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Therapeutic Application

Capturing the different health conditions that PAP may adress

Trip: Psychedelics, Alienation, and Change

December 26, 2021 / Substance Use Disorder / Leave a Comment / By

Trip: Psychedelics, Alienation, and Change. Tao Lin. Random House USA. ISBN: 9781101974513

After discovering the works of Terence McKenna, Lin embarks on a journey of personal discovery that aids his recovery from addiction, changes his world view and leads him to ask big questions such as: Why do we make art? Is the world made of language? What happens when we die? And is the imagination more real than the universe?

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How to Change Your Mind: The New Science of Psychedelics

December 25, 2021 / Anxiety Disorders / PTSD, Depressive Disorders, Palliative Care+ / Leave a Comment / By

How to Change Your Mind: The New Science of Psychedelics. Michael Pollan. The Penguin Press. ISBN: 9781594204227

A highly accessible and enjoyable read through the history of psychedelic research and use starting in the 1960s up to the present day. Pollan applies his quintessential experiential journalism approach to various psychedelic substances – starting off hesitantly, as he weaves through the research and has several personal experiences, Pollan becomes a measured advocate for the power psychedelics have to change our minds and more.

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The Dream Drugstore: Chemically Altered States of Consciousness

December 24, 2021 / Psychotic Disorders / Leave a Comment / By

The Dream Drugstore: Chemically Altered States of Consciousness. J. Allan Hobson. A Bradford Book. ISBN: 978-0262582209

American psychiatrist and renowned dream researcher compares REM sleep, psychosis and LSD-induced psychedelic states finding that the brain state, in terms of the neurotransmitters and part of the brain activated, are remarkably similar. This book is ideal for anyone who wants an in-depth understanding of the neuroscience behind these brain states. Hobson admits to a “deep-seated bias” against all drugs, and take the view that “the distinction between the legal and the illegal is now so blurred as to make us realize that we are living in a drug culture on both sides of the law.”

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Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study

February 6, 2022 / Iboga / Ibogaine, Papers, Substance Use Disorder / Leave a Comment / By / , , , , , ,

Abstract

Background and aims: Ibogaine is an indole alkaloid used in rituals of the African Bwiti tribe. It is also used in non-medical settings to treat addiction. However, ibogaine has been linked to several deaths, mainly due to cardiac events called torsades des pointes preceded by QTc prolongation as well as other safety concerns. This study aimed to evaluate the cardiac, cerebellar and psychomimetic safety of ibogaine in patients with opioid use disorder.

Design: A descriptive open-label observational study.

Setting: Department of psychiatry in a university medical center, the Netherlands.

Participants: Patients with opioid use disorder (n = 14) on opioid maintenance treatment with a lasting wish for abstinence, who failed to reach abstinence with standard care.

Intervention and measurements: After conversion to morphine-sulphate, a single dose of ibogaine-HCl 10 mg/kg was administered and patients were monitored at regular intervals for at least 24 hours assessing QTc, blood pressure and heart rate, scale for the assessment and rating of ataxia (SARA) to assess cerebellar side effects and the delirium observation scale (DOS) to assess psychomimetic effects.

Findings: The maximum QTc (Fridericia) prolongation was on average 95ms (range 29-146ms). Fifty percent of subjects reached a QTc of over 500ms during the observation period. In six out 14 subjects prolongation above 450ms lasted beyond 24 hours after ingestion of ibogaine. No torsades des pointes were observed. Severe transient ataxia with inability to walk without support was seen in all patients. Withdrawal and psychomimetic effects were mostly well-tolerated and manageable (11/14 did not return to morphine within 24 hours, DOS scores remained below threshold).

Conclusions: This open-label observational study found that ibogaine treatment of patients with opioid use disorder can induce a clinically relevant but reversible QTc prolongation, bradycardia, and severe ataxia.

Knuijver, T., Schellekens, A., Belgers, M., Donders, R., van Oosteren, T., Kramers, K., & Verkes, R. (2022). Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study. Addiction (Abingdon, England), 117(1), 118–128. https://doi.org/10.1111/add.15448

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Habenula Connectivity and Intravenous Ketamine in Treatment-Resistant Depression

January 6, 2022 / Depressive Disorders, Ketamine, Neuroscience, Papers / Leave a Comment / By / , , , , ,

Abstract

Background: Ketamine’s potent and rapid antidepressant properties have shown great promise to treat severe forms of major depressive disorder (MDD). A recently hypothesized antidepressant mechanism of action of ketamine is the inhibition of N-methyl-D-aspartate receptor-dependent bursting activity of the habenula (Hb), a small brain structure that modulates reward and affective states.

Methods: Resting-state functional magnetic resonance imaging was conducted in 35 patients with MDD at baseline and 24 hours following treatment with i.v. ketamine. A seed-to-voxel functional connectivity (FC) analysis was performed with the Hb as a seed-of-interest. Pre-post changes in FC and the associations between changes in FC of the Hb and depressive symptom severity were examined.

Results: A reduction in Montgomery-Åsberg Depression Rating Scale scores from baseline to 24 hours after ketamine infusion was associated with increased FC between the right Hb and a cluster in the right frontal pole (t = 4.65, P = .03, false discovery rate [FDR]-corrected). A reduction in Quick Inventory of Depressive Symptomatology-Self Report score following ketamine was associated with increased FC between the right Hb and clusters in the right occipital pole (t = 5.18, P < .0001, FDR-corrected), right temporal pole (t = 4.97, P < .0001, FDR-corrected), right parahippocampal gyrus (t = 5.80, P = .001, FDR-corrected), and left lateral occipital cortex (t = 4.73, P = .03, FDR-corrected). Given the small size of the Hb, it is possible that peri-habenular regions contributed to the results.

Conclusions: These preliminary results suggest that the Hb might be involved in ketamine’s antidepressant action in patients with MDD, although these findings are limited by the lack of a control group.

Rivas-Grajales, A. M., Salas, R., Robinson, M. E., Qi, K., Murrough, J. W., & Mathew, S. J. (2021). Habenula Connectivity and Intravenous Ketamine in Treatment-Resistant Depression. The international journal of neuropsychopharmacology, 24(5), 383–391. https://doi.org/10.1093/ijnp/pyaa089

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Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial

January 3, 2022 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology / Leave a Comment / By / , , , , , , ,

Abstract

Importance: Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression.

Objective: To investigate the effect of psilocybin therapy in patients with MDD.

Design, setting, and participants: This randomized, waiting list-controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population).

Interventions: Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay.

Main outcomes and measures: The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR).

Results: Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P < .001) and week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P < .001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 2.6; 95% CI, 1.8-3.5; P < .001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d = 2.3; 95% CI, 1.5-3.0; P < .001). In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score).

Conclusions and relevance: Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression.

Trial registration: ClinicalTrials.gov Identifier: NCT03181529.

Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021). Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA psychiatry, 78(5), 481–489. https://doi.org/10.1001/jamapsychiatry.2020.3285

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Posttraumatic Stress Disorder After a Psychedelic Experience, a Case Report

November 18, 2021 / Anxiety Disorders / PTSD, DMT, LSD, Papers / Leave a Comment / By / , ,

Abstract

In the last 2 decades, there is a renaissance in the scientific investigation of the therapeutic potential of psychedelic compounds. It is studied for the treatment of many psychiatric disorders, including posttraumatic stress disorder. The treatment is always done in the setting of psychedelic-assisted psychotherapy. A little is known about the potential effects, outside of the setting of psychedelic-assisted psychotherapy, on people diagnosed with a mental disorder or have a significant trauma history. In this case report, we present a young man who developed posttraumatic stress disorder after a psychedelic experience, induced by both Lysergic Acid Diethylamide (LSD) and N, N Dimethyltryptamine (DMT). In the psychedelic experience, a repressed memory of childhood sexual abuse was recovered. To our knowledge, this is the first report on posttraumatic stress disorder onset after a psychedelic experience. We believe that this case report is important since the history of trauma is prevalent among individuals with substance use disorder. Medical staff that treat people with either substance use disorder or trauma should be familiar with irregular presentations, such as the one described in this case.

Rubin-Kahana, D. S., Hassan, A. N., & Le Foll, B. (2021). Posttraumatic Stress Disorder After a Psychedelic Experience, a Case Report. Journal of addiction medicine, 15(3), 248–251. https://doi.org/10.1097/ADM.0000000000000734

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Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice

March 16, 2022 / Depressive Disorders, Mushrooms / Psilocybin, Neuroscience, Papers / Leave a Comment / By / , , , ,

Abstract

Depression is a widespread and devastating mental illness and the search for rapid-acting antidepressants remains critical. There is now exciting evidence that the psychedelic compound psilocybin produces not only powerful alterations of consciousness, but also rapid and persistent antidepressant effects. How psilocybin exerts its therapeutic actions is not known, but it is widely presumed that these actions require altered consciousness, which is known to be dependent on serotonin 2A receptor (5-HT2AR) activation. This hypothesis has never been tested, however. We therefore asked whether psilocybin would exert antidepressant-like responses in mice and, if so, whether these responses required 5-HT2AR activation. Using chronically stressed male mice, we observed that a single injection of psilocybin reversed anhedonic responses assessed with the sucrose preference and female urine preference tests. The antianhedonic response to psilocybin was accompanied by a strengthening of excitatory synapses in the hippocampus-a characteristic of traditional and fast-acting antidepressants. Neither behavioral nor electrophysiological responses to psilocybin were prevented by pretreatment with the 5-HT2A/2C antagonist ketanserin, despite positive evidence of ketanserin’s efficacy. We conclude that psilocybin’s mechanism of antidepressant action can be studied in animal models and suggest that altered perception may not be required for its antidepressant effects. We further suggest that a 5-HT2AR-independent restoration of synaptic strength in cortico-mesolimbic reward circuits may contribute to its antidepressant action. The possibility of combining psychedelic compounds and a 5-HT2AR antagonist offers a potential means to increase their acceptance and clinical utility and should be studied in human depression.

Hesselgrave, N., Troppoli, T. A., Wulff, A. B., Cole, A. B., & Thompson, S. M. (2021). Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice. Proceedings of the National Academy of Sciences of the United States of America, 118(17), e2022489118. https://doi.org/10.1073/pnas.2022489118

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Trial of Psilocybin versus Escitalopram for Depression

March 16, 2022 / Depressive Disorders, Mushrooms / Psilocybin, Papers / Leave a Comment / By / , , , , , , , , ,

Abstract

Background: Psilocybin may have antidepressant properties, but direct comparisons between psilocybin and established treatments for depression are lacking.

Methods: In a phase 2, double-blind, randomized, controlled trial involving patients with long-standing, moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, a selective serotonin-reuptake inhibitor, over a 6-week period. Patients were assigned in a 1:1 ratio to receive two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo (psilocybin group) or two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram (escitalopram group); all the patients received psychological support. The primary outcome was the change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16; scores range from 0 to 27, with higher scores indicating greater depression) at week 6. There were 16 secondary outcomes, including QIDS-SR-16 response (defined as a reduction in score of >50%) and QIDS-SR-16 remission (defined as a score of ≤5) at week 6.

Results: A total of 59 patients were enrolled; 30 were assigned to the psilocybin group and 29 to the escitalopram group. The mean scores on the QIDS-SR-16 at baseline were 14.5 in the psilocybin group and 16.4 in the escitalopram group. The mean (±SE) changes in the scores from baseline to week 6 were -8.0±1.0 points in the psilocybin group and -6.0±1.0 in the escitalopram group, for a between-group difference of 2.0 points (95% confidence interval [CI], -5.0 to 0.9) (P = 0.17). A QIDS-SR-16 response occurred in 70% of the patients in the psilocybin group and in 48% of those in the escitalopram group, for a between-group difference of 22 percentage points (95% CI, -3 to 48); QIDS-SR-16 remission occurred in 57% and 28%, respectively, for a between-group difference of 28 percentage points (95% CI, 2 to 54). Other secondary outcomes generally favored psilocybin over escitalopram, but the analyses were not corrected for multiple comparisons. The incidence of adverse events was similar in the trial groups.

Conclusions: On the basis of the change in depression scores on the QIDS-SR-16 at week 6, this trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients. Secondary outcomes generally favored psilocybin over escitalopram, but the analyses of these outcomes lacked correction for multiple comparisons. Larger and longer trials are required to compare psilocybin with established antidepressants.

Carhart-Harris, R., Giribaldi, B., Watts, R., Baker-Jones, M., Murphy-Beiner, A., Murphy, R., Martell, J., Blemings, A., Erritzoe, D., & Nutt, D. J. (2021). Trial of Psilocybin versus Escitalopram for Depression. The New England journal of medicine, 384(15), 1402–1411. https://doi.org/10.1056/NEJMoa2032994

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Mapping an Agenda for Psychedelic-Assisted Therapy Research in Patients with Serious Illness

March 16, 2022 / Palliative Care+, Papers / Leave a Comment / By / , , , , ,

Abstract

Background: With support from the Radcliffe Institute for Advanced Study at Harvard University, we convened researchers representing palliative care, psychosocial oncology, spiritual care, oncology, and psychedelic-assisted therapies. We aimed to define priorities and envision an agenda for future research on psychedelic-assisted therapies in patients with serious illness. Over two days in January 2020, participants engaged in an iterative series of reflective exercises that elicited their attitude and perspectives on scientific opportunities for this research. Objectives: The aim of the study is to identify themes that shape priorities and an agenda for research on psychedelic-assisted therapy for those affected by serious illness. Methods: We collected data through preconference interviews, audio recordings, flip charts, and sticky notes. We applied thematic qualitative analysis to elucidate key themes. Results: We identified seven key opportunities to advance the field of psychedelic-assisted therapies in serious illness care. Four opportunities were related to the science and design of psychedelic-assisted therapies: clarifying indications; developing and refining therapeutic protocols; investigating the impact of set and setting on therapeutic outcomes; and understanding the mechanisms of action. The other three pertained to institutional and societal drivers to support optimal and responsible research: education and certification for therapists; regulations and funding; and diversity and inclusion. Additionally, participants suggested epistemological limitations of the medical model to understand the potential value and therapeutic use of psychedelics. Conclusions: Medicine and society are witnessing a resurgence of interest in the effects and applications of psychedelic-assisted therapies in a wide range of settings. This article suggests key opportunities for research in psychedelic-assisted therapies for those affected by serious illness.

Beaussant, Y., Tulsky, J., Guérin, B., Schwarz-Plaschg, C., Sanders, J. J., & Radcliffe Institute for Advanced Study Working Group on Psychedelic Research in Serious Illness (2021). Mapping an Agenda for Psychedelic-Assisted Therapy Research in Patients with Serious Illness. Journal of palliative medicine, 24(11), 1657–1666. https://doi.org/10.1089/jpm.2020.0764

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