Psychedelic Research Recap April 2023

Psychedelic Research Recap April 2023

April was a month marked by nearly a dozen brain imaging studies on the effects of psychedelics. Jumping out from the pack is the highly anticipated extended DMT study which now has data on the psychological and physiological effects. Other studies (of the 20 total this month) investigate psychedelics for stuttering, its impact on narcissism, and our perception of time.

Welcome back to consensus reality

Last September, Lisa Luan presented the first results of the extended DMT study at ICPR. Since then, everyone has been eagerly awaiting the results of the DMT study, where 11 participants received a bolus (one big dose) and then an infusion to keep them at the same approximate level of high (both physiologically – blood plasma concentration, and psychologically, though the trip became slightly less intense at the end). The results have come back positive, meaning that the method of administration was effective, and participants were safe and tolerated (i.e. didn’t go bonkers) the infusion.

The participants in the study received multiple infusions, each with a strength between a very low dose to a dose that they consistently rated 9-10/10 on the intensity scale. Within 12 minutes after the infusion, they were back on earth with both feet.

Unlike many of the studies I cover here, this one isn’t looking directly at the application in mental health care. The study is primarily investigating what happens during the DMT experience. Extending it to over 30 minutes may help provide a clearer picture than what has been discovered in shorter (10-15min) trips after smoking or injecting only at the start.

More data from this study will come out later this year. It lays the groundwork for further explorations with extended DMT infusion, first theorized six years ago (in the scientific literature, though psychonauts probably have dreamt of this for much longer).

Sticking with DMT, a pharmacokinetics study sheds more light on how the body processes DMT (in this case, that from Small Pharma – SPL026). I covered the study when it came out as a pre-print, but it’s good to see it now being published so even more people have access to the information on how DMT and the body interact.

Narcissistic personalities, stuttering, long-term neurocognitive effects, and more outcomes

Before I dive back into the brain, there are more studies to cover that look at the outcomes of psychedelics. There is no big study that came out that looked at clinical populations, though MAPS did report – in a sparse press release – that their Phase IIIb results were on par with earlier published results.

An interview study of more than 100 people who had used ayahuasca found no significant change in self-reported narcissism. The study asked participants to complete questionnaires before, right after, and three months after the ceremonial use of ayahuasca. This is the fifth study (in our database) to look at narcissism, with onlya large survey finding connectedness and empathy correlated with decreased levels of narcissism.

By analysing posts on Reddit, researchers map out the effects of psychedelics on stuttering. Though the data is very rough (it’s just a scrape of what people have said online without any verification), 75% report benefitting from psychedelics (versus 10% saying it was detrimental). Future studies could dive into the mechanisms and possible therapeutic combinations that could help about 1% of the adult population.

However promising, negative responses to psychedelics are also possible, and a survey plus interview study dives into potential causal factors. Risk factors include unsafe environments, prior psychological vulnerabilities, unknown (or high) drug substances, and doing psychedelics at a young age. The researchers conducted interviews with only 15 people, so larger studies should be done to verify if these themes are common factors for others.

Four ketamine infusions, in those with treatment-resistant depression (TRD), led to improvements in cognition that lasted up to five weeks later. This open-label study matches more than a dozen other studies that find improvements in cognitive function after using psychedelics. But the small trial is in conflict with a 2022 meta-analysis that finds no effect on cognition after ketamine.

A re-analysis of microdosing (up to 20μg) LSD finds that LSD reduces the influence of our expectations (the top-down model) on what we think time should feel like. This aligns with other studies that point towards relaxed priors (expectations).

Finally, a Phase I trial conducted by ATMA Journey Centers finds psilocybin to be safe and without unhealthy changes in blood pressure.

Whole brain imaging

Seven more psychedelic brain imaging studies were published in April. One study focused on LSD’s impact on whole-brain effective connectivity, revealing decreased brain connectivity and increased self-inhibition in certain regions. An analysis of data from psilocybin therapy for treatment-resistant depression (TRD) found an elevated response to music after treatment, with significant correlations between ALFF in music-related clusters and subjective effects felt during dosing sessions.

A re-analysis of a ketamine trial on late-in-life treatment-resistant depression found increased neural complexity markers 30 minutes post-infusion, but no relationship between complexity and depressive symptom reduction. Another ketamine study, this time in mice, revealed that repeated ketamine administration leads to a dosage-dependent decrease of dopamine neurons in the midbrain and an increase in the hypothalamus, with divergently altered innervations in various brain areas.

A whole-brain simulation examined the entropic effects of serotonin 2A receptor activation, showing that increased entropy is primarily localized in visuo-occipital regions and is closely related to the brain’s anatomical connectivity. Another comparative study looked at the effects of nitrous oxide, ketamine, and LSD and found that all three drugs reduced connectivity within certain networks while enhancing connections between different networks, particularly in areas important for conscious experiences.

Finally, a double-blind study combining EEG with transcranial magnetic stimulation (TMS) found that psilocybin produces a chaotic pattern of brain activity but didn’t significantly impact the Perturbational Complexity Index (PCI) when compared to placebo.

These studies – which often go above my paygrade – collectively offer valuable insights into the neurobiological mechanisms underlying the effects of psychedelics and other substances on the brain. Researchers are uncovering potential biomarkers and therapeutic targets for various psychiatric conditions by identifying commonalities in how these substances affect brain connectivity. Moreover, the innovative use of neuroimaging techniques, such as fMRI, EEG, and TMS, is broadening our understanding of how these substances alter the brain’s dynamic properties and organisation.

The other studies that came out in April

A surveyasked people where they gathered information on psychedelics. Alas, there were more options than only Blossom (though other sites offer more info for recreational users). Internet websites (I’ll take it as a win), friends, discussion forums, books, and scientific journals were among the most often mentioned sources. Among the most trusted are journal articles, non-profits in the space, and university researchers.

Another survey, this time in Canada, adds more info on what psychedelics are being used in the land of hockey players. No surprises are found in the data, though slightly over half report a challenging psychedelic experience (also see earlier). Conversely, four out of five report positive life changes from psychedelics.

Finally, several esteemed researchers put forth a critique of the mystical experience measurements that are commonly used in psychedelic research. The article maps out the zeitgeist through which the current measures were developed and shapes a path towards non-mystical approaches to the overwhelming – especially after 30 minutes of DMT infusion – experiences one can have on psychedelics.