How Psychedelics May Change Treatment of Mental Health Disorders

Psilocybin’s Role Among Patients with Life-Threatening Cancers

By Mahreen Khan 

“Fast Eddie” Marritz finds it difficult to aptly describe his psilocybin experience. But what he does know, he says, is that it changed his relationship with his body and his cancer.

“I was struck,” he said. “I really collapsed. You know, when I got this diagnosis, I was on the floor.”

Marritz said that when he received his small cell carcinoma of the bladder diagnosis in January 2013, he felt as if his entire world had been shaken to the core.

Suddenly, he was responsible for weathering two of the most difficult storms of all – anxiety, in addition to bladder cancer. This first storm had been with him for years, following closely along.  In his first 20 years of life, it appeared often in what Marritz described as a “tense” household, due in part to his mother’s multiple sclerosis. Marritz’s fast-paced cinematographer lifestyle only added to the anxiety, and though he said he recognized himself as an “anxiety sponge” early on, it wasn’t until his diagnosis that he felt as if he were caught in the eye of tumult.

“I couldn’t sleep. I was just consumed with fear in a way that was inescapable.”

He said that he wanted to keep working, but that there was no escaping the reality of his diagnosis or the related psychiatric impact it was having on him.

“At some point, there was no hiding. Certainly, loss of income was daunting, I will say that. But I also knew, hey, we’re in the life and death theme now.”

Despite his innate skepticism, he remained open to the possibilities of healing. When his friend Paul Brody, a psychiatrist, suggested New York University’s Psilocybin Cancer Anxiety Study, Marritz took the initiative.

“You can feel quite invincible when you’re well,” he said. “You’re not pondering death. You’re not pondering your absence. You’re not pondering your family getting together, your wife, your son, your daughter, your son-in-law discussing what your plans are if you don’t make it.”

The anxiety had become crippling after the diagnosis and Brody prescribed Klonopin, a drug that works to calm the brain and nerves, to help control it. Marritz said he never took the drug during the day because of its major side effect: debilitating drowsiness, and never understood how people could while still functioning. For Marritz, Klonopin was primarily a sleep aid.

“There was something about the lights being out and going to sleep that I just wasn’t able to do.”

Marritz was accepted into the psilocybin – or as it is commonly referenced, magic mushroom study – after quite a few questionnaires and interviews, anxiety disorder measurements and tests, all of which were designed to determine how severe his symptoms were. The tests determined whether or not prospective patients met the required markers for depression and anxiety. The study, published in 2016, turned out to be what some might consider a magical journey – a clinical trial focused on the potential benefits of psilocybin, an active compound in hallucinogen psilocybe cubensis – to help reduce anxiety and depression among patients shaken by life-threatening cancers.

Psilocybin is just one of many psychedelic substances being studied by scientists across the world. MDMA, which also goes by the street names ecstasy and molly, received “breakthrough status” by the FDA just a year ago, making it easier for researchers to test its safety and efficacy in clinical trials. While psilocybin has not yet reached that level, active research is ongoing and shows great promise.

 

 

 

The view from First Ave. and 33rd St. Mahreen Khan photo

The U.S. is undergoing a significant shift, expanding past western medicine to investigate alternative forms of treatment like psychedelic therapy. At the forefront of this expansion are clinical trials, spearheaded by NYU and Johns Hopkins researchers and funded by major nonprofits like the Heffter Research Institute, the Usona Institute and the Multidisciplinary Association for Psychedelic Studies. Mahreen Khan photo

Greer explained that once psilocybin enters the brain, it causes a decrease in activity in the “default mode network,” a system of activity that is interrelated across regions but distinct from other networks. This network is “understood to be the focus of the everyday functioning of our egos,” Richards explained. Psilocybin, he said, triggers an overall increase in interconnectivity within the brain—a kind of “reset” that allows new neural patterns to become established or reestablished.

“Our focus is on discovering ways that psilocybin can be helpful in reducing suffering for patients in the hopes of generating the data that will justify government funding of large research trials,” Greer said. “This has happened in England and Switzerland, it just hasn’t happened here yet. We want to keep pushing the envelope for how psilocybin and psychedelics can help us understand the brain and the mind, and how they can help people.”

For federal funding to become more likely, the Food and Drug Administration (FDA) will need to revisit the current classification of psilocybin as a Schedule I drug, the category for substances deemed to have significant abuse potential and no approved medical use. Moving it to another category—and opening up federal research money—would require a demonstration of redeeming medical value and approval by the Drug Enforcement Agency (DEA). But in order for such medical value to be established, long-term studies must prove the mushroom’s ability to outperform standard treatment.

This next step – known as multi-site, or Phase III testing – is not yet underway for psilocybin, but is in the planning phases. Where Phases I and II determine whether a particular drug or treatment method is safe and effective, Phase III sets out to establish whether it is more successful than the current standard treatment, which for anxiety and depression is selective serotonin reuptake inhibitors, or SSRIs.

“The sort of standard treatment for anxiety or depression related to cancer is to treat it with antidepressants,” said Alexander Belser, a clinical research fellow at Yale University and co-author of the 2016 NYU study. “But standard SSRI antidepressants don’t outperform placebo in this population of patients.”

That is to say: For patients coping with the mental side of cancer, conventional antidepressants are virtually no better than sugar pills. “You have all these cancer patients that are dealing with existential distress, anxiety, depression, demoralization, spiritual issues,” Belser said. “And the leading treatment doesn’t outperform placebo. It’s one of the reasons we decided to work with cancer patients in our trial.”

A few months after Eddie Marritz’s cancer was detected, he underwent four grueling rounds of chemotherapy. According to the Centers for Disease Control and Prevention (CDC), an estimated 650,000 cancer patients receive chemotherapy annually. Marritz had become one of the 1.5 million people diagnosed with cancer in the United States each year, according to CDC statistics.

“There’s a vulnerability that happened to me,” Marritz said. “Mortality brought things into sharper focus.”

Despite this awakening, Marritz described himself as feeling nonchalant about the diagnosis, its symptoms and its realities. He said this nonchalance may have been a defense against his underlying distress. It was this worry and it was this distress that would churn through Marritz’s head throughout the day, probing a significant fear of death and dissociation between his mind and body. Repressed thoughts took hold and Marritz was running through the vicious mental cycle that often comes with significant medical diagnoses.

 

 

  • Rated psilocybin experience as the single-most or top five-most personally meaningful experience in life 70%

 

 

  • Psilocybin Group (Depression): experienced significant postive response in terms of depression 7 weeks post-treatment 83%
  • Placebo Group (Depression): experienced significant positive response in terms of depression 7 weeks post-treatment 14%

 

 

  • Psilocybin Group (Anxiety): experienced significant reduction in anxiety 7 weeks post-treatment 58%
  • Placebo Group (Anxiety): experienced significant reduction in anxiety 7 weeks post-treatment 14%

Today, Marritz’s anxiety is something he is mindful of and something he often senses coming on. He is better able to manage it – an outcome he credits in part to the psilocybin experience and in part to his meditation practice. He said he believes psilocybin has the potential to change civilization, but only if done ritually and with experienced and trained clinicians.

“It’s not to be done recreationally,” he said. “It’s medicine. It is the most powerful medicine you can take. It has the potential to shift how we are.” Marritz said it puts things in a kind of perspective that we don’t experience even slightly normally.

“In a way, I’m the lucky one. Okay, I got cancer, but I got to have this experience.”

According to the published results, the treatment proved very promising, with 58 percent of patients in the psilocybin group showing a significant reduction in anxiety post-treatment, as compared to only 14 percent in the placebo group. In terms of depression, 83 percent of participants in the psilocybin group presented with significant decreases in depression, again versus just 14 percent in the placebo group. Patients, including Marritz, felt these results at a six-and-a-half month follow-up – that is, six and a half months after a single dose of psilocybin.

Secondary measures yielded positive results as well, just two weeks after treatment. These measures included improvement in patients’ self-reported spiritual wellbeing and quality of life. People reported greater meaning and peace in their lives and higher degrees of faith. They reported greater positive attitudes about life and self, as well as an increase in altruism. Seventy percent of study participants rated the psilocybin experience as the singular or of the top five most personally meaningful experiences in their lives.

“These response rates are a very large magnitude,” Belser said.

“You don’t see these sort of response rates for any clinical treatment. We’ve had decades of prohibitionist attitude towards the production of scientific knowledge related to psychedelics. In the last decade or so, we’re seeing this psychedelic renaissance and my sincere hope is that it helps improve the lives of people who are suffering with depression, anxiety, addiction and other distressing disorders.”

Multi-site testing is already well underway for drugs like MDMA in treating symptoms of posttraumatic stress disorder. Greer estimates that in roughly five years, once Phase III testing on psilocybin commences, the FDA may review its classification and prompt the DEA to make a change in its status.

As for “Fast Eddie” Marritz? He said he has been coping well with his anxiety since the psilocybin treatment, and that the experience has helped him find his breath. While Marritz credits his long-term meditation practice in large part, he said the psilocybin helped him confront his fear of death and the way he formerly led his life.

“I’ll always be slightly neurotic, but I’m a lot less neurotic than I used to be. I understand the power of silence and listening,” he said. “I am not fast anymore. I pause. I take in a situation.”

"Fast Eddie" Marritz, Cinematographer

Participant, 2016 NYU Psilocybin Cancer Anxiety Study, "Sometimes I measure my own courage through my own vulnerability, you know. I just think fear and courage may not be so far apart."

Tisch Hospital, which is affiliated with NYU Langone Health, is located in Greenwich Village. Mahreen Khan photo
Psychologists and psychiatrists affiliated with NYU are working on groundbreaking research focused on psilocybin. Mahreen Khan photo 

William Richards, Ph.D., a psychologist from Johns Hopkins University School of Medicine, pioneered a study very similar to the one at NYU, also published in 2016. In the early 1960s, he began working in the psychotherapy field in Germany and continued that work for nearly 15 years.

But he had to discontinue his studies when he returned to the United States. In 1970, the Controlled Substances Act, first signed into law by President Richard Nixon, made Schedule I drugs like psilocybin illegal and put a quick halt to experimental research. This restrictive legislation came about at a time when psychedelic research was at its most promising, with hundreds of peer review publications making headlines and thousands of people being treated for legitimate substance use and mood disorders, among other mental health issues.

“Then came 22 years of dormancy in psychedelic research in the U.S.,” Richards said, “until [Dr.] Roland Griffiths and I initiated new research at the Johns Hopkins School of Medicine in 1999.”

It was in the mid-90s that psilocybin research resumed, largely under wraps at first and later permitted under the condition of specified medical studies. Richards said his belief in the potential of psilocybin is substantiated by medical evidence.

“Over the years I have repeatedly witnessed the rapid acceleration of psychotherapy, coupled with the discovery of profoundly meaningful states of consciousness during research,” he said.

He explained that it usually takes between 20 and 60 minutes after oral administration for psilocybin to bring about noticeable changes in consciousness. “Typically the changes in awareness last four to six hours,” Richards said. “Correlations with brain activity (often increased or decreased circulation/oxygen in different parts of the brain) are beginning to be studied, but correlation does not necessarily imply causation.”

At play in our brains are trillions of synapses, or points at which nerve impulses are sent and received. Once ingested, psilocybin binds to receptors for serotonin, a chemical in the brain involved in mood, appetite and sleep. Through these receptors, the psilocybin works to produce sensory distortion and hallucinations, which, coupled with the preceding psychotherapy sessions can help patients confront underlying causes of distress. What is less clear is how the compound communicates in the brain. Research by Giovanni Petri, published in the Journal of the Royal Society Interface in 2014, suggests that the brain becomes “hyperconnected,” allowing for increased communication between different regions. As a result, it is possible for various parts of the brain that normally wouldn’t interact to work in a synchronized fashion and stimulate long-range connections until the drug’s effects subside.

“It’s almost revolutionary in psychiatry that you have a treatment that you administer once and it has a beneficial effect for months afterward,” said Dr. George Greer, president of the nonprofit Heffter Research Institute.

Greer’s organization leads research on psilocybin and provides funding for major studies around the world – money that does not currently come from the federal government, but philanthropists and private donors.

 

 

I felt connected to myself. I felt more self-love and feeling of love for humanity very deeply. Spiritual experience connecting to myself and to the world—I felt more connected.  I don’t know how to say it, but it’s the first time I ever really felt like I was part of the world instead of separate from it.

Verbatim Comments from Study Participant

Qualitative Analysis, NYU Psilocybin Cancer Anxiety Study, Patient's Name Anonymized to Protect Privacy

 

 

 

 

 

The number of people diagnosed with cancer in the U.S. each year, as the Centers for Disease Control & Prevention report

I have a restored ease with life…the percentage of my life that I am able to be present in just a moment has increased dramatically, and it’s really just been restored from almost none existent to often existent.

Verbatim Comments from Study Participant

Qualitative Analysis, NYU Psilocybin Cancer Anxiety Study, Patient's Name Anonymized to Protect Privacy

 

 

“Maybe it happens to most people when they’re diagnosed with cancer, but for me, there’s a kind of openness to whatever might be helpful. I wouldn’t say I was desperate, but I was struck that I might not live as long as I expected.”

While no clear research has targeted the relationship between openness and effectiveness of treatment, researchers believe that each individual’s personal experience depends entirely on dosing and how receptive a patient is.

“The basic finding is that in psychology there are five major traits of a person’s personality, called the OCEAN theory – openness to new experience, conscientiousness, extraversion, agreeableness and neuroticism,” Belser explained. “Normally, when you’re an adult these things don’t change very quickly. They’re sort of set by the time you reach adulthood in terms of what your personality is like, and your temperament.”

Dr. Katherine MacLean, a research scientist studying the effects of mindfulness meditation and psychedelics at Johns Hopkins, has found that psilocybin helps cancer patients by allowing them to be significantly more open to new experiences after treatment. Specifically, the openness to new experiences relates to “aesthetic appreciation and sensitivity, imagination and fantasy, and broad-minded tolerance of others’ viewpoints and values,” the study states. Belser said this newfound openness is sometimes an indicator of greater wellbeing and mental health

The NYU study was double-blind, meaning that neither the 29 participants nor the research team knew whether the substance provided to patients in each dosing session was a placebo or an actual psilocybin dose. Preceding each of the two dosing sessions, patients met with the research team for therapy sessions and were briefed on the methods and procedures of the study. Patients were asked what they hoped to get out of the psilocybin experience, and what specific cancer-related psychological distress they struggled with.

In Marritz’s case, he and the researchers decided it would be best that he get the surgery needed for his gallbladder cancer before any clinical trial work began.

“I don’t know how this would have played out had it been in that rawer time, the time when you just don’t know,” Marritz said. “I mean, I had four rounds of chemo and then I knew that the surgery was going to be no less than four hours, not that you’re watching the clock. I knew that the recovery period was going to be three to more likely six months, so basically this began post-surgery, post-chemo. It doesn’t mean that I wasn’t feeling vulnerable, but I had crossed those bridges.”

Still, there were bridges that remained uncrossed until the actual experience. Marritz said the three therapy sessions helped him understand his intentions behind opting for the treatment.

“There’s an acknowledged spiritual aspect to it. The room that you meet in for your therapy, there’s a Persian rug. There’s not a lot of symbology, but it’s not an anonymous, cold room. And there’s a pill. There’s a pill in a ceramic chalice and we stated our intentions. I think there was even a length of rope there. There was just something to make it a ritual.”

The ritualization Marritz described has been used by researchers since the early 1960s –since even before the storied Woodstock era.

“All the research for a long time has used the same environment,” Greer explained. “Stanislov Grof was one of the main people that initiated this method of the patient just staying inside themselves, with headphones, with instrumental or ethnic music and eyeshades.”

Marritz, thinking back five years ago, said he recalled his anxiety even in waiting for the psilocybin to take effect.

“I laid there a really long time. I laid there no less than an hour with blindfolds on, listening to their playlist, right? And I think Jeff Guss [co-principal investigator of the NYU study] came over and he said,

‘It’s taking as long as it needs to take.’

And I would say no less than five to seven minutes after that, there’s a kind of… You’re basically, you’re just taken. Elevated. Whatever it is, it’s a passage and it’s very subtle and it’s very real.”

 

The eight-hour psilocybin dosing sessions at Johns Hopkins took place in what Dr. William Richards described as “an aesthetic living-room-like environment.” Courtesy William Richards

Researchers from NYU Langone, which is situated on the West Side of Manhattan, were behind the 2016 Psilocybin Cancer Anxiety Study. A similar co-occurring study was published out of Johns Hopkins that same year. Mahreen Khan photo