Psychedelics Research Recap July & August 2021
Psychedelic research continued at pace during the summer of 2021. New research focusing on the risks of psychedelics, the benefits when treating addictions, knowledge of different groups about psychedelics, and much more was published.
The transdiagnostic ability of psychedelics, meaning they can help with a variety of mental health and substance use disorders, continue to impress. With ever more papers coming out every day, we hope this overview gives one a way to keep up to date with the latest psychedelic research.
You can find all the papers in our database, and the ones that weren’t added in our July and August Link Overviews.
Randomized controlled trials (RCTs) for psychedelics
The goal of RCTs is to control for factors that aren’t under direct experimental control. There may be (unknown) differences between the participants in your study and by randomizing, assigning half to one ‘arm’ and the rest to the other, you can even out these differences. Psychedelics have no problem with achieving this part of the design of RCTs.
It is common for participants to be blinded to the experimental condition in a study, meaning they don’t know who got a medicine or other type of intervention. This part is much more difficult or near-impossible for psychedelic studies. A review argues that this has lead to an overestimation of outcomes and proposes several measures to tackle blinding issues. Giving the second group a small dose of psychedelics (or another drug) is one of the proposed measures.
If RCTs are even the right place to discover the effects that psychedelics have is questioned in an opinion paper. To better understand the effects on moral behavior, the authors advocate a complementary approach of culture-controlled trials that investigate this moral psychopharmacology under different social and cultural circumstances.
Another concern relating to the design of studies is the attrition rate, who drops out of a study. A survey of those who participated in an observational study (so not an RCT) found that people didn’t drop out because of psychedelic-specific factors such as challenging experiences or prior dispositions towards psychedelics. This study addresses some of the concerns relating to who participates and finished psychedelic studies.
Ayahuasca helps with stress, conflict, and self-compassion
There are currently less than a handful of clinical trials that have been conducted with ayahuasca. For one, the brew varies a lot per ceremony or tradition. Another possible reason might be the cultural stigma attached to ayahuasca (as with LSD) and the relative ease with which psilocybin can currently be studied. Still, there are many observational studies that help identify where ayahuasca could be of service.
A replication study, setting up with the same design as an earlier study from 2018, found reductions in stress up to four weeks later. A positive impact on depression wasn’t found in the current group of participants. The study did also find improvements in life satisfaction the day after the ceremony, but not four weeks later. Similar positive immediate effects were found in a study that looked at self-compassion and self-criticism which were respectively increased and decreased the day after a ceremony. And another analysis of earlier data finds inconsistent effects on the personality trait Openness, something that was found to be increased in other studies.
How ayahuasca may help in resolving conflict is investigated in three case studies that dove deeper into the relational processes in ayahuasca groups of Palestinians and Israelis. The revelatory events during a ceremony led the participants to develop resistance towards the dominant Israeli culture, the urge to deliver emancipatory messages to other participants (through song), and later also to expand the practice to other Palestinians.
Psychedelics do not come without risks
Another understudied psychedelics is ibogaine. The root bark of the iboga tree has been used for centuries in rituals and at least for decades in helping people kick addictions. A review of 18 studies finds that there are significant risks, mainly to the heart, that present themselves both acutely and after treatment. Standardizing the amount of product used (which is difficult if using natural products), at least in research settings, is vital to understanding what the right therapeutic and (relatively) safe dose is.
Hallucinogenic-persisting perception disorder (HPPD) is a rare disorder that encompasses persisting visual disturbances after the use of psychedelics. A review argues that the current characterization in the DSM-V is not encompassing all aspects of HPPD and identifies 64 unique symptoms. Most of the symptoms overlap with Alice in Wonderland syndrome (AIWS) which relate mostly to distorted perception and disorientation.
Combining psychedelics with medication is something that should not be taken lightly. In the case of antidepressants (SSRIs), it could dampen the positive therapeutic effects, or could possibly lead to serotonin syndrome when combined with MDMA. But one combination to really stay away from is that with lithium. An analysis of online reports find that lithium and classical psychedelics have led to seizures (47%), and emergency medical treatment (39%). A review dives deeper into the risks related to serotonin and psychedelics.
If everyone should be able to get (legal) access to psychedelics is questioned in an opinion paper that investigates two routes to legalization. When making psychedelics available for cultivation or noncommercial sharing, the authors argue that unreflective marketing, only promoting the benefits, may not indicate the (psychological) risks that come with taking psychedelics. However, one does need to take into account that currently, a large percentage of the population has been using psychedelics already. Conversely, drug checking services now also find that within the illegal trade some more toxic substances and novel psychedelics are being sold.
How do care providers look at psychedelics?
Those that will need to administer psychedelics are slowly warming up to the potential they have. Still, many psychiatrists (and others in healthcare) are not aware of the current state of research. A survey study asked psychiatrists at two conferences about their knowledge (many aware of the promise) and opinions/concerns (lack of training, logistics, patients with contraindications) regarding psychedelic therapy. Those who worked more in research, know more about psychedelics or were less concerned about the addictive potential scored higher in their beliefs on the effectiveness of psychedelic-assisted therapy.
More specifically, an interview study looked at the attitudes of cancer healthcare workers towards psychedelic-assisted therapy. In general, they were open to the concept, viewed it as an innovative approach, and acknowledged their responsibility towards alleviating suffering in advanced cancer patients. However, this view was also met with caution and highlights the need for further research to ensure efficacy and safety. Similar sentiments were found when interviewing five palliative care workers.
Psychedelics show promise in treating addiction to alcohol and drugs
One of the most successful and widely known ways of treating addiction is with a twelve-step program, which is applied by Alcoholics Anonymous (AA). A key pillar of the program is total abstinence of any drug (with the possible exception of caffeine). An opinion paper argues that making another exception for psychedelics may lead to synergies between the program and the therapeutic use of these substances. Although controversial, the founder of AA (Bill Wilson) did himself have positive experiences with psychedelics.
A large scale survey study finds that ayahuasca use is both strongly and consistently associated with very low (or even abstinence from) drug or alcohol use, with and without prior substance use disorders. The study covered 40 countries and participants indicated both the frequency of ayahuasca and use of alcohol, those who drank ayahuasca more often were more likely to drink less alcohol. Although observational, meaning it was no RCT as discussed before, it does provide good preliminary evidence for ayahuasca’s effect on drinking.
Earlier we talked about the risks of ibogaine and this is one of the main drivers for researchers to find related compounds that come with fewer of those risks, whilst still providing therapeutic benefits. A preprint (meaning no peer review has been done yet) argues that oxa-ibogaine alkaloids may have this coveted combination of characteristics. The rats in the study showed acute and long-lasting suppression of morphine self-administration in response to both single and repeated dosing regimes.
Ketamine remains the most studied psychedelics
Ketamine is not considered a classical (serotonergic) psychedelic and has a long history of being used as an anaesthetic. At the dosages being used in research, there are acute psychedelic (or dissociative) effects, and there are long-term positive effects from ketamine treatments. Because of its wide and less restricted access, ketamine has been studied in more people than all other psychedelics combined.
Because of the large sample size, a review was able to find if ketamine treatment for depression led to worse outcomes for those with a history of psychotic symptoms. The review found 41 cases and showed that the available literature does not support the assumption that ketamine will exacerbate psychotic symptoms in predisposed patients.
More debates are being had about the effectiveness of esketamine (one ‘half’ of ketamine). A pooled analysis, bringing together results from multiple studies, finds that for patients that don’t respond immediately to treatment for depression, continued treatment may still be beneficial. Another analysis of the same original study (TRANSFORM) finds that those who also have anxiety (72% of participants) respond just as well to treatment as those without. Another pooled analysis (this time of the ASPIRE studies) finds that esketamine improves depressive symptoms and suicidal ideation. These effects were found immediately after treatment and up to 25 days later. Finally, a review of 10 studies finds that only one short-term study finds benefits of esketamine over only antidepressants for depression, but does find a longer time to relapse and sustained improvements.
Ketamine has not been used in the treatment of PTSD often. A double-blind study investigated through which mechanisms it could work and compares the effects to that of midazolam (a sedative). Both midazolam and ketamine improved symptoms, which were most reliably predicted by the reduced excitation of the amygdala and ventromedial prefrontal cortex (vmPFC) during the processing of socio-emotional threat signals, but only ketamine-related improvement was associated with increased top-down inhibition of the amygdala by the vmPFC.
The rest of the studies in July and August 2021
A study in mice finds the possible route through which MDMA reverses social deficits, increased activity in the nucleus accumbens (NAc). The authors argue that enhancement of 5-HT release or direct 5-HT1b receptor activation may help with treating sociability deficits commonly found in those with autism spectrum disorder (ASD).
The mechanisms through which psychedelics work in the long term are under constant investigation. A survey study finds that among people of color (BIPOC population), psychological flexibility mediated the relationship between acute psychedelic effects (acute insight & challenging experiences) and decreases in racial trauma.
Psychedelics may provide a way to treat (traumatic) brain injury (TBI). A review proposes that psychedelic pharmacotherapies may fundamentally alter the future of brain injury treatment via modulation of neuroinflammation, neuroplasticity, hippocampal neurogenesis, and brain complexity.
How psychedelics change the connectivity in brains remains a topic where we can learn much more. A brain modelling study finds the topographic effects (where) LSD changes functional connectivity (FC) in the brain, via the modulation of serotonin 2A pyramidal cells.
Making psychedelics at scale (at low costs) is paramount and a new synthesis method using quorum-sensing-controlled bacterial small RNA increased the yield of psilocybin biosynthesis in E. coli by 302.9% without affecting cell growth.
Finally, an interview study asked recreational users of psychedelics why they used psychedelics. With all the focus on therapeutic use, it may be easy to forget the reasons why most people take psychedelics. Recreational use is mostly centred around curiosity and ‘having fun’ and less, but still so, about decreasing ego-inflated pathology and increasing existential awareness. Those who use psychedelics have a 23% lower odds of heart disease and a 12% lower odds of diabetes in the past year (though correlation doesn’t imply causation).
Papers Published in July 2021 & August 2021
47 studies from the Blossom database published these months.
Neuroimaging correlates and predictors of response to repeated-dose intravenous ketamine in PTSD: preliminary evidence
This preregistered randomised double-blind active placebo-controlled between-subjects study (n=21) measured brain activity while viewing facial stimuli in response to repeated and acute administration of ketamine (35mg/70kg) and midazolam (3.15mg/70kg), among patients with severe PTSD. Both midazolam and ketamine improved symptoms, which were most reliably predicted by the reduced excitation of the amygdala and ventromedial prefrontal cortex (vmPFC) during the processing of socio-emotional threat signals, but only ketamine-related improvement was associated with increased top-down inhibition of the amygdala by the vmPFC.
Psychedelics for Brain Injury: A Mini-Review
This review (2021) explores the latest studies that use psychedelic therapeutics to treat (traumatic) brain injury (TBI). It proposed that psychedelic pharmacotherapies may fundamentally alter the future of brain injury treatment via modulation of neuroinflammation, neuroplasticity, hippocampal neurogenesis, and brain complexity. The review concludes that further phase II trials could shed more light on the mechanisms of these promising drugs and how they could treat brain injury, especially TBI and reperfusion injury from stroke.
Turn on, Tune in, and Drop out: Predictors of Attrition in a Prospective Observational Cohort Study on Psychedelic Use
In a prospective web-based cohort of psychedelic users (baseline n=654), attrition at four weeks was predicted by baseline demographics (age and educational level) and personality traits (lower conscientiousness and higher extraversion), while baseline attitudes toward psychedelics and the intensity of challenging acute experiences did not predict dropout. These results align with attrition patterns seen in other longitudinal research and suggest that dropout in naturalistic psychedelic studies is unlikely to be driven by advocacy or negative drug experiences, reducing concerns about systematic bias.
Safer Tripping: Serotonergic Psychedelics and Drug Checking. Submission and Detection Rates, Potential Harms, and Challenges for Drug Analysis
This multinational harm-reduction study (2021) investigated the presence and proportion of serotonergic psychedelics submitted to drug checking services across the Netherlands, Spain, UK, Italy, Portugal, Belgium, Canada, and Australia. They found that a considerable amount of novel synthetic phenethylamine psychedelics, such as NBOMes that exhibit higher levels of toxicity and sometimes an unpredictably prolonged duration, have been detected in samples sold as LSD or MDMA.
Therapeutic Potentials of Ketamine and Esketamine in Obsessive-Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature
This review (2021, s=30) investigates the use of ketamine for OCD, addiction (SUD), and eating disorders (ED) and finds that glutamatergic neurotransmission dysregulation underlies these domains. In this area, ketamine can be helpful.
Transcriptomics-informed large-scale cortical model captures topography of pharmacological neuroimaging effects of LSD
This brain modelling study finds the topographic effects (where) LSD changes functional connectivity (FC) in the brain, via the modulation of serotonin 2A pyramidal cells.
Recreation and Realization: Reported Motivations of Use Among Persons Who Consume Psychedelics in Non-Clinical Settings
This qualitative interview study (n=30) finds that the motivation given by recreational users of psychedelics is mostly centred around curiosity and 'having fun' and less, but still so, about decreasing ego-inflated pathology and increasing existential awareness.
A Nationwide Study Comparing Mental Health Professionals' Willingness to Try Hallucinogenic Drugs in Basic Research or Clinical Practice
This survey study (n=347) examined Israeli mental health professionals' attitudes toward recreational drug users and willingness to use five hallucinogens (LSD, MDMA, ketamine, cannabis, psilocybin) in research or clinical practice. Compared to nurses and paramedics, psychiatrists were more familiar with the potential therapeutic role of psychedelics and had a higher willingness to conduct research or use such substances for clinical purposes. However, psychiatrists were also the most susceptible to personal bias, as evidenced by cases wherein negative attitudes toward recreational users impeded their support for psychedelic within the context of clinical treatments or research.
Associations between ayahuasca consumption in naturalistic settings and current alcohol and drug use: Results of a large international cross-sectional survey
In a large international cross‑sectional survey of 8,629 ayahuasca consumers, greater lifetime ayahuasca use in naturalistic settings was associated with lower current alcohol and other drug consumption, with stronger effects among those with prior substance use disorders. Stronger subjective spiritual experiences, personal insights and drinking within ayahuasca churches were also linked to reduced substance use, and associations persisted after adjusting for religious or social group membership.
Dissociative symptoms with intravenous ketamine in treatment-resistant depression exploratory observational study
In 49 inpatients with treatment‑resistant depression receiving eight 0.5 mg/kg IV ketamine infusions, dissociative symptoms showed significant transient increases (CADSS; P = .003) while psychomimetic symptoms (BPRS) did not significantly change, and both returned to “absent” within one hour and were not associated with treatment outcome. The results suggest a favourable acute safety profile for ketamine as an adjunct to standard pharmacotherapy, although the small, unblinded observational design limits power and causal inference.
Psychedelic drug use and schizotypy in young adults
Psychedelic use was only weakly associated with increased schizotypy in this large adult sample — an association that became non‑significant after controlling for psychiatric comorbidity and concomitant drug use. In a small experimental subsample, greater psychedelic exposure correlated with slightly improved evidence integration and markedly increased sensitivity of instructed fear responses, suggesting psychedelics may alter evidence‑integration and aversive‑learning processes relevant to therapeutic effects.
Systematized Review of Psychotherapeutic Components of Psilocybin-Assisted Psychotherapy
This review (2021; s=11) found that psilocybin-assisted psychotherapy consisted of three stages; 1) pretreatment sessions, 2) treatment sessions (dosing, non-directive support, music therapy), and 3) integration sessions.
The effect of esketamine in patients with treatment-resistant depression with and without comorbid anxiety symptoms or disorder
This post-approval, double-blind, placebo-controlled study (n=223, TRANSFORM-2) finds that those with comorbid anxiety (72%) responded just as well as those without anxiety to esketamine (56-84mg, 4 weeks, combined with SSRI) treatment.
Treatment Response With Esketamine Nasal Spray Plus an Oral Antidepressant in Patients With Treatment-Resistant Depression Without Evidence of Early Response: A Pooled Post Hoc Analysis of the TRANSFORM Studies
This pooled analysis of two phase III studies (n=518, TRANSFORM) finds that for those who didn’t respond, continued treatment may still be beneficial. This was both true for the esketamine group and the group that received a placebo.
Does psychedelic therapy have a transdiagnostic action and prophylactic potential?
The paper argues that psychedelic therapy’s core transdiagnostic and prophylactic action is its capacity to enhance neuronal and psychological plasticity, thereby increasing adaptability and resilience when combined with an appropriate psychotherapeutic context. The authors propose candidate neural and psychological markers and situate this plasticity model within a predictive processing framework to explain its broad therapeutic potential.
Exploring the Use of Psilocybin Therapy for Existential Distress: A Qualitative Study of Palliative Care Provider Perceptions
This qualitative interview study (n=5) examines the attitudes of palliative care workers towards the use of psilocybin therapy for death anxiety and identified common themes concerning the perceived barriers of treating existential distress and their uncertainty about the risks and benefits of psilocybin.
Working with Weirdness: A Response to “Moving Past Mysticism in Psychedelic Science”
This commentary (2021) argues against the removal of the mystical experience concept from psychedelic science, advocating instead for a research approach that embraces the variability and subjective depth of these experiences. The authors contend that acknowledging these transformative states is essential for understanding the therapeutic potential of psychedelics rather than relying solely on neurobiological explanations.
Trips and Neurotransmitters: Discovering Principled Patterns across 6,850 Hallucinogenic Experiences
Analysing 6,850 free-form testimonials across 27 hallucinogens with 40 neurotransmitter receptor proxies mapped to brain coordinates, the study uses pattern-learning to link distinct subjective experience themes to cortex-wide receptor density distributions. It finds that ego-dissolution relates to a 5-HT2A, D2, KOR and NMDA receptor constellation anchored in higher-order associative and visual cortices, and more broadly identifies association–sensory gradients that map the semantic structure of psychedelic experiences onto brain receptor architecture with potential therapeutic implications.
Associations between lifetime classic psychedelic use and cardiometabolic diseases
Using NSDUH 2005–2014 data, respondents reporting lifetime classic psychedelic use had lower adjusted odds of past‑year heart disease (aOR 0.77, 95% CI 0.65–0.92) and diabetes (aOR 0.88, 95% CI 0.78–0.99). The authors suggest classic psychedelics might benefit cardiometabolic health but emphasise the need for research to establish causal mechanisms.
Ketamine Treatment for Depression in Patients With a History of Psychosis or Current Psychotic Symptoms: A Systematic Review
This systematic review (2021) examines whether ketamine treatment in patients with a history of psychosis or current psychotic symptoms and found 9 pilot studies (n=41) which indicate that ketamine's side effects are mild and self-limiting even among these patients. While limited in sample size, the available literature does not support the assumption that ketamine will exacerbate psychotic symptoms in predisposed patients.
LSD, madness and healing: Mystical experiences as possible link between psychosis model and therapy model
In a randomized, double‑blind, placebo‑controlled crossover study of 24 healthy volunteers given 50 μg LSD, the drug produced psychosis‑like aberrant salience, increased suggestibility and robust mystical and ego‑dissolution experiences, with aberrant salience strongly correlating with mystical experiences and ego‑dissolution. The authors propose that mystical experiences may link the psychosis model and the therapeutic model of psychedelics, suggesting psychedelic‑assisted therapy could benefit from fostering meaning‑laden mystical states.
Psilocybin Induces Aberrant Prediction Error Processing of Tactile Mismatch Responses-A Simultaneous EEG-FMRI Study
Psilocybin reduced neural responses to surprising tactile stimuli, decreasing activity in frontal regions, visual cortex and cerebellum and attenuating frontal tactile mismatch negativity, consistent with aberrant prediction‑error processing and 5‑HT2A‑mediated disruption of bodily‑self integration. These findings link altered tactile deviancy processing to changes in self‑experience and suggest relevance for psychiatric disorders characterised by aberrant bodily self‑awareness.
Role of the 5-HT2A receptor in acute effects of LSD on empathy and circulating oxytocin
In a placebo‑controlled, double‑blind crossover study in 16 healthy volunteers, LSD dose‑dependently increased implicit and explicit emotional empathy and modestly elevated plasma oxytocin at 200 µg; pretreatment with the 5‑HT2A antagonist ketanserin reduced the oxytocin response but did not block the empathy enhancement. These findings indicate LSD enhances empathy by mechanisms at least partly independent of 5‑HT2A receptor activation, whereas LSD‑induced oxytocin release appears 5‑HT2A‑dependent.
Research abuses against people of colour and other vulnerable groups in early psychedelic research
This review of early psychedelic studies (the 50s-70s, s=48) finds that most (77%) would not pass ethical review today. The errors made in early research were extensive dosing, lack of consent, inadequate setting, and lack of scientific hypotheses. The authors make restorative justice and cultural competency suggestions.
Serotonin toxicity of serotonergic psychedelics
This review (2021) evaluates the safety of combining psychedelics and classical serotonin reuptake inhibitors (SSRIs), describes the signs, symptoms, and risk factors of serotonin toxicity, and outlines potential management strategies. They identify the major risk stemming from psychotropics such as ayahuasca that contain monoamine oxidase inhibitors (MAOI) and risk neurotoxicity via the increase intrasynaptic serotonin.
Using Psychedelics With Therapeutic Intent Is Associated With Lower Shame and Complex Trauma Symptoms in Adults With Histories of Child Maltreatment
In a survey of 166 adults with histories of child maltreatment, intentional therapeutic use of psychedelics was associated with significantly lower complex trauma symptoms and lower internalised shame despite similar maltreatment histories. Differences were largest in participants reporting more than five therapeutic uses—who also showed a moderating effect on the link between emotional abuse/neglect and complex trauma—while no associations were found with facial emotion recognition.
Ketamine for Refractory Chronic Migraine: an Observational Pilot Study and Metabolite Analysis
In this prospective observational pilot of six patients with refractory chronic migraine, both lidocaine and (R,S)-ketamine infusions produced short-term pain relief but pain had returned to baseline by follow-up, with ketamine giving a slightly larger yet clinically minimal greater reduction. Metabolite analysis showed (2R,6R)-hydroxynorketamine was the predominant ketamine metabolite during most of the infusion.
Naturalistic Entheogenics: Précis of Philosophy of Psychedelics
The précis defends a "naturalistic entheogenic" response to the Comforting Delusion Objection, arguing that psychedelic therapy produces its benefits primarily by altering the sense of self and one’s relation to their mind rather than by inducing non‑naturalistic metaphysical beliefs. Consequently, the book contends, entheogenic insights and forms of spiritual growth can be genuine and epistemically respectable within a naturalistic worldview.
Systemic enhancement of serotonin signaling reverses social deficits in multiple mouse models for ASD
This study in mice finds that MDMA (and a selective 5-HT1b receptor agonist) reverse social deficits through increased activity in the nucleus accumbens (NAc). The authors argue that enhancement of 5-HT release or direct 5-HT1b receptor activation may help with treating sociability deficits commonly found in those with autism spectrum disorder (ASD).
A dynamic and multilocus metabolic regulation strategy using quorum-sensing-controlled bacterial small RNA
This in vitro study (2021) developed a novel method of transcriptional gene repression within E. coli that increased the yield of psilocybin biosynthesis by 302.9% without affecting cell growth.
A Systematic Review of the MDMA Model to Address Social Impairment in Autism
This systematic review finds that postnatal MDMA administration produces prosocial behaviours and may alleviate social impairments in autism models, with the strongest evidence coming from animal studies. Clinical trials are now under way, but larger and longer studies are needed to confirm whether MDMA or MDMA-like compounds can treat social deficits in ASD.
On Revelations and Revolutions: Drinking Ayahuasca Among Palestinians Under Israeli Occupation
This qualitative case study (n=3) investigates the sociopharmacology of ayahuasca within the context of ritual ceremonies between Palestinians and Israelis and found that it occasioned revelatory events that confronted the participants with the oppressive nature of their surrounding political structure. These revelatory experiences led the participant to develop a universalist counterhegemonic worldview, which motivated them to restructure the ritual space of ayahuasca use to be more inclusive of Palestinians and their culture.
Efficacy and Safety of Intranasal Esketamine in Treatment-Resistant Depression in Adults: A Systematic Review
This review (2021, s=10) finds that only one of three short-term studies found favourable effects of esketamine over only antidepressants for depression, but other studies did find longer time to relapse or a longer sustained improvement in depressive symptoms.
Esketamine Nasal Spray for the Rapid Reduction of Depressive Symptoms in Major Depressive Disorder With Acute Suicidal Ideation or Behavior
In pooled data from two identically designed phase 3 randomised trials (N = 456), esketamine 84 mg nasal spray plus comprehensive standard of care produced a rapid and statistically significant greater reduction in depressive symptoms versus placebo plus standard of care as early as 4 hours and at 24 hours after the first dose (LS mean difference in MADRS −3.8 at 24 h), with a larger effect in those with a prior suicide attempt. Common adverse events included dizziness, dissociation, nausea, somnolence and headache.
Ayahuasca may help to improve self-compassion and self-criticism capacities
A pre–post study of 45 volunteers found that participation in an ayahuasca ceremony was associated with significant medium-to-large improvements in self‑compassion, reductions in self‑criticism and increases in self‑reassurance within 24 hours. These exploratory results suggest ayahuasca may enhance well‑being and have therapeutic potential for negative affect, but larger controlled trials are required to confirm the effect.
Psychedelic Knowledge and Opinions in Psychiatrists at Two Professional Conferences: An Exploratory Survey
This survey study (n=106) asked psychiatrists at two conferences about their knowledge (many aware of the promise) and opinions/concerns (lack of training, logistics, patients with contraindications) regarding psychedelic therapy. Those who worked more in research, know more about psychedelics, or were less concerned about the addictive potential scored higher in their beliefs on the effectiveness of psychedelic-assisted therapy.
The adverse events of ibogaine in humans: an updated systematic review of the literature (2015-2020)
This review (s=18) did a qualitative analysis of studies with ibogaine and describes the acute adverse events (cardiac, gastrointestinal, neurological) and long-lasting effects (persistent cardiac, psychiatric, neurological). The authors note that phase I studies with standardized products are necessary as the products quantity and mix was widely varied.
This Is Something That Changed My Life: A Qualitative Study of Patients' Experiences in a Clinical Trial of Ketamine Treatment for Alcohol Use Disorders
In semi‑structured interviews with 12 participants from a Phase II randomised controlled trial, ketamine infusions delivered in a supportive clinical setting produced varied acute experiences—including dissociation, ego dissolution and mystical/spiritual states—that participants linked to transformative changes in their relationship with alcohol. The authors conclude these broader psychoactive effects may mediate therapeutic benefit and recommend developing measures that capture the full spectrum of ketamine experiences.
The socialization of hallucinations. Cultural priors, social interactions and contextual factors in the use of psychedelics
Drawing on ethnography from a Peruvian Amazon shamanic centre and a dialogue with phenomenology and Bayesian social cognition, this paper introduces the "socialization of hallucinations": a two-level account showing that cultural priors and social interactions shape both how people relate to psychedelic experiences and the very phenomenological content of hallucinations via attention training, perceptual categorisation and the shaping of emotions and expectations. It further argues that psychedelics serve as potent vectors of cultural transmission, raises ethical concerns as their use spreads in the global North, and calls for an interdisciplinary methodology to study extrapharmacological factors.
On Perception and Consciousness in HPPD: A Systematic Review
This review (2021; n=97) finds that hallucinogen-persisting perception disorder (HPPD) encompasses more characteristics than currently recognized by the DSM-5. The most common (of the 64 unique) symptoms were 76% Alice in Wonderland syndrome (AIWS) characteristics (distorted perception and disorientation), 50% non-visual symptoms, and 38% perceptual symptoms not liked to earlier states under the influence.
Safety of ibogaine administration in detoxification of opioid dependent individuals: a descriptive open-label observational study
This open‑label study (n=14) of opioid‑dependent patients given a single 700 mg per 70kg dose of ibogaine‑HCl, treatment produced clinically relevant but reversible cardiac and cerebellar toxicity. The mean maximal QTc(F) prolongation was 95 ms, with 50% of participants exceeding 500 ms, accompanied by bradycardia and severe transient ataxia. Psychomimetic and withdrawal effects were generally manageable, and no torsades de pointes were observed.
Effects of ayahuasca on personality: results of two randomized, placebo-controlled trials in healthy volunteers
In two randomized, placebo-controlled trials in healthy volunteers, ayahuasca produced a significant increase in Openness at 21 days only in one study's placebo+ayahuasca group, with no consistent changes in other personality domains. Effects were therefore inconsistent and limited by small sample sizes and baseline differences, warranting larger controlled studies, particularly in clinical populations.
Increases in Psychological Flexibility Mediate Relationship Between Acute Psychedelic Effects and Decreases in Racial Trauma Symptoms Among People of Color
In a cross-sectional survey of 313 BIPOC, greater acute psychedelic insight and challenging experiences were associated with reductions in racial trauma symptoms, and increases in psychological flexibility partially mediated these relationships. The authors suggest psychedelics may reduce racial trauma among people of colour via enhanced psychological flexibility and recommend longitudinal clinical trials to test causality.
Two Models of Legalization of Psychedelic Substances: Reasons for Concern
This opinion paper (2021) raises concerns over the two concurrent models of legalizing the possession, personal use, and noncommercial sharing of psychedelics in California and clinical use in Oregon. In light of cautionary precedents involving the commercialisation of ketamine and cannabis, their chief concern is that non-evidence-based marketing strategies founded on one-sided enthusiasm for the benefits of psychedelics may supplant evidence-based practices, thereby putting vulnerable populations at risk of their potential side effects that have not been studied outside of the clinical population.
Cancer Healthcare Workers' Perceptions toward Psychedelic-Assisted Therapy: A Preliminary Investigation
This preliminary qualitative study interviewed 12 cancer healthcare professionals and found conditional openness to psychedelic-assisted therapy for advanced cancer, driven by unmet treatment needs and a desire to alleviate suffering. Acceptance was tempered by concerns about safety and risk, with participants emphasising the need for rigorous, well‑designed trials before clinical implementation.
Moral Psychopharmacology Needs Moral Inquiry: The Case of Psychedelics
The paper argues for a moral psychopharmacology of psychedelics that tests whether these substances act as non‑specific amplifiers of users' existing values or whether they bias moral‑political orientation (for example toward liberal, anti‑authoritarian views). It proposes integrating pharmacological and neuroscientific research with historical and anthropological evidence to illuminate the cultural plasticity of psychedelic effects and to inform the design of psychedelic pharmacopsychotherapies.
Psychonauts’ psychedelics: A systematic, multilingual, web-crawling exercise
This online study, using a web-crawler and then manual analysis of the data, found 994 previously unknown psychedelic molecules.