Steve Levine, MD

Medical Ethics Unpacked: Ethical Challenges of Carceral Healthcare

, hosts Dominic Sisti, PhD, a bioethicist from Penn Medicine, and Steve Levine, MD, a psychiatrist from Compass Pathways, unpack the ethical and clinical challenges of carceral healthcare, a topic many clinicians encounter in practice but rarely receive formal training in. The discussion features Rose Onyeali, MD, clinical assistant professor at Penn Medicine, and Penn student Chinelo Osakwe, who collaborate on initiatives aimed at improving health education and advocacy for incarcerated populations.

The episode explores how incarceration, particularly solitary confinement, can have lasting physical, 

l, and neurological effects. Onyeali described how deprivation of movement, sunlight, and social interaction can accelerate both cognitive and physical decline among incarcerated individuals.

Osakwe, a neuroscience major planning to pursue medicine, highlighted the neurological implications of prolonged isolation. She explained that extended periods without social interaction can alter brain structure and function, contributing to chronic stress responses and long-term mental health consequences after individuals leave solitary confinement.

“Humans are inherently social primates,” Osakwe said. “Your amygdala gets a little bit bigger; your hippocampus gets a little bit smaller. All these little things that are happening, your fight or flight, your hypothalamus, it's running like crazy…and then you come out…but you're still kept from outside the world. It has a big impact. Something as small as brushing your teeth with your non-dominant hand…can break apart the overly structured carceral environment. You can make it a little challenge. It's a little game now, and it's something that won't get you in trouble, won't get you put in the hole, or get your privileges revoked, because you're not doing anything outside of the structure. At the one hand, it's fun, it's a game, but on the other hand, it is literally good for your cognition.”

A major focus of the conversation is the rapidly aging prison population. Onyeali explained that correctional systems often classify individuals > 50 years as geriatric because incarceration accelerates aging and increases the prevalence of chronic disease and cognitive impairment. Yet clinicians working inside and outside correctional facilities may lack training to recognize conditions such as dementia in this population.

The episode also highlights systemic gaps in care for people transitioning out of incarceration. Even when individuals qualify for compassionate release or medical parole, many struggle to access housing, long-term care facilities, or coordinated medical follow-up. As Onyeali noted, “There's transition for people who…have drug issues or HIV, things of that nature…but there isn't a transition for especially the older adults with these chronic issues.”

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In this episode, experts discuss solitary confinement, aging in prison, and gaps in care for incarcerated populations.

COMP360 Safety Data in Phase 3 TRD Trials, With Steve Levine, MD

New phase 3 data from COMP005 and COMP006 further clarify the safety and tolerability profile of COMP360, a synthetic psilocybin, in treatment-resistant 

, Steve Levine, MD, chief patient officer at Compass Pathways, emphasized that most treatment-emergent adverse events (TEAEs) were transient and resolved within 24 hours of administration.

Unlike traditional oral antidepressants, which are associated with chronic daily exposure and cumulative adverse event burden, COMP360 is administered episodically in a supervised setting. Across both phase 3 trials, the majority of adverse events occurred on the dosing day and were generally mild to moderate in severity.

Adverse events were dose-dependent but typically resolved by the following day. The most commonly reported events included headache, nausea, fatigue, anxiety, and visual hallucinations.

“They were transient, and so it suggests a very tolerable profile for patients,” Levine told 

Suicidality remains a critical concern in TRD populations, where baseline risk is inherently elevated. Levine highlighted that across Part A of both COMP005 and COMP006, as well as longer-term follow-up through 26 weeks in COMP005, there was no imbalance in suicidal ideation or behavior between treatment arms. The study had < 1% reports of suicidality.

Questions remain regarding optimal retreatment frequency and long-term maintenance. Data to date suggest that 1 or 2 administrations may provide benefit lasting up to 6 months in responders. Additional 26-week data from COMP006 Part B are expected to further clarify retreatment intervals and inform real-world implementation, including payer considerations. Levine characterized the anticipated model as episodic rather than maintenance-based therapy.

Although COMP360 requires multi-hour supervised administration, Levine pointed to > 7000 US sites currently certified to administer esketamine nasal spray as a potential infrastructure foundation. The team-based delivery model used for esketamine, including psychiatrists, licensed healthcare professionals, and support staff, may be readily adaptable.

If approved, Levine suggested COMP360 could introduce a fundamentally different treatment paradigm in TRD, defined by rapid onset, limited dosing sessions, and durable benefit.

“For patients living with treatment-resistant depression, there currently is only one marketed pharmacologic option, which is Spravato,” Levine said. “That is a treatment that, while relatively rapidly acting, represents a high burden on patients and their caregivers given the frequency of induction treatment, as well as the frequency of maintenance treatment, which we [need] to maintain the effect. COMP360, with the rapidity and durability that we have now demonstrated in phase three, with the efficacy detectable on the first day following administration…represents an entirely new paradigm of care.”

A relevant disclosure for Levine includes Janssen Pharmaceuticals, Inc.

Compass Pathways Successfully Achieves Primary Endpoint in Second Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression. Compass Pathways. Published on February 17, 2026. Accessed on February 19, 2026. 

https://ir.compasspathways.com/News--Events-/news/news-details/2026/Compass-Pathways-Successfully-Achieves-Primary-Endpoint-in-Second-Phase-3-Trial-Evaluating-COMP360-Psilocybin-for-Treatment-Resistant-Depression/default.aspx

Derman C. COMP360 Psilocybin Meets Primary Endpoint in Second Phase 3 Trial for TRD. HCPLive. Published on February 19, 2026. Accessed on February 20, 2026. 

https://www.hcplive.com/view/comp360-psilocybin-meets-primary-endpoint-second-phase-3-trial-trd

Levine discusses 24-hour adverse event resolution, retreatment questions, and scalability of supervised psilocybin therapy for treatment-resistant depression.

COMP360 Psilocybin Shows Rapid, Durable Effect in TRD, With Steve Levine, MD

Following positive topline results from the phase 3 COMP006 trial, 

 spoke with Steve Levine, MD, chief patient officer of Compass Pathways, to contextualize the clinical relevance of COMP360 (synthetic psilocybin) for treatment-resistant 

“One of the most striking things about the data we've just presented from our 05 and 06 studies is the rapidity of onset,” Levine told 

. “In both cases, we were able to detect a clinically and statistically significant difference in MADRS reduction as of day 2, which is the first day after administration of COMP360. That is a rapidity of effect that we've never seen before.”

Levine said the rapid onset may reflect acute, network-level effects mediated through 5-HT2A receptor agonism. He noted that this mechanism appears distinct from those underlying currently available treatments for TRD.

In COMP006, two 25-mg doses of COMP360 administered 3 weeks apart demonstrated a –3.8-point least squares mean difference in Montgomery-Åsberg Depression Rating Scale (MADRS) score at week 6 compared with a 1-mg control (

 <.001). According to Levine, a 3-point MADRS difference is generally considered clinically meaningful in TRD, placing the 3.8-point separation above the accepted threshold for relevance.

He noted that the magnitude of effect is comparable to that observed in pivotal trials of esketamine (Spravato), currently the only FDA-approved medication specifically indicated for TRD. However, whereas esketamine’s approximately 4-point treatment difference was achieved after multiple administrations over 4 weeks, COMP360 demonstrated a similar effect size 6 weeks after a single administration in COMP005 and after 2 administrations in COMP006.

In Part B of COMP005, participants who achieved ≥ 25% reduction in MADRS at week 6 and received a second treatment demonstrated sustained benefit through week 26. Among those with an initial clinically meaningful response who underwent re-treatment, approximately 40% achieved remission. These findings suggest that 1 or 2 administrations may support symptom improvement lasting up to 6 months in responders.

Furthermore, in COMP005, 25% of participants receiving 25 mg achieved a ≥ 25% MADRS reduction versus placebo. In COMP006, 39% reached this threshold after a second administration.

“This is a level of improvement that is very likely to translate into really meaningful benefit for patients, particularly those who have treatment-resistant depression,” Levine said. “Even modest decreases in symptoms can have an outsized impact on the course of their care and the quality of their life.”

Levine breaks down Compass Pathways’ phase 3 data on COMP360, highlighting next-day onset and sustained symptom improvement through 26 weeks.

Medical Ethics Unpacked: Organ Donations

the story of a surgeon taking the organs out of Misty Hawkins, who was believed to be dead. She was not. After a surgeon made an incision in the 42-year-old’s chest and sawed through her breastbone, he discovered her beating heart.

Although Hawkins was an extreme case, many surgeons rush to get donor donations, leading to rash decision-making. Several donations come from people who are considered circulatory dead—currently alive, but on life support; doctors deem these patients near death. With circulatory death donations, a doctor can withdraw life support if the relatives agree. Once the person is declared dead, surgeons can take the organs.

, Arthur Caplan, PhD, the founding head of the Division of Medical Ethics at NYU Grossman School of Medicine, joins Dominic Sisti, PhD, from Penn Medicine, and Steve Levine, MD, from COMPASS Pathways, to discuss definitions of brain death, cardiac death, and the ethics surrounding organ transplantations. When are organ transplants ethical?

“People wonder whether we have the right criteria for brain death. Do we know what we're doing? I don't worry about that,” Caplan said. “I think we have very good definitions: totally reversible loss of brain function, no response when you try to breathe on your own.”

Brain death is determined via an apnea test. When people get off the machine and are still not breathing, still have no reflexes, this confirms brain death.

“We know what brain death is,” Caplan continued. “If you’re well-trained, you know what to do.”

What we do not necessarily know is the definition of cardiac death.

“If I wander around the NYU hospital and go floor to floor, and somebody said to me, 'How long do you wait after the heart stops before you declare somebody dead?’ If it's me, an ancient person of maybe less popularity to my colleagues for yelling at them all day long about ethics issues, maybe about 30 seconds,” Caplan said. “If it's a teenager who was just getting into the prime of life, you might try to resuscitate them 6 times, 7 times. If it's a 90-year-old with many comorbidities, and they've already had a resuscitation, you're going to call cardiac death relatively quickly.”

No proper definition of cardiac death creates problems for donations. Some places may wait 2 minutes to see if the heart does anything, while other places may wait 4 minutes.

Caplan added, “Now people are saying, ‘Hey, I think if you froze the body, or cooled the body down and maybe put the heart on a side pump just to keep it oxygenated, you're still dead, because we've called you both cardiac death and brain dead.’ But somebody else is saying, ‘Well, wait a minute, if you got the machine going and the heart is perfused and it's still pumping, then why did you think they were dead?’ The heart still works. And just to make things completely crazy, well, of course, the heart still works. That's why you're going to transplant it.”

Rosenthal BM, Tate J. A Push for More Organ Transplants Is Putting Donors at Risk. 

. https://www.nytimes.com/2025/07/20/us/organ-transplants-donors-alive.html. Published July 20, 2025.

In this episode, Dominic Sisti and Steve Levine discuss dilemmas surrounding donor transplants, brain death, and cardiac death in organ donations.

Steve Levine, MD

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