Psychedelic Research Recap July & August 2024

After a warm summer, autumn has announced itself, and we find ourselves back at the computer, therapists’ room or lab bench. Thoughts of blue seas and white beaches fade as we return to the groove of working and studying. But the summer break hasn’t been entirely devoid of activity. In the last two months, 20 more research papers caught my attention and have been added to the database.

The articles cover many new experiments, as well as important follow-up studies. One such study is the 12-month (and longer) follow-up of the LSD for anxiety study, showing durable effects. We also got the most complete analysis of the ‘desynchronized’ brain under the influence of psilocybin. On a more experiential level, researchers investigated the effects of false beliefs (vs genuine insights) one can pick up during a psychedelic experience. Let’s dive into the research.

Our supporting members have made this summer recap possible.

Check out the research link overview for all the studies we didn’t add to the database.

Desynchronization and Syncing with the Gut

A new brain imaging study examines how psilocybin affects the human brain. This study, employing functional magnetic resonance imaging (fMRI) on 24 healthy adults, discovered that a single dose of psilocybin (25mg) caused significant disruptions in brain network activity, far exceeding the changes observed with methylphenidate (Ritalin). These disruptions, primarily characterized by widespread desynchronization of brain activity, were most prominent in the default mode network (DMN), a network linked to our sense of self and introspection.

Interestingly, engaging in a perceptual task during the psilocybin experience seemed to mitigate these disruptions, suggesting a potential strategy for grounding individuals during psychedelic therapy (also see this recent study on context manipulation during a DMT experience). Notably, the study also found that psilocybin led to a persistent decrease in connectivity between the hippocampus, a brain region crucial for memory, and the DMN, lasting for several weeks after the psilocybin session. This long-lasting change in connectivity might hold the key to understanding psilocybin’s potential for promoting psychological flexibility and alleviating depressive symptoms.

Beyond its effects on brain networks, researchers are exploring the potential role of the gut microbiome in mediating the effects of psychedelics. A review challenges the prevailing notion that psychedelic mechanisms are solely explained by their interaction with serotonin receptors in the brain. Instead, it proposes that the gut microbiome, with its intricate communication with the brain through the gut-brain axis, may play a significant role in shaping the effects of psychedelic drugs on behaviour.

However, the use of psychedelics is not without potential drawbacks. A theoretical review cautions that while psychedelics can lead to profound insights and shifts in beliefs, they could also increase the likelihood of forming false insights and beliefs. Drawing parallels between research on false memories and the subjective effects of psychedelics, the authors suggest that the heightened state of suggestibility and altered perception induced by these substances might make individuals more susceptible to accepting inaccurate information as genuine insights.

LSD from Breakthrough to Microdose

Adding to the recent FDA breakthrough therapy designation for LSD to treat generalized anxiety disorder, a new wave of research further explores the therapeutic applications of this psychedelic, spanning from high-dose, guided experiences to repeated low-dose regimens.

A one-year follow-up study on LSD-assisted therapy for anxiety reinforces the drug’s potential for long-term benefits. Participants who had received LSD during a previous clinical trial (paper) exhibited sustained reductions in anxiety and depression scores up to 94 weeks later, highlighting the enduring positive effects of LSD-assisted therapy. These individuals also displayed positive shifts in personality traits, showing decreased neuroticism and increased extraversion, and largely attributed these positive changes to their psychedelic experience.

Moving from long-term effects to immediate brain changes, a crossover study employing fMRI sheds light on how LSD impacts the brain’s pain-processing mechanisms. This research revealed that LSD alters activity and connectivity within the pain neural network, suggesting its potential for managing pain conditions. Specifically, LSD led to changes in brain regions like the anterior cingulate cortex, thalamus, and insula, all known to play a role in pain perception and regulation.

Shifting focus to the subtle effects of low-dose LSD (26µg), a placebo-controlled study investigated its impact on emotional processing. By measuring event-related potentials (ERPs), brain responses to specific events, researchers found that a single low dose of LSD significantly altered brainwave patterns in response to neutral and happy faces. This suggests that even at low doses, LSD can influence how we perceive and process social and emotional cues, potentially explaining anecdotal reports of its mood-boosting effects.

Delving further into the realm of microdosing, another study explored the effects of repeated low doses of LSD (15µg) on arousal, attention, and memory. Interestingly, the study found that LSD’s effects were not uniform across all participants but depended on their baseline cognitive state. Individuals with low baseline arousal experienced the most pronounced stimulatory effects, showing increased alertness and attention, while those with high memory performance exhibited some inhibitory effects. Importantly, some of these effects, particularly on arousal and attention, persisted even one week after the last LSD dose, suggesting that microdosing might lead to lasting neuroadaptations in the brain.

Psilocybin Therapy Binary Effects

Recent research on psilocybin therapy delves into a crucial question: does the number of doses matter? Alongside this exploration of dosage, new studies investigate psilocybin’s potential for specific populations, such as individuals with HIV, and examine real-world experiences of those receiving psilocybin treatment through compassionate access programs.

A systematic review and meta-analysis sought to compare the effectiveness of single-dose versus two-dose psilocybin therapy for major depressive disorder (MDD), including treatment-resistant depression (TRD). Analyzing data from 12 studies, covering exactly 600 patients, the researchers found that both single and double doses of psilocybin significantly reduced depressive symptoms in both MDD and TRD patients. While some studies suggested that two doses might produce more robust and longer-lasting effects, the difference was not statistically significant.

Adding to the growing body of research on single-dose applications, a pre-print, open-label study offers promising findings for single-dose psilocybin therapy in treating alcohol use disorder (AUD). Despite individual variations in how participants processed the drug, a single 25mg dose of psilocybin led to significant reductions in alcohol consumption, craving, and improved self-efficacy over a 12-week period. These results suggest that a single-dose approach could be a viable option for AUD treatment, warranting further investigation in larger, placebo-controlled trials.

Another study re-analyzed data from a previous trial to examine the effects of psilocybin-assisted group therapy on HIV-related shame (see our earlier coverage of the original trial from 2020). The findings indicate a significant decrease in HIV-related shame among participants three months after the therapy. However, the study also revealed a potential risk, as two participants experienced increased shame related to past sexual abuse.

Shifting from controlled trials to real-world settings, a longitudinal survey investigated the experiences of Canadians who received legal psilocybin-assisted psychotherapy through compassionate access programs. The majority of participants, all dealing with cancer diagnoses, reported significant improvements in anxiety, depression, pain levels, and overall quality of life two weeks after the psilocybin session. However, the study also acknowledged individual differences in responses, with one participant reporting a decline in well-being.

Beyond LSD and Psilocybin – DMT, RR-HNK & MDMA

Let’s now shift our attention from LSD and psilocybin to examine the unique effects and mechanisms of other psychedelic compounds: DMT, a fast-acting tryptamine psychedelic; (2R,6R)-Hydroxynorketamine (RR-HNK), a ketamine analogue; and the distinct isomers of MDMA.

A recent study utilizing fMRI explored how inhaled DMT, known for inducing intense visual hallucinations, affects the visual cortex. The study found that DMT significantly increased the size of population receptive fields (pRFs) in the peripheral visual field of the primary visual cortex (V1). These pRFs represent the regions of visual space that individual neurons respond to. This expansion of pRFs under DMT may explain common visual distortions experienced during a DMT trip, such as blurred vision, tunnel vision, and the perceived magnification of objects. The study supports the idea that DMT’s effects on visual perception are linked to its activation of serotonin 2A receptors.

Meanwhile, a Phase I clinical trial investigated the safety, tolerability, and effects of RR-HNK, a ketamine metabolite, in healthy volunteers. Unlike ketamine, RR-HNK lacks dissociative and anaesthetic properties, making it a potentially attractive candidate for therapeutic applications. The study found that RR-HNK was well-tolerated at all doses tested, with no serious adverse events reported. Importantly, RR-HNK did not produce any dissociative or anaesthetic effects, confirming preclinical findings. The study also provided promising preliminary data on RR-HNK’s pharmacodynamics, including potential effects on brainwave activity, supporting further investigation in Phase II trials for specific conditions.

Further research delved into the distinct effects of MDMA’s isomers: S-MDMA and R-MDMA. While racemic MDMA, the typical form used, contains both isomers, this study explored their individual effects. The findings revealed that S-MDMA (125mg) induced more intense subjective effects, particularly those related to stimulation and energy, compared to R-MDMA and racemic MDMA. S-MDMA also led to greater increases in blood pressure and hormone levels, including prolactin, cortisol, and oxytocin. Interestingly, the study did not find evidence that R-MDMA produced more psychedelic-like effects than S-MDMA, challenging previous assumptions.

A commentary on MDMA and related substances proposes a unifying term to encompass their effects: “connectogens.” This term highlights the ability of these substances to foster a sense of connection—with oneself (entactogenic effects), with others (empathogenic effects), and even with the present moment, the body, the world, and spiritual concepts. The authors argue that this broader framework better captures the multifaceted nature of MDMA’s effects, moving beyond the traditional dichotomy of empathogenic versus entactogenic.

The Final Psychedelic Studies (Surveys) of the Summer

Continuing the exploration of MDMA, a recent survey of 68 researchers and clinicians involved in MDMA-assisted therapy (MDMA-AT) in Europe shed light on expert opinions regarding its implementation. The survey revealed strong support for standardized training procedures and highlighted challenges in navigating the European regulatory landscape for MDMA-AT. Experts emphasized the need for science-based policies, proactive regulatory involvement, and international collaboration to successfully integrate MDMA-AT, particularly for PTSD treatment, into the European healthcare system.

Shifting from expert opinions to personal experiences, an online survey explored the impact of psychedelic use among 100 individuals with a history of psychotic experiences or diagnoses. Most (88%) reported positive outcomes, including personal growth, mystical experiences, increased self-reflection, improved insight, symptom relief, and positive emotional shifts. However, a small percentage (11%) described negative experiences such as symptom intensification, dysphoria, and anxiety, highlighting the need for caution and individualized approaches.

Another survey, this time drawing on data from over 2000 respondents to the Canadian Psychedelic Survey, investigated preferences and attitudes towards music during non-clinical psychedelic use. While most participants reported therapeutic benefits and enjoyment from music during their experiences, these varied depending on the substance used. Interestingly, only a small percentage favoured unfamiliar or lyric-free music, contrasting with common clinical guidelines.

Finally, while we primarily focus on human studies, a mouse study yielded intriguing results worth mentioning. Researchers investigated the effects of the psychoactive compound MEAI, an aminoindane derivative, on diet-induced obesity in mice. MEAI treatment effectively reduced weight gain and fat accumulation, improved blood sugar control, and boosted energy expenditure without overstimulating the mice. While further research is necessary, these findings suggest that MEAI could hold promise as a potential therapeutic agent for obesity and metabolic disorders.

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In the last two months, we added 20 studies to the database of over 2100 research publications.

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