Although the development of psilocybin therapy has come as a surprise to many, modern research with the drug has been ongoing for 25 years. Psilocybin therapy is composed of psilocybin dosing sessions embedded within a wider process of psychoeducation, psychological support and integration. Early phase clinical trial evidence is promising, particularly for treatment-resistant depression. However, masking probably fails and expectancy effects may be a part of the mechanism of change. Disambiguating between drug and expectancy effects is a necessary part of the development process, yet this is difficult if masking fails. Hitherto, masking and expectancy have not been routinely measured in psilocybin or other medication trials. Doing so represents an opportunity for research and may influence psychiatry more widely. In this opinion piece I summarise the clinical development process of psilocybin therapy thus far, discussing the hope, the hype, the challenges and the opportunities along the way.

Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.

To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.

The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.

In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.

This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.

The increasingly large sample size requirements of modern adult mental health research suggests the need for a data collection and diagnostic application that can be used across a broad range of clinical and research populations.

To develop a data collection and diagnostic application that can be used across a broad range of clinical and research settings.

We expanded and redeveloped the OPCRIT system into a broadly applicable diagnostic and data-collection package and carried out an interrater reliability study of this new tool.

OPCRIT+ performed well in an interrater reliability study with relatively inexperienced clinicians, giving a combined, weighted kappa of 0.70 for diagnostic reliability.

OPCRIT+ showed good overall interrater reliability scores for diagnoses. It is now incorporated in the electronic patient record of the Maudsley and associated hospitals. OPCRIT+ can be downloaded free of charge at http://sgdp.iop.kcl.ac.uk/opcritplus.

In England and Wales mental health services need to take account of the Mental Capacity Act 2005 and the Mental Health Act 1983. The overlap between these two causes dilemmas for clinicians.

To describe the frequency and characteristics of patients who fall into two potentially anomalous groups: those who are not detained but lack mental capacity; and those who are detained but have mental capacity.

Cross-sectional study of 200 patients admitted to psychiatric wards. We assessed mental capacity using a semi-structured interview, the MacArthur Competence Assessment Tool for Treatment (MacCAT–T).

Of the in-patient sample, 24% were informal but lacked capacity: these patients felt more coerced and had greater levels of treatment refusal than informal participants with capacity. People detained under the Mental Health Act with capacity comprised a small group (6%) that was hard to characterise.

Our data suggest that psychiatrists in England and Wales need to take account of the Mental Capacity Act, and in particular best interests judgments and deprivation of liberty safeguards, more explicitly than is perhaps currently the case.