A new case report published in Clinical Neurophysiology describes the first known administration of psilocybin—a psychedelic compound found in certain mushrooms—to a woman in a minimally conscious state. Although there was no improvement on standard clinical assessments, the patient exhibited new spontaneous behaviors and a notable increase in brain complexity, suggesting altered internal experience. The findings raise the possibility that psychedelics could one day help treat patients with disorders of consciousness, though more research is needed.
Psilocybin has drawn increasing interest from scientists due to its powerful effects on the brain. It acts primarily on a serotonin receptor known as 5-HT2A and has been shown to increase the complexity and connectivity of brain activity. In healthy participants, this is often associated with intense changes in perception, emotion, and sense of self. Researchers are investigating whether these changes might also benefit people with impaired consciousness following brain injury, who typically have few treatment options.
In this case, a team of neuroscientists and clinicians documented the effects of psilocybin on a 41-year-old woman in a minimally conscious state with language-mediated responses—referred to as MCS+. One year earlier, she had suffered a traumatic brain injury. People in this state show intermittent signs of awareness, such as following commands or tracking objects with their eyes, but remain largely unresponsive. Despite prior attempts with various medications and brain stimulation techniques, she showed little improvement. Her diagnosis had been stable for about a year before the psilocybin session.
After trying various unsuccessful treatments, including medications and brain stimulation, her caregiver contacted one of the study authors about the possibility of trying psilocybin. The patient had used psilocybin once before her injury. In the weeks leading up to the study, she received small doses of the compound, which were associated with subtle new behaviors, such as movement in her right leg that had not been seen before.
On the main recording day, the patient received a 2.5-gram psilocybin tincture through a gastric tube while at home in Colorado, where the substance is decriminalized. Her environment was intentionally structured to be soothing: music was played, incense was lit, and she was blindfolded periodically to shape her sensory experience.
A doctor monitored her vital signs, and the researchers collected electroencephalography (EEG) data before and after the drug was administered. This allowed them to measure changes in brain activity, including complexity, spectral power, and connectivity. Standard behavioral assessments were also conducted before, during, and after the session.
Based on these clinical assessments, the patient’s level of consciousness fluctuated throughout the day. While initially scoring as MCS+, she was later assessed as unresponsive based on her inability to follow commands. However, she did display behaviors that had not been seen at rest before taking psilocybin, such as lifting both legs and holding them aloft, as well as a distinct shivering of the right leg. Her caregiver also noted that her eyes and mouth were wide open in a way not previously observed. These changes were not enough to shift her diagnostic category, but they may suggest the presence of a subjective internal experience, even without outward responsiveness.
The EEG recordings revealed striking changes. The researchers found a significant increase in Lempel-Ziv complexity, a measure of the richness and unpredictability of brain activity. This kind of signal has been linked to conscious awareness in prior studies and is typically reduced in people with disorders of consciousness. After taking psilocybin, the patient’s brain showed greater entropy—particularly a decrease in slower brain waves and an increase in higher-frequency activity, such as gamma waves. These changes mirror patterns observed in healthy individuals under the influence of psychedelics.
In terms of brain connectivity, the picture was more complex. The researchers observed a reduction in functional connectivity across most frequency bands, except for an increase in amplitude-based connectivity in the delta band. This decrease in connectivity could reflect the breakdown of rigid brain networks, a common hallmark of the psychedelic state, although some of these effects might also be influenced by changes in the strength of neural oscillations.
Importantly, no seizures or major adverse effects were observed, though the patient did experience a transient spike in blood pressure that required mild medical intervention. Interestingly, she also showed no signs of pain during physical movement after taking psilocybin, while earlier in the day she had responded to a painful stimulus. This aligns with past findings that suggest psychedelics may have analgesic effects, even in conditions involving chronic or difficult-to-treat pain.
Although intriguing, case reports have inherent limitations. A single patient cannot be used to draw general conclusions, and without a placebo condition or blinded evaluations, it’s impossible to rule out other influences, such as spontaneous fluctuations in consciousness. The patient’s behaviors may have emerged naturally, or they might have been influenced by environmental changes. It’s also unclear how the effects of psilocybin would vary across patients with different types of brain injury or different baseline levels of consciousness.
Still, this report carries unique value. In the absence of proven therapies for disorders of consciousness, exploratory research like this helps open new avenues for treatment. It also raises important questions about how consciousness should be measured. Standard behavioral tools may miss signs of internal experience that cannot be expressed through physical action, especially in people with severe motor impairments. More sensitive approaches—including continuous physiological monitoring and measures of spontaneous brain activity—could improve how we assess and treat consciousness disorders in the future.
The report also contributes to growing interest in the “entropic brain hypothesis,” which proposes that consciousness is associated with a certain degree of entropy—or unpredictability—in the brain’s spontaneous activity. Psychedelics are thought to push the brain into a more disordered, but potentially more flexible and integrated, state. If this holds true for patients with impaired consciousness, psychedelics might one day be used not only as a diagnostic tool, but also as a therapeutic agent.
Moving forward, the researchers call for controlled clinical trials using classic psychedelics like psilocybin in patients with disorders of consciousness. These trials should include placebo conditions, standard protocols, and larger samples to test whether the effects observed in this case can be replicated and expanded. They also note the importance of ethical oversight, particularly when administering mind-altering substances to individuals who cannot consent. In this case, the caregiver provided informed consent, as is standard in medical decisions involving patients with limited capacity.
The study, “Psilocybin for disorders of consciousness: A case-report study,” was authored by Paolo Cardone, Pablo Núñez, Naji L.N. Alnagger, Charlotte Martial, Glenn J.M. van der Lande, Robin Sandell, Robin Carhart-Harris, and Olivia Gosseries.
