Health

How do psychedelics combat anxiety and depression? MGH researchers are determined to find out.

"If something works we want to take a look at it."

By Ross Cristantiello

July 25, 2022

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“I’m a failure”

“Why can’t I do anything right?”

“I can’t believe I messed that up.”

Negative, self-deprecating thoughts like these are common for many, but can be particularly burdensome for those with mental health conditions like depression, anxiety, or obsessive-compulsive disorder. Often, these types of thoughts play on repeat inside one’s mind during what psychologists call rumination. This obsessional thinking involves excessive, repetitive thoughts that interfere with other forms of mental activity. 

Rumination is a serious concern for medical professionals and researchers. It gets in the way of feeling better, and multiple studies have found it can be predictive of serious episodes of depression and anxiety. 

Antidepressants and other commonly prescribed forms of medication help millions deal with rumination and its negative effects. But for those still in search of relief, a glimmer of hope could be found in an unlikely form: psychedelics. 

Specifically, psilocybin. This psychoactive compound and the “magic mushrooms” that contain it have been used for centuries by indigenous peoples and recreational users to induce hallucinogenic, psychedelic effects. 

Today, psychedelics like psilocybin are at the center of a growing movement in the scientific community to find better ways of treating depression, anxiety, PTSD, and more. In recent years, this research has found new life in Boston at the Center for the Neuroscience of Psychedelics at Massachusetts General Hospital. 

Launched in spring 2021, the Harvard-affiliated center eschews the infamous “turn on, tune in, drop out” mentality that led to Timothy Leary’s firing from the university in the early 60s. Instead, MGH researchers are using advanced imaging technology in an effort to objectively understand what the brain does when exposed to psychedelics. 

One notable finding that preceded the new work at MGH was that psilocybin could decrease activity in the default mode network. This term refers to the network of interacting regions of the brain that are active when a person is not focused on the outside world.

During rumination, the default mode network becomes overactive. So, if the compound truly decreases activity in a meaningful way, then it would track that it would also lead to a decrease in rumination. That could explain why psilocybin has been found to effectively treat some forms of depression.  

These topics piqued the interest of MGH psychiatrist Jerrold Rosenbaum, who then approached his colleague Sharmin Ghaznavi about taking a closer look. Ghaznavi, an instructor in psychiatry at Harvard Medical School, has been studying rumination and its relationship with depression since graduate school, she said. Beginning in 2019, Ghaznavi was already exploring how mindfulness could impact rumination, also by decreasing activity in the default mode network. 

Ghaznavi, prompted by Rosenbaum’s enthusiasm, took a deep look into the data surrounding psilocybin and rumination. What she found was very promising. 

“It presented a very hopeful treatment option for patients who are otherwise not getting relief with our current treatments. And also as a neuroscientist, it was really interesting because this was a mechanistic way to essentially address a phenomenon that affects not just patients with depression, but all of our patients,” she said. 

By 2021, Ghaznavi was serving as Associate Director and Director of Cognitive Neuroscience at the new MGH psychedelics research center. Ghaznavi’s work exploring psilocybin’s effect on treatment-resistant depression is one of the organization’s two foundational research studies. After more than a year getting the necessary approvals and materials, clinical trials are set to begin soon.

A changing landscape

Ghaznavi and her colleagues are not ignorant to the friction between new and old ways of thinking regarding psychedelics. 

“Sometimes there’s this sense of ‘oh wow, an academic medical center is exploring this,’ as though we wouldn’t because we’re a conservative institution or something. But the reality is, if something works we want to take a look at it,” she said 

Currently, MGH researchers are waiting for their study drugs to arrive, then screening for participants can begin and trials will soon follow. 

Screening, though, is no small task. As the newly-uncovered medical benefits of psychedelics drive a resurgence in cultural interest, more people than ever want to see those benefits firsthand. 

Much of this interest, Ghaznavi said, is being driven by Michael Pollan’s bestselling 2018 book “How to Change Your Mind,” and the accompanying Netflix documentary series released this year. Before the series debuted on July 12, Ghaznavi said the MGH center had received about 700 inquiries over the course of roughly one year from people looking to participate in the clinical trials. Now, she said that they’ve been getting between 40 and 70 inquiries a day. The first psilocybin/rumination study will only involve 20 people. 

While this massive spike in public interest has benefits, psilocybin and psychedelics should not be seen as a panacea. 

“It’s been transformative in terms of getting people to pay attention to this developing area of research and the potential it holds,” Ghaznavi said. “But we also have to temper the enthusiasm. The reality is, this could be really great for some people, but it doesn’t work for everyone.”

For example, researchers still don’t quite understand the various factors that determine whether or not a patient responds well to psilocybin.

On top of that, it’s important for the medical community to rein in expectations so that, if a patient can’t be a part of a clinical trial, they don’t turn to their own methods of psychedelic experimentation. 

“People who are desperate for treatment are going out and doing it themselves. These are treatments that have been successful in a controlled environment with trained therapists… It’s not the same as taking psychedelics recreationally,” Ghaznavi said.

Narrowing the field

The screening criteria used by the MGH center is largely based on requirements set by the U.S. Food and Drug Administration. For the trials concerning psilocybin and rumination, researchers are looking for people between the ages of 18 and 55 that have had a diagnosis of moderate to severe depression. Participants must also have had a poor response to antidepressants in the past.

“This is not a first line treatment, it’s for when other things have not worked for folks,” Ghaznavi said. 

Participants must also be able to tolerate MRIs, and be in relatively healthy physical condition due to the experimental nature of these treatments. 

Once the right participants are found, those at the MGH center will follow established protocols for psychedelic treatments in clinical trials. Before ingesting psilocybin, participants will be taken off of their current medication and undergo a few sessions of therapy to prepare them for the intense experience. 

Psilocybin will then be administered in a controlled environment. Participants will receive what’s considered a high dose, Ghaznavi said, and the experience can last up to eight hours. Although the dose used will be significant, it will be in line with the amount that elicited the best response in other clinical trials involving psilocybin. 

Two sessions of integration therapy will follow, designed to help participants understand their psychedelic experience and the ways in which it can help their mental health moving forward. 

“It’s new, it’s all new, these are early days. Since we established, there have been a number of other centers established across the country. This is sort of the early peak of academic medical centers taking note. The clinical trials are really promising, and if that’s the case, we need to be prepared and ready,” Ghaznavi said. 

A new outlook

Clinical trials like the ones being organized by MGH and related studies are multiplying, causing professionals to view the future of psychedelic research in an optimistic light. As studies grow, so too does the information available to medical professionals, better equipping them to address patient needs.  

There are also growing signs that funding for this type of research will become more accessible and long lasting. Right now most of the work being done in this area, including at MGH, is philanthropically funded, according to Ghaznavi. But more traditional avenues of funding, such as bodies like the National Institutes of Health, are growing more open to supporting psychedelic research. 

Overall, Ghaznavi said, these explorations into psychedelics and their impact on the mind should create hope for those struggling with mental illness. But nothing, including psilocybin, should be viewed as a last resort.

“This is really promising and it’s going to help a lot of people, but it’s not going to help everyone,” she said. “And for those that it doesn’t help, it doesn’t mean that they’re out of options.”