Psychedelic Research Recap February 2024
Psychedelic Research Recap February 2024
What happens if psychedelics become a regular part of therapy?
In a way, that is what the majority of research on psychedelics is trying to answer. Studies analysing the safety, to mapping out the effectiveness in various domains, including those featured here in February, help us understand psychedelics as medicines. But, a new study looking back at the therapeutic use of psychedelics in Switzerland put all of this in a new light, building on over 3000 sessions, it showcases how (in a limited setting) psychedelics can be used responsibly.
Other studies this month look at sexual functioning after psychedelics (better than after SSRIs), dive deeper into exploring expectancy effects, and we get a closer look at the effects of microdosing LSD in a controlled trial.
This month’s recap is made possible by our supporting members.
Check out the research link overview for all the studies we didn’t add to the database.
Controlled Trials Investigating AUD, Sexual Functioning & A Qualitative Follow-Up
A pilot fMRI study examined how psilocybin affected neural reactivity to alcohol and emotional cues in patients with alcohol use disorder. Participants received either psilocybin or placebo prior to the fMRI scans. Psilocybin increased activity in areas like the prefrontal cortex and caudate while decreasing activity in regions like the insula and cerebellum. These neural changes suggest psilocybin may enhance goal-directed behaviour, improve emotion regulation, and reduce craving.
A mixed-methods study combined data from a naturalistic survey (see more surveys later in the recap) and a controlled trial to investigate psychedelics’ effects on sexual functioning. In the survey, psychedelic use was associated with improved sexual pleasure, communication, partner satisfaction, and body image. The clinical trial found patients treated with psilocybin for depression reported positive sexual changes, unlike those treated with an SSRI antidepressant. Despite different populations, these converging results indicate psychedelics may have beneficial effects on sexual functioning.
Two separate studies looked at the impact of intravenous DMT on mental health in healthy volunteers. A placebo-controlled trial and prospective study showed significant reductions in depression scores 1 to 2 weeks after DMT administration. Reductions in trait neuroticism were only seen in the placebo-controlled group. Changes in depression and anxiety correlated with the intensity of peak experiences during the DMT session, suggesting these states may facilitate therapeutic effects.
Open-Label Studies, Opening New Doors
One fascinating recent study used machine learning to examine how baseline resting-state functional connectivity (FC) measured with fMRI could predict symptom improvement from psilocybin-assisted therapy for treatment-resistant depression (TRD). The results showed that connectivity in visual, default mode, executive, and salience networks could predict early symptom changes as well as longer-term responsiveness up to 24 weeks after treatment with a high degree of accuracy.
Moving to a different psychedelic, an open-label longitudinal study looked at the impact of ayahuasca use on aesthetic experiences. Participants reported increases in aesthetic experiences at both one-week and one-month follow-ups after attending an ayahuasca retreat, despite no correlation between acute subjective effects during the retreat and these longer-term changes.
Another study on the same subjects found significant increases in gratitude, nature relatedness, and nature appreciation at one week and one month after an ayahuasca retreat experience, compared to baseline. Ratings of mystical experiences and awe during the ayahuasca sessions correlated with these increases, suggesting their potential role. However, the quality of experiences was more important than quantity in influencing post-ayahuasca changes.
A different area receiving research attention is the legal medical use of classical psychedelics like LSD, MDMA, and psilocybin for psychotherapy in certain jurisdictions like Switzerland. A recent commentary provided insights into over 1000 case permits issued there since 2014, allowing an estimated 2000-3000 individual psychedelic-assisted therapy sessions so far. The authors discuss practical considerations like application procedures, treatment frameworks, ethical standards, and the need for ongoing therapist training as this modality continues developing.
Lastly, an open-label randomized waitlist-controlled trial evaluated the feasibility, safety, and preliminary efficacy of psilocybin-assisted psychotherapy specifically for treatment-resistant depression (TRD) in a complex clinical population. Participants received flexibly repeated doses of psilocybin along with psychotherapy, showing greater depression reduction compared to the waitlist period. Interestingly, repeated psilocybin doses were associated with further symptom improvements over time.
Surveying Psychonauts to Measure Outcome (Causes)
A prospective survey study explored the impact of psychedelic microdosing on emotional regulation, empathy, and ADHD symptoms in adults with severe ADHD, compared to those using conventional medications. Initial results showed benefits for microdosing in areas like cognitive reappraisal, expressive suppression, perspective-taking, and personal distress. However, when compared to a control group using standard ADHD meds after four weeks, only the improvement in expressive suppression persisted, while enhancements in cognitive reappraisal and empathy disappeared. The microdosing group did show reduced overall ADHD symptoms compared to the conventional medication group.
Analyzing self-reports from 766 individuals, mostly from Western countries, another study identified distinct consumer groups based on their MDMA consumption settings (party, private home, mixed) and intentions (euphoria/energy, self-insight, mixed). Those in the self-insight and mixed intentions clusters reported considerably more long-term socio-emotional benefits from MDMA use compared to those solely seeking euphoria and energy. No significant differences were observed between the setting clusters.
Through quantitative analysis of 240 online psychedelic trip reports, a third survey-like study tested two competing theories on the mechanisms behind psychedelics’ therapeutic potential: metaphysical belief theory and predictive self-binding theory. Path analysis supported the predictive self-binding model, showing psychological insight, rather than metaphysical beliefs, uniquely predicted beneficial outcomes. The positive effects of ego dissolution and therapeutic intent were fully mediated by psychological insight. These findings counter the notion that psychedelic benefits stem from adopting supernatural beliefs after mystical experiences.
Reviews Examining Psychedelic Interactions and Novel Compounds
A review by Balázs Szigeti and Boris Heifets explores the impact of participant expectations on psychedelic clinical trials, highlighting the challenge of maintaining effective blinding as doses increase and the potential bias introduced by positive expectancy. Covering both micro- and macrodose trials, the review suggests that understanding and managing expectancy could enhance trial rigour and treatment outcomes in future psychedelic research.
Turning our attention from the head towards the heart, another review outlines the effects of various hallucinogenic drugs, including psilocybin, LSD, DMT, and others, on cardiac function in humans. While primarily stimulating serotonin receptors like 5-HT2A to produce hallucinogenic effects in the brain, these substances can also impact the heart, potentially increasing contractility and heart rate, which could predispose individuals to arrhythmias.
Next to reviewing the literature, another group of researchers also conducted a meta-analysis synthesizing data from 10 contemporary studies (n=304) to evaluate the lasting effects of serotonergic psychedelics on cognition, creativity, emotional processing, and personality. Overall, no statistically significant effects were observed for most outcomes. However, a meta-analysis revealed faster reaction times in the psychedelic groups for recognizing disgust and sadness emotions.
How we got these insights is partly the work of neuroimaging techniques like fMRI, PET, and MEG/EEG in modern psychedelic research, providing insights into both the acute and longer-term therapeutic effects of these substances. Evidence from neuroimaging informs computational models, offering a comprehensive understanding of psychedelics’ effects on human consciousness and supporting the advancement of psychedelic therapies.
The Other Psychedelic Studies from February 2024
Next to these trials, open-label studies, surveys, and reviews there were a handful of other psychedelic studies of note that were published last month. Here is a quick mini recap of each one: A preclinical study showed methylone had rapid antidepressant and anxiolytic effects by affecting neuroplasticity gene expression in brain areas linked to PTSD and depression. Unlike MDMA, methylone showed no off-target receptor activity, suggesting potential for treating PTSD with higher specificity.
A hypothesis paper proposes psychedelics like LSD and psilocybin induce altered states by activating the 5-HT2A receptor system, leading to a state of “synthetic surprise.” This disrupts expectations and sensory input based on predictive coding, with implications for using psychedelics to induce surprise and promote change therapeutically.
A pre-print EEG study explored differences in brain activity between psychedelic users and non-users during self-related thought processing. One dataset suggested weaker alpha/beta power increases in users, especially in self-processing brain regions, but a second dataset did not replicate these effects, possibly due to sample size/resolution limits.
Papers Published in February 2024
24 studies from the Blossom database published this month.
Increases in Aesthetic Experience Following Ayahuasca Use: A Prospective, Naturalistic Study
In a prospective naturalistic study of 54 retreat attendees, participants showed increased aesthetic experience at one week and one month after an ayahuasca ceremony compared with baseline. These increases were not predicted by acute drug effects (mystical-type experiences, awe, ego dissolution), though the open‑label design limits causal conclusions.
Predicting the outcome of psilocybin treatment for depression from baseline fMRI functional connectivity
This machine learning study (n=16) examines baseline resting-state functional connectivity (FC) measured with fMRI as a predictor of symptom severity in psilocybin-assisted therapy for treatment-resistant depression (TRD). Results show that FC of visual, default mode, and executive networks predicted early symptom improvement, with the salience network predicting responders up to 24 weeks after treatment.
Expectancy effects in psychedelic trials
This review (2024) explores the impact of participant expectations on psychedelic clinical trials. It highlights the challenge of maintaining blinding as doses increase and discusses the potential bias introduced by positive expectancy. The review covers expectancy effects in both micro- and macrodose trials, suggesting that understanding and managing expectancy could enhance trial rigour and treatment outcomes in future psychedelic research.
Brain substates induced by DMT relate to sympathetic output and meaningfulness of the experience
Using simultaneous fMRI and EKG in 14 volunteers, the study identifies a DMT‑induced brain substate—hippocampal and medial parietal deactivation with increased superior temporal activity—linked to altered sense of time/space/self and vivid audio‑visual “entities”. Increased heart rate covaried with these deactivations and the experience of entities, suggesting a chain from sympathetic activation to specific neural and phenomenological effects that may relate to therapeutic changes in self‑referential processing.
Brain dynamics predictive of response to psilocybin for treatment-resistant depression
Using large-scale brain modelling and dynamic sensitivity analysis of resting-state data in responders versus non-responders, the study identified specific brain regions whose perturbation predicts a transition from depressive to healthy brain dynamics following psilocybin therapy. These regions co-localise with in vivo 5-HT2A and 5-HT1A receptor density maps, providing causal mechanistic evidence that serotonergic targets mediate psilocybin's therapeutic effect in treatment-resistant depression.
Psychedelics-assisted psychotherapy: Experiences with the limited medical use of LSD, MDMA, and psilocybin in Switzerland
This paper summarises Switzerland’s experience with limited medical use of LSD, MDMA and psilocybin since 2014—reporting over 1,000 exemption approvals and an estimated 2,000–3,000 treatments—and provides an overview of application procedures, indications, treatment settings and phases, plus recommendations on therapist training, ethics and quality assurance for integrating psychedelics‑assisted psychotherapy into clinical practice.
Effects of Psychedelic Microdosing versus Conventional ADHD Medication Use on Emotion Regulation, Empathy, and ADHD Symptoms in Adults with severe ADHD symptoms: A Naturalistic Prospective Comparison Study
Two naturalistic prospective studies in adults with severe ADHD symptoms found that psychedelic microdosing was associated with improved emotion regulation and a reduction in ADHD symptom severity over four weeks, with a persistent benefit on expressive suppression when compared with controls and conventional medication. There was no robust evidence that microdosing improved empathy.
Subjective long-term emotional and social effects of recreational MDMA use: the role of setting and intentions
Analysing self-reports from 766 predominantly Western recreational MDMA users with K-medoids clustering, the authors identified three consumption-setting types (party with friends, private home, mixed) and three intention types (euphoria/energy, self‑insight, mixed). Users with self‑insight or mixed intentions reported substantially greater long-term socio‑emotional benefits than those seeking euphoria/energy, while consumption setting was unrelated to these outcomes.
What Predicts Beneficial Outcomes in Psychedelic Use? A Quantitative Content Analysis of Psychedelic Health Outcomes
This analysis (n=240) of online trip reports examines the mechanisms behind the therapeutic potential of psychedelics, comparing metaphysical belief theory and predictive self-binding theory. Path analysis and structural equation modelling reveal that psychological insight, rather than metaphysical beliefs, uniquely predicts beneficial outcomes. Additionally, the positive effects of ego dissolution and therapeutic intent on beneficial outcomes are fully mediated by psychological insight, thereby supporting the predictive self-binding model over the metaphysical belief theory.
Exploring mechanisms of psychedelic action using neuroimaging
This review (2024) discusses the pivotal role of neuroimaging in modern psychedelic research, providing insights into the acute and longer-term therapeutic effects of these substances. Evidence from fMRI, PET, and MEG/EEG studies informs computational models, offering a comprehensive understanding of the effects of psychedelics on human consciousness as well as supporting the advancement of psychedelic therapies.
Effects of DMT on mental health outcomes in healthy volunteers
In healthy volunteers, intravenous DMT produced significant reductions in depressive symptoms one to two weeks after administration in both placebo-controlled and prospective samples, with trait neuroticism reduced only in the placebo-controlled group and symptom change correlated with the intensity of acute "oceanic boundlessness" peak experiences. The authors suggest IV DMT’s short, controllable action may alleviate depressive symptomatology via induced peak experiences and warrants further clinical investigation.
Membrane Permeation of Psychedelic Tryptamines by Dynamic Simulations
This computational study investigates the membrane permeability of 12 selected tryptamines, aiming to elucidate the impact of various structural modifications on their permeation behaviour. Using classical molecular dynamics simulations and umbrella sampling techniques, the study finds that dimethylation of the primary amine group and methoxy substitution at position 5 increase permeability, while positional substitutions on the indole groups and protonation decrease permeability.
Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA
Using in vitro receptor profiling and rat RNA‑seq, the authors show methylone is a monoamine uptake inhibitor/releaser that rapidly upregulates neuroplasticity‑related genes in frontal cortex and regulates myelin‑related genes in the amygdala. Unlike MDMA, methylone showed no off‑target activity across 168 GPCRs, indicating greater specificity and supporting its potential as a PTSD treatment.
Psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder: an fMRI pilot study
In an 11‑participant fMRI pilot, a single 25 mg dose of psilocybin altered neural responses to alcohol and emotional cues in patients with alcohol use disorder, increasing medial/lateral prefrontal cortex and left caudate activity while decreasing insula, motor, temporal, parietal and occipital cortices and cerebellum. Cue‑specific effects included supramarginal gyrus increases for negative cues and lateralised hippocampal changes for positive cues, patterns the authors interpret as reflecting enhanced goal‑directed control, improved emotional regulation and reduced craving, warranting larger neuroimaging studies.
Psychedelics and sexual functioning: a mixed-methods study
This mixed-methods study combined a large naturalistic sample and a controlled psilocybin versus escitalopram trial to assess post‑acute effects of psychedelics on sexual functioning. Results indicate psychedelic use—particularly psilocybin therapy—was associated with improvements in multiple domains of sexual functioning and satisfaction while escitalopram showed no such benefits, providing the first quantitative evidence that psychedelics may enhance sexual functioning and highlighting the need for further research.
Sublingual Ketamine for Depression and Anxiety: A Retrospective Study of Real-World Clinical Outcomes
This retrospective analysis (n=431) of at-home ketamine treatments (1x p/w, 50-400mg lozenges) for depression, generalized anxiety, and social anxiety found statistically significant improvements in symptoms measured via PHQ-9, GAD-7, and SAD-D-10 at all follow-up time points (1-2-3 months). Minor side effects were reported by 18.8% of patients, resolving within 24 hours, and the majority concluded treatment within ≤ 6 months. No significant differences were observed between treatment-resistant and non-resistant depression outcomes.
Modulation of long-term potentiation following microdoses of LSD captured by thalamo-cortical modelling in a randomised, controlled trial
In a randomised, placebo-controlled trial of 80 healthy men given 10 µg LSD every third day for six weeks, standard ERP peak analyses showed no acute or cumulative effects on visually induced long-term potentiation. Dynamic causal modelling with a thalamo-cortical model, however, revealed laminar-specific changes in excitatory and inhibitory connectivity in primary visual cortex, suggesting the modelling approach is more sensitive than classic ERP measures for detecting microdose-induced plasticity.
Patient perspectives and experiences with psilocybin treatment for treatment-resistant depression: a qualitative study
This qualitative study of 11 patients with treatment‑resistant depression who received a single psilocybin session identified three core themes—trust and expectation management, navigating the acute experience, and the need for more comprehensive care. Patients’ accounts suggest that optimising set and setting through individualised preparation, sustained therapeutic relationships, and offering additional sessions could improve safety, effectiveness and real‑world adoption of psilocybin treatment.
Strong Bipartisan Support for Controlled Psilocybin Use as Treatment or Enhancement in a Representative Sample of US Americans: Need for Caution in Public Policy Persists
This national survey (n=795) in the USA assesses public attitudes towards psilocybin use in licensed settings for psychiatric treatment and well-being enhancement. Participants from across the political spectrum overwhelmingly viewed the individual's decision as morally positive in both contexts, suggesting strong bipartisan support for supervised psilocybin use.
Effects of Ayahuasca on Gratitude and Relationships with Nature: A Prospective, Naturalistic Study
This longitudinal study (n=54) investigates the effects of ayahuasca retreat experiences on gratitude, nature relatedness, and nature appreciation. Findings reveal significant increases in these factors at one-week and one-month follow-ups compared to baseline. Ratings of mystical experiences and awe during ayahuasca sessions weakly-to-moderately correlate with these increases, highlighting their potential role in post-ayahuasca changes. Participant age negatively relates to the occurrence of mystical experiences and awe, indicating diminished effects with increased age. The study emphasizes the quality of experiences over quantity in influencing post-ayahuasca changes, suggesting potential mental health benefits associated with prosocial changes in gratitude and nature relationships.
Who Are You After Psychedelics? A Systematic Review and a Meta-Analysis of the Magnitude of Long-Term Effects of Serotonergic Psychedelics on Cognition/Creativity, Emotional Processing and Personality
This systematic review & meta-analysis (2024; s=10; n=304) synthesized data from contemporary studies, including both randomised and non-randomised controlled trials, to evaluate lasting effects of serotonergic psychedelics on cognition, creativity, emotional processing, and personality. Overall, no statistically significant effects were observed for most outcome measures; however, a meta-analysis of emotional recognition outcomes revealed faster reaction times in the active treatment groups for disgust and sadness.
Effects of hallucinogenic drugs on the human heart
This review (2024) outlines the effects of various hallucinogenic drugs on the human heart (contraction force & heart rate). These drugs, including bufotenin, psilocin, psilocybin, LSD, ergotamine, ergometrine, DMT, & 5-MeO-DMT, primarily stimulate serotonin receptors, particularly 5-HT2A receptors in the brain, leading to their hallucinogenic effects. However, they also impact the heart, potentially increasing cardiac contractility and heart rate, which could predispose individuals to arrhythmias.
Reports of self-compassion and affect regulation in psilocybin-assisted therapy for alcohol use disorder: An interpretive phenomenological analysis
This qualitative study (n=13) aimed to investigate the psychological mechanisms of change in psilocybin-assisted psychotherapy (PAT) for alcoholism (AUD). Participants reported that psilocybin treatment helped them process emotions related to past events, promoting self-compassion, self-awareness, and feelings of interconnectedness, which laid the foundation for better regulation of negative emotions and improved quality of relationships. The study suggests that integrating self-compassion training with psychedelic therapy may enhance psychological outcomes in treating AUD.
Synthetic surprise as the foundation of the psychedelic experience
This hypothesis paper proposes that psychedelic agents like LSD and psilocybin induce altered states of consciousness by activating the 5-HT2A receptor system, leading to a state of synthetic surprise. This concept is based on recent understandings of serotonin's role in signaling surprise and is framed within the predictive coding framework, where surprise is seen as a mismatch between expectations and sensory input. The paper suggests that psychedelics disrupt maladaptive patterns by dynamically interacting with top-down expectations and sensory data, with implications for their clinical use, particularly emphasizing their ability to induce surprise to promote therapeutic effects.