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Psychiatry

Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review

September 22, 2017 / Anxiety disorders / PTSD, LSD, Mushrooms / Psilocybin, Other substances, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , , , , ,

Abstract

Anxiety and depression are some of the most common psychiatric symptoms of patients suffering with life-threatening diseases, often associated with a low quality of life and a poor overall prognosis. 5-HT2A-receptor agonists (serotonergic hallucinogens, ‘psychedelics’) like lysergic acid diethylamide (LSD) and psilocybin were first investigated as therapeutic agents in the 1960s. Recently, after a long hiatus period of regulatory obstacles, interest in the clinical use of these substances has resumed. The current article provides a systematic review of studies investigating psychedelics in the treatment of symptoms of existential distress in life-threatening diseases across different periods of research, highlighting how underlying concepts have developed over time. A systematic search for clinical trials from 1960 to 2017 revealed 11 eligible clinical trials involving a total number of N=445 participants, of which 7 trials investigated the use of lysergic acid diethylamide (LSD) (N=323), 3 trials investigated the use of psilocybin (N=92), and one trial investigated the use of dipropyltryptamine (DPT) (N=30). The 4 more recent randomized controlled trials (RCTs) (N=104) showed a significantly higher methodological quality than studies carried out in the 1960s and 1970s. Evidence supports that patients with life threatening diseases associated with symptoms of depression and anxiety benefit from the anxiolytic and antidepressant properties of serotonergic hallucinogens. Some studies anecdotally reported improvements in patients´ quality of life and reduced fear of death. Moreover, low rates of side effects were reported in studies that adhered to safety guidelines. Further studies are needed to determine how these results can be transferred into clinical practice.
Reiche, S., Hermle, L., Gutwinski, S., Jungaberle, H., Gasser, P., & Majić, T. (2017). Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 10.1016/j.pnpbp.2017.09.012
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Developing Guidelines and Competencies for the Training of Psychedelic Therapists

September 1, 2017 / MDMA, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychotherapy / By /

Abstract

Research since the 1950s has shown that psychedelic-assisted psychotherapy has had significant positive effects in reductions of specific clinical symptoms and increases in quality of life as measured on a variety of indices. The intensity of focus on evidence-based outcomes, however, has resulted in a paucity of active discussions and research on the core competencies of the therapists themselves. The context of the history of psychedelic research reveals how this neglect of therapist variables occurred. With current discussions of Phase 3 and expanded access research programs for psilocybin-assisted and MDMA-assisted psychotherapies, there will be a great need for competent therapists trained in this clinical specialty. This is particularly the case if less restricted, legal medical use is approved within the next 6 to 10 years. This article is the first review and compilation of psychedelic therapist competencies derived from the psychedelic literature. These six therapist competencies are empathetic abiding presence; trust enhancement; spiritual intelligence; knowledge of the physical and psychological effects of psychedelics; therapist self-awareness and ethical integrity; and proficiency in complementary techniques. A further contribution of this review is a delineation of the 12 fundamental curricular domains of study for the training and development of these therapist competencies. As current legal restrictions evolve, aspects of these training guidelines will develop accordingly.
Phelps, J. (2017). Developing Guidelines and Competencies for the Training of Psychedelic Therapists. Journal of Humanistic Psychology, 57(5), 450-487. 10.1177/0022167817711304
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Serotonin and brain function: a tale of two receptors

August 31, 2017 / Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / ,

Abstract

Previous attempts to identify a unified theory of brain serotonin function have largely failed to achieve consensus. In this present synthesis, we integrate previous perspectives with new and older data to create a novel bipartite model centred on the view that serotonin neurotransmission enhances two distinct adaptive responses to adversity, mediated in large part by its two most prevalent and researched brain receptors: the 5-HT1A and 5-HT2A receptors. We propose that passive coping (i.e. tolerating a source of stress) is mediated by postsynaptic 5-HT1AR signalling and characterised by stress moderation. Conversely, we argue that active coping (i.e. actively addressing a source of stress) is mediated by 5-HT2AR signalling and characterised by enhanced plasticity (defined as capacity for change). We propose that 5-HT1AR-mediated stress moderation may be the brain’s default response to adversity but that an improved ability to change one’s situation and/or relationship to it via 5-HT2AR-mediated plasticity may also be important – and increasingly so as the level of adversity reaches a critical point. We propose that the 5-HT1AR pathway is enhanced by conventional 5-HT reuptake blocking antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), whereas the 5-HT2AR pathway is enhanced by 5-HT2AR-agonist psychedelics. This bipartite model purports to explain how different drugs (SSRIs and psychedelics) that modulate the serotonergic system in different ways, can achieve complementary adaptive and potentially therapeutic outcomes.
Carhart-Harris, R. L., & Nutt, D. J. (2017). Serotonin and brain function: a tale of two receptors. Journal of Psychopharmacology (Oxford, England), 31(9), 1091. 10.1177/0269881117725915
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Psychedelic Drugs as Therapeutics: No Illusions About the Challenges

August 24, 2017 / Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychotherapy / By / ,

Abstract

Interest in the potential therapeutic benefits of psychedelic agents has recently increased. In addition to psilocybin, a wide variety of agents with psychedelic properties have been proposed and partially tested. However, the challenges of obtaining approval to market a restricted psychotomimetic agent are formidable.
Sellers, E. M., & Leiderman, D. B. (2017). Psychedelic Drugs as Therapeutics: No Illusions About the Challenges. Clinical Pharmacology & Therapeutics. 10.1002/cpt.776
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MDMA Impairs Both the Encoding and Retrieval of Emotional Recollections

August 21, 2017 / MDMA, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , , ,

Abstract

The psychoactive drug ±3,4-methylenedioxymethamphetamine (MDMA) is increasingly used for its perceived emotional effects (eg, prosociality, empathy, psychotherapy), but surprisingly little research has been aimed at identifying the effect of the drug on emotional episodic memory in humans. Here, we report the first double-blind placebo-controlled study to examine the effects of MDMA on emotional memory separately during encoding and retrieval in healthy participants. Participants viewed emotionally negative, neutral, and positive pictures and their labels. Forty-eight hours later, they were given cued recollection and recognition memory tests designed to assess recollection and familiarity for the studied pictures. Participants were randomly assigned to one of three groups who received MDMA (1 mg/kg) either during encoding (Encoding group; N=20), retrieval (Retrieval group; N=20), or neither (Placebo group; N=20). Although MDMA administered at either phase did not affect overall memory accuracy, it did alter the recollection of details associated specifically with emotional memories as estimated using a dual process signal detection analysis of confidence judgments and subjective ‘remember’ judgments. In the Encoding group, MDMA reduced recollection estimates for negative and positive pictures but had little to no effect on neutral items or familiarity estimates. There was evidence for similar trends in the Retrieval group. These findings indicate that MDMA attenuates the encoding and retrieval of salient details from emotional events, consistent with the idea that its potential therapeutic effects for treating posttraumatic stress disorder are related to altering emotional memory.
Doss, M. K., Weafer, J., Gallo, D. A., & de Wit, H. (2017). MDMA Impairs Both the Encoding and Retrieval of Emotional Recollections. Neuropsychopharmacology. 10.1038/npp.2017.171
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Psychedelics and connectedness

August 10, 2017 / Consciousness, LSD, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , , , ,

Abstract

Psychedelic drugs are creating ripples in psychiatry as evidence accumulates of their therapeutic potential. An important question remains unresolved however: how are psychedelics effective? We propose that a sense of connectedness is key, provide some preliminary evidence to support this, and suggest a roadmap for testing it further.
Carhart-Harris, R. L., Erritzoe, D., Haijen, E., Kaelen, M., & Watts, R. (2017). Psychedelics and connectedness. Psychopharmacology, 1-4. 10.1007/s00213-017-4701-y
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Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy prolong the therapeutic effects of single ketamine infusion on post-traumatic stress disorder and comorbid depression: a pilot randomized, placebo-controlled, crossover clinical trial

August 2, 2017 / Anxiety disorders / PTSD, Depression, Ketamine, Papers, Psychiatry, Psychology, Psychotherapy / By / , , , , , ,

Abstract

Background and objectives: Trauma memories lay at the core in etiopathogenesis of post-traumatic stress disorder (PTSD). Using pharmacological and cognitive behavioral treatments that specifically target trauma memories can improve the outcome. Ketamine has been shown to rapidly improve symptoms in PTSD and comorbid depression, but unfortunately these effects are short-lived. Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy is a type of mindfulness based cognitive behavioral therapy that targets the trauma memories. TIMBER psychotherapy in combination with (R,S)-ketamine are increasingly used to treat PTSD and comorbid depression. This study aims to determine if the combination of (R,S)-ketamine chemotherapy and TIMBER psychotherapy would produce a positive synergistic response in patients with PTSD.
Design: This is a randomized, placebo-controlled, cross-over clinical study.
Methods: Because response to ketamine alone is short-lived, this study combined TIMBER with a single infusion of 0.5 mg/kg (R,S)-ketamine to sustain its therapeutic effects. Ten patients with chronic and refractory PTSD were randomly assigned to two groups (n = 5 each): TIMBER-K group patients received ketamine infusion in combination with 12 TIMBER sessions (3 sessions in the first week followed by 9 sessions conducted on a weekly basis) and TIMBER-P group patients received placebo (normal saline infusion) in combination with 12 TIMBER sessions. The patients in the TIMBER-P group were switched to those in the TIMBER-K group after they experienced a sustained relapse.
Outcome measures: PTSD Checklist (PCL), Clinician Administered PTSD Scale for DSM-IV (CAPS), the 17-item Hamilton Rating Scale for Depression (Ham-D-17, clinician rated), Beck Anxiety Inventory (BAI), and Montreal Cognitive Assessment (MoCA) at baseline and 8 hours after infusion were used to investigate if ketamine selectively affected trauma memories leaving the general memory intact. The mindfulness interventions in TIMBER were personalized based on subject’s scores on Assessment Scale for Mindfulness Interventions which was administered at baseline, and after 5 sessions and 9 sessions (completion) of TIMBER. In this study, scores on CAPS and PCL scales were the primary outcome measures.
Results: In the acute phase trial ( first 3 months after infusion), nine out of 10 subjects showed robust response in primary outcome measures (PCL and CAPS scores for PTSD) and in the secondary outcome measures (Ham-D-17 and Beck Anxiety Inventory for depression and anxiety respectively) with a sustained response of 31.78 ± 18.29 days. The TIMBER-K group had a more sustained response (33 ± 22.98 days) compared to the TIMBER-P group (25 ± 16.8 days, P = 0.545). After switch from TIMBER-P group to TIMBER-K, patients experienced significantly prolonged response (49 vs. 25 days, P = 0.028). There were no intolerable side effects or dropouts during the 18-month follow-up period.
Conclusion: TIMBER psychotherapy augmented with low dose (R,S)-ketamine prolongs the therapeutic effects of the later and may be a valuable treatment option for PTSD.
Pradhan, B. K., Wainer, I. W., Moaddel, R., Torjman, M. C., Goldberg, M., Sabia, M., … & Pumariega, A. J. (2017). Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy prolong the therapeutic effects of single ketamine infusion on post-traumatic stress disorder and comorbid depression: a pilot randomized, placebo-controlled, crossover clinical trial. Asia Pacific Journal of Clinical Trials: Nervous System Diseases, 2(3), 80. 10.4103/2542-3932.211589
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Psychotherapy with Adjuvant use of Serotonergic Psychoactive Substances: Possibilities and Challenges

August 2, 2017 / Anxiety disorders / PTSD, Depression, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychotherapy, Substance Use Disorder / By / , , , , ,

Abstract

Background Recently, scientific interest in the therapeutic potential of serotonergic and psilocybin hallucinogens (psychedelics) such as lysergic acid diethylamide (LSD) and entactogens like 3,4-methylendioxymethamphetamine (MDMA) within the framework of psychotherapy has resumed. The present article provides an overview on the current evidence on substance-assisted psychotherapy with these substances.
Method A selective search was carried out in the PubMed and Cochrane Library including studies investigating the clinical use of serotonergic psychoactive substances since 2000.
Results Studies were found investigating the following indications: alcohol (LSD and psilocybin) and tobacco addiction (psilocybin), anxiety and depression in patients suffering from life-threatening somatic illness (LSD and psilocybin), obsessive-compulsive disorder (OCD) (psilocybin), treatment-resistant major depression (psilocybin), and posttraumatic stress disorder (PTSD) (MDMA).
Discussion Substance use disorders, PTSD and anxiety and depression in patients suffering from life-threatening somatic illness belong to the indications with the best evidence for substance-assisted psychotherapy with serotonergic psychoactive agents. To date, studies indicate efficacy and relatively good tolerability. Further studies are needed to determine whether these substances may represent suitable and effective treatment options for some treatment-resistant psychiatric disorders in the future.
Majić, T., Jungaberle, H., Schmidt, T. T., Zeuch, A., Hermle, L., & Gallinat, J. (2017). Psychotherapy with Adjuvant use of Serotonergic Psychoactive Substances: Possibilities and Challenges. Fortschritte der Neurologie-Psychiatrie, 85(7), 383. 10.1055/s-0043-103085
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