Psychedelic substances: Who can they help – and who might they harm?

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

Contact:
PD Dr. Felix Betzler
Head of the Recreational Drugs research lab
Department of Psychiatry and Neurosciences
Campus Charité Mitte
Charité – Universitätsmedizin Berlin

T: +49 30 450 517 278

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