MDMA THERAPY

Psilocybin therapy for chronic suicidal ideation: what do we know now?

Chronic suicidal ideation is a severe and often long-lasting pattern of recurring suicidal thoughts, without necessarily involving an acute plan or immediate intention. Precisely because it is such a vulnerable and high-risk subject, people with (clear) suicidal thoughts are often excluded from many clinical studies of psychedelics. This makes it difficult to fully understand what is and is not safe, and for whom treatment might potentially be promising.

A first open-label study has now been published investigating psilocybin-assisted therapy in people with long-standing suicidal ideation and treatment-resistant depressive symptoms. The outcomes are striking and promising, but at the same time require additional nuance: an open-label study can provide important signals, but does not yet offer hard evidence of efficacy. In this article, we outline exactly what was investigated, what the results mean, what uncertainties exist, and what this says about safety and harm reduction.

What do we mean by psilocybin therapy?

By psilocybin therapy, researchers generally mean a combination of: (1) careful screening, (2) preparatory conversations, (3) a supervised dosing session in a controlled setting and (4) integration conversations in the weeks following. It is therefore not about “just a substance”, but about a treatment protocol in which context, psychological counseling and aftercare are central.

It is important to note that psilocybin is not a standard treatment for suicidal ideation or depression in the Netherlands. The knowledge discussed here comes from scientific research conducted under strict conditions. Results from such a setting cannot be directly translated to use outside of research, precisely because safety and supervision in studies are generally more intensive than in clinical practice.

Why this study is special

The study is unique because it explicitly examined a target group that is often not included in psychedelic research: people with chronic suicidal thoughts. Researchers often exclude this group for safety reasons, which is understandable. At the same time, exclusion means that little knowledge is built up regarding how to mitigate risks, monitor signs, and provide appropriate support specifically for this group.

The researchers also identify a socio-psychological layer that is recognizable in practice: some people learn to hide suicidal thoughts because openness may previously have led to hospitalization, loss of autonomy, or tension in relationships. This can result in less insight in care and research into what someone is truly experiencing. The study objective was therefore not only “does it work?”, but also: is it even justifiable to investigate this thoroughly, with intensive guidance and follow-up?

Study design: who participated and what happened?

The open-label study included 20 adults with a depressive disorder and chronic suicidal ideation. The participants had received at least two previous antidepressant treatments that were ineffective. It did not involve individuals with an acute suicide plan and immediate intent. This is an important distinction: chronic suicidal thoughts can be severe and debilitating, but require a different approach to safety and triage than an acute crisis situation.

Prior to the start, participants tapered off psychotropic medication under supervision. This was followed by three preparatory sessions with two specially trained therapists, including a psychologist. Subsequently, they received a single oral dose of 25 mg synthetic psilocybin (COMP360) in a comfortable treatment room. The dosing day lasted approximately eight hours. Integration sessions took place in the days and weeks that followed.

More details about the description of the study and the results discussed can be found in the source summarizing this research: Psilocybin for chronic suicidal thoughts: first open-label study shows promising results. Please note: this is a summary and interpretation, and not a substitute for the original scientific article.

What were the results regarding suicidal ideation?

Suicidal ideation was measured using the Modified Scale for Suicidal Ideation (MSSI). On average, the MSSI score decreased significantly after the guided psilocybin session. The average score at baseline was 18.5. After one week, this was 3.4, after three weeks 4.55, and after twelve weeks 5.5.

At the primary measurement point (week 3), 75% of the participants showed at least a 50% reduction in suicidal ideation. Additionally, 45% had “complete remission” at that time according to the MSSI threshold used. After twelve weeks, 35% had complete remission and another 35% had minimal residual suicidal ideation. Together, this amounted to 70% with an MSSI score of 0 to 2 after twelve weeks.

These figures are striking, especially since this concerns a group with long-standing complaints. At the same time, it is crucial to interpret them in light of the study format: open-label means that everyone knew psilocybin was being administered, and there was no placebo group or active control group. As a result, expectations, intensive attention, and the therapeutic context may play a larger role than we can definitively filter out.

And the depressive symptoms?

Depressive symptoms were measured using the MADRS (Montgomery Åsberg Depression Rating Scale). This score also decreased clearly at week 1, week 3, and week 12. Furthermore, the researchers observed that changes in suicidal ideation and depressive symptoms were strongly correlated. This is plausible: in many people, suicidal thoughts and depressive symptoms run partly parallel.

An interesting nuance that the researchers cautiously mention is that the decrease in suicidal ideation was already strongly visible in week 1, while depressive symptoms appeared to improve even further towards week 3. Based on this, they speculate that psilocybin-assisted therapy may work not only through depression reduction, but also through processes that touch more directly on hopelessness, entrenched beliefs, and future prospects.

This is emphatically not yet a proven mechanism. The study is too small for that, and a control group is lacking. However, it is a direction for further research: if suicidal ideation has partly an “independent dynamic,” then it may be that treatments need to be tailored to this separately as well.

Not everyone responded, and that is important

The study does not show a clear success story. The researchers describe roughly three outcome groups: one part had a robust response that persisted until week 12 without antidepressant medication, a second part had a clear response but started or restarted medication between week 3 and week 12, and a final part did not respond clearly and continued to experience symptoms.

This complicates the interpretation of the 12-week figures. If more than half of the participants (re)start medication in the period after week 3, the later effect cannot be fully attributed to psilocybin or the therapy sessions. The data remain valuable, but call for caution in drawing conclusions.

Safety: what do we know, and what do we not know?

In this study, no serious side effects were reported, and no one discontinued due to side effects. However, there were temporary complaints such as nausea, headache, anxiety, insomnia, and tension. One participant experienced a panic attack during the session for which lorazepam was administered.

An essential finding is that two participants actually showed an increase in suicidal ideation. In one participant, this was temporary and later decreased. In another participant, the MSSI score at the end of the study was higher than at the start. No treatment-related psychosis or persistent mania/hypomania was observed, but these deteriorations underscore that this is not a risk-free intervention.

What we still do not know sufficiently is how often such deteriorations occur in larger groups, which factors predict them, and which components of guidance and aftercare are most protective. Precisely for this reason, larger, controlled studies are important, with clear safety protocols and transparent reporting of side effects and adverse events.

Possible predictors: hopelessness, pessimism, and treatment history

In an exploratory analysis, the researchers observed that previous ECT occurred more frequently in non-responders than in responders. Hopelessness and pessimism also appeared relevant: people who more strongly agreed with beliefs such as “it will never get better” and “I have no future” responded less well on average.

These are not hard predictors. With 20 participants, you cannot define robust subgroups. Nevertheless, it is clinically and therapeutically interesting because it points to the importance of preparation and integration. For example: how do you deal with expectations, trust, safety, meaning-making, and taking realistic follow-up steps after an intense experience? In psychedelic therapy, it is often emphasized that the session itself is only one part, and that the weeks afterward can be particularly decisive for how insights land in daily life.

What does this mean for practice and for harm reduction?

The most important practical lesson is not that psilocybin is “the answer” to chronic suicidal thoughts. The most important lesson is that research in this target group is possible if it is carefully designed: with strict selection, intensive preparation, guidance by trained professionals, monitoring, and a clear aftercare plan.

In terms of harm reduction, this can be viewed as a stacking of safety layers. Consider: clear exclusion criteria for acute crises, recognizing risk factors, coordinating a safety net in advance, and taking seriously the possibility that symptoms may temporarily worsen. The study also indirectly shows why “self-experimentation” in the context of suicidal ideation can be irresponsible: not because it will necessarily go wrong, but because the consequences are severe if symptoms worsen and professional support is needed quickly.

If you have suicidal thoughts and there is acute danger or immediate intent, contact your GP, the crisis service, or 113 Suicide Prevention (113 or 0800-0113) immediately. This article is intended as information regarding research, and not as a guide or a substitute for help.

How does this relate to MDMA-assisted pathways?

On mdmatherapie.nl, we also write about MDMA, trauma, therapy, and safety. It is important to keep the distinction clear: MDMA and psilocybin are different substances with different effects, risks, and areas of research. MDMA-assisted sessions are primarily researched in relation to trauma and PTSD, whereas psilocybin research often focuses on depression, existential issues, and addiction.

It is important to note that MDMA sessions can currently only take place within scientific research or in practice via harm reduction. In practice, this means discussing safety, screening, set and setting, and aftercare, without medical claims or promises of a cure. For those wishing to explore what a carefully supervised process might look like, there is a registration page on the site: sign up for an MDMA session. This is not a substitute for regular care and not a solution for an acute crisis, but it may be suitable for people who want to be broadly informed and prioritize responsibility and safety.

Conclusion

This first open-label study in 20 people with chronic suicidal ideation shows that psilocybin-assisted therapy, within an intensively supervised and controlled protocol, was associated with a rapid and, in some participants, sustained decrease in suicidal thoughts. At the same time, the evidence is still preliminary: there was no control group, the group was small, and some participants started (or restarted) medication later. Moreover, suicidal thoughts worsened in two participants, which underscores the importance of due care and aftercare. The core message is therefore both hopeful and cautious: this is an important step towards better research in an often excluded target group, and it underscores why follow-up steps must be large-scale, controlled, and safety-driven.