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Psychiatry

Why Psychiatry Needs 3,4-Methylenedioxymethamphetamine: A Child Psychiatrist’s Perspective

May 5, 2017 / Anxiety disorders / PTSD, MDMA, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By /

Abstract

Since the late 1980s the psychoactive drug 3,4-methylenedioxymethamphetamine (MDMA) has had a well-known history as the recreationally used drug ecstasy. What is less well known by the public is that MDMA started its life as a therapeutic agent and that in recent years an increasing amount of clinical research has been undertaken to revisit the drug’s medical potential. MDMA has unique pharmacological properties that translate well to its proposed agent to assist trauma-focused psychotherapy. Psychological trauma—especially that which arises early in life from child abuse—underpins many chronic adult mental disorders, including addictions. Several studies of recent years have investigated the potential role of MDMA-assisted psychotherapy as a treatment for post-traumatic stress disorder, with ongoing plans to see MDMA therapy licensed and approved within the next 5 years. Issues of safety and controversy frequently surround this research, owing to MDMA’s often negative media-driven bias. However, accurate examination of the relative risks and benefits of clinical MDMA—in contrast to the recreational use of ecstasy—must be considered when assessing its potential benefits and the merits of future research. In this review, the author describes these potential benefits and explores the relatives risks of MDMA-assisted psychotherapy in the context of his experience as a child and adolescent psychiatrist, having seen the relative limitations of current pharmacotherapies and psychotherapies for treating complex post-traumatic stress disorder arising from child abuse.

Sessa, B. (2017). Why Psychiatry Needs 3, 4-Methylenedioxymethamphetamine: A Child Psychiatrist’s Perspective. Neurotherapeutics, 1-9. 10.1007/s13311-017-0531-1
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Anxiolytic-like effects of noribogaine in zebrafish

May 4, 2017 / Anxiety disorders / PTSD, Iboga / Ibogaine, Papers, Psychiatry, Psychology, Publications / By / , ,

Abstract

Noribogaine is the main psychoactive metabolite of the hallucinogenic drug ibogaine, and is a particularly interesting compound potentially useful to treat dependence and various psychiatric disorders. Here, we report the effects of noribogaine on anxiety and locomotion in zebrafish (Danio rerio), a new promising model organism in neurobehavioral and psychopharmacological research. Adult zebrafish were subjected to the 5min novel tank test (NTT) following an acute, 20-min drug immersion in 1, 5 and 10mg/L noribogaine. Overall, noribogaine produced robust anxiolytic-like behavior in zebrafish (increasing the time spent and transitions to the top half compartment and reducing freezing bouts) without overt effects on fish locomotion. Taken together, these results indicate that noribogaine modulates the components of the acute stress response related to emotionality and anxiety behaviors, implicating this drug as a potentially useful non-sedative anxiolytic agent.
Kalueff, A. V., Kaluyeva, A., & Mailet, E. L. (2017). Anxiolytic-like effects of noribogaine in zebrafish. Behavioural Brain Research, 330, 63-67. 10.1016/j.bbr.2017.05.008
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A single administration of the hallucinogen, 4-acetoxy-dimethyltryptamine, prevents the shift to a drug-dependent state and the expression of withdrawal aversions in rodents

May 4, 2017 / Mushrooms / Psilocybin, Neuroscience, New substances, Papers, Psychiatry, Psychology, Psychopharmacology, Substance Use Disorder / By / , , , , ,

Abstract

Despite several studies suggesting the therapeutic use of 5-hydroxytryptamine receptors type 2A (5-HT2A) agonists in the treatment of substance use disorders, the neurobiological basis accounting for such effects are still unknown. It has been observed that chronic exposure to drugs of abuse produces molecular and cellular adaptations in ventral tegmental area (VTA) neurons, mediated by brain-derived neurotrophic factor (BDNF). These BDNF-induced adaptations in the VTA are associated with the establishment of aversive withdrawal motivation that leads to a drug-dependent state. Growing evidence suggests that 5-HT2A receptor signaling can regulate the expression of BDNF in the brain. In this study, we observed that a single systemic or intra-VTA administration of a 5-HT2A agonist in rats and mice blocks both the aversive conditioned response to drug withdrawal and the mechanism responsible for switching from a drug-naive to a drug-dependent motivational system. Our results suggest that 5-HT2A agonists could be used as therapeutic agents to reverse a drug dependent state, as well as inhibiting the aversive effects produced by drug withdrawal.
Vargas‐Perez, H., Grieder, T. E., Ting‐A‐Kee, R., Maal‐Bared, G., Chwalek, M., & van der Kooy, D. (2017). A single administration of the hallucinogen, 4‐acetoxy‐dimethyltryptamine, prevents the shift to a drug‐dependent state and the expression of withdrawal aversions in rodents. European Journal of Neuroscience. 10.1111/ejn.13572
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Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications.

May 3, 2017 / Depression, Ketamine, Medicine, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , , ,

Abstract

Current therapeutic approaches to depression fail for millions of patients due to lag in clinical response and non-adherence. Here we provide new support for the antidepressant effect of an anesthetic drug, ketamine, by Inverse-Frequency Analysis of eight million reports from the FDA Adverse Effect Reporting System. The results of the examination of population scale data revealed that patients who received ketamine had significantly lower frequency of reports of depression than patients who took any other combination of drugs for pain. The analysis also revealed that patients who took ketamine had significantly lower frequency of reports of pain and opioid induced side effects, implying ketamine’s potential to act as a beneficial adjunct agent in pain management pharmacotherapy. Further, the Inverse-Frequency Analysis methodology provides robust statistical support for the antidepressant action of other currently approved therapeutics including diclofenac and minocycline.
Cohen, I. V., Makunts, T., Atayee, R., & Abagyan, R. (2017). Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications. Scientific Reports, 7. 10.1038/s41598-017-01590-x
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Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

May 1, 2017 / Anxiety disorders / PTSD, Ayahuasca, Depression, Neuroscience, Papers, Psychiatry, Psychology / By / ,

Abstract

Over more than 60 years, monoamine oxidase (MAO) inhibitors are available for therapy of central nervous diseases. Although they have shown to be efficacious specifically in the treatment of major depressive disorders and treatment-resistant depression, they became less a therapeutic choice for the physicians mostly due to severe side effects, such as liver failure and hypertensive crisis associated specifically with the first generation of inhibitors. Nevertheless, this class of drugs is still being used for treatment specifically as more selective and reversible inhibitors became available and will provide clinicians with additional treatment options. The current review revisits monoamine oxidase inhibitors and their potential in the treatment of human diseases, such as anxiety, depression, mood and personality disorders, and pain and introduces current ideas and developments.
Entzeroth, M., & Ratty, A. K. (2017). Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle. Open Journal of Depression, 6(02), 31. 10.4236/ojd.2017.62004
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1001. Neurocognitive Effects of Repeated Ketamine Infusions in Co-Occurring Posttraumatic Stress Disorder and Treatment-Resistant Depression

April 29, 2017 / Depression, Ketamine, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , , , , , ,

Albott, C., Lim, K., Forbes, M., Erbes, C., Thuras, P., Tye, S., … & Shiroma, P. (2017). 1001-Neurocognitive Effects of Repeated Ketamine Infusions in Co-Occurring Posttraumatic Stress Disorder and Treatment-Resistant Depression. Biological Psychiatry, 81(10), S405. 10.1016/j.biopsych.2017.02.728
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Detoxification from methadone using low, repeated, and increasing doses of ibogaine: A case report

April 28, 2017 / Iboga / Ibogaine, Papers, Psychiatry, Psychology, Substance Use Disorder / By / , , , , , ,

Abstract

Background and aims

Ibogaine is a natural alkaloid that has been used in the last decades as an adjuvant for the treatment of opiate withdrawal. Despite the beneficial results suggested by animal studies and case series, there is a lack of clinical trials to assess the safety and efficacy of ibogaine. Moreover, the majority of reports described cases of heroin-dependent individuals, with and without concomitant use of methadone, using high doses of ibogaine. Therefore, it is not clear if ibogaine at low doses could be used therapeutically in people on methadone maintenance treatments (MMT).

Methods

Case report of a female on MMT for 17 years who performed a self-treatment with several low and cumulative doses of ibogaine over a 6-week period.

Results

The patient successfully eliminated her withdrawals from methadone with ibogaine. Each administration of ibogaine attenuated the withdrawal symptoms for several hours, and reduced the tolerance to methadone until all signs of withdrawal symptoms disappeared at the end of the treatment. No serious adverse effects were observed, and at no point did the QTc measures reach clinically significant scores. Twelve months after the treatment, she was no longer on MMT.

Conclusions

To our knowledge, this is the first case report describing an ibogaine treatment using low and cumulative doses in a person on MMT. Although preliminary, this case suggests that low and cumulative doses of ibogaine may reduce withdrawal symptoms in patients undergoing MMT.

Wilkins, C., dos Santos, R. G., Solá, J., Aixalá, M., Cura, P., Moreno, E., … & Bouso, J. C. (2017). Detoxification from methadone using low, repeated, and increasing doses of ibogaine: A case report. Journal of Psychedelic Studies, 1(1), 29-34. 10.1556/2054.01.2017.005
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Patient Experiences of Psilocybin-Assisted Psychotherapy: An Interpretative Phenomenological Analysis

April 28, 2017 / Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , , , , , ,

Abstract

The psychological mechanisms of action involved in psilocybin-assisted psychotherapy are not yet well understood. Despite a resurgence of quantitative research regarding psilocybin, the current study is the first qualitative study of participant experiences in psilocybin-assisted psychotherapy. Semistructured interviews were carried out with 13 adult participants aged 22 to 69 years (M = 50 years) with clinically elevated anxiety associated with a cancer diagnosis. Participants received a moderate dose of psilocybin and adjunctive psychotherapy with an emphasis on the process of meaning-making. Verbatim transcribed interviews were analyzed by a five-member research team using interpretative phenomenological analysis. General themes found in all or nearly all transcripts included relational embeddedness, emotional range, the role of music as conveyor of experience, meaningful visual phenomena, wisdom lessons, revised life priorities, and a desire to repeat the psilocybin experience. Typical themes found in the majority of transcripts included the following: exalted feelings of joy, bliss, and love; embodiment; ineffability; alterations to identity; a movement from feelings of separateness to interconnectedness; experiences of transient psychological distress; the appearance of loved ones as guiding spirits; and sharing the experience with loved ones posttreatment. Variant themes found in a minority of participant transcripts include lasting changes to sense of identity, synesthesia experiences, catharsis of powerful emotion, improved relationships after treatment, surrender or “letting go,” forgiveness, and a continued struggle to integrate experience. The findings support the conclusion that psilocybin-assisted psychotherapy may provide an effective treatment for psychological distress in cancer patients. Implications for theory and treatment are discussed.

Belser, A. B., Agin-Liebes, G., Swift, T. C., Terrana, S., Devenot, N., Friedman, H. L., … & Ross, S. (2017). Patient experiences of psilocybin-assisted psychotherapy: An interpretative phenomenological analysis. Journal of Humanistic Psychology, 0022167817706884.
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Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial

April 28, 2017 / Depression, Ketamine, Papers, Psychiatry, Psychology, Publications / By / , , , , , ,

Abstract

OBJECTIVES: To evaluate feasibility and effects of a sub-anesthetic infusion dose of ketamine versus midazolam on suicidal ideation in bipolar depression. Neurocognitive, blood and saliva biomarkers were explored.

METHODS: Sixteen participants with bipolar depression and a Scale for Suicidal Ideation (SSI) score of ≥4 were randomized to ketamine (0.5 mg/kg) or midazolam (0.02 mg/kg). Current pharmacotherapy was maintained excluding benzodiazepines within 24 hours. The primary clinical outcome was SSI score on day 1 post-infusion.

RESULTS: Results supported feasibility. Mean reduction of SSI after ketamine infusion was almost 6 points greater than after midazolam, although this was not statistically significant (estimate=5.84, SE=3.01, t=1.94, P=.074, 95% confidence interval ([CI)]=-0.65 to 12.31). The number needed to treat for response (SSI <4 and at least 50% below baseline) was 2.2, and for remission (SSI=0) was 3.2. The strongest neurocognitive correlation was between memory improvement on the Selective Reminding Test (SRT) and reduction in SSI score on day 1 after ketamine (ρ=-.89, P=.007). Pre- to post-infusion decrease in serum brain derived neurotrophic factor (BDNF) correlated with reduction in SSI from baseline to day 1 after ketamine (n=5, ρ=0.90, P=.037) but not midazolam (P=.087).

CONCLUSIONS: The study demonstrated feasibility. Suicidal thoughts were lower after ketamine than after midazolam at a trend level of significance, likely due to the small pilot sample. Memory improvement and BDNF are promising biomarkers. Replication is needed in an adequately powered full-scale trial.

Grunebaum, M. F., Ellis, S. P., Keilp, J. G., Moitra, V. K., Cooper, T. B., Marver, J. E., … & Mann, J. J. (2017). Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam‐controlled randomized clinical trial. Bipolar Disorders. 10.1111/bdi.12487

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Ketamine’s dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders

April 26, 2017 / Anxiety disorders / PTSD, Depression, Ketamine, Papers, Psychiatry, Psychology, Psychotherapy / By / , , , , ,

Abstract

The N-methyl-D-aspartate receptor antagonist ketamine has rapid onset activity in treatment-resistant depression, post-traumatic stress disorder and obsessive compulsive disorder. Due to similarities in brain network activity in depression and anxiety disorders, we hypothesized that ketamine might also be active in other refractory anxiety disorders. We evaluated the efficacy and safety of ketamine in 12 patients with refractory generalized anxiety disorder and/or social anxiety disorder who were not currently depressed, using an ascending single dose study design (0.25, 0.5, 1 mg/kg administered subcutaneously) at weekly intervals. Within 1 h of dosing, patients reported reduced anxiety, which persisted for up to seven days. A dose-response profile was noted for anxiolytic effects, dissociative side effects, and changes in blood pressure and heart rate, with minor changes at 0.25 mg/kg, and progressively greater and more durable changes at the higher doses. Ten of 12 patients were treatment responders at 0.5–1 mg/kg. Ketamine was safe and well tolerated in this population. Ketamine may be a potential therapeutic alternative for patients with refractory generalized anxiety disorder/social anxiety disorder. Along with its demonstrated effectiveness in patients with treatment-resistant depression, obsessive compulsive disorder and post-traumatic stress disorder, these data raise the intriguing possibility that ketamine may have broad efficacy in disorders characterized by negative emotional states, and that these disorders may share a common precipitating neurobiology.
Glue, P., Medlicott, N. J., Harland, S., Neehoff, S., Anderson-Fahey, B., Le Nedelec, M., … & McNaughton, N. (2017). Ketamine’s dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders. Journal of Psychopharmacology, 0269881117705089.
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