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Psychotherapy

Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants

January 7, 2022 / Depression, Ketamine, Neuroscience, Other substances, Papers, Psychiatry, Psychopharmacology, Psychotherapy / Leave a Comment / By / , , , , , ,

Abstract

Background: The glutamatergic modulator ketamine has created a blueprint for studying novel pharmaceuticals in the field. Recent studies suggest that “classic” serotonergic psychedelics (SPs) may also have antidepressant efficacy. Both ketamine and SPs appear to produce rapid, sustained antidepressant effects after a transient psychoactive period.

Methods: This review summarizes areas of overlap between SP and ketamine research and considers the possibility of a common, downstream mechanism of action. The therapeutic relevance of the psychoactive state, overlapping cellular and molecular effects, and overlapping electrophysiological and neuroimaging observations are all reviewed.

Results: Taken together, the evidence suggests a potentially shared mechanism wherein both ketamine and SPs may engender rapid neuroplastic effects in a glutamatergic activity-dependent manner. It is postulated that, though distinct, both ketamine and SPs appear to produce acute alterations in cortical network activity that may initially produce psychoactive effects and later produce milder, sustained changes in network efficiency associated with therapeutic response. However, despite some commonalities between the psychoactive component of these pharmacologically distinct therapies-such as engagement of the downstream glutamatergic pathway-the connection between psychoactive impact and antidepressant efficacy remains unclear and requires more rigorous research.

Conclusions: Rapid-acting antidepressants currently under investigation may share some downstream pharmacological effects, suggesting that their antidepressant effects may come about via related mechanisms. Given the prototypic nature of ketamine research and recent progress in this area, this platform could be used to investigate entirely new classes of antidepressants with rapid and robust actions.

Kadriu, B., Greenwald, M., Henter, I. D., Gilbert, J. R., Kraus, C., Park, L. T., & Zarate, C. A. (2021). Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants. The international journal of neuropsychopharmacology, 24(1), 8–21. https://doi.org/10.1093/ijnp/pyaa087

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Classical Psychedelics as Therapeutics in Psychiatry – Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders

February 6, 2022 / Addiction, Depression, Other substances, Papers, Psychiatry, Psychotherapy / Leave a Comment / By / ,

Abstract

Classical psychedelics, primarily psilocybin and lysergic acid diethylamide (LSD), have been used and extensively studied in Western medicine as part of substance-assisted psychotherapy in the 1950s and 1960s. Modern clinical research is currently gaining momentum and provides new evidence for the safety and efficacy of classical psychedelics (primarily psilocybin, but also LSD and ayahuasca) in the treatment of different psychiatric conditions, including substance use and mood disorders.In this review article, we outline common pathological mechanisms of substance use disorders (SUD) and unipolar depression. Next, the current literature on the effects of psychedelics is summarized in order to generate hypotheses regarding their potential therapeutic mechanisms of action in treating these psychiatric conditions. Finally, we review and discuss clinical trials published since 2011 investigating the effects of psychedelics in SUD and depression.While results from those modern clinical trials are promising, most of them do not meet the methodological requirements to allow firm conclusions on the clinical efficacy of psychedelics. Larger, blinded, randomized controlled trials (RCT) with clearly defined patient groups and well-defined primary endpoints are needed. Additionally, the therapeutic mechanisms of classical psychedelics are currently unknown. This review presents hypotheses derived from preclinical and human studies that need to be tested in future trials to better understand the clinical potential of psychedelic substances in modern psychiatry.

Mertens, L. J., & Preller, K. H. (2021). Classical Psychedelics as Therapeutics in Psychiatry – Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders. Pharmacopsychiatry, 54(4), 176–190. https://doi.org/10.1055/a-1341-1907

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Pharmacological-assisted Psychotherapy for Post-Traumatic Stress Disorder: a systematic review and meta-analysis

February 21, 2022 / Anxiety disorders / PTSD, MDMA, Papers, Psychotherapy / Leave a Comment / By / , , , , , , , , ,

Abstract

Background: Pharmacological-assisted psychotherapies, using conventional and novel drug agents, are increasingly being used both in clinical and experimental research settings, respectively. Objective: To determine the efficacy of conventional and novel pharmacological-assisted psychotherapies in reducing PTSD symptom severity. Method: A systematic review and meta-analysis of randomised-controlled trials were undertaken; 21 studies were included. Results: MDMA-assisted therapy was found to statistically superior to active and inactive placebo-assisted therapy in reduction of PTSD symptoms (standardised mean difference -1.09, 95% CI -1.60 to -0.58). There was no evidence of superiority over placebo for any other intervention. Conclusions: MDMA-assisted therapy demonstrated an impressive effect size; however, it is difficult to have confidence at this stage in this intervention due to the small numbers of participants included, and more research in this area is needed. There was no evidence to support the efficacy of any other drug-assisted interventions.

Hoskins, M. D., Sinnerton, R., Nakamura, A., Underwood, J., Slater, A., Lewis, C., Roberts, N. P., Bisson, J. I., Lee, M., & Clarke, L. (2021). Pharmacological-assisted Psychotherapy for Post-Traumatic Stress Disorder: a systematic review and meta-analysis. European journal of psychotraumatology, 12(1), 1853379. https://doi.org/10.1080/20008198.2020.1853379

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Classic serotonergic psychedelics for mood and depressive symptoms: a meta-analysis of mood disorder patients and healthy participants

February 6, 2022 / Depression, Other substances, Papers, Psychotherapy / Leave a Comment / By / , , , , , ,

Abstract

Rationale: Major depressive disorder is one of the leading global causes of disability, for which the classic serotonergic psychedelics have recently reemerged as a potential therapeutic treatment option.

Objective: We present the first meta-analytic review evaluating the clinical effects of classic serotonergic psychedelics vs placebo for mood state and symptoms of depression in both healthy and clinical populations (separately).

Results: Our search revealed 12 eligible studies (n = 257; 124 healthy participants, and 133 patients with mood disorders), with data from randomized controlled trials involving psilocybin (n = 8), lysergic acid diethylamide ([LSD]; n = 3), and ayahuasca (n = 1). The meta-analyses of acute mood outcomes (3 h to 1 day after treatment) for healthy volunteers and patients revealed improvements with moderate significant effect sizes in favor of psychedelics, as well as for the longer-term (16 to 60 days after treatments) mood state of patients. For patients with mood disorder, significant effect sizes were detected on the acute, medium (2-7 days after treatment), and longer-term outcomes favoring psychedelics on the reduction of depressive symptoms.

Conclusion: Despite the concerns over unblinding and expectancy, the strength of the effect sizes, fast onset, and enduring therapeutic effects of these psychotherapeutic agents encourage further double-blind, placebo-controlled clinical trials assessing them for management of negative mood and depressive symptoms.

Galvão-Coelho, N. L., Marx, W., Gonzalez, M., Sinclair, J., de Manincor, M., Perkins, D., & Sarris, J. (2021). Classic serotonergic psychedelics for mood and depressive symptoms: a meta-analysis of mood disorder patients and healthy participants. Psychopharmacology, 238(2), 341–354. https://doi.org/10.1007/s00213-020-05719-1

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The acute effects of classic psychedelics on memory in humans

February 6, 2022 / Other substances, Papers, Psychology, Psychotherapy / Leave a Comment / By /

Abstract

Rationale: Memory plays a central role in the psychedelic experience. The spontaneous recall and immersive reliving of autobiographical memories has frequently been noted by researchers and clinicians as a salient phenomenon in the profile of subjective effects of classic psychedelic drugs such as psilocybin, LSD, and ayahuasca. The ability for psychedelics to provoke vivid memories has been considered important to their clinical efficacy.

Objective: This review aims to examine and aggregate the findings from experimental, observational, and qualitative studies on the acute modulation of memory by classic psychedelics in humans.

Method: A literature search was conducted using PubMed and PsycInfo as well as manual review of references from eligible studies. Publications reporting quantitative and/or qualitative findings were included; animal studies and case reports were excluded.

Results: Classic psychedelics produce dose-dependently increasing impairments in memory task performance, such that low doses produce no impairment and higher doses produce increasing levels of impairment. This pattern has been observed in tasks assessing spatial and verbal working memory, semantic memory, and non-autobiographical episodic memory. Such impairments may be less pronounced among experienced psychedelic users. Classic psychedelics also increase the vividness of autobiographical memories and frequently stimulate the recall and/or re-experiencing of autobiographical memories, often memories that are affectively intense (positively or negatively valenced) and that had been avoided and/or forgotten prior to the experience.

Conclusions: Classic psychedelics dose-dependently impair memory task performance but may enhance autobiographical memory. These findings are relevant to the understanding of psychological mechanisms of action of psychedelic-assisted psychotherapy.

Healy C. J. (2021). The acute effects of classic psychedelics on memory in humans. Psychopharmacology, 238(3), 639–653. https://doi.org/10.1007/s00213-020-05756-w

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The acute effects of classic psychedelics on memory in humans

February 21, 2022 / Ayahuasca, LSD, Mushrooms / Psilocybin, Papers, Psychology, Psychopharmacology, Psychotherapy / Leave a Comment / By /

Abstract

Rationale: Memory plays a central role in the psychedelic experience. The spontaneous recall and immersive reliving of autobiographical memories has frequently been noted by researchers and clinicians as a salient phenomenon in the profile of subjective effects of classic psychedelic drugs such as psilocybin, LSD, and ayahuasca. The ability for psychedelics to provoke vivid memories has been considered important to their clinical efficacy.

Objective: This review aims to examine and aggregate the findings from experimental, observational, and qualitative studies on the acute modulation of memory by classic psychedelics in humans.

Method: A literature search was conducted using PubMed and PsycInfo as well as manual review of references from eligible studies. Publications reporting quantitative and/or qualitative findings were included; animal studies and case reports were excluded.

Results: Classic psychedelics produce dose-dependently increasing impairments in memory task performance, such that low doses produce no impairment and higher doses produce increasing levels of impairment. This pattern has been observed in tasks assessing spatial and verbal working memory, semantic memory, and non-autobiographical episodic memory. Such impairments may be less pronounced among experienced psychedelic users. Classic psychedelics also increase the vividness of autobiographical memories and frequently stimulate the recall and/or re-experiencing of autobiographical memories, often memories that are affectively intense (positively or negatively valenced) and that had been avoided and/or forgotten prior to the experience.

Conclusions: Classic psychedelics dose-dependently impair memory task performance but may enhance autobiographical memory. These findings are relevant to the understanding of psychological mechanisms of action of psychedelic-assisted psychotherapy.

Healy C. J. (2021). The acute effects of classic psychedelics on memory in humans. Psychopharmacology, 238(3), 639–653. https://doi.org/10.1007/s00213-020-05756-w

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Psychedelic Medicines in Major Depression: Progress and Future Challenges

March 14, 2022 / Depression, Papers, Psychopharmacology, Psychotherapy / Leave a Comment / By / , , ,

Abstract

The volume of research on the therapeutic use of psychedelic drugs has been increasing during the last decades. Partly because of the need of innovative treatments in psychiatry, several studies have assessed the safety and efficacy of drugs like psilocybin or ayahuasca for a wide range of mental disorders, including major depression. The first section of this chapter will offer an introduction to psychedelic research, including a brief historical overview and discussions about appropriate terminology. In the second section, the recently published clinical trials in which psychedelic drugs were administered to patients will be analysed in detail. Then, in the third section, the main neurobiological mechanisms of these drugs will be described, noting that while some of these mechanisms could be potentially associated with their therapeutic properties, they are commonly used as adjuvants in psychotherapeutic processes. The last section suggests future challenges for this groundbreaking field of research and therapy.

Bouso, J. C., Ona, G., Dos Santos, R. G., & Hallak, J. (2021). Psychedelic Medicines in Major Depression: Progress and Future Challenges. Advances in experimental medicine and biology, 1305, 515–533. https://doi.org/10.1007/978-981-33-6044-0_26

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Set and Setting: A Randomized Study of Different Musical Genres in Supporting Psychedelic Therapy

March 16, 2022 / Addiction, Other disciplines, Papers, Psychotherapy / Leave a Comment / By / , ,

Abstract

Mounting evidence supports the serotonin 2A receptor agonist psilocybin as a psychiatric pharmacotherapy. Little research has experimentally examined how session “set and setting” impacts subjective and therapeutic effects. We analyzed the effects of the musical genre played during sessions of a psilocybin study for tobacco smoking cessation. Participants (N = 10) received psilocybin (20-30 mg/70 kg) in two sessions, each with a different musical genre (Western classical versus overtone-based), with the order counterbalanced. Participants chose one genre for a third session (30 mg/70 kg). Mystical experiences scores tended to be higher in overtone-based sessions than in Western classical sessions. Six of ten participants chose the overtone-based music for a third session. Biologically confirmed smoking abstinence was similar based on musical choice, with a slight benefit for participants choosing the overtone-based playlist (66.7% versus 50%). These data call into question whether Western classical music typically used in psychedelic therapy holds a unique benefit. Broadly, we call for experimentally examining session components toward optimizing psychedelic therapeutic protocols.

Strickland, J. C., Garcia-Romeu, A., & Johnson, M. W. (2020). Set and Setting: A Randomized Study of Different Musical Genres in Supporting Psychedelic Therapy. ACS pharmacology & translational science, 4(2), 472–478. https://doi.org/10.1021/acsptsci.0c00187

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A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis

February 6, 2022 / Anxiety disorders / PTSD, MDMA, Papers, Psychiatry, Psychotherapy / Leave a Comment / By / , , , , , ,

Abstract

Rationale: Novel, evidence-based treatments are required for treatment-resistant post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine (MDMA) has beneficially augmented psychotherapy in several small clinical trials.

Objective: To review the use of MDMA-assisted psychotherapy in treatment-resistant PTSD.

Methods: Systematic searches of four databases were conducted from inception to February 2020. A meta-analysis was performed on trials which were double-blinded, randomised, and compared MDMA-assisted psychotherapy to psychotherapy and placebo. The primary outcomes were the differences in Clinician Administered PTSD Scale (CAPS-IV) score and Beck’s Depression Inventory (BDI). Secondary outcome measures included neurocognitive and physical adverse effects, at the time, and within 7 days of intervention.

Results: Four randomised controlled trials (RCTs) met inclusion criteria. When compared to active placebo, intervention groups taking 75 mg (MD -46.90; 95% (confidence intervals) CI -58.78, -35.02), 125 mg (MD -20.98; 95% CI -34.35, -7.61) but not 100 mg (MD -12.90; 95% CI -36.09, 10.29) of MDMA with psychotherapy, had significant decreases in CAPS-IV scores, as did the inactive placebo arm (MD -33.20; 95% CI -40.53, -25.87). A significant decrease in BDI when compared to active placebo (MD -10.80; 95% CI -20.39, -1.21) was only observed at 75 mg. Compared to placebo, participants reported significantly more episodes of low mood, nausea and jaw-clenching during sessions and lack of appetite after 7 days.

Conclusion: These results demonstrate potential therapeutic benefit with minimal physical and neurocognitive risk for the use of MDMA-assisted psychotherapy in TR-PTSD, despite little effect on Beck’s Depression Inventory. Better powered RCTs are required to investigate further.

Illingworth, B. J., Lewis, D. J., Lambarth, A. T., Stocking, K., Duffy, J. M., Jelen, L. A., & Rucker, J. J. (2021). A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis. Journal of psychopharmacology (Oxford, England), 35(5), 501–511. https://doi.org/10.1177/0269881120965915

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Consciousness, Religion, and Gurus: Pitfalls of Psychedelic Medicine

March 14, 2022 / Other subjects, Papers, Psychotherapy / Leave a Comment / By /

Abstract

This viewpoint identifies pitfalls in the study of psychedelic compounds, including those that pose challenges for the potential use of psychedelics as medicines. They are as follows: (1) Sloppiness regarding use of the term “consciousness”. (2) Inappropriate introduction of religious/spiritual beliefs of investigators or clinicians. (3) Clinical boundaries and other ethical challenges associated with psychedelic treatments.

Johnson M. W. (2020). Consciousness, Religion, and Gurus: Pitfalls of Psychedelic Medicine. ACS pharmacology & translational science, 4(2), 578–581. https://doi.org/10.1021/acsptsci.0c00198

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7 May - Psychedelics, Nature & Mental Health with Sam Gandy

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