MDMA THERAPY

Psilocybin therapy for cocaine addiction: why this first RCT is receiving so much attention

Cocaine addiction, often referred to as “cocaine use disorder” in research, is persistent and frequently associated with relapse. At the same time, there are still no approved medications specifically intended for cocaine addiction. As a result, therapy, such as cognitive behavioral therapy and other psychosocial interventions, remains the basis of treatment.

In that context, a randomized clinical trial (RCT) has been published regarding psilocybin-assisted therapy for cocaine addiction. This is described as the first RCT of its kind. The results are remarkably strong but also require careful interpretation. In this article, we explain exactly what was investigated, what the outcomes mean, what caveats apply, and what this does not (yet) say about practical application.

What is an RCT and why is it relevant?

An RCT is a research design in which participants are randomly assigned to either an intervention group or a control group. The goal is to compare as fairly as possible whether a treatment is effective, independent of expectations or other confounding factors. This is particularly important in substance use research, because motivation, setting, therapeutic support, and expectations can strongly influence the outcome.

Moreover, the study in question was placebo-controlled and designed to be “quadruple-blind.” This means that participants, practitioners, and researchers were unaware as much as possible of who received which substance. With psychedelics, blinding is difficult in practice because subjective effects are often recognizable. Precisely for this reason, it is relevant that researchers try to organize this as strictly as possible, but also that we remain critical of how well the blinding actually worked.

What did the treatment in the study look like?

The study was conducted at the University of Alabama at Birmingham and included 40 adults with cocaine addiction who wanted to quit. Important detail: it was not “just a psilocybin session.” Both groups received an extensive psychotherapeutic program with cognitive behavioral therapy, before and after a full session day. The psilocybin or placebo was therefore embedded in an intensive treatment program.

Subsequently, one group received a high dose of psilocybin (25 mg per 70 kg of body weight). The control group received an active placebo: 100 mg of diphenhydramine. An active placebo is intended to produce some physical or subjective effect, making it more difficult to guess which group someone is in.

The follow-up extended to 180 days. This is relevant because relapse often does not occur until after weeks or months. An effect that disappears after a few days is clinically less interesting than an effect that persists for a longer period, especially in an addiction with chronic characteristics.

What were the main results?

According to the report, the psilocybin group showed clearly better outcomes than the placebo group. Participants who received psilocybin had a higher percentage of cocaine-free days during the 180-day follow-up period. They were also more frequently completely abstinent, and the risk of relapse was lower.

The researchers reported, among other things, a statistically significant increase in cocaine-free days (β = 28.95), a much greater chance of complete abstinence (approximately 18 times greater), and a lower risk of relapse (72% lower over time). These numbers sound impressive. At the same time, it is important to realize that these are outcome measures within a specific study population, with a specific treatment package, and with relatively few participants. As a result, effect estimates may turn out larger than in later, larger studies.

More background and a summary of the study can be found via the source page: Psilocybin in cocaine addiction: remarkably strong results in first randomized study.

Why the group of participants is remarkable

An important point that recurs in the discussion is the composition of the participants. Approximately 83% of the participants were Black, and 65% had an annual income of $20,000 or less. Historically, many psychedelic studies actually had more participants with a higher socioeconomic status or a different demographic composition.

This makes this study particularly relevant, as it helps to gain a broader picture of how these types of therapies play out in groups that are sometimes underrepresented in research. At the same time, it remains a single study at a single location, meaning generalizability remains an open question. Replication in other settings, with different teams and in larger groups, is necessary to determine whether the results hold up.

Safety: what has been reported and what do we not yet know?

No serious side effects were reported. However, temporary effects did occur, such as emotional dysregulation (e.g., crying), headache, increased blood pressure, and altered perception during or shortly after the session. This is consistent with what is frequently seen in psilocybin research, particularly in a controlled setting with preparation, guidance, and aftercare.

However, “no serious side effects in this study” is not the same as “always safe”. This trial was small, and participants with certain psychiatric disorders were largely excluded. As a result, it remains uncertain what the risks and outcomes would be for people with, for example, severe comorbidity, unstable mood, psychotic vulnerability, or complex medical issues. Furthermore, a research setting with screening and professional guidance conveys something different than use outside that context.

The biggest nuance: psilocybin is not a standalone solution here.

A key point is that the treatment consisted of a complete therapeutic trajectory. The session did not stand alone, but was embedded in preparation and integration, plus an intensive program of cognitive behavioral therapy. This makes it plausible that the effect is not attributable solely to the material, but to the combination of factors: the therapeutic relationship, motivation, structured behavioral change, the session experience, and the follow-up thereafter.

This is also relevant to how we talk about it: the research usually concerns “psilocybin-assisted therapy,” meaning therapy in which a psychedelic session can be supportive within a treatment model. Consequently, the research primarily says something about a treatment protocol, not about “psilocybin in itself.”.

Methodological notes: small, intensive, and blinding remains difficult

The researchers and the accompanying commentary emphasize that this is a relatively small pilot study (40 participants). Small studies can be valuable for finding a signal, but they are more vulnerable to chance, selection bias, and overestimation of effects. Larger follow-up studies are needed to more reliably estimate the true magnitude of the effect.

In addition, the psychotherapy component was intensive. This is positive from a care perspective, but it also raises the question of what exactly was “effective.” Would a similar effect occur with less intensive therapy, or is precisely that intensity essential? That remains unknown.

Blinding also remained difficult, as many participants were able to correctly guess whether they had received psilocybin. This is a known problem in psychedelic research: expectations can influence outcomes, for example through greater trust in the treatment or greater involvement in the therapy process. This does not mean that the results are “therefore incorrect,” but it is a reason to remain cautious and await replication with improved methods.

What does this mean in practice now?

This study suggests that psilocybin-assisted therapy could be a promising research direction for cocaine addiction. At the same time, this is not yet proof that it is ready for widespread application. More research is needed into dosage, optimal therapeutic protocols, safety in different target groups, and the long-term sustainability of the effect.

Furthermore, the way in which psychedelic sessions can be discussed and offered is context-dependent. In the Netherlands, sessions involving substances such as MDMA can currently only be discussed within scientific research or in clinical practice in a harm-reduction context. This distinction is important: scientific research has strict protocols and monitoring, whereas harm reduction focuses on limiting risks and promoting safety and proper preparation, without medical claims or treatment guarantees.

Anyone considering a guided session would generally do well to critically examine screening, preparation, setting, aftercare, and transparency regarding risks, boundaries, and expectations. If you would like to discuss this in a harm-reduction context, you can sign up for an intake via https://mdmatherapie.nl/aanmelden-mdma-sessie/. Such a conversation is not individual medical advice and not a substitute for regular addiction care, but it can help to clarify options, safety, and preconditions.

Conclusion

The first randomized study of psilocybin-assisted therapy for cocaine addiction shows remarkably strong results regarding cocaine-free days, abstinence, and relapse. At the same time, the evidence remains preliminary, as it involves a small pilot study with intensive therapy and limitations regarding blinding and generalizability. The findings primarily serve as a strong impetus for larger, more rigorous follow-up studies, not an endpoint. Anyone delving into psychedelics and therapy would do well to clearly distinguish between research, anecdotal evidence, and practical harm-reduction information.