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Psychedelics and Dying Care: A Historical Look at the Relationship Between Psychedelics and Palliative Care

March 1, 2020 / Anxiety Disorders / PTSD, LSD, Papers, Psychology, Publications / By /

Abstract

This article examines the historical relationship between psychedelics and palliative care. Historians have contributed to a growing field of studies about how psychedelics have been used in the past, but much of that scholarship focused on interrogating questions of legitimacy or proving that psychedelics had therapeutic potential. Palliative care had not yet developed as medical sub-specialty, more often leaving dying care on the margins of modern, pharmaceutical-based treatments. As psychedelic researchers in the 1950s began exploring different applications for psychoactive substances such as LSD and mescaline, however, dying care came into clearer focus as a potential avenue for psychedelics. Before that application gained momentum in clinical or philosophical discussions, psychedelics were criminalized and some of those early discussions were lost. This article looks back at historical discussions about LSD’s potential for easing the anxiety associated with dying, and considers how those early conversations might offer insights into today’s more articulated discussions about psychedelics in palliative care.
Dyck, E. (2019). Psychedelics and dying care: A historical look at the relationship between psychedelics and palliative care. Journal of psychoactive drugs, 51(2), 102-107., https://doi.org/10.1080/02791072.2019.1581308
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Microdosing psychedelics: Demographics, practices, and psychiatric comorbidities.

February 28, 2020 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

RATIONALE:
Microdosing psychedelics – the practice of consuming small, sub-hallucinogenic doses of substances such as LSD or psilocybin – is gaining attention in popular media but remains poorly characterized. Contemporary studies of psychedelic microdosing have yet to report the basic psychiatric descriptors of psychedelic microdosers.
OBJECTIVES:
To examine the practices and demographics of a population of psychedelic microdosers – including their psychiatric diagnoses, prescription medications, and recreational substance use patterns – to develop a foundation on which to conduct future clinical research.
METHODS:
Participants (n = 909; Mage = 26.9, SD = 8.6; male = 83.2%; White/European = 79.1%) recruited primarily from the online forum Reddit completed an anonymous online survey. Respondents who reported using LSD, psilocybin, or both for microdosing were grouped and compared with non-microdosing respondents using exploratory odds ratio testing on demographic variables, rates of psychiatric diagnoses, and past-year recreational substance use.
RESULTS:
Of microdosers, most reported using LSD (59.3%; Mdose = 13 mcg, or 11.3% of one tab) or psilocybin (25.9%; Mdose = 0.3 g of dried psilocybin mushrooms) on a one-day-on, two-days-off schedule. Compared with non-microdosers, microdosers were significantly less likely to report a history of substance use disorders (SUDs; OR = 0.17 (95% CI: 0.05-0.56)) or anxiety disorders (OR = 0.61 (95% CI: 0.41-0.91)). Microdosers were also more likely to report recent recreational substance use compared with non-microdosers (OR = 5.2 (95% CI: 2.7-10.8)).
CONCLUSIONS:
Well-designed randomized controlled trials are needed to evaluate the safety and tolerability of this practice in clinical populations and to test claims about potential benefits.
Rosenbaum, D., Weissman, C., Anderson, T., Petranker, R., Dinh-Williams, L. A., Hui, K., & Hapke, E. (2020). Microdosing psychedelics: Demographics, practices, and psychiatric comorbidities. Journal of Psychopharmacology, 0269881120908004., https://doi.org/10.1177/0269881120908004
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Self-reported negative outcomes of psilocybin users: A quantitative textual analysis

February 21, 2020 / Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Psilocybin, a substance mainly found in mushrooms of the genus psilocybe, has been historically used for ritualistic, recreational and, more recently, medicinal purposes. The scientific literature suggests low toxicity, low risk of addiction, overdose, or other causes of injury commonly caused by substances of abuse, with growing interest in the use of this substance for conditions such as treatment-resistant depression. However, the presence of negative outcomes linked to psilocybin use is not clear yet. The objective of this study is to investigate the negative effects of psilocybin consumption, according to the users’ own perception through self-reports extracted from an online platform. 346 reports were analyzed with the assistance of the IRAMUTEQ textual analysis software, adopting the procedures of Descending Hierarchical Classification, Correspondence Factor Analysis and Specificities Analysis. The text segments were grouped in 4 main clusters, describing thinking distortions, emergencies, perceptual alterations and the administration of the substance. Bad trips were more frequent in female users, being associated with thinking distortions. The use of multiple doses of psilocybin in the same session or its combination with other substances was linked to the occurrence of long-term negative outcomes, while the use of mushrooms in single high doses was linked to medical emergencies. These results can be useful for a better understanding of the effects of psilocybin use, guiding harm-reduction initiatives.

 
Bienemann, B., Ruschel, N. S., Campos, M. L., Negreiros, M. A., & Mograbi, D. C. (2020). Self-reported negative outcomes of psilocybin users: A quantitative textual analysis. Plos one, 15(2), e0229067., https://doi.org/10.1371/journal.pone.0229067
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Subacute Effects of the Psychedelic Ayahuasca on the Salience and Default Mode Networks

February 21, 2020 / Ayahuasca, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

Background: Neuroimaging studies have just begun to explore the acute effects of psychedelics on large-scale brain networks’ functional organization. Even less is known about the neural correlates of subacute effects taking place days after the psychedelic experience. This study explores the subacute changes of primary sensory brain networks and networks supporting higher-order affective and self-referential functions 24 hours after a single session with the psychedelic ayahuasca.
Methods: We leveraged task-free functional magnetic resonance imaging data 1 day before and 1 day after a randomized placebo-controlled trial exploring the effects of ayahuasca in naïve healthy participants (21 placebo/22 ayahuasca). We derived intra- and inter-network functional connectivity of the salience, default mode, visual, and sensorimotor networks, and assessed post-session connectivity changes between the ayahuasca and placebo groups. Connectivity changes were associated with Hallucinogen Rating Scale scores assessed during the acute effects.
Results: Our findings revealed increased anterior cingulate cortex connectivity within the salience network, decreased posterior cingulate cortex connectivity within the default mode network, and increased connectivity between the salience and default mode networks 1 day after the session in the ayahuasca group compared to placebo. Connectivity of primary sensory networks did not differ between groups. Salience network connectivity increases correlated with altered somesthesia scores, decreased default mode network connectivity correlated with altered volition scores, and increased salience default mode network connectivity correlated with altered affect scores.
Conclusion: These findings provide preliminary evidence for subacute functional changes induced by the psychedelic ayahuasca on higher-order cognitive brain networks that support interoceptive, affective, and self-referential functions.

Pasquini, L., Palhano-Fontes, F., & de Araujo, D. B. (2019). Subacute effects of the psychedelic ayahuasca on the salience and default mode networks. medRxiv, 19007542., https://doi.org/10.1177/0269881120909409
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Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance

February 21, 2020 / Anthropology & Sociology, Papers, Psychology, Publications / By / , , , , , ,

Abstract

The efficacy of psychedelic-assisted therapies for mental disorders has been attributed to the lasting change from experiential avoidance to acceptance that these treatments appear to facilitate. This article presents a conceptual model that specifies potential psychological mechanisms underlying such change, and that shows substantial parallels between psychedelic therapy and cognitive behavioral therapy: We propose that in the carefully controlled context of psychedelic therapy as applied in contemporary clinical research, psychedelic-induced belief relaxation can increase motivation for acceptance via operant conditioning, thus engendering episodes of relatively avoidance-free exposure to greatly intensified private events. Under these unique learning conditions, relaxed avoidance-related beliefs can be exposed to corrective information and become revised accordingly, which may explain long-term increases in acceptance and corresponding reductions in psychopathology. Open research questions and implications for clinical practice are discussed.

Wolff, M., Evens, R., Mertens, L. J., Koslowski, M., Betzler, F., Gründer, G., & Jungaberle, H. (2020). Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance. Frontiers in Psychiatry, 11, 5.; 10.3389/fpsyt.2020.00005
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Posttraumatic Growth After MDMA‐Assisted Psychotherapy for Posttraumatic Stress Disorder

February 19, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, MDMA, Papers, Psychology, Publications / By / , , , , , ,

Abstract

3,4‐Methylenedioxymethamphetamine (MDMA)–assisted psychotherapy for posttraumatic stress disorder (PTSD) has been shown to significantly reduce clinical symptomatology, but posttraumatic growth (PTG), which consists of positive changes in self‐perception, interpersonal relationships, or philosophy of life, has not been studied with this treatment. Participant data (n = 60) were pooled from three Phase 2 clinical studies employing triple‐blind crossover designs. Participants were required to meet DSM‐IV‐R criteria for PTSD with a score higher than 50 on the Clinician‐Administered PTSD Scale (CAPS‐IV) as well as previous inadequate response to pharmacological and/or psychotherapeutic treatment. Data were aggregated into two groups: an active MDMA dose group (75–125 mg of MDMA; n = 45) or placebo/active control (0–40 mg of MDMA; n = 15). Measures included the Posttraumatic Growth Inventory (PTGI) and the CAPS‐IV, which were administered at baseline, primary endpoint, treatment exit, and 12‐month follow‐up. At primary endpoint, the MDMA group demonstrated more PTG, Hedges’ g = 1.14, 95% CI [0.49, 1.78], p < .001; and a larger reduction in PTSD symptom severity, Hedges’ g = 0.88, 95% CI [−0.28, 1.50], p < .001, relative to the control group. Relative to baseline, at the 12‐month follow‐up, within‐subject PTG was higher, p < .001; PTSD symptom severity scores were lower, p < .001; and two‐thirds of participants (67.2%) no longer met criteria for PTSD. MDMA‐assisted psychotherapy for PTSD resulted in PTG and clinical symptom reductions of large‐magnitude effect sizes. Results suggest that PTG may provide a new mechanism of action warranting further study.
Gorman, I., Belser, A. B., Jerome, L., Hennigan, C., Shechet, B., Hamilton, S., … & Feduccia, A. A. (2020). Posttraumatic Growth After MDMA‐Assisted Psychotherapy for Posttraumatic Stress Disorder. Journal of Traumatic Stress., https://doi.org/10.1002/jts.22479

N,N-dimethyltryptamine reduces infarct size and improves functional recovery following transient focal brain ischemia in rats

December 2, 2021 / DMT, Neuroscience, Papers, Psychiatry & Medicine / Leave a Comment / By / , , , , , , , ,

Abstract

Background and purpose: N,N-dimethyltryptamine (DMT) is an endogenous ligand of the Sigma 1 receptor (Sig-1R) with documented in vitro cytoprotective properties against hypoxia. Our aim was to demonstrate the in vivo neuroprotective effect of DMT following ischemia-reperfusion injury in the rat brain.

Methods: Transient middle cerebral occlusion (MCAO) was induced for 60 min in male Wistar rats using the filament occlusion model under general anaesthesia. Before the removal of the filament the treatment group (n = 10) received an intra-peritoneal (IP) bolus of 1 mg/kg-body weight (bw) DMT dissolved in 1 ml 7% ethanol/saline vehicle, followed by a maintenance dose of 2 mg/Kg-bw/h delivered over 24 h via osmotic minipumps. Controls (n = 10) received a vehicle bolus only. A third group (n = 10) received a Sig-1R antagonist (BD1063, 1 mg/kg-bw bolus +2 mg/kg-bw/h maintenance) in parallel with the DMT. Lesion volume was measured by MRI 24 h following the MCAO. Shortly after imaging the animals were terminated, and the native brains and sera were removed. Four rats were perfusion fixed. Functional recovery was studied in two separate group of pre-trained animals (n = 8-8) using the staircase method for 30 days. The expression levels of proteins involved in apoptosis, neuroplasticity and inflammatory regulation were assessed by real-time qPCR and ELISA.

Results: DMT treated rats were characterized by lower ischemic lesion volume (p = .0373), and better functional recovery (p = .0084) compared to the controls. Sig-1R was expressed both in neurons and in microglia in the peri-infarct cortex, and the DMT induced change in the lesion volume was hindered by BD1063. Lower APAF1 expression (mRNA and protein) and higher BNDF levels were documented on DTM, while decreased TNF-α, IL1-β, IL-6 and increased IL-10 expressions indicated the compound’s anti-inflammatory potential.

Conclusion: Our results indicate a Sig-1R dependent reduction of the ischemic brain injury following exogenous DMT administration in rats, presumably through a combined anti-apoptotic, pro-neurotrophic and anti-inflammatory treatment effect.

Nardai, S., László, M., Szabó, A., Alpár, A., Hanics, J., Zahola, P., Merkely, B., Frecska, E., & Nagy, Z. (2020). N,N-dimethyltryptamine reduces infarct size and improves functional recovery following transient focal brain ischemia in rats. Experimental neurology, 327, 113245. https://doi.org/10.1016/j.expneurol.2020.113245

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Benefit-Risk Assessment of Esketamine Nasal Spray vs. Placebo in Treatment-Resistant Depression

December 6, 2021 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

This post hoc analysis assessed the benefit-risk profile of esketamine nasal spray + oral antidepressant (AD) induction and maintenance treatment in patients with treatment-resistant depression (TRD). The Benefit-Risk Action Team framework was utilized to assess the benefit-risk profile using data from three induction studies and one maintenance study. Benefits were proportion of remitters or responders in induction studies and proportion of stable remitters or stable responders who remained relapse-free in the maintenance study. Risks were death, suicidal ideation, most common adverse events (AEs), and potential long-term risks. Per 100 patients on esketamine + AD vs. AD + placebo in induction therapy, 5-21 additional patients would remit and 14-17 additional patients would respond. In maintenance therapy, 19-32 fewer relapses would occur with esketamine. In both cases, there was little difference in serious or severe common AEs (primarily dissociation, vertigo, and dizziness). These findings support a positive benefit-risk balance for esketamine + AD as induction and maintenance treatment in patients with TRD.
McIntyre, R. S., Rosenblat, J. D., Nemeroff, C. B., Sanacora, G., Murrough, J. W., Berk, M., … & Stahl, S. (2021). Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation. American Journal of Psychiatry, appi-ajp., https://doi.org/10.1002/cpt.2024
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A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses

January 30, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Psychotic Disorders, Publications, Substance Use Disorder / By / ,

Abstract

Though there was initial interest in the use of psychedelic drugs for psychiatric treatment, bad outcomes and subsequent passage of the Substance Act of 1970, which placed psychedelic drugs in the Schedule I category, significantly limited potential progress. More recently, however, there has been renewal in interest and promise of psychedelic research. The purpose of this review is to highlight contemporary human studies on the use of select psychedelic drugs, such as psilocybin, LSD, MDMA and ayahuasca, in the treatment of various psychiatric illnesses, including but not limited to treatment-resistant depression, post-traumatic stress disorder, end-of-life anxiety, and substance use disorders. The safety and efficacy as reported from human and animal studies will also be discussed. Accumulated research to date has suggested the potential for psychedelics to emerge as breakthrough therapies for psychiatric conditions refractory to conventional treatments. However, given the unique history and high potential for misuse with popular distribution, special care and considerations must be undertaken to safeguard their use as viable medical treatments rather than drugs of abuse.

Chi, T., & Gold, J. A. (2020). A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses. Journal of the Neurological Sciences, 116715., 10.1016/j.jns.2020.116715
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Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey.

January 22, 2020 / Anthropology & Sociology, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

Background: Observational data and preliminary studies suggest serotonin 2A agonist psychedelics may hold potential in treating a variety of substance use disorders (SUDs), including opioid use disorder (OUD).

Aims: The study aim was to describe and analyze self-reported cases in which naturalistic psychedelic use was followed by cessation or reduction in other substance use.

Methods: An anonymous online survey of individuals reporting cessation or reduction in cannabis, opioid, or stimulant use following psychedelic use in non-clinical settings.

Results: Four hundred forty-four respondents, mostly in the USA (67%) completed the survey. Participants reported 4.5 years of problematic substance use on average before the psychedelic experience to which they attributed a reduction in drug consumption, with 79% meeting retrospective criteria for severe SUD. Most reported taking a moderate or high dose of LSD (43%) or psilocybin-containing mushrooms (29%), followed by significant reduction in drug consumption. Before the psychedelic experience 96% met SUD criteria, whereas only 27% met SUD criteria afterward. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced substance misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with greater reduction in drug consumption.

Conclusions: While these cross-sectional and self-report methods cannot determine whether psychedelics caused changes in drug use, results suggest the potential that psychedelics cause reductions in problematic substance use, and support additional clinical research on psychedelic-assisted treatment for SUD.

Garcia-Romeu, A., Davis, A. K., Erowid, E., Griffiths, R. R., & Johnson, M. W. (2020). Persisting reductions in cannabis, opioid, and stimulant misuse after naturalistic psychedelic use: An online survey. Frontiers in psychiatry, 10, 955; 10.3389/fpsyt.2019.00955
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