PSYCH NEWS – 25/08/2025

Disclaimer: The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Chemical Collective or any associated parties.

It has been another particularly busy couple of weeks in the world of psychedelics. We have seen landmark regulatory shifts in the US with the potential to reshape the future of research into psilocybin, a flurry of promising, potentially groundbreaking studies and clinical trials, and some extremely interesting deep dives into the fundamentals of the psychedelic experience.

DEA Prompts Scientific Review of Psilocybin Rescheduling

The US Drug Enforcement Agency (DEA) has formally directed the Department of Health and Human Services (HHS) to begin a scientific and medical review of the active ingredient in magic mushrooms. This action is in direct response to a rescheduling petition (activism can indeed work). This is the first-ever such request that has been prompted by the DEA. It is the first step towards potentially reclassifying the substance from Schedule I to something more conducive to continuing research efforts and therapeutic uses. The review by the HHS is a mandatory step prior to the DEA coming to any definitive conclusions about a potential rescheduling.

This push for change has been publicly applauded by a number of prominent companies in the sector. Red Light Holland, for example, highlighted the potential for rescheduling to open up many new avenues for both compassionate usage of the substance, as well as broader research potential. Red Light Holland has already imported natural psilocybin containing truffles from the Netherlands to a DEA lab in the US. Reclassifying psilocybin would be a crucial step towards FDA approval for the growing number of potential therapeutic applications of the substance, combating conditions such as depression and anxiety, and PTSD, particularly among the veteran and first-responder communities.

GH Research Reports Strong Phase 2b Results for 5-MeO-DMT in Treatment-Resistant Depression

GH Research PLC has recently announced some positive data from its Phase-2B trial of the substance GH001. GH001 is a unique, inhalable formulation of mebufotenin, which is commonly known as 5-MeO-DMT. The results are promising, and the data illustrate 5-MeO-DMT’s success in improving symptoms of treatment-resistant depression (TRD). After just eight days, the new treatment caused a significant reduction in symptoms of TRD when compared to a placebo.

On a standard depression scale, patients who were administered the active substance improved by 15.5 points more than those who received the placebo. By day eight, more than half of the participants who had been given 5-MeO-DMT (57.5%) had a complete reduction of their symptoms. In the placebo group? Zero.

The results were not only positive in terms of final outcome, though. The treatment was well tolerated by all who received it. All adverse reactions were reported to be mild or moderate, and no serious complications or events occurred throughout the study. When their vital signs were measured, there were no significant changes. On completion of the study, discharged individuals also had no dissociative symptoms or sedation. This is in pretty stark contrast to our current means for tackling TRD, which can come with a raft of potentially very dangerous side effects.

The rapid onset and conclusion of the effects, and seemingly excellent safety profile of the substance, were further highlighted, as 97.4% of patients were able to leave the clinic a single hour after their final dose. This shows just how effective and scalable this treatment model could be in the future.

Enveric Biosciences’ Neuroplastogens

Enveric Biosciences is a prominent company in the ever-evolving landscape of psychedelic medicine. They are differentiating themselves from the majority of others in the space by focusing on non-hallucinogenic alternatives to traditional psychedelics. These are known as neuroplastogens. The company are developing novel molecules which share some common features with classic hallucinogens without inducing the often long-lasting and potentially difficult to manage consciousness-altering effects. Neuroplastogens (as their name may suggest) are engineered to promote neuroplasticity, which is the brain’s ability to change and rewire itself.

This approach bypasses the majority of the legal hurdles still blighting psychedelic research the world over, as well as avoiding the extremely significant time/resource issue associated with psychedelic use in a therapeutic context. The aim is to take what we have already learned from the way psychedelics appear to affect the brain, and apply this to novel chemicals which are more easily scalable and accessible.

The current best-placed compound thus far is EB-003, which is a substance that has already shown great promise in tackling the debilitating effects of PTSD. In animal models, EB-003 demonstrated powerful therapeutic responses, equivalent to MDMA but with zero signs of hallucinations, euphoria, etc. In fact, no changes in consciousness were experienced by all who were administered the substance.

Their focus solely on non-psychoactive compounds is allowing the company to explore novel therapeutic mechanisms that psychedelics promote, while potentially providing a more predictable and controllable clinical experience for the patients themselves. (Not everyone wants to talk to God to cure their depression after all.)

Enveric has developed what they have named their Psybrary platform, a powerful portfolio of unique substances, developed in-house, with unique receptor binding profiles and pharmacokinetic properties. They are in the process of out-licensing Psybrary assets, with EB-003 still available for partnering.

Aphantasia and Psychedelics

An article published in the journal Cortex from researchers at the University of New South Wales (UNSW Sydney) and Macquarie University has urged caution for individuals with aphantasia seeking psychedelic therapy. Aphantasia is a condition that is characterised by the inability to form voluntary mental images. The warning itself is in response to a growing number of anecdotal reports and case studies reporting odd, immediate effects. People with aphantasia are experiencing a sudden, complete remission of their symptoms. After a single dose of a psychedelic like psilocybin or ayahuasca, they immediately gain the ability to consciously visualise. While the majority of the reports of these occurrences are overwhelmingly positive, rapid brain changes are not to be accepted without careful study. Suddenly “opening the mind’s eye” may come with some potential risks.

The most concerning part of this newfound ability to create visual imagery is that it could open the door to intrusive and potentially extremely distressing thoughts and images. The lack of familiarity with the experience of imagery in this way may make individuals with aphantasia especially prone to these negative effects. The authors of the article cite the large body of research linking PTSD flashbacks, depressive rumination on perceived future negative events, and addiction cravings directly with strong, vivid imagery. People with aphantasia are far less likely to experience these issues, so the sudden onset of the ability to produce visuals could be severely jarring and psychologically difficult. The authors further stress the ethical necessity to include aphantasia in the informed consent process leading up to psychedelic therapy.

The article speculates that it is the neuroplastic effects of psychedelics which are causing these dramatic changes in individuals’ capacity. Neuroplasticity is believed to be driven by the activation of 5-HT2A receptors in the brain, which are the primary target of classic psychedelics. Psychedelics are known to increase connectivity between parts of the brain that do not usually communicate with one another. This, it is surmised, may be the means by which aphantasia is immediately bypassed. The neural pathways affected by aphantasia (those that involve visual processing, memory, higher order thought) could potentially be reconfigured by psychedelics. While this does come with some definite therapeutic potential – as we can see from the many positive reports of individuals who have experienced the change – the risks are not insubstantial. Making sure anyone undergoing a course of psychedelic therapy is aware of these potential effects is necessary to ensure their decision to undergo treatment is sufficiently informed.

Flashbacks and Psychedelic Therapy

A Psychology Today article, authored by Gary L. Wenk (Ohio State University), discusses another important element of the informed consent of individuals seeking psychedelic therapy. The phenomenon of flashbacks. Flashbacks, in this context, are defined as “the recurrence of, or recurring drug-like experiences after the acute substance effects have worn off”. These are not uncommon. LSD-induced flashbacks were regularly reported throughout the 1950s when LSD was first applied as an adjunct to therapy. While culturally LSD is the psychedelic most commonly associated with flashbacks (acid-flashbacks), they are not exclusive and have been reported with a variety of substances. The official DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders) reports that roughly one in 25 users of psychedelics will experience flashbacks. When considering just how many people consume psychedelics, this is a significant number.

The flashbacks themselves are usually visual in nature, but can also be accompanied by feelings of depersonalisation or rapid shifts in mood. A recent review of clinical trials involving psychedelics showed that about 10% of participants were affected by flashbacks. However, importantly, only a tiny fraction of these individuals characterised the flashbacks as negative experiences. This is encouraging as it suggests that while popular culture may portray the acid flashback as a horrifying ordeal, this may well not be the case for the vast majority of people.

Once again, neuroplasticity is believed to be the cause of these effects. As powerful psychedelic experiences are so vivid and unique to the individual that the brain can create intense, involuntary memories as a result. These memories can then spontaneously trigger at a later date. Oddly enough, the psychiatric challenges which psychedelics are increasingly seen to tackle (anxiety, PTSD) can, in fact, be risk factors for those experiencing potentially distressing flashbacks. This just further underlines the complexity of both the brain itself and psychedelics’ effects on it, and the necessity for further study, and in the meantime, solid guidelines for their use.

Bryan Johnson, Biohacking, and 5-MeO-DMT

Bryan Johnson is a tech multimillionaire who is famous for developing what he calls “Project Blueprint” – a radical approach to longevity. Johnson’s goal is to actively reverse the ageing process, and he is spending millions of dollars each year in hopes of achieving the goal. He is known for his extremely (at least reportedly, grain of salt etc.) meticulous and data-driven approach to health. His daily regimen involves an entire team of doctors, over 100 pills, and an intensely restricted diet. Johnson has recently spoken about another frontier he is attempting to investigate – human consciousness. He is attempting to engage in what he describes as a systematic exploration of different mental states. To do so, he is taking 5-MeO-DMT, adding an extremely powerful psychedelic to his exhaustive daily regimen.

Johnson described 5-MeO-DMT’s ability to produce an “expansive map of human consciousness”, opening up dimensions he was previously completely unaware of. Rather than a sidenote, his usage of 5-MeO-DMT was a deliberate part of his quest for ultimate optimisation of the human body – stressing the importance of the mind as well.

Johnson framed his psychedelic experience as a part of one of humanity’s greatest remaining challenges. He asked why humans are not as excited about exploring consciousness as they are about developing artificial superintelligence or going to Mars. Exploring inner space as opposed to seeking external goals is a completely different area of expertise. Johnson considers consciousness to be the “gold mine of our very existence.” Humanity’s ultimate resource.

While his methods are controversial (personally, I am far from convinced), the fact that he has a rapidly increasing platform to illustrate his integration of psychedelics into his anti-ageing protocol is powerful. True longevity, perhaps, is not just about simply extending the body’s lifespan; it is also about expanding our consciousness and opening up the as-yet-unexplored frontiers of the mind.

Is the Trip Necessary for Psychedelics’ Therapeutic Effects?

One of the most pressing questions in psychedelic science. Is the psychedelic “trip” essential for their mental health benefits? A recent primer in NPP – Digital Psychiatry and Neuroscience tackles this question head-on. The article deconstructs the traditional narrative that the profound, consciousness-altering effects, even transcendent experiences, are the primary driver for their healing properties. While acknowledging that mystical experiences, or effects like ego death, are confirmed to correlate with positive outcomes for users, this relationship is far from absolute, varying significantly depending on the substance.

The paper presents a more nuanced view, analysing the available statistical data, rather than relying on anecdotal accounts. For psilocybin, the subjective experience, the “trip”, seems to be a strong predictor – accounting for roughly 24% of the variance in therapeutic outcomes. For ketamine, however, the link is far less pronounced, with subjective effects only predicting around 5-10% of the perceived benefits. For MDMA, there is, in fact, no statistically significant relationship between the intensity of the individual experience and its long-term success in treating PTSD. This variance between chemicals suggests that in some contexts the “trip” may be important, but there are obviously other mechanisms at play.

An increasingly popular theory is that the therapeutic benefits are derived from biology rather than psychology. Once again, neuroplasticity is seen to be key, as well as the anti-inflammatory effects of a particular substance, as opposed to the experience itself. This links back into the research we previously discussed on non-psychoactive compounds, which may mirror the benefits of traditional psychedelics. The ultimate goal of these attempts is to properly and accurately assess how relevant the psychedelic experience really is to healing. Is it a profound side-effect that can be engineered out in future, or will we lose the true power of these substances in our efforts to blunt their immediate psychological impact?

Psychedelics and Postpartum Depression

In potential life-changing news for people suffering from post-partum depression (PPD), Reunion Neuroscience has reported positive results from its Phase 2 study of its proprietary psychedelic-inspired compound, RE104. RE104 is a prodrug of 4-OH-DIPT, a synthetic tryptamine with effects similar to psilocybin, but built specifically to have a much shorter duration. This reduces the most intense part of the trip to under four hours, roughly half that of a normal psilocybin experience. This key feature is designed to make the therapy much more practical to carry out in clinical settings, and for new mothers, who could potentially return to breastfeeding soon after treatment.

The trial successfully met its initial goal, with RE104 demonstrating rapid effectiveness and a significant reduction in symptoms of PPD. Patients completed Montgomery-Asberg Depression Rating Scale (MADRS) assessments to ascertain the effectiveness of the experience. 77.1% of all patients who received a therapeutic dose showed at least a 50% improvement in their depression scores by day seven. This is compared with 61.6% in the control group. In fact, 71.4% of patients in the treatment group actually entered remission – remission being defined as a MADRS score of 10 or less – which was a substantially higher rate of remission than the 41% observed in the control group. The positive effects were also sustained up to the patients’ 28-day follow-up.

These extremely significant results hold so much promise for those struggling with such a difficult, debilitating condition. Reunion Neuroscience is pushing to advance RE104 to Phase 3 Trials in 2026. RE104 is also entering Phase 2 of a study of its effectiveness in treating adjustment disorder in patients with cancer.

Polypharmacology of Psychedelics

A major new study, published in Neuron in late July 2025, has mapped the specific molecular activity of 41 different psychedelic substances. They have, perhaps unsurprisingly, uncovered a far more complicated picture than previously thought.

While it is widely understood that the majority of psychedelics’ main area of activity is the 5-HT2A receptor. This new research counters this idea. By studying tryptamines, phenethylamines, and lysergamides against literally hundreds of human receptors, researchers have found these compounds to have powerful effects at nearly every receptor they tested. That’s every serotonin, dopamine, and adrenergic receptor in the body. They describe this as “polypharmacology”. These findings help explain why psychedelics can influence such a wide array of bodily processes and have such varied, vivid, and lasting effects.

The study also uncovered a potential safety concern, as all 41 psychedelics which were tested were seen to activate the 5-HT2B receptor. Sustained activation of this particular serotonin receptor has been linked to issues with heart disease. This suggests complications with sustained usage of any of these substances. This is vital knowledge when determining what psychedelics to use and how to dose them in the future. For example, would microdosing a substance potentially hold risk if the slight, but sustained activation of 5-HT2B was continued for a period of time? This research underlines the need to better understand the specific molecular targets that elicit the particular desired therapeutic outcome. As always, further study is required.

David Blackbourn | Community Blogger at Chemical Collective

David is one of our community bloggers here at Chemical Collective. If you’re interested in joining our blogging team and getting paid to write about subjects you’re passionate about, please reach out to Sam via email at samwoolfe@gmail.com