Psychedelics Research Recap April 2020
April has been a slow month (probably related to COVID-19). There are many ongoing trials with ketamine and researchers should note them and not only look at finished studies to determine their research direction. Microdosing psychedelics remains interesting, yet not studied in a very controlled way.
Authors: Bahareh Peyrovian, RogerS. McIntyre, Lee Phan, Leanna M.W. Lui, Hartej Gill, Amna Majeed, David Chen-Li, Flora Nasri & Joshua D. Rosenblat
Published: 9 Apr 2020
One sentence summary: There are currently 140 registered ketamine trials, mostly for mood disorders, mostly via intravenous administration, mostly phase I and II.
“As interest has grown in the potential psychiatric applications of ketamine, the number of registered clinical trials has grown substantially. Herein, we summarize and analyze clinical trials registered with ClinicalTrials.gov that assess the treatment of any psychiatric disorder with ketamine or ketamine enantiomers (e.g., S-ketamine, R-ketamine), with a focus on ongoing clinical trials. A ClinicalTrials.gov search on February 21, 2020 returned 140 registered trials. Frequency data was analyzed to determine the distribution of study designs. The majority of trials (70%) investigated the therapeutic effect of ketamine in mood disorders (unipolar: 60%, bipolar: 0.7%, both: 5.7%). Suicidal ideation (13.1%), post-traumatic stress disorder (5.4%), and obsessive-compulsive disorder (3.6%) were also investigated. Intravenous (IV) administration was the most common route with 87% of the studies using IV ketamine. Single-dose studies represented 50% of IV ketamine studies. Few studies were assessing maintenance treatment. Most studies were phase I or II with few definitive phase III trials registered. Given the large number of ongoing studies assessing psychiatric application of ketamine, researchers and relevant stakeholders should consider not only completed, published studies, but also ongoing registered studies in adjudicating the most relevant research questions. More definitive phase III trials and maintenance studies of IV ketamine for mood disorders are required, as numerous completed and ongoing studies have already assessed and demonstrated the proof-of-concept of acute antidepressant effects in phase I and II trials.“
Authors: Rotem Petranker, Thomas Anderson, Larissa Maier, Monica Barratt, Jason Ferris & Adam Winstock
Published: 14 Apr 2020 (pre-print linked)
One sentence summary: Microdosing had fewer side-effects than previously found, this was measured with the Global Drug Survey 2019.
“Background: Microdosing psychedelics – the practice of taking small, sub-hallucinogenic doses of substances like LSD or psilocybin-containing mushrooms – is becoming increasingly popular. Despite its surging popularity, little is known about the effects of this practice. Aims: This research had two main aims. First, we attempted to replicate previous findings in the literature regarding the subjective benefits and challenges reported for microdosing. Second, we measured whether people who microdose test their substances for purity before consumption and whether having an approach-intention to microdosing was predictive of more reported benefits. Methods: The Global Drug Survey (GDS) runs the world’s largest drug survey. Participants responding to GDS2019 who reported last year use of LSD or psilocybin were offered the opportunity to answer a specialist sub-section on microdosing. Results: Data from 6,753 people who reported microdosing at least once in the last 12 months were used for analyses. Our results suggest a partial replication of previous benefits and challenges with the present sample often reporting enhanced mood, creativity, focus, and sociability. Against our prediction and quite remarkably, the most common challenge participants associated with microdosing was “none”. As predicted, most participants reported not testing their substances. Counter to our hypothesis, approach-intention predicted less rather than more benefits when microdosing. We discuss alternate theoretical frameworks that may better capture the reasons people microdose. Conclusion: Our results suggest that the benefits associated with microdosing greatly outweigh the challenges. Microdosing may have utility for a variety of uses while having minimal side-effects. However, double-blind, placebo-controlled experiments are still required in order to substantiate these reports.”
Related papers
Use CTRL/CMD+F to quickly search if anything relevant for you has been published this month.
- Psychedelic Psychiatry’s Brave New World (commentary by David Nutt, David Erritzoe, Robin Carhart-Harris)
- One Dose of Psilocybin in Late Adolescence Mitigates Deleterious Effects of Developmental Stress on Cognition and Behavioral Despair in Adult Female Rats (very specific research in rats, sponsored by Eleusis – researching anti-inflammatory aspects of psychedelics)
- The Efficacy of Psilocybin Compared to Selective Serotonin Reuptake Inhibitors in the Treatment of Adults with Major Depressive Disorder (literature study, 7 articles, positive comparison of psilocybin versus SSRIs for treatment of major depression)
- MDMA interactions with pharmaceuticals and drugs of abuse (MDMA has interactions with other drugs, but much is not studied yet)
- Dynamic coupling of whole-brain neuronal and neurotransmitter systems (dMRI, fMRI, and PET study with psilocybin to link anatomy and function of the brain)
- Subacute effects of the psychedelic ayahuasca on the salience and default mode networks (subacute changes in higher-order brain networks)
Papers Published in April 2020
12 studies from the Blossom database published this month.
Survey of entity encounter experiences occasioned by inhaled N,N-dimethyltryptamine: Phenomenology, interpretation, and enduring effects
In an online survey of 2,561 people reporting their most memorable inhaled N,N-dimethyltryptamine (DMT) entity encounter, participants described predominantly visual and extrasensory (telepathic) interactions with apparently conscious, intelligent and benevolent beings—labelled guides, spirits, aliens or helpers—that communicated messages and evoked strong emotions of love, kindness and joy despite fear in many cases. These encounters were rated as highly meaningful, spiritual and insightful, produced persistent increases in life satisfaction, purpose and altered worldviews (including many former atheists abandoning atheism), and closely resembled non‑drug religious, alien‑abduction and near‑death entity experiences.
A Single Administration of the Atypical Psychedelic Ibogaine or Its Metabolite Noribogaine Induces an Antidepressant-Like Effect in Rats
This rodent study investigates behavioral effects of acute ibogaine and noribogaine administration in rats. It found that both produced a dose-and time-dependent antidepressant effect without substantial changes in animal locomotor activity.
Isness: Using Multi-Person VR to Design Peak Mystical Type Experiences Comparable to Psychedelics
This study (n=57) assessed the experiences of people undergoing a Virtual Reality (VR) journey using the Mystical Experience Questionnaire (MEQ30). 'Isness' is a VR experience developed using concepts, methods and analysis strategies from psychedelic research. It was found that Isness participants reported Mystical Type Experiences comparable to those reported in double-blind clinical studies after high doses of psilocybin and LSD.
Subjective effects of MDMA ('Ecstasy') on human sexual function
The study found that both the Arabic General Health Questionnaire (AGHQ) and the SRQ‑20 are valid screens for ICD‑10 psychiatric disorders in an Arab community in Al Ain (AGHQ: sensitivity 86%, specificity 85%, AUC 0.93; SRQ‑20: sensitivity 83%, specificity 83%, AUC 0.90), with the AGHQ performing significantly better overall, especially in males and those under 30. The abstract appears unrelated to the paper’s title on MDMA and sexual function.
Dynamic coupling of whole-brain neuronal and neurotransmitter systems
The authors present a multimodal neuroimaging framework demonstrating fundamental principles of bidirectional coupling between whole-brain neuronal dynamics and neurotransmitter systems, and use it to causally link 5‑HT2A receptor stimulation by psilocybin to observed functional brain effects in healthy humans. This approach offers a mechanistic basis for understanding how serotonergic modulation may underlie psilocybin’s therapeutic potential in neuropsychiatric disorders.
Subacute Effects of the Psychedelic Ayahuasca on the Salience and Default Mode Networks
In a randomised placebo-controlled trial, 24 hours after a single ayahuasca session healthy participants showed increased anterior cingulate connectivity within the salience network, reduced posterior cingulate connectivity within the default mode network and strengthened salience–default mode coupling, with no change in primary sensory networks. These subacute network shifts correlated with acute subjective effects (somesthesia, volition and affect), suggesting ayahuasca transiently modulates higher-order interoceptive, affective and self‑referential brain systems.
Psychedelic Psychiatry’s Brave New World
This popular commentary article (2020) describes the current resurrection of research into psychedelics (both neuroscience and therapeutic applications). It describes the evidence for the serotonin receptor (5-HT2a) agonism (psychedelics binding to that receptor) and the possible mechanisms through which long-lasting therapeutic effects can be found.
A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses
This review (2020) presents modern human studies into psychedelic drugs, including psilocybin, LSD, MDMA, and ayahuasca in treating various psychiatric illnesses, including treatment-resistant depression, post-traumatic stress disorder, end-of-life anxiety, and substance use disorders. Safety and efficacy data are also presented from both human and animal studies.
A single psilocybin dose is associated with long-term increased mindfulness, preceded by a proportional change in neocortical 5-HT2A receptor binding
This open-label study (n=10) found a significant increase in mindfulness (MAAS) and openness (NEO PI-R) after a single high dose (14-21mg) of psilocybin.
Antidepressant and neurocognitive effects of serial ketamine administration versus ECT in depressed patients
This open-label between-subjects study (n=49) compared the antidepressant efficacy of serial R(-)ketamine treatment (35mg/70kg) versus electroconvulsive therapy (ECT) for patients with depression. Ketamine produced faster antidepressant effects and improved neurocognitive functioning, especially attention and executive functions, which implicate that it may be a more favorable treatment option in the short-term.
Decreased directed functional connectivity in the psychedelic state
This MEG study (n=63) found that psilocybin, ketamine, and LSD all decreased directed functional connectivity in the brain. LSD was additionally found to increase undirected functional connectivity.
Preliminary report on the effects of a low dose of LSD on resting-state amygdala functional connectivity
This double-blind, placebo-controlled fMRI study (n=20) examined the effects of a single microdose of LSD (13 μg) on functional brain connectivity in healthy adults. Results show altered connectivity in limbic circuits, specifically between the amygdala and frontal regions, which correlated with subtle increases in positive mood despite negligible subjective effects.