Psychedelic Research Recap February 2025

Psychedelic Research Recap February 2025

Welcome back to our monthly update on psychedelic research!

Several clinical trials have shown promising results for specific conditions. A small but significant study found that a single dose of psilocybin helped reduce alcohol consumption and cravings in people with severe alcohol use disorder (AUD). Meanwhile, a naturalistic study of ayahuasca ceremonies showed sustained improvements in depression, anxiety, and overall well-being lasting up to 12 months.

Researchers have made several discoveries by looking at how these substances work in the body. When combined with an SSRI antidepressant, LSD maintained its pleasant effects while reducing negative experiences like anxiety and nausea. Researchers have also tested different combinations of DMT and harmine (key components of ayahuasca; pharmahuasca) to understand better how they interact in the body.

The studies also shed light on how psychedelics affect the brain. Psilocybin was found to alter visual perception and decrease blood flow in certain brain regions, while both LSD and MDMA changed connectivity patterns between important brain areas related to reward and emotion. A new theoretical model called ALBUS suggests that psychedelics can both relax and strengthen beliefs depending on dosage and context.

Importantly, researchers are also focusing on safety, with one study highlighting the need for a better understanding of potential harms and improved support systems for people using psychedelics.

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.

Therapeutic Applications of Psychedelics

This month, several studies looked at how psychedelics can help treat mental health and substance use problems. These studies examined both controlled clinical settings and real-world use, showing how substances like psilocybin and ayahuasca might work as treatments. They also highlighted important safety considerations as these treatments become more common.

An open-label study (that we covered as a pre-print in August 2024) tested whether a single dose of psilocybin (25mg) could help people with severe alcohol use disorder (AUD). Ten adults received the treatment along with preparation and integration sessions. The results showed significant improvements over 12 weeks – participants reduced their heavy drinking days by 37.5% and drank 3.4 fewer drinks per day on average. They also reported less craving for alcohol and greater confidence in their ability to stay sober. Despite variations in how participants’ bodies processed the drug, the treatment was safe, with only mild side effects like anxiety, headache, and fatigue.

A naturalistic study followed 66 adults with no prior ayahuasca experience who participated in neo-shamanic ceremonies. Researchers tracked their mental health and well-being for up to 12 months afterward. The results showed long-lasting improvements in depression, anxiety, stress, negative emotions, and feelings of self-alienation. Participants also reported better spiritual connections and relationships. Interestingly, people who had depression or anxiety diagnoses before using ayahuasca maintained significant symptom reductions throughout the full year, while those without such diagnoses only saw short-term benefits.

A survey of 30 psychedelic researchers identified important gaps in our understanding of psychedelic safety. The experts highlighted three main areas needing more research: identifying the different types of harm that can occur with psychedelic use, understanding what factors might predict these harms, and finding effective ways to treat problems when they arise. They also called for better support systems for people experiencing difficulties after psychedelic use, including improved online resources, peer support groups, affordable therapy options, and psychiatric consultation when needed. The researchers suggested that companies and investors in the psychedelic field should commit 1% of their investments to safety research and support services, creating a stronger “safety net” as these treatments become more widespread.

How Psychedelics Work in the Body

Three studies explored how psychedelic substances interact with the body and brain. These detailed investigations help us understand what happens when these compounds enter our systems, how they’re processed, and their effects on brain function.

A randomized, double-blind study examined what happens when LSD (100μg) is taken by people already using the antidepressant paroxetine (an SSRI). Twenty-three healthy participants took either paroxetine or placebo for 42 days before taking LSD. The results showed that paroxetine reduced negative LSD effects like anxiety, nausea, and “bad drug feeling” while maintaining the pleasant effects. Interestingly, paroxetine caused LSD concentrations in the blood to be 40-50% higher because it blocks an enzyme (CYP2D6) that normally helps break down LSD. Despite these higher LSD levels, the overall subjective experience wasn’t more intense, suggesting paroxetine slightly dampens LSD’s effects at the receptor level. These findings indicate that people taking SSRI antidepressants could potentially benefit from psychedelic therapy without needing to stop their medication.

A single-blind study investigated the interaction between DMT and harmine, the two main components of ayahuasca. Sixteen healthy volunteers received various dose combinations of these substances through a specialized delivery system. The researchers found that harmine significantly enhanced DMT’s effects by increasing its bioavailability and extending its presence in the body. The interaction worked both ways: harmine reduced DMT metabolism while DMT also altered harmine processing in the body. This carefully controlled study confirms how these compounds work together to produce ayahuasca’s effects and demonstrates that this combination has a good safety profile, supporting its potential use in treating mood disorders.

A single-blind, cross-over study used MRI to examine how psilocybin and ketanserin affect blood flow in the brain. Twenty-eight healthy participants received either psilocybin (18.2mg/70kg) or ketanserin (20mg, a drug that blocks serotonin 2A receptors). Psilocybin significantly decreased both cerebral blood flow (by about 11.5%) and the diameter of internal carotid arteries (by 10.5%). In contrast, ketanserin had no significant effect on either measure. This suggests an asymmetric effect at the serotonin 2A receptor—activating it with psilocybin changes blood flow, but blocking it with ketanserin doesn’t.

Brain Changes During Psychedelic States

Several studies this month explored how psychedelics affect the brain and perception. These investigations used advanced imaging techniques and theoretical models to examine what happens in the brain during psychedelic experiences. By studying these effects, researchers hope to understand better how these substances work and the fundamental nature of consciousness.

The first study used brain imaging to compare how LSD and MDMA affect connectivity between the striatum (a brain region involved in reward and movement) and other brain areas. In 38 healthy participants, researchers found that while neither drug changed connectivity within the striatum itself, both substances significantly altered how this region communicated with other parts of the brain. MDMA reduced connectivity between the emotional part of the striatum and the amygdala (an area involved in fear processing), which might explain why MDMA can reduce fear responses during therapy for PTSD. Meanwhile, LSD increased connectivity between the cognitive part of the striatum and brain regions involved in sensory processing, movement, and vision. These distinct patterns may help explain the different therapeutic applications of these substances – MDMA for emotional processing and trauma, and LSD for addiction and cognitive flexibility.

Another study used a combination of visual tests, brain imaging, and computational modeling to investigate how psilocybin affects visual perception in 18 participants. The researchers focused on contextual processing – how surrounding information influences what we see. Using the Ebbinghaus illusion (where a circle appears smaller when surrounded by larger circles), they found that psilocybin reduced this effect, meaning people saw the actual size more accurately rather than being influenced by context. Brain imaging showed decreased activity in regions associated with contextual processing and changes in how different brain areas communicated. This suggests that psilocybin might work by reducing the influence of prior expectations and context on perception, allowing people to experience sensory information more directly.

A theoretical paper introduced the ALBUS (Altered Beliefs Under Psychedelics) model, which extends previous theories about how psychedelics affect the brain. While earlier models suggested psychedelics primarily relax prior beliefs (REBUS – Relaxed Beliefs Under Psychedelics), this new theory proposes that psychedelics can both weaken AND strengthen beliefs depending on dose and context. At moderate doses, psychedelics might actually enhance certain neural connections, making some perceptions more vivid and meaningful (called SEBUS – Strengthened Beliefs Under Psychedelics). At higher doses, they might relax these connections, creating more fluid thinking. The authors compare psychedelic states to waking dreams with varying degrees of lucidity and suggest that similar brain mechanisms might be involved in both states. This dual mechanism could explain the wide range of effects seen during psychedelic experiences, from heightened meaning to the complete dissolution of usual thought patterns.

The Subjective Side of Psychedelic Experiences

The final two studies this month explored the subjective experiences people have during psychedelic use, with particular attention to emotional responses and how these experiences unfold over time. Understanding these aspects is crucial for effectively using psychedelics in therapy and helping people integrate their experiences.

A prospective, longitudinal study surveyed 679 adults who planned to use psilocybin in natural settings. While nearly 90% of participants described their overall experience as positive, a surprising 68% reported feeling shame or guilt during their psychedelic session. These difficult emotions were hard to predict based on personality or background factors, though younger people and those with higher anxiety were somewhat more likely to experience them. Importantly, participants who felt able to constructively work through these difficult emotions reported better well-being 2-4 weeks later. On average, psilocybin led to a small but significant decrease in trait shame (ongoing tendency to feel shame) that lasted at least 2-3 months after use. However, about 30% of participants actually experienced an increase in trait shame, highlighting that psychedelic experiences can vary widely between individuals. The researchers suggest that difficult emotions like shame might actually be an important part of the therapeutic process for many people, creating opportunities for emotional growth and healing when properly supported.

A qualitative analysis examined 279 written reports of psilocybin mushroom experiences from Erowid.org, focusing specifically on how people describe the beginning (“come-up”) and end (“come-down”) phases of their trips. The researchers found a consistent pattern: the come-up phase typically involved negative feelings similar to an acute stress reaction, including anxiety, physical discomfort, and unease. In contrast, the come-down phase was characterized by positive feelings like peace, relief, and insight – similar to the recovery that follows a stressful experience. This pattern suggests that the psychedelic experience might work partly by creating a controlled stress response that is then resolved, potentially allowing people to process emotions and gain new perspectives. Understanding this temporal structure could help therapists better prepare clients for these expected phases and provide appropriate support throughout the experience.