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Psychiatry

The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future

April 26, 2017 / Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychotherapy / By / ,

Abstract

Plant-based psychedelics, such as psilocybin, have an ancient history of medicinal use. After the first English language report on LSD in 1950, psychedelics enjoyed a short-lived relationship with psychology and psychiatry. Used most notably as aids to psychotherapy for the treatment of mood disorders and alcohol dependence, drugs such as LSD showed initial therapeutic promise before prohibitive legislature in the mid-1960s effectively ended all major psychedelic research programs. Since the early 1990s, there has been a steady revival of human psychedelic research: last year saw reports on the first modern brain imaging study with LSD and three separate clinical trials of psilocybin for depressive symptoms. In this circumspective piece, RLC-H and GMG share their opinions on the promises and pitfalls of renewed psychedelic research, with a focus on the development of psilocybin as a treatment for depression.
Carhart-Harris, R. L., & Goodwin, G. M. (2017). The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology. 10.1038/npp.2017.84
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Anxiety, panic, and hopelessness during and after ritual ayahuasca intake in a woman with generalized anxiety disorder: A case report

April 24, 2017 / Anxiety disorders / PTSD, Ayahuasca, Papers, Psychiatry, Psychology / By / , , ,

Abstract

Background and aims

Ayahuasca is a dimethyltryptamine- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of Northwest Amazonian for ritual and therapeutic purposes. Animal and human studies suggest that ayahuasca has antidepressant and anxiolytic potentials and has a good safety profile. However, anxiety-like reactions may also occur after ayahuasca intake, although they are rare.

Methods

Case report.

Results

Here, we describe a case of a non-medicated, symptom-free young female with generalized anxiety disorder, who experienced intense anxiety, panic, and hopelessness during and for 3 days after participating in an ayahuasca ritual. The symptoms appeared in the first hours after ayahuasca intake and were gradually reducing in the following hours/days, but were intense enough to cause significant suffering to her, who needed to seek psychiatric help and restarted pharmacological treatment.

Conclusions

Although “bad/horror trips” with anxiety features may occur during the acute effects of ayahuasca and other hallucinogens, to the best of our knowledge, this is the first report of a subacute/prolonged anxiety-like reaction to this substance. Ayahuasca should be used with caution in people with a history of anxiety disorders.

dos Santos, R. G., Osório, F. L., Crippa, J. A. S., & C. Hallak, J. E. (2017). Anxiety, panic, and hopelessness during and after ritual ayahuasca intake in a woman with generalized anxiety disorder: A case report. Journal of Psychedelic Studies, 1(1), 35-39. 10.1556/2054.01.2017.004
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MDMA does not alter responses to the Trier Social Stress Test in humans

April 21, 2017 / MDMA, Other subjects, Papers, Philosophy, Psychiatry, Psychotherapy / By / , ,

Abstract

Rationale

±3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a stimulant-psychedelic drug with unique social effects. It may dampen reactivity to negative social stimuli such as social threat and rejection. Perhaps because of these effects, MDMA has shown promise as a treatment for post-traumatic stress disorder (PTSD). However, the effect of single doses of MDMA on responses to an acute psychosocial stressor has not been tested.

Objectives

In this study, we sought to test the effects of MDMA on responses to stress in healthy adults using a public speaking task. We hypothesized that the drug would reduce responses to the stressful task.

Methods

Volunteers (N = 39) were randomly assigned to receive placebo (N = 13), 0.5 mg/kg MDMA (N = 13), or 1.0 mg/kg MDMA (N = 13) during a stress and a no-stress session. Dependent measures included subjective reports of drug effects and emotional responses to the task, as well as salivary cortisol, heart rate, and blood pressure.

Results

The stress task produced its expected increase in physiological responses (cortisol, heart rate) and subjective ratings of stress in all three groups, and MDMA produced its expected subjective and physiological effects. MDMA alone increased ratings of subjective stress, heart rate, and saliva cortisol concentrations, but contrary to our hypothesis, it did not moderate responses to the Trier Social Stress Test.

Conclusions

Despite its efficacy in PTSD and anxiety, MDMA did not reduce either the subjective or objective responses to stress in this controlled study. The conditions under which MDMA relieves responses to negative events or memories remain to be determined.

Bershad, A. K., Miller, M. A., & de Wit, H. (2017). MDMA does not alter responses to the Trier Social Stress Test in humans. Psychopharmacology, 1-8. 10.1007/s00213-017-4621-x
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New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity

April 11, 2017 / Depression, Ketamine, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , ,

Abstract

Major depressive disorder is a severe and complex mental disorder. Impaired neurotransmission and disrupted signalling pathways may influence neuroplasticity, which is involved in the brain dysfunction in depression. Traditional neurobiological theories of depression, such as monoamine hypothesis, cannot fully explain the whole picture of depressive disorders. In this review, we discussed new treatment directions of depression, including modulation of glutamatergic system and noninvasive brain stimulation. Dysfunction of glutamatergic neurotransmission plays an important role in the pathophysiology of depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and lasting antidepressive effects in previous studies. In addition to ketamine, other glutamatergic modulators, such as sarcosine, also show potential antidepressant effect in animal models or clinical trials. Noninvasive brain stimulation is another new treatment strategy beyond pharmacotherapy. Growing evidence has demonstrated that superficial brain stimulations, such as transcranial magnetic stimulation, transcranial direct current stimulation, cranial electrotherapy stimulation, and magnetic seizure therapy, can improve depressive symptoms. The antidepressive effect of these brain stimulations may be through modulating neuroplasticity. In conclusion, drugs that modulate neurotransmission via NMDA receptor and noninvasive brain stimulation may provide new directions of treatment for depression. Furthermore, exploring the underlying mechanisms will help in developing novel therapies for depression in the future.
Huang, Y. J., Lane, H. Y., & Lin, C. H. (2017). New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity. Neural plasticity, 2017. 10.1155/2017/4605971
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Use of repeated intravenous ketamine therapy in treatment-resistant bipolar depression with suicidal behaviour: a case report from Spain

April 7, 2017 / Depression, Ketamine, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , , , ,

Abstract

The rapidly-acting antidepressant properties of ketamine are a trend topic in psychiatry. Despite its robust effects, these are ephemeral and can lead to certain adverse events. For this reason, there is still a general concern around the off-label use of ketamine in clinical practice settings. Nonetheless, for refractory depression, it should be an indication to consider. We report the case of a female patient admitted for several months due to a treatment-resistant depressive bipolar episode with chronic suicidal behaviour. After repeated intravenous ketamine infusions without remarkable side effects, the patient experienced a complete clinical recovery during the 4 weeks following hospital discharge. Unfortunately, depressive symptoms reappeared in the 5th week, and the patient was finally readmitted to hospital as a result of a suicide attempt.
López-Díaz, Á., Fernández-González, J. L., Luján-Jiménez, J. E., Galiano-Rus, S., & Gutiérrez-Rojas, L. (2017). Use of repeated intravenous ketamine therapy in treatment-resistant bipolar depression with suicidal behaviour: a case report from Spain. Therapeutic advances in psychopharmacology, 7(4), 137-140. 10.1177/2045125316675578
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A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial

April 4, 2017 / Ketamine, Papers, Psychiatry, Psychology, Substance Use Disorder / By / , , , , ,

Abstract

Background

Worldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group.

Methods/design

This is a phase II, randomised, double-blind, placebo-controlled, parallel-group clinical trial taking place in two sites in the UK: the South West of England and London. Ninety-six recently detoxified alcoholics, with comorbid depressive symptoms, will be randomised to one of four treatment arms. Patients will receive either three sessions of ketamine (0.8 mg/kg administered intravenously (IV) over 40 minutes) or placebo (50 ml saline 0.9% IV over 40 minutes) plus either seven sessions of manualised psychological therapy or an alcohol education control. Patients will be assessed at 3 and 6 months on a range of psychological and biological variables. The primary endpoints are (1) relapse rates at 6 months and (2) percentage days abstinent at 6 months. Secondary endpoints include 3 and 6 month percentage days abstinence, tolerability (indicated by dropout), adverse events, depressive symptoms, craving and quality of life.

Discussion

This study will provide important information on a new combined psychological and pharmacological intervention aimed at reducing relapse rates in alcoholics. The findings would have broad application given the worldwide prevalence of alcoholism and its associated medical, psychological and social problems.

McAndrew, A., Lawn, W., Stevens, T., Porffy, L., Brandner, B., & Morgan, C. J. (2017). A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial. Trials, 18(1), 159. 10.1186/s13063-017-1895-6
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Clinical predictors of antidepressant response to ketamine in unipolar treatment-resistant depression

April 1, 2017 / Depression, Ketamine, Papers, Psychiatry, Psychology / By / , , , , , ,

Abstract

Introduction

The non-competitive N-methyl-d-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in treatment-resistant depression (TRD). However, only a few studies have investigated which clinical characteristics predict a response to ketamine.

Objectives

To assess sociodemographic variables and clinical markers that predict response to ketamine in unipolar TRD patients.

Methods

Searches of Pubmed, NCBI and Google Scholar were conducted for clinical trials and systematic reviews, through October 2016, using the keywords:
ketamine, N-methyl-d-aspartate receptor antagonist, rapid-acting antidepressant, depression, treatment-resistant depression, clinical predictors.

Results

Findings support the following clinical predictors:
– sociodemographic variables: positive family history of alcohol abuse disorder in first-degree relative (increased antidepressant response and fewer depressive symptoms for up to 4 weeks post-infusions), higher BMI (improvement in depression severity at 230 minutes and one day post-infusion), negative history of suicide attempt (greater improvement at day 7);
– infusion-associated events: greater dissociation during infusion (better antidepressant response at 230 minutes and one week post-infusion); rapid response to first infusion (sustained response to subsequent infusions in one-third responders for up to 83 days);
– symptomatology: anxious depression (fewer depression symptoms at day one up to 25 associated with longer time to relapse); neurocognitive performance (lower attention) predicts change in severity of depressive symptoms over six infusions.

Conclusions

Findings suggest that specific clinical characteristics are predictors of ketamine response in TRD. Future studies confirming reliable predictors will assist clinicians to implement efficacious and individualized treatment for TRD patients.

Del Sant, L. C., Magalhães, E., Lucchese, A. C., Alves, H. P., Sarin, L. M., Del Porto, J. A., & de Lacerda, A. T. (2017). Clinical predictors of antidepressant response to ketamine in unipolar treatment-resistant depression. European Psychiatry, 41, S525-S526. 10.1016/j.eurpsy.2017.01.704
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A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders

April 1, 2017 / Depression, Ketamine, Papers, Psychiatry, Psychology, Safety / By / , , , , , ,

Abstract

IMPORTANCE:
Several studies now provide evidence of ketamine hydrochloride’s ability to produce rapid and robust antidepressant effects in patients with mood and anxiety disorders that were previously resistant to treatment. Despite the relatively small sample sizes, lack of longer-term data on efficacy, and limited data on safety provided by these studies, they have led to increased use of ketamine as an off-label treatment for mood and other psychiatric disorders.
OBSERVATIONS:
This review and consensus statement provides a general overview of the data on the use of ketamine for the treatment of mood disorders and highlights the limitations of the existing knowledge. While ketamine may be beneficial to some patients with mood disorders, it is important to consider the limitations of the available data and the potential risk associated with the drug when considering the treatment option.
CONCLUSIONS AND RELEVANCE:
The suggestions provided are intended to facilitate clinical decision making and encourage an evidence-based approach to using ketamine in the treatment of psychiatric disorders considering the limited information that is currently available. This article provides information on potentially important issues related to the off-label treatment approach that should be considered to help ensure patient safety.

Sanacora, G., Frye, M. A., McDonald, W., Mathew, S. J., Turner, M. S., Schatzberg, A. F., … & Nemeroff, C. B. (2017). A consensus statement on the use of ketamine in the treatment of mood disorders. Jama psychiatry, 74(4), 399-405. 10.1001/jamapsychiatry.2017.0080
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Use of Ketamine in Clinical PracticeA Time for Optimism and Caution

April 1, 2017 / Depression, Ketamine, Papers, Psychiatry, Psychology / By / ,

Abstract

Increasing evidence, primarily from small studies, supports the idea that the dissociative anesthetic ketamine has rapid antidepressant effects in patients with treatment-refractory major depression.1 The beneficial effects of ketamine are observed within hours of administration and can last approximately 1 week. Given that up to one-third of patients with major depression fail current treatments,2 there is a clear need for novel and more effective treatments. Results to date have led to increasing off-label use of ketamine in clinical practices, with little guidance about clinical administration. In this issue of the JAMA Psychiatry, Sanacora and colleagues3 provide a much-needed consensus statement to help guide clinical use of ketamine.
Zorumski, C. F., & Conway, C. R. (2017). Use of ketamine in clinical practice: a time for optimism and caution. Jama psychiatry, 74(4), 405-406. 10.1001/jamapsychiatry.2017.0078
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An online survey of tobacco smoking cessation associated with naturalistic psychedelic use

March 28, 2017 / LSD, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychotherapy, Publications, Substance Use Disorder / By / , , ,

Abstract

Data suggest psychedelics such as psilocybin and lysergic acid diethylamide (LSD) may hold therapeutic potential in the treatment of addictions, including tobacco dependence. This retrospective cross-sectional anonymous online survey characterized 358 individuals (52 females) who reported having quit or reduced smoking after ingesting a psychedelic in a non-laboratory setting ⩾1 year ago. On average, participants smoked 14 cigarettes/day for 8 years, and had five previous quit attempts before their psychedelic experience. Of the 358 participants, 38% reported continuous smoking cessation after psychedelic use (quitters). Among quitters, 74% reported >2 years’ abstinence. Of the 358 participants, 28% reported a persisting reduction in smoking (reducers), from a mode of 300 cigarettes/month before, to a mode of 1 cigarette/month after the experience. Among reducers, 62% reported >2 years of reduced smoking. Finally, 34% of the 358 participants (relapsers) reported a temporary smoking reduction before returning to baseline smoking levels, with a mode time range to relapse of 3–6 months. Relapsers rated their psychedelic experience significantly lower in personal meaning and spiritual significance than both other groups. Participants across all groups reported less severe affective withdrawal symptoms (e.g. depression, craving) after psychedelic use compared with previous quit attempts, suggesting a potential mechanism of action for psychedelic-associated smoking cessation/reduction. Changes in life priorities/values were endorsed as the most important psychological factor associated with smoking cessation/reduction. Results suggest psychedelics may hold promise in treating tobacco addiction as potentially mediated by spiritual experience, changed priorities/values, and improved emotional regulation.

Johnson, M. W., Garcia-Romeu, A., Johnson, P. S., & Griffiths, R. R. (2017). An online survey of tobacco smoking cessation associated with naturalistic psychedelic use. Journal of Psychopharmacology, 0269881116684335. 10.1177/0269881116684335
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