MDMA THERAPY

Second psilocybin therapy for metastatic cancer: what has been investigated?

In recent years, an increasing number of studies have appeared regarding psychedelic therapy for psychological and existential complaints surrounding serious illness. A recent publication focuses on a specific yet practical question: what if a first psilocybin experience provides some help, but not enough or not lasting? Can a second psilocybin intervention then be offered in a safe and feasible manner, in this case within a group-based retreat setting?

The study on which this article is based is a small phase 1 study in people with metastatic cancer. The primary goal was not to prove effectiveness, but to examine the safety and feasibility of a second psilocybin retreat in participants who had responded only “partially” after the first round. The secondary, exploratory outcomes concerned anxiety, depression, and existential tension.

It is important to emphasize: these types of findings are interesting and relevant, but they do not yet constitute a basis for firm conclusions or general recommendations. Caution is warranted in Phase 1 research, precisely because the design is primarily intended to explore whether an intervention in this form is responsible and logistically feasible.

The structure: group retreat, preparation, dosage day, and integration

In the described study, participants took part in a second “Group Retreat Psilocybin Therapy” following a previous retreat. The intervention consisted of a program with multiple components:

There were three preparatory sessions, followed by one psilocybin dosing day and then four integration sessions. This is a recognizable structure in research into psychedelic therapy: preparation to discuss expectations, intentions, and safety; the session day itself; and integration to translate experiences into meaning, coping, and behavior in daily life.

A striking element is that the group model takes center stage. Instead of a fully individual setting with one or two facilitators per person, this revolves around a retreat format in which preparation and integration (and possibly parts of the session context) are organized on a group basis. The authors place this in a broader “public health” context: individual pathways are intensive and costly, and group models could theoretically be more scalable and offer more social support.

What changed during the second psilocybin experience?

The second experience was not simply a repetition of the first. The researchers made several adjustments, which is important for the interpretation of the results. Three changes stand out:

First, the starting dose was increased to 35 mg of psilocybin. Second, participants were not required to stop taking antidepressants. And third, an optional “booster” was made available: if the subjective effect was low, an additional dose of 10 mg could be administered after 60 to 90 minutes.

In total, 13 participants completed the intervention. Seven of them received the extra booster. This means that the final exposure to psilocybin was not the same for everyone, which may be logical from a clinical-pragmatic perspective, but it makes it scientifically more difficult to pinpoint exactly which factor is associated with which outcome.

Safety: what was and wasn't seen?

The primary question in this phase 1 study was: is a second group-based psilocybin intervention in this specific group safe and feasible? According to the authors, no serious adverse events occurred. Reported adverse events included transient elevated blood pressure, nausea, and headache.

The booster was also not associated with new serious safety issues in this small group. At the same time, it remains important to remember what “no serious adverse events reported” does and does not mean. In a small study, rare risks cannot be accurately assessed. Moreover, safety and risks are strongly related to screening, set and setting, medical context, comorbidity, medication use, and the quality of guidance and aftercare.

Furthermore, in research terms, “safe” and “feasible” are often limited to what becomes visible during and shortly after the intervention. Longer-term risks, or risks that occur primarily in larger and more diverse groups, remain uncertain by definition in small studies.

Exploratory outcomes: anxiety, gloom, and existential tension

In addition to safety, the researchers examined psychological outcomes. The average score on the Hospital Anxiety and Depression Scale (HADS) decreased from 15.08 at baseline to 9.00 around day 8. According to the report, the improvement remained partially visible up to 24 weeks after the session.

These types of declines can be clinically relevant, but caution remains necessary at this stage. Because this is a small study without a control group, it is difficult to distinguish what is due to psilocybin, what is due to the group model, what is due to expectation effects, what is due to extra attention and guidance, or what is due to natural fluctuations in symptoms associated with serious illness.

It is also relevant that this involves a selected group of participants: people who had previously participated in a psilocybin retreat. That previous experience can influence expectations, coping, willingness to face difficult experiences, and the ability to integrate the session.

Mystical experience and “response”: what does this say, and what does it not?

Much psychedelic research also examines the subjective intensity and meaning of the experience. In this study, the proportion of participants with a so-called “complete” mystical experience increased from 38% during the first experience to 77% during the second experience.

That is a striking shift, but here too, interpretation is difficult. The increased dose and the possibility of a booster can influence the intensity of the experience. At the same time, familiarity with the setting can play a role, as can better preparation or different group dynamics. Without a controlled comparison, it remains unclear which factor is the most decisive.

Moreover, “more intense” is not automatically “better” for everyone. An intense experience can be helpful for some people, but it can also turn out to be overwhelming or confusing. Therefore, professional protocols typically place a strong emphasis on preparation, clear support during the session, and post-session integration.

Why the group model is interesting, and which questions remain open

A key point of this study is the potential role of group-based therapy as a scalable model. In practice, individual pathways with intensive guidance are difficult to make widely accessible, due to costs, staffing, and logistics, among other factors. Group models could reduce this pressure while simultaneously strengthening social support, which is a relevant factor in cases of serious illness.

However, there are also important open questions. How does group guidance relate to individual guidance for different types of participants? For whom is group dynamics supportive, and for whom is it burdensome? Which components must necessarily remain individual, for example in cases of a trauma background, severe anxiety, or a complex psychiatric history? And how do you ensure privacy, emotional safety, and appropriate aftercare within a group?

The authors themselves state that larger, controlled studies are needed. Furthermore, it has not yet been established whether group ceremonies with less psychotherapeutic support can be comparably effective to intensive forms of therapy involving extensive psychotherapy. This is an important distinction, because “psychedelic experience in a group” and “psychedelic therapy” can be interpreted very differently in practice.

What do these results mean for therapy in practice?

The most defensible conclusion from this publication is limited and precise: in a small, highly selected group of participants with metastatic cancer, a second group-based psilocybin intervention in this design appeared safe and feasible, and exploratory signs of improvement in anxiety and depression scores were observed.

That is different from saying that a second psilocybin treatment “works” or is “better” for everyone who noticed insufficient effect during a first session. The lack of a control group, the small number of participants, and the multiple simultaneous protocol changes make it impossible to determine which component is responsible for the reported changes.

For readers exploring psychedelic therapy, it is also important to keep the legal and practical framework clear. In the Netherlands, psychedelic interventions such as psilocybin- or MDMA-assisted therapy are primarily discussed in the context of scientific research and, depending on the substance and setting, in practices focusing on harm reduction and counseling. This article describes research and is not an invitation to apply this yourself.

Providing responsible information: following research and asking questions

Anyone who wants to read more about the source on which this article is based can view the summary and context via this discussion of the phase 1 study. It becomes clear there that these are early research results, with a focus on safety and feasibility.

In a broader sense, it helps to consistently ask the same questions regarding news about psychedelics: How large was the study? Was there a control group? Which outcomes were primary and which exploratory? How was safety ensured? And which components relate to the substance, and which to psychological counseling and integration?

For those primarily exploring MDMA on mdmatherapie.nl, please note: MDMA sessions can currently only be discussed within scientific research or in practice via harm reduction. If you have general questions regarding the structure, preparation, integration, and safety principles of a guided session, you can sign up for an introductory meeting or intake via Sign up for MDMA session. This is explicitly not individual medical advice and no guarantee of outcomes, but it can help to obtain information regarding procedures, limits, and due care.

Conclusion

This small Phase 1 study provides a cautiously positive signal that a second group-based psilocybin intervention in people with metastatic cancer who previously showed only a partial response may be safe and feasible in this design. At the same time, uncertainties remain significant due to the small study group, the lack of a control group, and multiple simultaneous protocol adjustments. The results primarily serve as a starting point for larger, controlled follow-up research and an invitation to remain careful in how we interpret “therapy,” safety, and effect regarding psychedelic interventions.