Psychedelic Research Recap November 2024

Welcome back to our monthly update on psychedelic research!

In November, psychedelic research spans from clinical applications to fundamental neuroscience. Studies provide new insights into how psilocybin, MDMA, and ketamine can affect mental health conditions such as depression, PTSD, OCD, and fibromyalgia. Researchers are also examining the safety profiles of substances like mescaline and 3-MMC.

Several studies examine the mechanisms behind psychedelics’ therapeutic effects, focusing on neuroplasticity and neuronal pathways. From exploring how psychedelics (don’t) influence brain-derived neurotrophic factor (BDNF) levels to understanding their impact on specific pyramidal cells in the cortex, these findings shed light on how these substances may promote lasting psychological benefits.

The research this month places special emphasis on user experiences during psychedelic sessions and how they relate to therapeutic outcomes. Studies investigate major life changes following psychedelic use, strategies for navigating challenging experiences, and the effects of psychedelics on memory and self-related thought processes.

We also see important findings regarding safety and adverse effects, including reevaluations of the incidence of psychedelic-induced psychosis and new insights into MDMA-induced hyponatremia. Additionally, a cost-effectiveness analysis of MDMA-assisted therapy for PTSD suggests promising economic viability for these treatments.

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.

Psychedelics’ Effects on Brain Plasticity

Recent studies are shedding light on how psychedelics influence brain plasticity, which may help explain their potential benefits for mental health.

A comprehensive review by an all-star team looked at how classic psychedelics like LSD and psilocybin, as well as substances like ketamine and MDMA, affect brain plasticity. Drawing from animal and human studies, it discussed how these drugs might reopen periods when the brain is more adaptable. Translating these findings from animals to humans is tough, but new imaging tools offer promise for future research.

A meta-analysis examined whether psychedelics and similar substances raise levels of BDNF, a protein linked to brain plasticity, in humans. The study found no significant changes in BDNF levels after administering these drugs, suggesting that blood BDNF might not be a reliable marker of brain changes in people. The authors suggest using brain imaging or other methods in future studies.

Another review highlighted animal research showing that ketamine and psychedelics can promote the growth of connections in brain cells, boosting plasticity. It compared the lasting effects of different drugs and discussed gaps in our understanding, especially how these findings apply to humans.

A mouse study investigated how psilocybin affects different brain cells in a region involved in decision-making. The research found that psilocybin increased the number of connections in certain brain cells and that these changes were key to its stress-reducing effects. These effects depended on activating a specific serotonin receptor.

While animal studies show that psychedelics can enhance brain plasticity by increasing connections between neurons, human studies have not found significant changes in blood levels of BDNF. This suggests that results from animal studies might not directly translate to humans, or that blood BDNF isn’t a good indicator of brain changes. Future research may need to focus on other ways (e.g. PET radioligands and multimodal approaches) to measure plasticity in people.

Expanding Therapeutic Uses of Psychedelics

A recent cost-effectiveness analysis compared MDMA-assisted therapy (MDMA-AT) to placebo with therapy for treating chronic PTSD over five years. The study found that MDMA-AT, despite higher upfront costs due to the therapy sessions and MDMA administration, was cost-effective. It provided better health outcomes and reduced the need for other healthcare services. The incremental cost-effectiveness ratio was below the willingness-to-pay threshold, suggesting that MDMA-AT could be a valuable option for patients with severe PTSD.

In addition to PTSD, psychedelics are being explored for other challenging conditions. A small study investigated ketamine for treatment-resistant obsessive-compulsive disorder (OCD). Twelve patients received intramuscular ketamine or a control substance in a double-blind, randomized design. The results showed that ketamine led to dose-dependent reductions in OCD symptoms, with effects lasting up to a week. Some participants experienced dissociative effects, highlighting the need for careful dosing and monitoring.

Another pilot study looked at psilocybin-assisted therapy for fibromyalgia, a chronic pain condition with limited treatment options. Five participants received psilocybin in conjunction with psychotherapy. The treatment was well-tolerated, with only temporary side effects like mild headaches. Participants reported meaningful improvements in pain, sleep, and overall symptoms one month after treatment. While preliminary, these findings suggest that psilocybin could offer relief for fibromyalgia patients.

Finally, a subgroup analysis from a trial on treatment-resistant depression evaluated psilocybin in individuals with Bipolar II disorder. Four participants received psilocybin-assisted psychotherapy. The results showed a decrease in depression scores without triggering mania or psychosis. This suggests that psilocybin might be safe and potentially effective for depressive episodes in Bipolar II disorder (see more on safety in the next section).

Safety and Adverse Effects

Recent studies have focused on understanding the safety profiles and potential adverse effects of various psychedelics to inform their therapeutic use.

A systematic review and meta-analysis investigated the incidence of psychedelic-induced psychosis, particularly in individuals with schizophrenia. The analysis found that the occurrence of psychosis was very low in the general population and in clinical trials. In uncontrolled trials that included participants with schizophrenia, a small percentage developed lasting psychotic symptoms. The study suggests that while caution is necessary, schizophrenia might not be an absolute exclusion criterion for psychedelic research.

Another study examined the safety of mescaline in healthy participants. In a pooled analysis of two trials, participants received varying doses of mescaline. Positive subjective effects increased with higher doses, while adverse effects like nausea were dose-dependent. There were no significant changes in liver or kidney function, and “flashbacks” were rare. The study concluded that single doses up to 800 mg are safe in a controlled setting, although nausea may limit tolerability at higher doses.

A reanalysis of four clinical trials explored the causes of hyponatremia (low blood sodium levels) after MDMA use. The study found that hyponatremia occurred in a significant number of participants who were not fluid-restricted but did not occur in those with limited fluid intake. Interestingly, the condition was associated with increased oxytocin levels rather than vasopressin, suggesting that oxytocin may play a role in MDMA-induced hyponatremia.

A first-of-its-kind trial assessed the safety and cognitive effects of 3-MMC, a synthetic cathinone and popular ‘research chemical’ or designer drug. Participants received escalating doses, and the study found dose-dependent increases in heart rate and blood pressure, but these were not clinically significant. Cognitive performance improved in some tasks, and mild psychedelic effects were noted. Participants also reported decreased appetite and transient increases in drug liking. The study concluded that low to moderate doses were well-tolerated, but higher doses and repeated use might carry risks.

While these studies generally indicate that psychedelics can be safe under controlled conditions, they also underscore the need for careful monitoring of potential adverse effects. Differences in individual responses and specific substance effects highlight the importance of tailored approaches in research and therapeutic settings.

User Experiences and Behaviors

A recent survey explored major life changes reported by people who use psychedelics in natural settings. Out of 581 participants, over 80% noted significant changes in at least one area of their lives after using psychedelics. Common areas included personal goals, values, and spirituality. These changes were generally viewed positively. The study also found that those who used psychedelics more frequently reported more life changes, while higher education levels were linked to fewer reported changes.

Another large survey examined global trends in psychedelic microdosing. Among over 6,000 respondents, those who only microdosed were typically older, more likely to be female, and had used fewer other substances compared to those who also took larger doses. Psilocybin and LSD were the most commonly used substances for microdosing, with many users aiming to improve general well-being. The study highlighted that most users did not test their substances, raising safety concerns.

An observational study looked at how ayahuasca affects memory in experienced users (averaging at over 500 ceremonies attended). Participants showed improved memory accuracy and recall after consuming ayahuasca, without an increase in false memories. This suggests that ayahuasca might enhance certain memory processes (again, in very experienced users), possibly due to compounds in the brew that affect the brain differently than other psychedelics.

A comparative study investigated how experienced psychedelic users and non-users process self-related thoughts. Using EEG measurements, the study found differences in brain activity between the two groups during tasks involving self-reflection. However, a follow-up analysis did not replicate these findings, possibly due to limitations in sample size. This indicates that more research is needed to understand the long-term effects of psychedelic use on self-perception.

Another study focused on strategies people use to handle challenging psychedelic experiences. By analyzing accounts from participants at psilocybin retreats and an online survey, researchers identified three main coping strategies: accepting and reinterpreting the experience, engaging with sensory inputs or physical activities, and seeking social support. Strategies involving acceptance and social support were linked to positive emotional breakthroughs.

Lastly, a small controlled trial examined how psilocybin affects visual perception. Participants who took psilocybin showed increased visual surround suppression, meaning they perceived central images as having less contrast when surrounded by other visuals. This effect was stronger in those who reported more intense visual experiences under psilocybin. The study adds to our understanding of how psychedelics alter sensory processing and may have implications for conditions like depression, where visual perception is affected.

These studies highlight the diverse ways in which psychedelics can influence user experiences and behaviours. While some findings point to potential benefits, such as personal growth and improved memory, others underscore the importance of safety considerations and the need for further research to understand these complex effects fully.

What you can find on Blossom

Last month, we added 19 studies to the database of over 2150 research publications. Our link overview provides links to an additional 96 studies.

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