been shown to induce feelings of sociability, a positive emotional bias and enhanced empathy. While previous research has used only visual emotional stimuli, communication entails more than that single dimension and it is known that auditory information is also crucial in this process. In addition, it is, however, unclear what the neurobiological mechanism underlying these MDMA effects on social behaviour is. Previously, studies have shown that MDMA-induced emotional excitability and positive mood are linked to the action on the serotonin (5-HT) 2A receptor.
AIM:
The present study aimed at investigating the effect of MDMA on processing of sounds (Processing of Affective Sounds Task (PAST)) and cognitive biases (Approach-Avoidance Task (AAT)) towards emotional and social stimuli and the role of 5-HT2A receptor in these effects.
METHODS:
Twenty healthy recreational users entered a 2 × 2, placebo-controlled, within-subject study with ketanserin (40 mg) as pre-treatment and MDMA (75 mg) as treatment. Behavioural (PAST, AAT) measures were conducted 90 min after treatment with MDMA, respectively, 120 min after ketanserin. Self-report mood measures and oxytocin concentrations were taken at baseline and before and after behavioural tests.
RESULTS:
Findings showed that MDMA reduced arousal elicited by negative sounds. This effect was counteracted by ketanserin pre-treatment, indicating involvement of the 5-HT2 receptor in this process. MDMA did not seem to induce a bias towards emotional and social stimuli. It increased positive and negative mood ratings and elevated oxytocin plasma concentrations. The reduction in arousal levels when listening to negative sounds was not related to the elevated subjective arousal.
CONCLUSION:
It is suggested that this decrease in arousal to negative stimuli reflects potentially a lowering of defences, a process that might play a role in the therapeutic process.
Kuypers, K. P. C., de la Torre, R., Pizarro, N., Xicota, L., & Ramaekers, J. G. MDMA-induced indifference to negative sounds is mediated by the 5-HT2A receptor. Psychopharmacology, 1-10. 10.1007/s00213-017-4699-1
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