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Awe: a putative mechanism underlying the effects of classic psychedelic-assisted psychotherapy

September 27, 2018 / Papers, Psychology, Publications / By /

Abstract

A psychological model of classic psychedelic-assisted psychotherapy informed by contemporary scientific data is presented in this paper. It is suggested that classic psychedelic-occasioned mystical experience is characterized by profound awe, a discrete emotion experienced in the presence of a vast stimulus requiring accommodation of mental structures. Awe, in turn, promotes the small self, a construct that, in the extreme, is analogous to those of unitive experience and ego dissolution. The small self is conceptualized as key to understanding the downstream effects of mystical experience occasioned in the context of classic psychedelic-assisted psychotherapy. With this novel theoretical framework in mind, a number of clinical implications and recommendations are provided so as to advance this incipient field of study.
Hendricks, P. S. (2018). Awe: a putative mechanism underlying the effects of classic psychedelic-assisted psychotherapy. International Review of Psychiatry, 30(4), 331-342., 10.1080/09540261.2018.1474185
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Understanding Central Nervous System Effects of Deliriant Hallucinogenic Drugs through Experimental Animal Models

September 25, 2018 / Neuroscience, Papers, Psychiatry & Medicine, Publications / By / , , , , , ,

Abstract

Hallucinogenic drugs potently alter human behavior and have a millennia-long history of use for medicinal and religious purposes. Interest is rapidly growing in their potential as CNS modulators and therapeutic agents for brain conditions. Antimuscarinic cholinergic drugs, such as atropine and scopolamine, induce characteristic hyperactivity and dream-like hallucinations and form a separate group of hallucinogens known as “deliriants”. Although atropine and scopolamine are relatively well-studied drugs in cholinergic physiology, deliriants represent the least-studied class of hallucinogens in terms of their behavioral and neurological phenotypes. As such, novel approaches and new model organisms are needed to investigate the CNS effects of these compounds. Here, we comprehensively evaluate the preclinical effects of deliriant hallucinogens in various animal models, their mechanisms of action, and potential interplay with other signaling pathways. We also parallel experimental and clinical findings on deliriant agents and outline future directions of translational research in this field.

Volgin, A. D., Yakovlev, O. A., Demin, K. A., Alekseeva, P. A., Kyzar, E. J., Collins, C., … & Kalueff, A. V. (2018). Understanding Central Nervous System Effects of Deliriant Hallucinogenic Drugs through Experimental Animal Models. ACS chemical neuroscience., 10.1021/acschemneuro.8b00433

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Psychedelics and the new behaviourism: considering the integration of third-wave behaviour therapies with psychedelic-assisted therapy

September 25, 2018 / Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

This narrative review examines evidence related to the potential for third wave behaviour therapies to serve as adjuncts to psychedelic-assisted therapy. It identifies shared theoretical foundations for both approaches, and notes enhanced mindfulness, decentering, emotion regulation, and distress tolerance as common mechanisms of action. It also identifies potential targets for which both approaches have demonstrated therapeutic potential, including problematic substance use, self-directed and other-directed violence, and mood disorders. Based on these commonalities, there is a call for research on the potential integration of psychedelic-assisted therapy and third wave behaviour therapies including Dialectical Behaviour Therapy, Acceptance and Commitment Therapy, and Mindfulness Based Cognitive Therapy.

Walsh, Z., & Thiessen, M. S. (2018). Psychedelics and the new behaviourism: considering the integration of third-wave behaviour therapies with psychedelic-assisted therapy. International Review of Psychiatry, 30(4), 343-349., 10.1080/09540261.2018.1474088
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Psychedelics and music: neuroscience and therapeutic implications

September 21, 2018 / Papers, Psychology, Publications / By / , ,

Abstract

From the beginning of therapeutic research with psychedelics, music listening has been consistently used as a method to guide or support therapeutic experiences during the acute effects of psychedelic drugs. Recent findings point to the potential of music to support meaning-making, emotionality, and mental imagery after the administration of psychedelics, and suggest that music plays an important role in facilitating positive clinical outcomes of psychedelic therapy. This review explores the history of, contemporary research on, and future directions regarding the use of music in psychedelic research and therapy, and argues for more detailed and rigorous investigation of the contribution of music to the treatment of psychiatric disorders within the novel framework of psychedelic therapy.
Barrett, F. S., Preller, K. H., & Kaelen, M. (2018). Psychedelics and music: neuroscience and therapeutic implications. International Review of Psychiatry, 30(4), 350-362., 10.1080/09540261.2018.1484342
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Psychoplastogens: A Promising Class of Plasticity-Promoting Neurotherapeutics

September 19, 2018 / Neuroscience, Papers, Psychology, Publications / By /

Abstract

Neural plasticity-the ability to change and adapt in response to stimuli-is an essential aspect of healthy brain function and, in principle, can be harnessed to promote recovery from a wide variety of brain disorders. Many neuropsychiatric diseases including mood, anxiety, and substance use disorders arise from an inability to weaken and/or strengthen pathologic and beneficial circuits, respectively, ultimately leading to maladaptive behavioral responses. Thus, compounds capable of facilitating the structural and functional reorganization of neural circuits to produce positive behavioral effects have broad therapeutic potential. Several known drugs and experimental therapeutics have been shown to promote plasticity, but most rely on indirect mechanisms and are slow-acting. Here, I describe psychoplastogens-a relatively new class of fast-acting therapeutics, capable of rapidly promoting structural and functional neural plasticity. Psychoplastogenic compounds include psychedelics, ketamine, and several other recently discovered fast-acting antidepressants. Their use in psychiatry represents a paradigm shift in our approach to treating brain disorders as we focus less on rectifying “chemical imbalances” and place more emphasis on achieving selective modulation of neural circuits.
Olson, D. E. (2018). Psychoplastogens: A Promising Class of Plasticity-Promoting Neurotherapeutics. Journal of experimental neuroscience, 12, 1179069518800508., 10.1177/1179069518800508
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Dimensions of consciousness and the psychedelic state

September 19, 2018 / Anthropology & Sociology, Ayahuasca, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications, Salvia / Salvinorin A / By / ,

Abstract

It has often been suggested in the popular and academic literature that the psychedelic state qualifies as a higher state of consciousness relative to the state of normal waking awareness. This article subjects this proposal to critical scrutiny, focusing on the question of what it would mean for a state of consciousness to be ‘higher’. We begin by considering the contrast between conscious contents and conscious global states. We then review the changes in conscious global state associated with psychedelic drug use, focusing on the effects of two serotonergic hallucinogens: psilocybin and lysergic acid diethylamide. Limiting our review to findings obtained from lab-based experiments and reported in peer-reviewed journals, we prioritize the more common and reliably induced effects obtained through subjective questionnaires and psychophysical measures. The findings are grouped into three broad categories (sensory perception, cognitive function, and experiences of unity) and demonstrate that although certain aspects of consciousness are improved or enhanced in the psychedelic state, many of the functional capacities that are associated with consciousness are seriously compromised. Psychedelic-induced states of consciousness are indeed remarkable in many ways, but it is inappropriate to regard them as ‘higher’ states of consciousness. The fact that psychedelics affect different aspects of consciousness in fundamentally different ways provides evidence against the unidimensional (or ‘level-based’) view of consciousness, and instead provides strong support for a multidimensional conception of conscious states. The final section of the article considers the implications of this analysis for two prominent theories of consciousness: the Global Workspace Theory and Integrated Information Theory.

Bayne, T., & Carter, O. (2018). Dimensions of consciousness and the psychedelic state. Neuroscience of consciousness, 2018(1), niy008., 10.1093/nc/niy008
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Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: A randomized, double blind, placebo controlled trial.

September 17, 2018 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

BACKGROUND:
Several studies indicate that ketamine has rapid antidepressant effects in patients with treatment-resistant depression (TRD). The extent to which repeated doses of ketamine (versus placebo) reduce depression in the short and long term among outpatients with TRD and chronic, current suicidal ideation remains unknown.
METHODS:
Twenty-six medicated outpatients with severe major depressive disorder with current, chronic suicidal ideation were randomized in a double-blind fashion to six ketamine infusions (0.5 mg/kg over 45 minutes) or saline placebo over three weeks. Depression and suicidal ideation were assessed at baseline, 240 min post-infusion, and during a three-month follow-up phase.
RESULTS:
During the infusion phase, there was no differences in depression severity or suicidal ideation between placebo and ketamine (p = 0.47 and p = 0.32, respectively). At the end of the infusion phase, two patients in the ketamine group and one in the placebo group met criteria for remission of depression. At three-month follow-up, two patients in each group met criteria for remission from depression.
LIMITATIONS:
Limitations include the small sample size, uncontrolled outpatient medication regimens, and restriction to outpatients, which may have resulted in lower levels of suicidal ideation than would be seen in emergency or inpatient settings.
CONCLUSIONS:
Repeated, non-escalating doses of ketamine did not outperform placebo in this double-blind, placebo controlled study of patients with severe TRD and current, chronic suicidal ideation. This result may support our previously published open-label data that, in this severely and chronically ill outpatient population, the commonly used dose of 0.5 mg/kg is not sufficient.
Ionescu, D. F., Bentley, K. H., Eikermann, M., Taylor, N., Johnson-Akeju, O., Swee, M. B., … & Alpert, J. E. (2019). Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: A randomized, double blind, placebo controlled trial. Journal of Affective Disorders, 243, 516-524, 10.1016/j.jad.2018.09.037
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Hemorheological and metabolic consequences of renal ischemia-reperfusion and their modulation by N,N-dimethyl-tryptamine on a rat model

September 14, 2018 / DMT, Papers, Psychiatry & Medicine, Publications / By / , , , , ,

Abstract

BACKGROUND:
Micro-rheological relations of renal ischemia-reperfusion (I/R) have not been completely elucidated yet. Concerning anti-inflammatory agents, it is supposed that sigma-1 receptor agonist N,N-dimethyl-tryptamin (DMT) can be useful to reduce I/R injury.
OBJECTIVE:
To investigate the micro-rheological and metabolic parameters, and the effects of DMT in renal I/R in rats.
METHODS:
In anesthetized rats from median laparotomy both kidneys were exposed. In Control group (n = 6) no other intervention happened. In I/R group (n = 10) the right renal vessels were ligated and after 60 minutes the organ was removed. The left renal vessels were clamped for 60 minutes followed by 120-minute reperfusion. In I/R+DMT group (n = 10) DMT was administered 15 minutes before the ischemia. Blood samples were taken before/after ischemia and during the reperfusion for testing hematological, metabolic parameters, erythrocyte deformability and aggregation.
RESULTS:
Lactate concentration significantly increased and accompanied with decreased blood pH. Enhanced erythrocyte aggregation and impaired deformability were observed from the 30th minute of reperfusion. In I/R+DMT group we found diminished changes compared to the I/R group (lactate, pH, electrolytes, red blood cell deformability and aggregation).
CONCLUSIONS:
Metabolic and micro-rheological parameters impair during renal I/R. DMT could reduce but not completely prevent the changes in this rat model.
Peto, K., Nemeth, N., Mester, A., Magyar, Z., Ghanem, S., Somogyi, V., … & Nemes, B. (2018). Hemorheological and metabolic consequences of renal ischemia-reperfusion and their modulation by N, N-dimethyl-tryptamine on a rat model. Clinical hemorheology and microcirculation, (Preprint), 1-11. 10.3233/CH-170361
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Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study.

September 8, 2018 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , , , , ,

Abstract

RATIONALE:
Standard therapeutic approaches to reduce social anxiety in autistic adults have limited effectiveness. Since 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy shows promise as a treatment for other anxiety disorders, a blinded, placebo-controlled pilot study was conducted.
OBJECTIVES:
To explore feasibility and safety of MDMA-assisted psychotherapy for reduction of social fear and avoidance that are common in the autistic population.
METHODS:
Autistic adults with marked to very severe social anxiety were randomized to receive MDMA (75 to 125 mg, n = 8) or inactive placebo (0 mg, n = 4) during two 8-h psychotherapy sessions (experimental sessions) in a controlled clinical setting. Double-blinded experimental sessions were spaced approximately 1 month apart with 3 non-drug psychotherapy sessions following each. The primary outcome was change in Leibowitz Social Anxiety Scale (LSAS) Total scores from Baseline to one month after the second experimental session. Outcomes were measured again six months after the last experimental session.
RESULTS:
Improvement in LSAS scores from baseline to the primary endpoint was significantly greater for MDMA group compared to the placebo group (P = 0.037), and placebo-subtracted Cohen’s d effect size was very large (d = 1.4, CI - 0.074, 2.874). Change in LSAS scores from baseline to 6-month follow-up showed similar positive results (P = 0.036), with a Cohen’s d effect size of 1.1 (CI - 0.307, 2.527). Social anxiety remained the same or continued to improve slightly for most participants in the MDMA group after completing the active treatment phase.
CONCLUSIONS:
This pilot trial demonstrated rapid and durable improvement in social anxiety symptoms in autistic adults following MDMA-assisted psychotherapy. Initial safety and efficacy outcomes support expansion of research into larger samples to further investigate this novel treatment for social anxiety.
Danforth, A. L., Grob, C. S., Struble, C., Feduccia, A. A., Walker, N., Jerome, L., … & Emerson, A. (2018). Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Psychopharmacology, 235(11), 3137-3148., 10.1007/s00213-018-5010-9
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Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study.

September 8, 2018 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , , , , ,

Abstract

RATIONALE:
Standard therapeutic approaches to reduce social anxiety in autistic adults have limited effectiveness. Since 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy shows promise as a treatment for other anxiety disorders, a blinded, placebo-controlled pilot study was conducted.
OBJECTIVES:
To explore feasibility and safety of MDMA-assisted psychotherapy for reduction of social fear and avoidance that are common in the autistic population.
METHODS:
Autistic adults with marked to very severe social anxiety were randomized to receive MDMA (75 to 125 mg, n = 8) or inactive placebo (0 mg, n = 4) during two 8-h psychotherapy sessions (experimental sessions) in a controlled clinical setting. Double-blinded experimental sessions were spaced approximately 1 month apart with 3 non-drug psychotherapy sessions following each. The primary outcome was change in Leibowitz Social Anxiety Scale (LSAS) Total scores from Baseline to one month after the second experimental session. Outcomes were measured again six months after the last experimental session.
RESU LTS:
Improvement in LSAS scores from baseline to the primary endpoint was significantly greater for MDMA group compared to the placebo group (P = 0.037), and placebo-subtracted Cohen’s d effect size was very large (d = 1.4, CI - 0.074, 2.874). Change in LSAS scores from baseline to 6-month follow-up showed similar positive results (P = 0.036), with a Cohen’s d effect size of 1.1 (CI - 0.307, 2.527). Social anxiety remained the same or continued to improve slightly for most participants in the MDMA group after completing the active treatment phase.
CONCLUSIONS:
This pilot trial demonstrated rapid and durable improvement in social anxiety symptoms in autistic adults following MDMA-assisted psychotherapy. Initial safety and efficacy outcomes support expansion of research into larger samples to further investigate this novel treatment for social anxiety.
Danforth, A. L., Grob, C. S., Struble, C., Feduccia, A. A., Walker, N., Jerome, L., … & Emerson, A. (2018). Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Psychopharmacology, 235(11), 3137-3148, 10.1007/s00213-018-5010-9
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