The Use of Psychedelics in the Treatment of Disorders of Consciousness

In this interview, we discuss the use of psychedelic drugs as a promising treatment in disorders of consciousness. Psilocybin, a classic psychedelic, is currently undergoing substantial clinical investigations in healthy volunteers, but also in clinical populations. Recently, experts in the field of psychedelics have addressed the attractive possibility to use such psychedelics on patients suffering from disorders of consciousness. Building on her empirical and theoretical research on disorders of consciousness, Olivia Gosseries gives us her opinion. Implementing rigorous clinical trials with psychedelics on patients with disorders of consciousness will allow their clinical efficacy to be tested. We finish the interview by briefly addressing the ethical and legal challenges and discussing other related non-pathological modified states of consciousness. keywords: psychedelic, disorder of consciousness, treatment, psilocybin, patient You are well known for your impressive work on disorders of consciousness (DOC) and you have recently become the co-director of the Coma Science Group (with Dr. Aurore Thibaut), succeeding Prof. Steven Laureys who founded the Coma Science Group. Can you please introduce yourself and explain what brought you to work with patients with DOC? Yes of course. I am a neuropsychologist who pursued a PhD in biomedical and pharmaceutical sciences. Currently I am studying altered states of consciousness, with a focus on diagnosis, prognosis and treatments of braininjured patients with DOC. Olivia Gosseries – Psychedelics in the Treatment of DOC ALIUS Bulletin n°4 (2020) aliusresearch.org/bulletin 51 In 2005, I spent 6 months at the University of Quebec in Montreal as part of the Socrates II program (Erasmus). During this time, I participated in a neuropsychology workshop for which I went to a rehabilitation institute every Wednesday. The aim was to interact with patients and provide a diagnosis, without having access to their medical files. My first patient did not talk and did not respond to me. I was very confused. How can I give a diagnosis in such a situation? The diagnosis of this patient was mixed aphasia: he did not understand me (sensory aphasia) and he was not able to speak (motor aphasia). Meeting with many patients over the weeks, I noticed that they all had previously fallen into a coma. Some patients had vague memories of the coma, some reported dream-like experiences and some had no recollection. I was very intrigued by this peculiar state: what is it like to be in a coma? Where is the mind in such a state? Why do some patients recover while some don’t? When I came back to Belgium, I wanted to do my internship and master’s thesis on this topic. I contacted Dr. Steven Laureys who openly welcomed me and I started working as an undergrad at the Coma Science Group in 2006. Seeing patients in a coma in the intensive care units was a unique and shattering experience. I was really compelled to find a cure for coma. After completing my master’s, I spent 4 months at the Moss Rehabilitation Institute in Philadelphia with Dr. John Whyte to get more familiar with the daily recovery of patients with DOC. I learned that most of these patients (if not all) do not remember their time in rehabilitation, and that a good proportion of them do not recover well. Time post-injury, etiology and the patients’ clinical status upon admission were however predictors of early recovery (Whyte et al., 2009). After this enriched experience, I was ready to pursue a PhD with comatose patients. Following the PhD and several postdoctoral positions, I recently became a research associate at F.R. S-FNRS and co-director of the Coma Science Group. After 14 years working in the field, there is still no cure for coma. My aim is to find one (wishful thinking) and to continue improving the care of patients with DOC. I also want to contribute to the understanding of human consciousness and promote public awareness of this fascinating topic. For a review on how to measure consciousness in DOC, see Gosseries et al. (2014a), Olivia Gosseries – Psychedelics in the Treatment of DOC ALIUS Bulletin n°4 (2020) aliusresearch.org/bulletin 52 and our video Dance my PhD 2018 the (un)conscious brain (https://www.youtube.com/watch? v=eYMmVNei2Hc&t). Recently, you published a review in ‘The Lancet Neurology’ (Thibaut et al., 2019) highlighting the rarity of effective treatment options for patients with DOC. What are the main reasons that efficient treatments are rare in these situations? In addition, have we observed an increase of interests in the search for treatments over the past few years? Yes indeed, we crucially lack effective therapeutic options for patients with DOC. I think there are four main reasons at play: 1) DOC is considered a rather new and rare disease, 2) it is a challenging patient population, 3) previous work mostly focused on diagnosis and prognosis rather than treatment specifically, and 4) we need to understand the mechanisms of consciousness recovery before developing targeted treatments. Before the 1950’s, patients with severe brain injuries would die. With the advent of the ventilators, such patients can now live, and the definition of death changed from cardiac death (now called “clinical death”) to brain death (official definition of death). Unfortunately, a proportion of these patients may remain alive but without recovering. DOC is an umbrella term that includes coma (no arousal, no awareness), unresponsive wakefulness syndrome (previously known as vegetative state; wakefulness but reflexive behaviors only), and minimally conscious state (wakefulness and behavioral signs of consciousness without functional communication) (Bodart et al., 2013). Coma is an acute state in which patients will never open their eyes and it lasts more than one hour, up to a few weeks. In contrast, patients with an unresponsive wakefulness syndrome or in a minimally conscious state have their eyes open, and these states can be acute, prolonged (more than a month), or chronic (more than several months, sometimes decades). Chronic DOC is considered a rare disease because it affects between 0.2 and 17 individuals out of 100 000 in Europe and the United-States. DOC are not classified as complications of common diseases but as pathologies per se, because they have specific International Classification of Diseases (ICD) codes. Patients with DOC are sadly often neglected by healthcare systems and private companies have little financial incentive to develop new Olivia Gosseries – Psychedelics in the Treatment of DOC ALIUS Bulletin n°4 (2020) aliusresearch.org/bulletin 53 treatments for such rare patients. We consequently have an urgent need to investigate therapies with the support of universities and other organizations. The second reason for the scarcity of treatment options is that management of patients with DOC is very challenging because they cannot communicate, have severe motor disability and are dependent on others for all care. Most current rehabilitation therapies need active participation of the patients, which is not possible with these patients. The third reason is that previous work has mainly investigated diagnostic and prognostic indicators of consciousness. In medicine, before prescribing a treatment, we need to know what the diagnosis is, and in our case an accurate diagnosis of the level of consciousness (“is the person conscious? ”). This can be a hard task because we primarily use behavior to infer consciousness, but responsiveness does not always equate consciousness. This may lead to a high rate of misdiagnosis (Stender et al., 2014), which can in turn lead to inadequate medical decisions, such as withdrawal of life-sustaining care. The second difficulty that arises after the diagnosis is the prognosis (“is the patient going to recover? ”). With time, the patient may recover spontaneously, however we only think of treatments when patients do not recover. After more than three decades of research, we are slowly moving towards treatments. The last and probably most important reason why we have not yet found a cure is that to treat a condition, we need to understand it. Only when we will comprehend the mechanisms of consciousness recovery, will we be able to develop effective and specific therapies. So far all the tested treatments are repurposed, meaning that they are available on the market for other pathologies and we try them with our patients. Here is an illustration based on our recent review (Thibaut et al., 2019) to show you what has been tested so far with pharmacological and brain stimulation treatments, We consequently have an urgent need to investigate therapies with the support of universities and other organizations “ ” Olivia Gosseries – Psychedelics in the Treatment of DOC ALIUS Bulletin n°4 (2020) aliusresearch.org/bulletin 54 Figure 1. Pharmacological and brain stimulation treatments in patients with DOC. and how we think they act on the damaged brain based on the mesocircuit model (Schiff, 2010). I took the liberty to add the psilocybin as this is the main topic of this interview. To answer your second question, it is clear that recently there is more interest in treatments. There are many new research groups working on coma and related states, and many new clinical trials are being conducted around the world. The interest for DOC treatment was probably pushed forward with the publication of a landmark paper on amantadine in 2012 (Giacino et al., 2012). Very recently, the Curing Coma Campaign has been launched by the Neurocritical Care Society with the aim to develop and implement coma treatment strategies. This is the first global public health initiative created to tackle the unifying concept of coma as a treatable medical entity. I have great hope of success and invite everyone interested to join this campaign (www.curingcoma.org). Only when we will comprehend the mechanisms of consciousness recovery