Could psychedelics be used to treat psychosis?

In psychedelic research today, people with a personal or family history of psychotic disorders can't participate in clinical trials, sadly excluding many who may need treatment most. But several researchers are investigating the potential of psychedelics to treat disorders like bipolar and schizophrenia. We investigate, what's the real relationship between psychedelics and psychosis?

In 1940, the British psychiatrist G. T. Stockings noted that mescaline, the active compound in peyote, produced "a medley of all known psychotic symptoms." He was among the many early psychedelic researchers who regarded these drugs as "psychotomimetics" - capable of mimicking psychotic and schizophrenic states. 

Because of this psychotomimetic effect, Humphrey Osmond, another psychedelics pioneer, suggested an "endogenous hallucination model." The model proposes psychotic disorders could be explained by an accumulation of naturally occurring psychedelic molecules in the body. 

As these early researchers learned more about psychedelics and their therapeutic effects, they began disentangling the link between psychedelics and psychosis. "While some aspects of drug-induced psychoses resemble some symptoms of schizophrenic reactions, the differences in many particulars and most of all in some are considerable," wrote Clinician Leo Hollister in 1962. 

However, the notion of psychedelics as a trigger for psychosis remains firm in the public dialogue. The 1970s War on Drugs campaign hugely fueled these narratives, warning LSD would cause suicides, reckless behavior, and total loss of sanity. 

Though these "acid casualties" were reported, data shows their occurrence was likely overstated in a political agenda to decrease the use of psychedelics. "We are not claiming that no individuals have ever been harmed by psychedelics," wrote Matthew Johnson, a researcher from Johns Hopkins University. "Anecdotes about acid casualties can be very powerful — but these instances are rare."

In 2015, a Norwegian study challenged beliefs around psychedelics and psychosis. By analyzing over 135,000 US drug survey responses, the researchers found no heightened risk of mental health problems, including psychosis, among individuals who used classical psychedelics. "We failed to find evidence that psychedelic use is an independent risk factor for mental health problems," concluded the study authors, Pål-Ørjan Johansen and Teri Suzanne Krebs. 

Another study published in 2021 found young adults had no differences in schizophrenia-like symptoms if they'd used classical psychedelics compared to those who hadn't. However, the researchers needed to account for other participants' drug use to reveal this effect. 

The REBUS model, proposed by Dr. Robin Carhart-Haris, describes how psychedelics and psychosis may share mechanisms in the brain. He explains that activity in the brain's "top-down" networks is reduced in both states. These networks could be likened to gatekeepers of reality, using expectations, beliefs, and past experiences to sift through incoming sensory information and help create a coherent worldview. As such, when this control weakens, it can lead to a confused perception, offering insight into why delusions and hallucinations may occur.

In his 2018 paper, REBUS and the Anarchic Brain, Carhart-Haris points out that while these states may overlap, there are inherent differences. He describes that in psychosis, network changes can persist, potentially leading to long-term chronic disorders. In psychedelics, however, the brain typically reverts to its baseline state once the drug effects are over. 

Nonetheless, though psychedelics may not directly cause ongoing psychosis, they could trigger some underlying brain mechanisms involved in the onset of psychotic disorders. Hence, the reported cases of prolonged mania and delusion following psychedelic use. 

Haley Dourron, a Ph.D. student at the University of Alabama, is currently researching the differences and similarities between the psychedelic and psychotic state, using first-hand experience reports from psychedelic users with psychotic disorders. Though she's only collected results from a small subsample, her results show the psychedelic experience itself doesn't appear to be any different between people with and without psychosis. 

The participants, in fact, had powerful benefits from their experiences, including increased insight, clarity, and reduced negative symptoms. One participant described, "After the second psilocybin trip, it just sort of gave me loads of motivation, a reduction in anxiety. I could actually continue life and function a lot more normally."

"It felt like there was a lot of trauma caused by the psychosis that magic mushrooms would bring up and then clear out. Not in terms of bringing the flashbacks to my psychosis, but more like reminding me of how those things felt and how they impacted my self image… Every time that I've come out of the magic mushrooms state, I've felt less psychotic, I've felt less unhinged, I feel less at risk to myself," said another. 

In light of such potential benefits, researchers have questioned whether psychedelics could be used therapeutically to treat psychotic and bipolar disorders. Dr Benjamin Mudge is one of these researchers, currently investigating ayahuasca to treat bipolar in light of his own recovery journey. His study involves finding suitable ayahuasca formulas that won't increase the chance of mania.

University of Hebrew researchers have also suggested psychedelics could be helpful in treating schizophrenia, specifically through their cellular mechanisms. "We consider the possibility that psychedelic drugs could have a role in treating cortical atrophy (brain shrinking) and cell loss in schizophrenia, and ameliorating the negative symptoms associated with these pathological manifestations," they described in a perspectives article. Like Mudge, the researchers highlight the necessity of strategies to help decrease psychosis-evoking risks if psychedelics were used in these instances. 

In psychedelic research today, people with a personal or family history of psychotic disorders can't participate in clinical trials. Though this measure is intended to prevent harm, it also limits the potential for psychedelics to help vast numbers of the mental health patient population. Research shows psychedelic therapy can significantly benefit things like anxiety, depression, and substance abuse, which are common problems in psychotic disorders. 

"What we ultimately need to do is have psychedelics administered to people in a clinical trial, very cautiously, to find out what's going on," said Douronn in a Breaking Convention lecture. 

"Other drugs that can increase psychotic symptoms such as THC have even been used in an fMRI in people with psychotic disorders so there's no reason to think psychedelics could be especially bad, compared to what's already been done."