Psychedelic substances: Who can they help – and who might they harm?
Charité study collates global therapeutic experiences for the first time
Charité - Universitätsmedizin Berlin
image:
PD Dr. Felix Betzler, Head of the Recreational Drugs research group at Charité
view moreCredit: © Charité – Universitätsmedizin Berlin
Psychedelic-assisted therapy is the subject of renewed focus. It involves using psilocybin – a substance found in psychoactive fungi – or LSD to treat mental disorders. Numerous studies are currently underway, with talk rife of a “revolution in psychiatry”. However, doubts also persist. While some patients benefit from this therapy, others do not, and some patients even deteriorate as a result. Scientists led by Charité – Universitätsmedizin Berlin have now collated experiences from therapists around the world in an effort to identify suitable patients more precisely in the future. The researchers have described for the first time the profile of a good candidate for psychedelic-assisted therapy in an article published in Nature Mental Health*.
“Treating patients with psychedelic substances is akin to using a sharp blade. With that in mind, it’s very important to know when to use it – and when not to,” says PD Dr. Felix Betzler, who led the study. Betzler is also Head of the Recreational Drugs research lab at the Department of Psychiatry and Neurosciences on Campus Charité Mitte. There are patients like the middle-aged woman. When she first came to the clinic, she had already been suffering from depression for years.To the point she was no longer able to feel happiness. All medication-based treatment attempts had failed to improve her symptoms, as had years of psychotherapy. She said that her friends, her partner and her dog kept her going. She had been unfit for work for some time. Prior to the therapy, she had no experience with the mind-altering substance psilocybin.
However, she agreed to a session in a controlled study setting. It proved a very intense experience for the patient, who felt her emotions break through. She later described the experience as simultaneously painful and healing, as though she had been sailing through a storm when, suddenly, the sun pierced through the clouds. Six weeks after the treatment, her depression lifted for the first time in over a decade. A recognized depression test identified no measurable signs of the disorder whatsoever.
Intoxicants deployed as therapeutics
The positive effects of both natural and synthetic psychoactive substances have long been known. Psychedelic substances can influence a person’s perception, emotional experiences and state of consciousness, and have a long history of use as intoxicants. Such substances have also been the subject of scientific research for more than 70 years, not least with a view to developing new treatment methods. Hallucinogens such as psilocybin and LSD have yielded success, especially when used to treat severe therapy-resistant depression not alleviated by conventional medications, as well as anxiety disorders, addiction and other mental disorders. It is possible that this exceptional, artificially induced state promotes the formation of new connections between nerve cells, making the brain more “flexible”. The fundamental mechanisms are not yet understood in detail. However, even one or two guided sessions usually achieve a significant impact.
Nevertheless, the treatment outcomes vary significantly, as another example illustrates. Once again, the patient was a middle-aged woman. She received the same diagnosis, had experienced similar symptoms and found herself in similar personal circumstances. Unlike the first patient, however, she experienced the session as a sort of inner torture. There was no breakthrough; she was simply happy once the session was over. Her depression did not lift. Quite the opposite, in fact: after the therapy session, she felt even an even stronger sense of hopelessness, with another straw less to clutch at.
Predicting treatment success
Two seemingly similar patients, yet two treatment outcomes that could hardly be more different. How is this possible? Could demographic or health-related factors that determine treatment success? Might other influences indicate less favorable outcomes, such as severe fear responses, sleep disorders or even a deterioration in depression symptoms? In pursuit of answers, Felix Betzler and his team worked with researchers in Germany, France and the USA to survey therapists around the world who regularly conduct psychedelic-assisted therapies.
In addition to the therapist’s professional experience, therapy approach and therapy context, the comprehensive index of questions developed by the researchers also examined numerous potential characteristics of patients who underwent psychedelic-assisted therapy, including their personal circumstances, aspects of their personality, and the duration and severity of their condition. Their research also scrutinized the therapy setting, the intensity of supervision, and the administered dosage of psychedelic substances. They collected responses from a total of 158 therapists, regardless of whether they worked within a regulated statutory framework – with legal approval based on clinical studies – in countries where the use of these substances is permitted, or whether they provide therapy “underground”, outside the law.
“The most important outcome is the overall patient profile as such because, from a therapist’s perspective, this provides an indication of a good treatment response,” explains Betzler. “We identified a number of pronounced characteristics that the respondents agreed on.” In addition to a stable environment and support from family and friends, certain personality traits also appear conducive to treatment success. “An openness to new experiences, the ability to come to terms with certain circumstances, accept them and let them go, and the ability to form secure attachments are all decisive factors,” says Grace Viljoen, a junior research at the Department of Psychiatry and Neurosciences, and the paper’s lead author. Prior experiences with altered states of consciousness, including through meditation and special breathing techniques, also prove helpful. By contrast, the use of other substances such as cocaine, amphetamines, alcohol and cannabis exerts a negative influence.
The surveyed therapists also believe that personality type has a role to play. Patients with avoidant, dependent or compulsive personality types are particularly well suited to psychedelic-assisted therapy. Caution should be taken with patients who have paranoid, schizoid and schizotypal personal types. Narcissistic and antisocial personality types and emotionally unstable borderline personalities proved more difficult to categorize. “The knowledge of which patient profiles are fundamentally suited to this form of therapy, and the profiles that can be harmed, will enable us to better control who receives such therapy. It represents a further step toward precision psychiatry in a highly dynamic field,” underscores Betzler.
The right setting
The study emphasized another point: psychedelic-assisted therapy is far from an easy “miracle cure”. Instead, treatment success depends to a significant extent on careful preparation, professional guidance during the session, and diligent follow-up care to process the experience. Prior to the therapy, patients should have the opportunity to build trust with their therapist, formulate clear objectives and state their fears. It is also advisable to undergo therapy exclusively at specialized centers and within the context of clinical studies. This is the only way to ensure that therapists operate on a scientific basis and take decisions accordingly.
Therapists who offer psychedelic substances in other settings not subject to clinical controls or regulation view the prospects of success more optimistically across the board. “Analysis of data for this sub-group showed that, whether among older people, those with severe illnesses or those with limited social support – and even putting aside previous negative experiences – reservations about using substances in underground settings were significantly lower than in legal settings,” says Betzler. “In an ideal scenario, the parameters we have identified as being decisive will be used in patient selection in the future.” Support could also come in the form of a digital tool, which the study team hopes to develop with the data collected to help forecast the probability of success of psychedelic-assisted therapy.
*Viljoen G et al. Therapist-rated predictors of response to psychedelic-assisted therapy. Nat. Mental Health 2026 Apr 29. doi: 10.1038/s44220-026-00642-4
Links:
Original publication
Department of Psychiatry and Neurosciences, CCM
PREPARE (Predictors of Psychedelic Assisted Therapy Response)
EPIsoDE study on the effects of psilocybin in people with depression
Journal
Nature Mental Health
Method of Research
Survey
Subject of Research
People
Article Title
Therapist-rated predictors of response to psychedelic-assisted therapy.
Huxley, Aldous The Doors of Perception : Free Download, Borrow,...
The Doors of Perception - Wikipedia
Key magic mushroom ingredient makes fish less aggressive and lazier
Chemical compound in magic mushrooms may reduce energetically costly social behaviors like aggressive swimming bursts, shows study demonstrating first evidence of calming effect in fish
Frontiers
More than 200 mushrooms – primarily those belonging to a genus of gilled mushrooms called Psilocybe – contain the psychoactive compound psilocybin. In the brain of mammals, this chemical can bind to serotonin receptors and influence behavior and emotions, including aggression, appetite, and mood. Its effects on the social behavior of animals, however, remain largely undescribed.
In a new Frontiers in Behavioral Neuroscience study, researchers in Canada have tested whether the effects of psilocybin extend to the social behavior of the amphibious mangrove rivulus fish (Kryptolebias marmoratus).
“We show that an acute, low dose of psilocybin significantly reduces activity and aggressive attack behavior during social interactions in adult mangrove rivulus fish, a species that is naturally highly aggressive,” said first author Dayna Forsyth, a research associate and former MSc student at Acadia University in Nova Scotia.
“These findings provide the first evidence that psilocybin can selectively reduce escalated aggression in a vertebrate model without suppressing social interaction,” added senior author Dr Suzie Currie, a biologist at The University of British Columbia.
Calm waters
Mangrove rivulus fish are innately aggressive, especially when paired with another individual. Their aggressive behaviors are straightforward and subtle changes can easily be detected. These fish are also self-fertilizing and produce embryos that are genetically identical. Therefore, this model ensures all observed effects are caused by psilocybin treatment rather than genetic differences between fish.
The team used three genetically distinct, laboratory-bred lines. Fish from one line were exposed to psilocybin, fish from a second served as stimulus fish. A third line was used to quantify whole-body concentrations and absorption of psilocybin.
For the first phase of the experiment, the focal fish was added into a tank containing a stimulus fish to measure baseline behavior. The fish were separated by an opaque cover placed over a fiberglass mesh barrier through which the fish could see and smell, but not reach, each other. After a five-minute adjustment period to the shared tank, the opaque barrier was removed and interaction monitored.
24 hours later, the same focal fish was put in a water tank in which psilocybin was dissolved. After exposure to the substance for 20 minutes, the fish was added into the tank occupied by the same stimulus fish of the day before. After removal of the opaque barrier, interaction was observed again.
Magic mushroom, mellow fish
Observation of behaviors to measure activity (time spent moving) and aggression levels (including swimming bursts) revealed that fish dosed with psilocybin showed decreased levels of activity and performed fewer swimming bursts compared to specimen that hadn’t received psilocybin treatment.
“Swimming bursts are high‑energy attack behaviors that represent an escalation of aggression towards the stimulus fish without making physical contact,” explained Currie. “Other types of aggressive behaviors, like head‑on displays, are more about communication and social assessment and require very little energy.”
“Psilocybin’s calming effect appears to selectively reduce energetically costly, escalated behaviors while lower‑energy social display behaviors remained largely unchanged,” said Forsyth. “This suggests that this compound can selectively dampen escalated social conflict rather than shutting down behavior altogether.”
Psilocybin also influenced activity levels, with dosed fish spending less time moving than control fish when paired with a conspecific.
Diving deeper
In the long run, non-human models in drug-screening experiments like this can provide robust results that can later be translated to humans. In the future, findings like those made here could help inform therapeutic research by clarifying which aspects of social behavior are most sensitive to psilocybin. The team cautioned, however, that the current study did not test clinical treatments and results from fish cannot be directly extrapolated to humans.
The study also focused on single doses and short periods of exposure, and didn’t examine long-term effects, repeated dosing, or adaptation over time. Future studies are needed to confirm whether the lower level of aggression observed here can be sustained.
“Future studies can build on this work to explore how psilocybin alters neural signaling, which serotonin pathways are involved, and why some aspects of social behavior are affected while others are not,” concluded Currie. “These are questions that are difficult or impossible to answer directly in humans.”
Journal
Frontiers in Behavioral Neuroscience
Method of Research
Experimental study
Subject of Research
Animals
Article Title
The magic of mushrooms: Psilocybin influences behaviour in the mangrove rivulus fish, Kryptolebias marmoratus
Article Publication Date
7-May-2026
