The last few years have witnessed a revival of interest in the clinical potential and utility of psychedelics in mental health. Psychedelics and related compounds such as LSD, psilocybin, cannabis, and ketamine can have varying and contradictory effects. In some instances, they may act as risk factors in the development of psychosis and other mental disorders. However, more recently research has focused on exploring their medicinal value, suggesting that they may offer new opportunities for treatment for mental health conditions such as depression and anxiety.
A single day symposium entitled “Making Psilocybin into a Medicine: A Multidisciplinary Approach” was recently held at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s College London (KCL). The purpose was to explore what makes psychedelic research unique, and how researchers might capitalise on the therapeutic potential of such compounds. The day was entirely funded by the National Institute for Health Research’s Clinician Scientist Programme and the KCL Neuroscience and Society Network.
Psilocybin, a hallucinogen, is a chemical produced by more than 100 species of mushrooms worldwide. Reports about taking psilocybin consistently say that users experience intense emotions, mystical experiences, and enter a dreamlike state. Many also report a dissolving sense of a bounded self, coupled with a feeling of increased connectedness with others and the rest of the world.
The symposium bought together patients—such as myself—therapists, psychiatrists, scientists, lobbyists and the pharmaceutical industry. It consisted of lectures and plenary discussions focused on the development of medical psilocybin, both through the clinical trials process and the wider socio-political context. The aim was to initiate a narrative approach to understanding the therapeutic potential of psilocybin and discuss the regulatory and logistical challenges of “making psilocybin into a medicine”, as indeed it was prior to 1970, when it was legally classified as a schedule 1 drug under the UK Misuse of Drugs Regulations and as class A drug under the UK Misuse of Drugs Act 1971.
The event was opened by James Rucker and Allan Young of the Centre for Affective Disorders (CfAD) at KCL. They explained that although psilocybin with psychological support shows some promise as a treatment in psychiatry, its therapeutic mechanisms remain poorly understood.
The CfAD has recently been awarded a large grant from the NIHR to investigate the safety, feasibility, and efficacy of psilocybin delivered with psychological support and medical supervision as a treatment for clinical depression that has not improved with standard treatments. This study the PsiDeR (Psilocybin in Depression Resistant to Standard Treatments) trial—will be led by James Rucker in the form of a randomised, placebo-controlled trial. It aims to recruit up to 60 participants with current depression which is unresponsive to the usual treatments, such as selective serotonergic antidepressants (e.g. fluoxetine) and cognitive behavioural therapy (CBT). PsiDeR will collect data on adverse events as well as comparing participant’s ratings of their depressive symptoms before and after treatment. Biological data will also be collected via blood tests and brain scans to better understand how psilocybin works in the brain and inform future research into which biomarkers may indicate how someone will respond to psilocybin treatment.
Robin Carhart-Harris presented his pilot study, the PSILODEP-PILOT, (PSILOcybin in patients with treatment-resistant DEPression: a PILOT study) which ran at Imperial Clinical Research Facility, Hammersmith Hospital (UK) from April 2015 to December 2015. The aim of the study was to test the hypothesis that Psilocybin will reduce symptoms of depression in patients diagnosed with treatment-resistant depression. The potential psychological effects of psilocybin were fully described to all patients before they consented to participate in the study. Carhart-Harris described how the research team helped participants to feel prepared for their experience before taking the drug and were taught ways to relax to reduce anxiety and promote a positive drug experience. A positive environment was created during the study so that participants felt relaxed and didn’t feel worried. All dosing sessions were supervised by a medical doctor with follow-up meetings taking place after each dosing session to help manage any bad feelings experienced by participants.
When Carhart-Harris and his team assessed the study’s participants three months after treatment, they found that most of the participants showed reduced depressive symptoms, with almost 50% in complete remission. As one participant later reported “I got a new positivity that I didn’t have for some time.”
Carhart-Harris also presented evidence for how psychedelics work at each level of brain functioning, highlighting that the causal links between these conceptual layers have yet to be derived from the current body of research. As a mathematician as well as a patient, I am aware it may be possible to delineate such relationships by the application of ontological analysis; a form of artificially intelligent knowledge representation and reasoning, deploying description logics. This is a technique well-known to bioinformatics and has shown itself to be of practical use deriving meaning from diverse sources of clinical data.
Following on from this was a panel discussion chaired by James Rucker in which I was fortunate to participate. The discussion focused on the nature of psilocybin therapy, who might benefit from it, and how to optimise treatment effects. My role on the Trial Steering Committee of the PsiDeR trial is a somewhat novel one; for although I have experienced depression and am currently being treated for it, my depression has proven amenable to conventional treatment. As such it had never crossed my mind that one day I would find myself on the Steering Committee of a clinical feasibility trial of the anti-depressive effects of a psychedelic. During the panel discussion I advocated for the need for research into psilocybin. Given the current impasse and relative disinvestment in the development of new psychotropic drugs for mental health conditions, in my view, there is a clear need for clinical research into the use of different kinds of psychotropic drugs and different treatment paradigms, such as single dosing with psychological support.
There was also discussion about some of the challenging experiences that some participants in Carhart-Harris’s pilot study had, and the value of therapeutic interpersonal connection in protecting against and preventing the emergence of more destructive states of mind. Listening to the testimonies of the participants made it clear to me that the use of psilocybin in this treatment context holds value and should be investigated further. I was moved by individual accounts of the positive experience on taking the drug; of being released from the darkness and sheer misery of depression into freer, more adaptive, positive and gregarious states of mind. For one participant in the PSILODEP-PILOT the positive effects had remained with him (albeit with occasional down days) whereas for another participant, although the salient benefits of the therapy had dissipated, he still retained useful concepts, thoughts, and experiences that were of daily use to him. Another trial participant, who was also a psychotherapist discussed the crucial importance of the therapeutic setting. “The drug doesn’t do the work alone; setting and mindset or intention are so important.”
The fact that formal clinical research into psilocybin as a medicine is taking place is ground-breaking. As is the nature and extent of public and patient involvement in the upcoming PsiDeR trial. For example, a website is being set up which will be an information repository for the trial with protected access for future trial participants. The website content is currently in development and will have to be approved by the ethics committee and Medicines and Healthcare products Regulatory Agency (MHRA). The trial logo was also created by some of the PSILODEP-PILOT trial participants. It will be interesting to see how the media represent and respond to the use of stigmatised, and class A classified, drugs such as psilocybin to treat mental health conditions. History suggests there may be a backlash should large numbers of people be prescribed psilocybin for depression, as this has been the fate of other potent psychiatric treatments.
This in turn may lead to under-use and further stigmatisation. Therefore it is crucial that events such as the symposium are used to record a narrative of how psilocybin could be re-introduced into clinical research and potentially clinical practice, given the sociocultural history it has. Quoting James Rucker, “Aside from the political sensitivities it is also a drug with a rich and enduring relationship with the human race. I think we owe it to the history to make sure others can look back at what we were doing and understand our rationale, and that we were doing it in a way that was respectful to the cultural heritage of the drug.”
Sarah Markham is an academic mathematician and patient representative currently pursuing a second PhD in theoretical computer science. She is a member of the BMJ Patient Advisory Panel. Twitter: @DrSMarkham
Competing interests: None declared.