Inducing Paranoia: Using THC to decode the mechanisms underlying psychosis
- Amir Englund
- 2 hours ago
- 4 min read
Authors' Note: This article was written in collaboration with Syeda Tahir, Mitul Mehta, and Joseph Barnby. Prof Mitul Mehta is a senior neuropsychiatric researcher with over 25 years of experience, specialising in neuroimaging, psychosis models, and experimental medicine, and holds multiple leadership roles at King’s College London. Syeda Tahir is an expert by experience in public and patient involvement, with a background in advisory roles and proposal review, and is actively engaged in shaping the project's PPI strategy. Dr Joseph Barnby is a leading computational psychiatry researcher known for his work on social learning, paranoia, and mentalising.
The 19th-century French psychiatrist Jacques-Joseph Moreau is often credited as one of the first scientists to systematically study the effects of psychoactive substances on the mind. Interested in the mechanisms of mental illness, he conducted personal experiments with hashish (also known as hash or cannabis resin) to explore altered states of consciousness. Moreau founded the Club des Hashischins (Club of the Hashish-Eaters) in Paris during the 1840s — a group of writers and artists who gathered to consume large amounts of cannabis and discuss its effects. These experiments and observations formed the basis of his book Du hachisch et de l'aliénation mentale (Hashish and Mental Illness): a book that remains historically significant in the fields of psychiatry and psychopharmacology.
Moreau’s central thesis was that cannabis could serve as a tool to understand the origins and nature of mental illness. He believed that by inducing altered mental states using cannabis, it provided a way for clinicians to experience the symptoms their psychiatric patients were experiencing. He wrote:
“Hashish gives to whoever submits to its influence the power to study in himself the mental disorders that characterise insanity, or at least the intellectual modifications that are the beginning of all forms of mental illness”
Moreau fell prey to this when he experienced paranoid beliefs about his friend Aubert. Paranoia is the unjustified belief that someone intends to harm you. Aubert had supplied him with cannabis, which Moreau found to be much stronger than he expected and became convinced Aubert had tried to poison him. Aubert’s attempts to reassure him that this was not the case only increased Moreau’s conviction in his paranoia.
Moreau’s experiences are a living reality for many people who experience psychosis, causing great distress and disability. However, the reasons why Moreau’s beliefs were so immutable have been difficult to explain. This is because there has been a lack of causal experiments that can precisely map the impact of cannabis on moment-to-moment cognitive processes and associated brain mechanisms.
At King’s College London, we have conducted several studies investigating the effects of intravenous THC (the active component of cannabis) administration in healthy volunteers. Across these studies, we have observed several instances of participants experiencing transient paranoid thoughts. Some volunteers expressed suspicion or mistrust. For example, one participant remarked, “Your ID picture doesn’t really look like you. For a little while, I didn’t believe you were who you said you were.” Another described a heightened sense of meaning in their surroundings, stating, “Every occurrence, cough, object, test, has deeper and connected meaning… All deliberate, planned… some sort of prank, to make a fool of people.” Others questioned the integrity of the study procedures, asking, “Were you filming me during the cognitive tasks?” These subjective reports provide valuable insight into the acute psychological effects of THC and underscore the importance of understanding its impact on perception and cognition.
Importantly, approaches to understanding this phenomenon must contain a convincing connection between biology and phenomenology. Moreau’s personal use of experimental compounds was not unusual for psychiatrists in the late 19th and early 20th centuries (at least the ones who wrote about it). This early form of experimental medicine paved the way for fascinating insights into how known neurochemistry is connected to detailed and intimate personal experience. As modern science advanced, animal models gradually replaced humans in the process of treatment development to gain mechanistic precision. While understandable, this development lost much of the subjective human experience in the process.
We now have a chance to investigate this debilitating phenomenon so that we can better support those who most need it. We have been awarded a 4-year research grant by the Wellcome Trust to study paranoia in the brain, in behaviour, and across social contexts. By giving THC to healthy volunteers, we can induce paranoia to study it in a controlled and safe environment. Using computer models, we can whittle down the precise reasons as to why paranoia may arise, and how it changes the way we understand others around us. Taking inspiration from the pioneering psychiatrists of the early 19th and 20th centuries, like Moreau, we want to deeply understand how paranoia is related to subtle changes in the brain.
Any study that actively involves individuals with lived experiences can be greatly enhanced by the sharing of their expertise. With this in mind, we have constructed a pathway that ensures these voices are included at all stages of our study. We have appointed an expert-by-experience as a co-lead on service user involvement for the project. We will continue to build on this by ensuring that we provide a comfortable, neutral, and collaborative space where experts work alongside those with lived experience. Individuals who will be part of the lived experience advisory panel (LEAP) will often have had similar experiences to those quoted above. This is why it is vital to have their involvement and perspective to fully understand the impact of paranoia and communicate the potential of the research. LEAP members will also have the opportunity for further training and get involved in other ways, including in the dissemination of study findings.
By combining scientific methods with the insights of those who have experienced paranoia firsthand, this research aims to build a more complete understanding of how and why these experiences arise. Taking inspiration from early pioneers like Moreau, we hope to reconnect biological mechanisms with human lived experiences. Through this approach, we aim to generate findings that are not only scientifically robust but also meaningful and relevant to those most affected.