Psychedelics Research Recap January 2020
This very first psychedelic research analysis by Blossom features two outstanding papers on psychedelics that were published in January 2020.
The first looks at how the (naturalistic) use of psychedelics is associated with a more positive mood, especially for those with a low well-being score and high neuroticism scores. The second paper presents a review of psychedelics for the treatment of psychiatric illnesses.
Authors: Natasha L. Mason, Patrick C. Dolder & Kim P. C. Kuypers
Published: 30 Jan 2020
One-sentence summary: Based on a large-scale survey (n=1967), overall psychedelics-use is found to relate to a (change to) positive mood, the biggest change is for those with low well-being and high neuroticism scores.
“Background It has been suggested that the outcome of the psychedelic experience is dependent on set and setting. While scientific research into the therapeutic potential of psychedelics is growing, it is clear that in clinical populations an optimal set and setting will not always be attainable. It was aimed to assess under which emotional and environmental circumstances psychedelic users use psychedelics, and the outcome of use given clinical characteristics, defined as low well-being and higher rates of neuroticism. Methods Online respondents (N = 1967) provided information about their psychedelic use, environment they consume the substance in (setting), and mood state pre/post-substance (set). Based on subjective mental well-being, respondents were separated into two groups, those with low (N = 643), and those with normal well-being (N = 1324). Personality traits, with a particular focus on neuroticism, were also assessed. Results Findings showed that psychedelics such as lysergic acid diethylamide and psilocybin were most commonly used at home and methylenedioxymethamphetamine (MDMA) in a party/festival setting. In most instances, all substances were used when individuals were in a positive mood, and this remained in general positive, or, when not initially positive, shifted to positive, after use. Individuals with low well-being were more likely to experience a positive mood change after use of lysergic acid diethylamide, psilocybin or MDMA than individuals with normal well-being. Furthermore, as neuroticism scores increased, so did likelihood of positive mood change, as well as likelihood of experiencing negative side effects. Conclusion It is demonstrated that psychedelics are used in varying emotional states and environmental settings. Importantly in the light of future clinical studies with patients, individuals with low psychological well-being and higher scores of neuroticism report consuming such substances with positive outcomes.”
Also reported in PsyPost, Interesting Engineering and HappyMag.
Authors: Tingying Chi & Jessica A. Gold
Accepted: 31 Jan 2020
One-sentence summary: Review of research into psychedelics for the treatment of mental disorders, with caution on how to proceed.
“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 a 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.”
Papers Published in January 2020
22 studies from the Blossom database published this month.
Reported effects of psychedelic use on those with low well-being given various emotional contexts
In an online survey of 1,967 psychedelic users the authors report that LSD and psilocybin were most often taken at home while MDMA was common at parties, and that use typically occurred in or shifted to a positive mood. Crucially, people with low psychological well‑being — and those higher in neuroticism — were more likely to report positive mood changes after LSD, psilocybin or MDMA, though higher neuroticism also predicted greater likelihood of negative side‑effects.
Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey
This cross-sectional survey study (n=444) analyzed self-reported cases of reduced substance abuse disorder after using psychedelics and found that that the number of responders who fulfilled the criteria for their disorder dropped by 59% thereafter. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with a greater reduction in drug consumption, and most respondents claimed lasting improvements for over 1 year after using a psychedelic.
Management of treatment-resistant depression: Challenges and strategies
This review (2020) details the background and therapeutic challenges associated with treatment-resistant depression. A wide range of treatments are evaluated, including novel therapeutics such as ketamine and psilocybin.
Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials
This review (2020) presents the results of 11 randomised-controlled clinical trials (n=567) involving the therapeutic administration of LSD (20-800μg). Multiple variables regarding LSD treatment, therapeutic approach, and quality of experience were revealed and related to therapeutic outcomes. The authors find the most substantial evidence for the use of LSD in the treatment of alcoholism but highlight the lack of double-blind studies.
Transformative experience and social connectedness mediate the mood-enhancing effects of psychedelic use in naturalistic settings
Across six multiday mass gatherings in the US and UK with over 1,200 participants, psychedelic use was significantly associated with increased positive mood, an effect sequentially mediated by self‑reported transformative experiences and heightened social connectedness. These relationships remained after controlling for demographics and other psychoactive substances and were particularly pronounced for use within the preceding 24 hours.
Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression
In 19 patients with treatment-resistant depression, a single open‑label 25 mg dose of psilocybin reduced ventromedial prefrontal cortex–right amygdala functional connectivity during fearful and neutral (but not happy) face processing and increased amygdala connectivity with occipito‑parietal cortices. The decrease in vmPFC–amygdala coupling correlated with one‑week rumination scores, consistent with the hypothesis that psilocybin restores emotional responsiveness as a key therapeutic mechanism.
Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers.
This study (n=48) investigates the ‘afterglow’ effects of ayahuasca, focusing on improved mindfulness and cognitive flexibility to study its psychological mechanisms using Five Facets Mindfulness Questionnaire (FFMQ), Experiences Questionnaire (EQ), Cognitive Flexibility Scale (CFS), Wisconsin Picture Card Sorting Task (WPCST) and Stroop tests. The study findings reported that further changes in cognitive flexibility in the ‘afterglow’ period do occur and also supports the therapeutic potential of ayahuasca to improve mindfulness for naïve and experienced ayahuasca users.
Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer
In a 3.2–4.5 year follow-up of cancer patients (n=15) from a prior crossover trial, single-dose psilocybin-assisted psychotherapy produced large, sustained reductions in anxiety, depression, hopelessness, demoralisation and death anxiety, with about 60–80% maintaining clinically significant antidepressant or anxiolytic responses. Participants overwhelmingly reported enduring positive, personally meaningful and spiritually significant life changes.
A qualitative descriptive analysis of effects of psychedelic phenethylamines and tryptamine
From in‑depth interviews with 39 adults who had used 36 different psychedelic phenethylamines and tryptamines, the study characterised common subjective effects across compounds. 2C‑B was described favourably and likened to MDMA and LSD, NBOMe was generally viewed unfavourably, DOx were criticised for their excessive 12–36 hour duration, and 4‑AcO‑DMT was reported to mimic psilocybin, information useful for education and harm reduction.
Predictive feedback, early sensory representations and fast responses to predicted stimuli depend on NMDA receptors
Using high-density EEG, Bayesian modelling and machine learning in an audio-visual delayed match-to-sample task, the study shows that frontal alpha activity and predictive beta feedback pre-activate sensory templates and account for trial-by-trial reaction times. Low-dose ketamine, an NMDA receptor blocker—but not dexmedetomidine—disrupted these behavioural and neural predictive signatures, indicating that NMDA receptors are necessary for predictive feedback and fast responses to expected stimuli.
A proof-of-principle study of the short-term effects of 3,4-methylenedioxymethamphetamine (MDMA) on tinnitus and neural connectivity
This double-blind, randomised, controlled cross-over study (n=13) explores MDMA's (30-70mg) impact on tinnitus through behavioural and rs-fMRI assessments. No notable effects were observed at the lower dose. However, the 70 mg dose significantly reduced tinnitus annoyance and ignore ratings post-administration. Neurophysiological analysis revealed decreased connectivity in emotion and memory-related brain regions (hippocampal and amygdala) and increased connectivity in sensory processing and attention areas (right post-central gyrus, posterior and superior temporal gyrus, thalamus, and frontoparietal network) with MDMA versus placebo.
A rapid positive influence of S-ketamine on the anxiety of patients in palliative care: a retrospective pilot study
A retrospective pilot study of eight palliative care patients given an intravenous S-ketamine infusion (0.25 mg/kg) found a rapid, significant reduction in anxiety compared with matched controls, with no significant change in depression or lasting analgesic effects. Findings are limited by the small, non-randomised retrospective design and need confirmation in prospective randomised trials.
Classic psychedelics as therapeutics for psychiatric disorders
This chapter (49, Handbook of Behavioural Neuroscience) reviews the use of classical psychedelics and the resurgence of research of them as therapeutics for psychiatric disorders.
Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder: A systematic review and meta-analysis.
This systematic review and meta-analysis (2020) found 5 trials (n=106) that found large reductions in PTSD symptoms after MDMA-assisted psychotherapy. The studies showed large improvements, but were only moderate in quality.
LSD Overdoses: Three Case Reports
This case series describes the medical consequences of accidental LSD overdoses in three individuals, including one case of massive intranasal ingestion (550 times the recreational dose). Results indicate no fatal or lasting negative outcomes, with reports of sustained improvements in mood, pain levels, and withdrawal symptoms following the events.
Microdosing psychedelics: Motivations, subjective effects and harm reduction
This survey study (n=525) found that the motivation for microdosing (psilocybin and LSD) was mainly to improve mental health, personal development, and cognitive enhancement. Four out of five participants used one or more harm reduction techniques on microdosing days (e.g. not dosing when unwell, no alcohol, avoiding driving).
Neuropharmacological modulation of the aberrant bodily self through psychedelics
This review article argues that psychedelics may (re)mediate (dys)functional prediction coding that underlies many psychiatric disorders.
Psilocybin-assisted therapy of major depressive disorder using Acceptance and Commitment Therapy as a therapeutic frame
This theory-building paper (2020) argues for the synergy between Acceptance and Commitment Therapy (ACT) and psilocybin-assisted therapy, describes the process, and limitations to using this framework.
Psychedelics, placebo effects, and set and setting: insights from common factors theory of psychotherapy
This commentary paper (pre-print) examines four common factors of psychedelic (healing) experiences and how those factors contribute, next to the molecules themselves, to the therapeutic effects. The factors are: 1) therapeutic relationship/alliance, 2) setting, 3) rationale/set, and 4) ritual.
Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety
This survey study (n=985) finds that psychological flexibility fully mediated the effects of mystical/peak experiences on depression/anxiety.
The use of the psychological flexibility model to support psychedelic assisted therapy
This theory-building paper (2020) presents the ACE (Accept, Connect, Embody) model and how it's being used in a trial (Psilodep 2) with psilocybin-assisted therapy for depression.
Therapeutic use of serotoninergic hallucinogens: A review of the evidence and of the biological and psychological mechanisms
This review (2020) of the therapeutic potential of psychedelics (serotonergic hallucinogens) highlights the research that show both acute and long-term (subacute) positive effects after therapeutic psychedelic use.