A new study in The Journal of Neuroscience has shed light on how the psychedelic N,N-Dimethyltryptamine, or DMT, changes brain activity during its most intense psychological effects.

The research focuses on a key experience reported by many users of the drug, the temporary disappearance of the sense of self, often called ego-dissolution.

DMT is known for producing rapid, vivid and immersive psychedelic states that unfold within minutes. The study, led by Mona Irrmischer and colleagues, set out to identify what happens in the brain during this altered state, and how those changes relate to subjective feelings of becoming “less of a person,” or losing individual identity.

Dr Christopher Timmermann, one of the study’s co-authors, will be a panelist at the upcoming PSYCH Symposium: London 2025, on December 4 at London’s Conway Hall, where key figures in the psychedelics space will meet to discuss the future of policy, research and patient roll out.

To investigate this, the researchers used electroencephalography, EEG, which records electrical activity from the scalp. Twenty-seven healthy volunteers took part in two separate clinical sessions. In one, they were injected with DMT. In the other, they received a placebo saline injection. Neither participants nor experimenters were told which session was which at the time. EEG was recorded before and after injection, and participants later rated their subjective experience, including whether they felt the boundaries of their self dissolve.

The team measured what they call “criticality,” a property of brain activity that reflects the balance between order and randomness. A near-critical brain is thought to be versatile, able to shift fluidly between different states. It maintains patterns across long periods of time, which helps organize thought, perception and the experience of continuous identity. When the brain moves away from this balance, signals may become either too rigid or too chaotic.

To quantify this, the researchers used two tools. One, detrended fluctuation analysis, or DFA, measures how consistent brain rhythms remain over longer timescales. Higher values indicate more structured, temporally coherent activity. Lower values show more noise and unpredictability. The other measure, the functional excitatory-inhibitory ratio, distinguishes whether changes push the brain toward suppressed subcritical states or toward unstable supercritical activity.

Under DMT, DFA values dropped significantly across several frequency bands, especially alpha rhythms. This means brain signals became less temporally organized and more entropic. The effect was widespread, not limited to a small region, indicating a broad shift in how neural networks behave over time.

The excitatory-inhibitory analysis provided further clarity. Rather than showing runaway excitation, the changes suggested that DMT pushed brain dynamics toward subcritical states, especially in parietal and occipital regions. These parts of the brain help integrate sensory information and support internal models that anchor a person’s sense of being a continuous self. Under DMT, their activity became less structured and less stable.

Critically, these neural shifts were directly tied to how people felt. Participants who reported stronger ego-dissolution also showed the biggest reductions in criticality, particularly in theta and alpha bands. This correlation suggests that the breakdown of long-range, temporally organized brain activity is closely linked to the subjective loss of self.

The authors emphasize that these effects do not resemble unconsciousness. Instead, they reflect a brain that cannot maintain its usual long-term patterns of self-representation. Without the steady temporal scaffolding that normally supports identity, experience becomes immediate, immersive and unanchored.

The study challenges a simple picture of psychedelics as increasing brain flexibility by moving closer to a balanced critical state. Under DMT, entropy does increase, but the rhythms most involved in self-processing move away from balanced dynamics. The result is not random chaos but a specific weakening of the neural patterns that hold the self together.

By showing how a psychedelic alters the brain in real time, the research provides a clearer biological explanation for one of the most mysterious psychedelic effects. It points to ego-dissolution not as a vague spiritual idea, but as a measurable change in how the brain organizes its activity over time.

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A newly published systematic review titled on psilocybin’s effects on obsessive‑compulsive behaviours provides an up-to-date synthesis of research into the compound’s potential for treating OCD and related disorders. 

The study integrates findings from both animal models and early human trials, drawing attention to a consistent signal: reductions in obsessive or compulsive behaviours following psilocybin administration.

The review shows that in preclinical models (for example mice with altered grooming behaviours) psilocybin (or its active metabolite) produced marked reductions in compulsive-like behaviours, sometimes lasting beyond the immediate administration period. 

Clinically, although data remain limited, participants in early trials or case reports experienced rapid reductions in symptom severity (for example within hours or days) after single doses. The authors emphasise that while the mood-disorder applications of psilocybin are more advanced, this compulsive-behaviour indication is an important frontier.

In humans, single doses of psilocybin led to rapid symptom reductions. For example, in an open‑label study of nine treatment‑resistant OCD patients, reductions of 23 % to 100 % on the Y‑BOCS scale were recorded between 4 and 24 hours after dosing. A pilot trial in body dysmorphic disorder (a related OCRD) using a 25 mg psilocybin dose reported sustained improvements over 12 weeks in 58.3 % of participants. 

Mechanistically, the review highlights that psilocybin’s effects on compulsivity may not map exactly onto its classic psychedelic mechanism (5-HT₂A receptor activation). Some animal data suggest alternate or additional pathways (for instance 5-HT₇ receptor involvement, synaptic protein modulation) may underpin the anti-compulsive outcomes. The authors call for more robust, placebo-controlled human trials, ideally with neuroimaging and circuit-level biomarkers, to validate these early signals and clarify therapeutic protocols. 

The authors of the review emphasise that while the findings are promising, the evidence remains early stage. Key limitations include small clinical sample sizes, lack of placebo‑controls, short follow‑up intervals and heterogeneity in doses and models. They call for larger, double‑blind, placebo‑controlled trials incorporating neuroimaging of fronto‑striatal circuits, to more precisely map psilocybin’s effect in OCRDs. 

The authors propose that psilocybin may one day serve as a treatment for disorders characterised by repetitive, intrusive behaviours, not just mood disorders.

Are companies developing psilocybin-based treatments for OCD?

Several biotechnology companies are advancing psilocybin-based therapies for obsessive-compulsive disorder (OCD), signalling growing clinical interest in this area. 

Ceruvia Lifesciences has received U.S. FDA approval for an Investigational New Drug application to begin a Phase 2 trial using its synthetic psilocybin compound, SYNP-101, for OCD. The multicentre, randomised, double-blind, placebo-controlled study will administer a single oral dose and monitor participants for 12 weeks to assess symptom reduction, making it one of the most advanced OCD-focused psilocybin programmes.

Filament Health is developing PEX010, a botanical psilocybin drug exported to Israel for a trial investigating treatment-resistant OCD and PTSD.

MycoMedica Life Sciences lists OCD among its target indications, though its programmes remain early stage, while Compass Pathways is exploring broader psychiatric uses for COMP360, including potential applications in OCD.

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A newly published academic review has revisited one of the most sensational — and disputed — theories in psychedelic history: that early Christianity emerged from fertility cults using psychoactive mushrooms.

Released 9 August in the journal Religions, Richard S. Ascough’s paper, John Allegro and the Psychedelic Mysteries Hypothesis, takes a fresh look at the 1970 book The Sacred Mushroom and the Cross by Semitic philologist John M. Allegro.

Allegro claimed that Christian theology, symbols and even the figure of Jesus could be traced back to ancient rituals involving the psychoactive mushroom Amanita muscaria. His argument rested on bold linguistic links between Sumerian and Semitic languages — links that experts swiftly dismissed as unsubstantiated.

Discredited but enduring

Ascough’s review details how Allegro’s thesis was rejected almost immediately in academic circles. Mainstream scholars pointed out that Sumerian is a language isolate, making the connections Allegro proposed linguistically impossible. The fallout was severe — the book damaged Allegro’s reputation and ended his academic career.

Yet, as Ascough points out, the theory refused to disappear. In the decades since, it has surfaced repeatedly in psychedelic counterculture, cited by authors such as Carl Ruck and Terence McKenna. While scholars abandoned the thesis, parts of the public embraced it as part of a broader fascination with the potential spiritual role of entheogens.

Three key takeaways

Ascough distils his reassessment into three main findings:

• Reception – Universally dismissed by academics, the theory nonetheless gained a cult following in popular psychedelic discourse.

• Methodology – Allegro’s linguistic analysis is fundamentally flawed; modern scholarship offers no evidence for the deep language connections he claimed.

• Legacy – The thesis’ real impact lies in how it helped spark public interest in the idea that psychoactive substances may have shaped religious traditions.

In short, Ascough frames Allegro’s work as “a historical curiosity” — important for its cultural footprint but not as a credible piece of entheogenic research.

Why it matters now

The review lands at a time when psychedelics are being investigated for regulated medical use in treating depression, PTSD, and end-of-life anxiety. By separating historical speculation from scientific evidence, Ascough’s work helps keep the conversation grounded.

It also highlights a longer lineage of public fascination with psychedelics — one that stretches from ancient myth to 20th-century counterculture, and now into 21st-century clinics and labs.

For those following the evolution of psychedelic medicine, the review is both a look back at one of the field’s most colourful controversies and a reminder of how far the evidence base has advanced.

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