Psychedelic Research Recap May 2022
We’re now almost halfway through 2022, and psychedelic research shows no signs of slowing down. Over May, we continued to gain a better understanding of how psychedelics work in the brain while new scales to measure aspects of the psychedelic experience were developed. Several potential new indications for psychedelic medicine were also put forward.
You can find all the papers in our database and those that weren’t added in our May Link Overview.
What’s going on in the brain?
Several studies published over the month of May further explored the effects psychedelics have on the brain. Some researchers used the latest neuroimaging techniques to see what’s going on at the physiological level, while others assessed the impact of psychedelics on different cognition features.
This meta-analysis (n=1,014) investigated the effects ketamine and esketamine have across several domains of cognition in healthy volunteers. Deficits in verbal learning/memory were most prominent, whereas response inhibition was the least affected. Adverse effects were dependent on infusion dose and plasma level but unaffected by enantiomer type, route of administration, sex or age.
Sticking with ketamine, this study (n=86) assessed the effects of six infusions of ketamine (35mg/70kg) over two weeks on suicidality in patients with depression. Several scales were used to assess response to treatment, including the Montgomery-Asberg Depression Rating Scale (MADRS). MADRS total score and processing speed (but not other cognitive domains) were significant partial mediators of the association between ketamine treatment and improvements in suicidal ideation.
At Johns Hopkins, Manoj Doss and his colleagues explored the effects of different psychoactive drugs on episodic memory and cognition by reanalysing data from ten previously published datasets in this preprint. Sedatives, dissociatives, psychedelics, stimulants, and cannabinoids had unique patterns of effects on these mnemonic processes dependent on which phase of memory while all drugs at encoding, except stimulants impaired recollection, and sedatives, dissociatives, and cannabinoids at encoding impaired familiarity. Psychedelics at encoding tended to enhance familiarity and did not impact metamemory.
Researchers from the University of Basel investigated the effects of LSD, d-amphetamine and MDMA on thalamocortical intrinsic functional connectivity (iFC) in this study. Each substance elicited auditory-sensorimotor-thalamic-hyperconnectivity compared to placebo, despite predominantly distinct pharmacological actions and subjective effects. LSD produced salience (SAL) hyperactivity, whereas MDMA and amphetamine produced hypoconnectivity with SAL. This range of activity is similar to that seen in patients with psychotic disorders.
In this paper, some of the most well-known authors in the field of psychedelics review 42 studies where resting-state functional magnetic resonance imaging (fMRI) was used and assess methodological variations across studies. Nearly all studies varied in data processing and analysis methodology. Guidelines are proposed to ensure consistency across the field.
Findings from an animal study suggest that the sensitising effects of MDMA are not due to changes in MDMA-produced synaptic overflow of serotonin but are more likely related to alterations in serotonin receptor mechanisms and/or dopamine neurotransmission.
New Tools & Questionable Methods
This paper explores historical and sociological influences on current psychedelic administration in mainstream European and American clinical research settings. It considers these dynamics in relation to cognitive-behavioural therapies (CBT) and acceptance and commitment therapy (ACT). The paper advocates for CBTs for several reasons in psychedelic research and discusses the different types of CBTs and how they can be used to inform the preparation, session, and integration phases of psychedelic psychotherapy.
Another theory put forth this month describes the development and initial validation of the Integration Engagement Scale (IES) to capture positive behavioural engagement with integration and the Experienced Integration Scale (EIS) to capture internal aspects of feeling integrated following a psychedelic experience. The scales were designed to inform the creation of enhanced integration support, and the initial data indicates the scales are valid and reliable.
Balázs Szigeti and the team at Imperial College London have proposed that a placebo control group is not sufficient to control for expectancy effects in microdosing trials, arguing that placebo-controlled studies are more fallible than conventionally assumed. In the preprint, they use computational modelling to show that the combination of weak blinding and positive treatment expectancy can lead to activated expectancy bias (AEB), which is an uneven distribution of expectancy effects between the treatment arms due to patients recognising their treatment allocation in psychedelic microdosing randomised controlled trials.
On the chemistry side of things, researchers published a new method for synthesising 5-MeO-DMT from a cell line from tissue obtained from the parotoid gland (saliva) of the Sonoran Desert toad (Incilius alvarius).
Insights from surveys
This survey study (n=474) assessed participants’ perception, potential usage, and recommendations for psychedelic drugs being used to treat mental illnesses. Results show that participants were not open to their usage of psychedelics but were more open to recommending psychedelic therapy to their loved ones.
Another survey (n=980) assessed the perspectives of patients with functional neurological disorders (FND) (e.g. multiple sclerosis, stroke) on novel treatments like psychedelic therapy. 15% of respondents reported using illicit substances to manage their symptoms, with the majority experiencing no or minimal physical and psychological sequelae. 46% of respondents said that they would be willing to try medically supervised psychedelic therapy.
A survey in the Netherlands (n=377) found that regular participants in ayahuasca ceremonies showed better general well-being, fewer lifestyle-related diseases, more physical activity, and a more balanced diet than Dutch normative data. Ceremony attendees also used less alcohol throughout the COVID-19 pandemic, but they did use more illegal drugs than the general population.
New indications, more reviews & the rest
This animal study explored the effects of psilocybin and metformin (a drug used to manage blood sugar) in a rat model of obesity. In the low – not medium – and high dose psilocybin groups, a significant decrease in body weight was observed compared to controls. The metformin group produced a more substantial reduction in body weight than either the psilocybin group or the control. The medium dose psilocybin group was terminated from the study as they were incorrectly treated with the drug.
A case has again been made for using psychedelics to treat body dysmorphic disorder (BDD). Preliminary evidence suggests the safety, feasibility, and potential efficacy of psychedelic treatments in disorders that share similar psychopathological mechanisms with BDD. A Phase II study is suggested – luckily, there is one underway from COMPASS Pathways.
This paper proposes that the dream, hypnagogic, and psychedelic states share common features that make them conducive to supporting some aspects of scientific creativity and examines the putative underlying neurophenomenological and cognitive processes involved.
Using the most up-to-date research, this review explores the potential of psychedelics in treating mental health disorders, their short- and long-term effects on recreational users, and the neurological and cognitive processes responsible for their effects.
This meta-analysis assessed the effects of psilocybin in treating depression and anxiety. Despite achieving statistical significance in reducing depression and anxiety symptoms compared to controls in multiple subgroups, more trials need to be conducted with larger patient populations over longer periods.
The value of the social sciences tends to be overlooked by biomedical researchers. Yet, its methods can provide insights into phenomena beyond the scope of biomedical research (take the very public dispute that arose from this paper as an example).
In this sociology-based paper, the concept of American socio-psychedelics imaginaries is introduced, i.e., collective visions articulated and enacted to reintegrate psychedelics legally and responsibly into society. These imaginaries diverge and converge around several politics: politics of access, politics of responsibility, politics of naming, politics of assimilation and social change, and politics of epistemic credibility.
Papers Published in May 2022
22 studies from the Blossom database published this month.
Group VR experiences can produce ego attenuation and connectedness comparable to psychedelics
Using a distributed multi‑person VR framework called Isness‑D, the authors show that group VR experiences can induce self‑transcendent states—marked reductions in ego‑sense and increased connectedness—that are statistically indistinguishable from recent psychedelic studies on four established self‑report scales (N = 58). This demonstrates that distributed VR can reliably evoke embodied intersubjective "energetic coalescence" and may offer a non‑pharmacological route to psychedelic‑like therapeutic phenomenology.
Postpartum depression: A role for psychedelics?
This review (2022) makes the case for using psychedelics in the treatment of postpartum depression (PDD). The effects we see in other clinical trials with psychedelics may translate to PPD such as 'reconnection.' This effect in PPD, by fostering a sense of ‘reconnection’ for the mother, may allow for improved mood and maternal sensitivity towards the infant, which can positively impact maternal role gratification and the mother-infant relationship.
Ayahuasca and Public Health II: Health Status in a Large Sample of Ayahuasca-Ceremony Participants in the Netherlands
This survey study (n=377) assessed the association regular ayahuasca ceremony participation has with a person's health. Compared to normative Dutch data, regular participants in ayahuasca ceremonies showed better general well-being, fewer lifestyle-related diseases, more physical activity, and a more balanced diet. Ceremony attendees also used less alcohol over the course of the COVID-19 pandemic but they did use more illegal drugs than the general population.
Psychedelic Therapy for Body Dysmorphic Disorder
This paper (2022) makes the case for using psychedelic-assisted psychotherapy (PAP) for the treatment of body dysmorphic disorder (BDD). Preliminary evidence suggests the safety, feasibility, and potential efficacy of psychedelic treatments in disorders that share similar psychopathological mechanisms with BDD. A Phase II study is suggested with thoughts on how to proceed with this research.
Unique Effects of Sedatives, Dissociatives, Psychedelics, Stimulants, and Cannabinoids on Episodic Memory: A Review and Reanalysis of Acute Drug Effects on Recollection, Familiarity, and Metamemory
This preprint (2022) assessed the effects of different psychoactive drugs on episodic memory and cognition by reanalysing episodic memory confidence data from 10 previously published datasets. Sedatives, dissociatives, psychedelics, stimulants, and cannabinoids had unique patterns of effects on these mnemonic processes dependent on which phase of memory while all drugs at encoding, except stimulants impaired recollection, and sedatives, dissociatives, and cannabinoids at encoding impaired familiarity. Psychedelics at encoding tended to enhance familiarity and did not impact metamemory.
New insights into the clinical and nonclinical effects of psychedelic substances: An integrative review.
This review (2022) explores the potential of psychedelics in treating mental health disorders, their short- and long-term effects on recreational users, and the neurological and cognitive processes responsible for their effects using the most up to date research. The positive findings of psilocybin for depression (MDD) and anxiety are highlighted. The mystical experience (MEQ) also plays a large role, but individual differences (for whom does it work) are still not well examined.
Psychedelics and Psychotherapy: Cognitive-Behavioral Approaches as Default
This paper (2022) explores historical and sociological influences on current psychedelic administration in mainstream European and American clinical research settings. It considers these dynamics in relation to cognitive-behavioural therapies (CBT) and acceptance and commitment therapy (ACT). The paper advocates for CBTs for several reasons, such as the large base of empirical evidence they have. Several types of CBTs are discussed and how they can be used to inform the preparation, session, and integration phases of psychedelic psychotherapy.
The Psychedelic Integration Scales: Tools for Measuring Psychedelic Integration Behaviors and Experiences
This theory-building paper (2022) describes the development and initial validation of the Integration Engagement Scale (IES) to capture positive behavioural engagement with integration and the Experienced Integration Scale (EIS) to capture internal aspects of feeling integrated following a psychedelic experience. The scales were designed to inform the creation of enhanced integration support and the initial data indicates the scales are valid and reliable.
Incilius alvarius cell-based synthesis of 5-MeO-DMT
The authors established a cell line from Incilius alvarius parotoid gland tissue and confirmed in vitro biosynthesis of 5‑MeO‑DMT by LC‑MS/MS. This provides a cruelty‑free, sustainable source of naturally derived toad secretions (and potentially accompanying entourage molecules) for research and drug development, potentially reducing pressure on wild populations.
Traditional Amazonian medicine in addiction treatment: Qualitative results
This open-ended interview study was followed by thematic analysis to assess the perspective of patients (n=9) who underwent treatment with ayahuasca in the Takiwasi Center (rehabilitation centre). While the therapeutic effects are supported, the complexities are also discussed.
Chronic Treatment With Psilocybin Decreases Changes in Body Weight in a Rodent Model of Obesity
Chronic administration of psilocybin to cafeteria-diet-induced obese rats produced modest but significant reductions in weight gain, high-calorie food intake and central adiposity at the low and high doses. An intermediate psilocybin dose required premature termination, and the positive control metformin produced larger reductions in weight gain than psilocybin.
Psychedelic Resting-state Neuroimaging: A Review and Perspective on Balancing Replication and Novel Analyses
This paper (2022) by some of the most well-known authors in the field of psychedelics, reviews 42 studies where resting-state functional magnetic resonance imaging (fMRI) was used and assessed methodological variations across studies. Nearly all studies varied in data processing and analysis methodology. Guidelines are proposed to ensure consistency across the field.
Psychedelics as potential catalysts of scientific creativity and insight
This theory-building article (2022) proposes that the dream, hypnagogic and psychedelic states share common features that make them conducive to supporting some aspects of scientific creativity and examines the putative underlying neurophenomenological and cognitive processes involved. The psychedelic state may have the potential to enhance creativity as a result of phenomena like brain hyperconnectivity, meta-cognitive awareness and more.
Self-Care Practices with Psychedelics - A Qualitative Study of Users’ Perspectives
This qualitative interview study (n=19) explored the relationship between psychedelic use and self-care practices in naturalistic settings. Results indicate that for many participants, psychedelics enhanced self-care abilities through mechanisms of altered self-perception and existential meaningfulness.
Special considerations for evaluating psilocybin-facilitated psychotherapy in vulnerable populations
This report (2022) explores the challenges and opportunities associated with evaluating psilocybin-facilitated psychotherapy (PAP) in vulnerable populations. The authors propose that working with vulnerable populations requires special attention to their context. Recommendations for future research include an emphasis on recruitment strategies, the appropriate communication and assessment of subjective effects, building a therapeutic alliance, multicultural competence, and flexible study designs.
Pharmacokinetics of N,N-dimethyltryptamine in Humans
This Phase I study provides the first detailed human pharmacokinetic characterisation of intravenous DMT fumarate (SPL026), demonstrating dose‑proportional exposure across 9–21.5 mg, rapid peak plasma concentrations (~10 min), a short elimination half‑life (9–12 min), ~70% unbound fraction and good tolerability. In vitro data indicate mitochondrial MAO‑A‑mediated metabolism with modulation by CYP2D6 and CYP2C19, supporting the design of DMT infusion regimens for major depressive disorder.
Hallucinogenic Persisting Perception Disorder: A Case Series and Review of the Literature
This retrospective series of 13 patients and review of 24 case reports found that HPPD commonly causes visual snow, floaters, palinopsia, photophobia and nyctalopia despite normal ophthalmic and neurological investigations, producing a phenotype that overlaps substantially with Visual Snow Syndrome. The authors argue DSM‑5 diagnostic criteria should be expanded to include these symptoms, that VSS patients be screened for prior hallucinogen use, and that controlled studies compare primary and secondary VSS to clarify pathophysiology and treatment.
Lay Perceptions of Treating Mental Illness with Psychedelic Assisted Therapy
This survey study (n=474) assessed participants' perception, potential usage, and recommendations for psychedelic drugs being used as a treatment for mental illnesses. Results show that participants were not open to their personal usage of psychedelics but were more open to recommending psychedelic therapy to their loved ones.
Hallucinogen persisting perceptual disorder: a scoping review covering frequency, risk factors, prevention and treatment
This scoping review (2022) explores the prevalence, risk factors and pathophysiology of hallucinogen persisting perception disorder (HPPD) among different psychedelics. While HPPD is uncommon, current interest in psychedelic research affords the opportunity to characterize HPPD in its frequency, risk and protective factors, key characteristics, and potential treatments.
Cognitive Function Mediates the Anti-suicide Effect of Repeated Intravenous Ketamine in Adult Patients With Suicidal Ideation
In adults with unipolar or bipolar depression and suicidal ideation, six intravenous ketamine infusions over two weeks produced significant reductions in suicidal ideation. Mediation analyses showed these anti‑suicide effects were partially mediated by reductions in depressive symptom severity and by improved processing speed, but not by other cognitive domains.
LSD, afterglow and hangover: Increased episodic memory and verbal fluency, decreased cognitive flexibility
This trial (n=24) investigated the effects LSD (50 μg) has on cognition in healthy volunteers. It was found that LSD sub-acutely improved visuospatial memory and phonological verbal fluency and impaired cognitive flexibility when compared to placebo.
MDMA-assisted therapy significantly reduces eating disorder symptoms in a randomized placebo-controlled trial of adults with severe PTSD
This trial (n=90) used the Eating Attitudes Test (EAT-26) to assess the impact MDMA-assisted therapy has on symptoms of eating disorders (ED) in participants with PTSD. There was a significant reduction in total EAT-26 scores in the total group of PTSD participants following MDMA-AT versus placebo (p = .03). Overall, MDMA-AT significantly reduced ED symptoms compared to therapy with placebo among participants with severe PTSD.