Psychedelic Research Recap January 2023
Psychedelic Research Recap January 2023
This January, outcomes of psychedelic use were closely examined. Studies looked at how experiences are integrated, how challenging experiences lead to growth, and the relationship between psychedelic use and nature-relatedness.
We also saw the first (case) study of changing menstrual patterns after psychedelic use, and the safety of psychedelics for those immunocompromised. In this review, we cover the 20 most interesting papers that came out this January.
The consequences of psychedelic use
A representative survey finds six out of ten recreational users have never had a bad trip. Of the 600 who had used psychedelics, 9% indicated having a bad trip lasting beyond the day of dosing. One in 40 had sought help after a distressing experience.
An analysis of NSDUH survey data (6300 psychedelic users) finds correlations between psychedelic use and substance abuse disorders. Those who used LSD and psilocybin were likelier, while those who used mescaline were less likely to abuse other substances.
The previous study contrasts with a third survey (3800 participants) which found that those who took psilocybin were higher on a score of nature-relatedness. The researchers see a relationship between nature-relatedness and other positive traits. Noted should be that all these effects are correlational, and other factors (e.g. socio-economic) can also explain the relationships.
Looking specifically at those going to a retreat, an interview study finds one in three experiencing challenges in integration. The participants, who went to a Synthesis retreat, reported challenges, including a lack of support or spiritual bypassing. But, having a challenging experience correlated with positive after-effects, including long-term remission of significant health conditions.
Investigating psilocybin-assisted therapy (PAT), researchers identified characteristics of patient ‘readiness’. The theory-building article discusses intrapersonal (e.g. openness to experience & motivation) and interpersonal (e.g. therapeutic alliance) factors that would help identify who will be most helped by PAT.
New areas under investigation
Women’s health and psychedelics is a topic that is rarely, if ever, talked about in psychedelic research. An interview study (three participants) breaks this pattern and finds diverse reactions to psychedelics. One participant had a resumption of menstruation, another found it came earlier, whilst the third interviewee reported improved regularity.
Microdosing has been regularly covered in psychedelic research. What is novel about a naturalistic studyis the focus on emodiversity (the diversity of emotions) whilst microdosing. The study finds a decrease in positive and overall emodiversity. Though participants reported more awe, there were fewer happy, glad, and joyful emotions.
The cost-effectiveness of ketamine, but how sure are we?
An economic modelling study argues that esketamine is cost-effective for treatment-resistant depression (TRD). The study compares the costs to several models of societal outcomes in Italy. Though promising, the evidence for (es)ketamine treatment, especially on long-term outcomes, is still quite limited.
That is also what a recent review argues that looked at 22 studies, four of which were RCTs (the gold standard). The review covers data from over 2300 patients, and identifies antidepressant effects but also cautions that there is a high chance of bias in the RCTs.
Still, that hasn’t stopped smaller studies from further investigating the (short-term) effectiveness of ketamine in different populations. One such study finds comparable effects between those with bipolar and unipolar treatment-resistant depression. It even finds the anxiety-reducing effects to be greater for the bipolar group.
Similarly, a case series (four patients) finds ketamine an effective add-on treatment for those with psychotic treatment-resistant depression. The ability to use ketamine next to other drugs (e.g. antidepressants) is, next to the wide availability, what sets it apart from classical psychedelics.
The other studies that came out in January
Two studies propose theories of 1) how ayahuasca works and 2) the underlying structure of brain signals that produce (or at least correlate with) consciousness. The first synthesises the psychotherapeutic and neurobiological processes that go on and is a perfect, and very up-to-date, overview of the effects of ayahuasca. The second shows that patterns of brain activity (structure-function coupling) are a generalisable indicator of consciousness. An increase in coupling indicates lower/no consciousness (e.g. anaesthesia) and psychedelics are associated with decoupling.
Further analysis of the creativity studies by Wießner and colleagues finds lower complexity of language whilst under the influence of a low dose of LSD. Though we generally believe psychedelics to increase certain processes (lighting up the brain in scans), this study and the previously discussed microdosing study also show lowered complexity (of language and emotions respectively).
What isn’t lowered is the immune response of cells (T cells and monocyte immune response) when exposed to several classical psychedelics. Though the study is in cells, the researchers argue that it provides evidence for the safety of psychedelics for those with terminal illnesses (for whom they can provide psychological relief).
Finally, two studies look further at MDMA-assisted therapy for PTSD. The first investigates fMRI data from veterans and first responders. It finds a correlation between reductions in PTSD and amygdala-hippocampal connectivity, and 2) reduced amygdala-precuneus connectivity during memory recall. The second study is a pre-print which finds that participants had significant improvements in self-experience (e.g. the ability to identify and describe emotions one experiences). Bessel van der Kolk (The Body Keeps The Score) is the first author of the study.
In January, we added 20 research papers to our database. We also linked over 95 papers in our January Link Overview. With psychedelics research showing no signs of slowing down, we at Blossom will continue to make information on psychedelics as medicine easily accessible.
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Papers Published in January 2023
20 studies from the Blossom database published this month.
Psychotherapeutic and neurobiological processes associated with ayahuasca: A proposed model and implications for therapeutic use
This theory-building article (2023) proposes a model of psychotherapeutic processes associated with ayahuasca consumption. It identifies five key effects: somatic effects, introspection and emotional processing, increased self-connection, increased spiritual connection, and gaining of insights and new perspectives.
Distributed harmonic patterns of structure-function dependence orchestrate human consciousness
This theory-building paper (2023) shows that structure-function coupling (patterns of brain activity) is a generalisable indicator of consciousness. An increase in functional coupling indicates a loss of consciousness (e.g. brain-inured patients or anaesthesia), and opposite changes (decoupling of brain function from structure) are seen under the influence of psychedelics (e.g. LSD or ketamine).
Optimizing outcomes in psilocybin therapy: Considerations in participant evaluation and preparation
This theory-building article (2023) proposes that a patient's 'readiness' (eligibility & capacity) is taken into account to optimise the outcomes of psilocybin/psychedelic-assisted therapies (PAT). Factors discussed include intrapersonal (e.g. openness & motivation) and interpersonal (e.g. therapeutic alliance) factors.
Menstrual Changes and Reversal of Amenorrhea Induced by Classic Psychedelics: A Case Series
This interview study (n=3) examines menstrual changes after using classical psychedelics. It finds 1) resumption of menstruation, 2) earlier menstruation, and 3) improved menstrual regularity. A possible underlying mechanism is the (in)direct effects of 5-HT2a agonism on the hypothalamic-pituitary-gonadal axis.
Classic psychedelics do not affect T cell and monocyte immune responses
This cell study finds no (negative) effect of classical psychedelics on T cell and monocyte immune responses. This indicates that they can be used by people with life-threatening diseases who are immunocompromised.
Cost-Utility Analysis of Esketamine for Patients with Treatment-Resistant Depression in Italy
This economic analysis (Markov modelling) of esketamine treatment for depression (TRD) in Italy shows that it may be cost-effective from a societal perspective.
Oral Ketamine for Depression: An Updated Systematic Review
This systematic review (2023) finds that oral ketamine (35mg-85mg/70kg) has antidepressive effects, but that the evidence (n=2336, s=22) is still quite limited (only 4 RCTs with a high chance of bias).
Microdosing psychedelics - Does it have an impact on emodiversity?
This observational naturalistic study (n=18) on microdosing found that it led to a decrease in positive and overall emotional diversity (emodiversity). Participants experienced more awe, wonder, or amazement and ashamed, humiliated, or disgraced emotions during microdosing days and fewer joyful, glad, or happy emotions.
Psychedelic integration challenges: Participant experiences after a psilocybin truffle retreat in the Netherlands
In a qualitative study of 30 participants at a three‑day legal psilocybin truffle retreat in the Netherlands, nine (30%) spontaneously reported transient post‑experience integration challenges—such as mood fluctuations, “post‑ecstatic blues,” disconnection from community, re‑experiencing, spiritual bypass and perceived lack of support—that arose immediately or within weeks and resolved over time. These challenges were associated with positive long‑term health effects and echo the “spiritual emergency” literature, highlighting the need for robust integration and harm‑reduction practices in psychedelic settings.
Psychedelic-supportive psychotherapy: A psychotherapeutic model for, before and beyond the medicine experience
The paper proposes "Psychedelic‑Supportive Psychotherapy," a transtheoretical model enabling qualified psychotherapists to ethically and legally support clients before and after (but not during) psychedelic medicine experiences, combining harm reduction with facilitation of emotional, psychological and spiritual processing. It presents a foundational structure with criteria, parameters and practical recommendations that centralise the therapeutic relationship as the primary change agent and aim to expand access for diverse communities.
Ketamine as Add-On Treatment in Psychotic Treatment-Resistant Depression
This case series (n=4) reflects on the use of ketamine (35mg/70kg, up to 8x) as an adjunct treatment for psychotic treatment-resistant depression (TRD). It finds that all participants were in remission after treatment and that suicidal ideation went down.
Treating Bipolar Depression with Esketamine: Safety and Effectiveness data from a naturalistic multicentric study on Esketamine in Bipolar versus Unipolar Treatment-Resistant Depression
This open-label study (n=70) compared the effect of esketamine (28-84mg; 8x) in those with bipolar treatment-resistant depression (B-TRD, n=35) and those with unipolar TRD. There was no significant difference between the two groups on depression scores, and both responded to treatment. Those in the B-TRD group had more anxiety-reducing effects. This study is part of the REAL-ESK study.
5-HT2ARs Mediate Therapeutic Behavioral Effects of Psychedelic Tryptamines
This rodent study suggests that activating serotonin 2A receptors is essential for tryptamine-based psychedelics to produce antidepressant-like effects in rodents. The study also suggests that psychedelic tryptamines can induce hallucinogenic and therapeutic effects through activation of the same receptor. It highlights the need for full mechanistic understanding of how these molecules produce therapeutic effects.
Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity
In male rats a single dose of methylone produced a rapid, robust and durable antidepressant-like effect in the forced swim test—reducing immobility by ~95% and lasting at least 72 hours—while also showing anxiolytic behaviour in the open field and exceeding the effect of fluoxetine. Fluoxetine pretreatment did not alter methylone’s effect, and behavioural patterns suggest methylone is less serotonergic than MDMA, supporting its potential as a fast-acting treatment for depression and anxiety.
The association between naturalistic use of psychedelics and co-occurring substance use disorders
Using 2017 NSDUH data (n=56,276), the authors found past naturalistic use of peyote/mescaline was associated with lower odds of past-year substance dependence or abuse (adjusted OR 0.68, p<0.001), whereas past LSD and psilocybin use were associated with increased odds; none of the classic psychedelics were linked to nicotine dependence. The paper notes it is unclear whether these differences reflect pharmacological properties or the cultural/ceremonial contexts of peyote/mescaline use.
A Phase II, Open-Label Clinical Trial of Intranasal Ketamine for Depression in Patients with Cancer Receiving Palliative Care (INKeD-PC Study)
In an open‑label phase II trial of intranasal racemic ketamine (50–150 mg) given over one week to 20 advanced‑cancer palliative care patients with moderate–severe major depressive disorder, 70% achieved ≥50% MADRS response and 45% achieved remission by Day 8, with mean MADRS falling from 31 to 11 (p<0.001) and partial maintenance to Day 14. Treatment was feasible and generally well tolerated—adverse effects were mostly mild and transient—supporting larger randomised controlled trials.
Among psychedelic-experienced users, only past use of psilocybin reliably predicts nature relatedness
A combined reanalysis of five datasets (N = 3817) found that among psychedelic-experienced individuals only past use of psilocybin reliably predicts self-reported nature relatedness (with weaker, less reliable effects for DMT), and this pattern holds when psychedelic-naïve participants are included. Among participants exclusively experienced with psilocybin, greater use frequency was associated with higher nature relatedness, suggesting future work should investigate psilocybin-specific pharmacological or contextual factors.
Psilocybin sex-dependently reduces alcohol consumption in C57BL/6J mice
This mice study found that psilocybin reduced alcohol consumption for three days, but this effect was only present in male mice.
Replication of distinct trajectories of antidepressant response to intravenous ketamine
This study (n=298) sought to replicate treatment response findings using previously collected data from a community-based sample of patients with depression receiving intravenous (IV) ketamine. Using growth mixture modelling and the QIDS-SR as the measure of depression, the same three antidepressant treatment response trajectories were observed. A history of childhood maltreatment was associated with more optimal treatment outcomes for patients reporting a severe level of depression at baseline, and measures of suicidality followed similar improvement patterns.
Views on Using Psychoactive Substances to Self-Manage Functional Neurological Disorder: Online Patient Survey Results
This survey study (n=980) assessed the perspectives of patients with functional neurological disorders (FND) (e.g. multiple sclerosis, stroke) on novel treatments like psychedelic therapoy. 15% of respondents reported using illicit substances to manage their symptoms, with the majority expereincing no or minimal physical and psychological sequale. 46% of respondents reported that they would be willing to try medically supervised psychedelic therapy.