Over April, we continued to learn more about psychedelic medicine. Researchers argued that psilocybin increases global integration in the depressed brain and that classic psychedelic use is associated with lower odds of opioid use disorders. In other exciting papers, the role of therapy and therapists themselves in psychedelic therapy was further explored.
Psychedelics remain under the microscope
While April may not have brought as many clinical trials as previous months, psychedelics continued to be put to the test using various research over the past month. Most notably, further analysis of data from two clinical trials where depressed patients received psilocybin assisted therapy found that global integration in the brain increases after treatment. However, some aren’t so sure of these findings.
Across both trials included in the study, the antidepressant response to psilocybin was rapid and sustained, correlating with decreases in fMRI brain network modularity. Other analyses indicated that serotonin (5-HT) 2A receptor-rich higher-order functional networks became more functionally interconnected and flexible after a psilocybin treatment. The researchers at Imperial College London suggest that these findings point to global increases in brain network integration as an antidepressant mechanism in psilocybin therapy.
Manoj Doss, Fred Barrett and Phil Corlett criticised these findings in a response to the article published in Nature. Some of their key points included the authors picking the depression measure that showed the most significant difference and that we ought to be careful taking fMRI measures as they can introduce bias.
Fred Barrett and Aviv Aharon-Almagor investigated the association between psychedelic use, macroscale brain structure, personality, cognitive ability, and illicit drug use in a naturalistic sample. It was found that psychedelic users scored higher on measures of openness to new experiences and cognitive ability, and this was associated with changes in white matter.
In a separate study, another look at the brain under the influence of psilocybin revealed decreases in amygdala activity and a reduction in depressive symptoms was observed in depressed participants. In contrast, in healthy participants, changes in functional connectivity and activation of prefrontal limbic structures, specifically the ventral medial prefrontal cortex and amygdala, were observed.
In an open-label study, the effectiveness of six ketamine infusions over 12 days on neurocognitive function in veterans with comorbid PTSD and major depressive disorder (MDD) was assessed. Significant improvement was observed in working memory following completion of the infusion series. In contrast, more significant improvements in PTSD and MDD symptoms were associated with lower working memory, slower processing speed and faster set-shifting at baseline.
When comparing electroconvulsive therapy (ECT) to intravenous ketamine in depressed patients across five clinical trials in this study, ECT emerged as a superior treatment concerning response rate, remission rate, time to response, time to remission, and magnitude of improvement at the treatment endpoint.
The role of therapy and therapists in psychedelic medicine
Thirty integration therapists were interviewed to better define integration and any challenges/concerns that they associated with the practice. Common themes included expressing concern about nonresponsive clients, defining integration as a bridge between the psychedelic experience and daily life, and apprehensions about the commercialisation of psychedelic psychotherapy.
This trial assessed the relationships between therapeutic alliance and rapport, the quality of the acute psychedelic experience and treatment outcomes in depressed patients. Following a second psilocybin session, the therapeutic alliance had a direct impact on final depression scores, not mediated by the acute experience, with a weaker alliance ahead of the second psilocybin session predicting higher absolute depression scores at the endpoint.
Group therapy is yet to receive widespread attention in psychedelic trials. This study from Peter Oehen and Peter Gasser used data from private practice in Switzerland where MDMA and LSD were administered in a group context. They found that psychedelic therapy addresses symptoms like regulation of emotions and impulses, negative self-perception, alterations in relationships with others, and meaning, recall, and processing of traumatic memories. Without any serious adverse events reported, group therapy may be a viable model.
A scoping review found that hallucinogen persisting perception disorder (HPPD) among different psychedelics is uncommon, but current interest in psychedelic research affords the opportunity to characterise HPPD in its frequency, risk and protective factors, key characteristics, and potential treatments.
A review of 27 studies that addressed ketamine for suicidal ideation (SI) found that only four reported mixed or negative results. Out of nine reviews, esketamine was significantly beneficial in five. Despite the majority of studies being of critically low quality, the short-term efficacy of ketamine in suicidality was noted in most.
Interesting surveys & the rest
This survey used data from the U.S. National Survey on Drug Use and Health (2015–2019) (N = 214,505) to assess the association between psychedelic use and opioid use disorder (OUD). Lifetime psilocybin use was associated with lowered odds, while no other substances, including other classic psychedelics, were associated with reduced odds of OUD.
In this survey (n=1,661), a higher number of lifetime uses of psychedelics predicted greater positive and lower negative emotional reactivity while measures of self-consciousness predicted greater reflection and internal state awareness, reduced rumination tendency and public self-consciousness. The intensity of past mystical and ego-dissolution experiences mediated almost all the observed relationships between the lifetime number of psychedelic uses and psychological variables.
When assessing the prevalence and nature of magic mushroom-related adverse reactions resulting in emergency medical treatment-seeking, this survey (n=9,233) found that 0.2% of respondents sought emergency medical treatment, the most common symptoms being anxiety/panic and paranoia/suspiciousness. Poor ‘mindset’, poor ‘setting’ and mixing of substances were the most reported reasons for incidents.
This study analysed 3,778 DMT experiences posted on the r/DMT Reddit to understand the phenomenology of the DMT experience better. Common themes identified include physical and somatic experiences, the content of visualisations and imagery, entity encounters, structural characteristics, the scenery of the “DMT world”, emotional responses, and more.
Nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) were used to study the composition of ayahuasca samples. For the first time, fructose was detected as a major component of the samples, while harmine was found to be present in the solids suspended in the beverage.
The methodological challenges in psychedelic clinical trials are further discussed in this paper. Some of the difficulties discussed include difficulties with masking participants and expectancy effects.
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