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Johns Hopkins claims many medical firsts, including the first use of rubber gloves during surgery, the first radical prostatectomy for prostate cancer, the first implant of an automatic defibrillator in a patient.
In September, Hopkins launched what the school believes to be another, more unusual first: the first US Center for Psychedelic and Consciousness Research, funded by $17 million from a private foundation and 4 philanthropists, including author and technology investor Tim Ferriss.
While “psychedelic” might bring to mind Peter Max and flower power, center director Roland Griffiths, PhD, a professor of behavioral biology, thinks that the drugs—which include lysergic acid diethylamide (LSD), psilocybin, and dimethyltryptamine (DMT)—hold great promise in treating conditions such as early Alzheimer disease, depression, anorexia nervosa, and substance use disorders.
Up to now, “most of our funding has come from sources other than those interested in psychedelics,” noted Griffiths, who began studying the drugs more than 2 decades ago with the help of small grants from private donors. “I see the establishment of our center as an important event culturally.”
Griffiths spoke with JAMA about the recent history of psychedelics, the obstacles to studying the drugs, and the lasting impact they have on people who use them. The following is an edited version of that conversation.
JAMA:How did you become interested in studying psychedelics?
Dr Griffiths:About 25 years ago, I undertook a meditation practice. That got me very interested in the types of emergent phenomena that occur with sustained meditation. As a clinical psychopharmacologist, I became reacquainted with the 1950s and 1960s literature suggesting that classic psychedelics might occasion the kinds of experiences one encounters in meditation. We launched a study in 2000 in which we gave a high dose of psilocybin, the active constituent of so-called magic mushrooms, to healthy volunteers with no prior experience with psychedelics. The results were nothing short of astounding. It has riveted my attention since.
JAMA:People studying psychedelics have faced legal and regulatory obstacles. How much harder has that made your work?
Dr Griffiths:Psychedelics entered clinical practice in the 1950s and 1960s and were thought to be promising drugs. However, it was years before there was some understanding of the importance of set and setting in terms of harnessing potential therapeutic effects. In the 1960s, the research jumped off the rails. We had an interesting cultural situation with individuals like Timothy Leary, who started out as a legitimate scientist and then became a proponent for widespread use. Nonmedical use got associated with the antiwar and antiestablishment movement, and a narrative developed that the risks from exposure to these compounds under any condition overrode any possible benefits. Clinical research with them became marginalized, and federal funding dried up.It was only in the 1990s that investigator Rick Strassman [MD] began some studies with DMT in drug-experienced volunteers, and our first psilocybin study followed. Those were hard-fought battles because the demonization of these drugs led most people on review committees to be skeptical that we could do this work safely. I was skeptical as well, but at Johns Hopkins, we have administered psilocybin to over 350 volunteers in about 700 sessions, and we now know that we can do so safely if participants are carefully screened and prepared and supported during sessions.The narrative has been changing. More academic institutions are showing interest in initiating studies. In addition to Johns Hopkins, there are groups at New York University; Yale University; University of Wisconsin–Madison; University of California, Los Angeles; University of California, San Francisco; and the University of Alabama at Birmingham, to mention the ones that come immediately to mind. We expect federal funding to increase substantially over the next several years.
JAMA:Could you describe a psilocybin treatment session?
Dr Griffiths:We administer psilocybin under carefully curated conditions that we think are important to maximizing effects. We want to screen out individuals who might be vulnerable to adverse reactions, such as people with family histories of psychotic illness. Volunteers have up to 8 contact hours with our clinical team during which they review life circumstances. The purpose of this is to develop trust and rapport because the administration of a high dose of psilocybin can really open up an incredible sense of personal vulnerability.On the session day, people come to our unit. They've had a light breakfast. They take a capsule containing synthesized pharmaceutical-grade psilocybin. They are encouraged to lie on a couch and use eye shades and headphones to listen to music and to direct their attention inward. Throughout the 6- to 8-hour session, they're in the presence of 2 clinical guides. Those guides are not doing therapy; they're there to create a safe space for the volunteer. At about 30 minutes, there may be cognitive or visual effects, which peak at 2 to 3 hours, then dissipate over the afternoon. People are generally ready to go home at 5 or 6, and a family member or friend drives them.Some people report great experiences of love, joy, or gentleness, but they also may experience anxiety, fear, or panic. We tell people this is an opportunity to investigate the nature of their own consciousness. The remarkable piece, though, is that people come out saying they have had among the most meaningful experiences of their entire lifetimes. They'll compare it to the birth of their first child. The qualities of that experience include a sense of positive mood and, sometimes, transcendence of time and space.At the end of the session, when I walk in and ask them how today was, the first thing they'll say is “I can't possibly tell you.” And then movingly and hauntingly, they will grasp for words to describe their experience. Sometimes it comes out in terms of connectedness to ultimate reality. Sometimes there will be memories from childhood or family situations or insights into their lives.It's often a mixture of different qualities, some of which can be out-and-out anxiety and fearfulness. We prepare people to encounter feelings and objects and thoughts they might find terrifying. But, curiously, those kinds of experiences don't shape a final sense of the value of the experience. The most remarkable feature is something emerges that feels transformative and benevolent.
JAMA:You’ve written about how people who have used psychedelics describe their experience as one of the most meaningful and significant of their lives, engendering persistent positive changes in life satisfaction. Do these experiences suggest psychedelics may benefit healthy people?
Dr Griffiths:The experiences are those we would expect from the classic hallucinogens: visual or perceptual changes and changes in mood and cognitive function. Volunteers often report a reframing of their worldview and sense of self, to which they attribute enduring positive changes in attitudes, moods, and behaviors months after the session.These experiences appear to have therapeutic benefits in a number of disease entities. We have given high doses of psilocybin to people with a life-threatening cancer diagnosis, and we see large, rapid, and sustained decreases in depression and anxiety from a single session. Likewise, with a session or 2, we see big decreases in cigarette smoking among people who want to quit. As a matter of fact, our initial pilot data suggested abstinence rates of up to 80% at 6 months, which is astounding. We've just completed a study in major depressive disorder showing, again, large decreases after people have had such an experience.This intervention is quite different from any other in psychiatry. Most interventions involve repeated administration of drug or sessions of psychotherapy, and sometimes the effect sizes aren't as large as we would hope. This kind of intervention occurs in a single session, and we're seeing sustained and enduring effects.
JAMA:What is known about the mechanism of action of psychedelics?
Dr Griffiths:We do know that these drugs initiate their pharmacological effects through serotonin 2A receptor agonism. But from then on, there is a cascade of neural events that are very poorly understood, and we don't understand how people are changed enduringly.We know that there are changes in certain brain network functions that occur acutely with the administration of psilocybin. It decreases, in the default mode network often thought to underlie self-referential processing, the sense of repetitive-cognitive generation of a sense of self or thinking about oneself. Some people might describe it as an ego function, and that appears to be damped down very significantly with psilocybin.Interestingly, the default mode network is also very much suppressed in long-term meditators, and that fits with this idea that the default mode network tends to be increased in people with depressive disorders.People really end up with an altered sense of self. In the case of the cigarette smoker, these are people coming in who have quit many times and failed. After an experience of this sort, they think, “I'm wedded to achieving larger life goals, and I recognize smoking is an impediment.” These astounding changes in patterns of addictive behavior appear to cut across different substances. In addition to the addictions, there are major changes in conditions such as depression.
JAMA:Have drug companies expressed interest in pursuing treatments with psychedelics?
Dr Griffiths:Initially, absolutely not. There was no thought that this could even be an approvable indication. Increasingly, though, companies have shown interest. Right now, 2 entities are [applying] to [the] FDA [US Food and Drug Administration] for approval of psilocybin for treatment of either major depression or treatment-resistant depression. One is the for-profit Compass Pathways in the UK [United Kingdom], and the other is the nonprofit Usona Institute in Madison, Wisconsin.We are at the very early stages of understanding (1) how these compounds work, (2) optimal conditions for administration, and (3) what therapeutic conditions we're going to have efficacy in. We are working with just a single classic drug here, psilocybin, but there are many psychedelic agents that we know of from preclinical pharmacology that could be studied.
JAMA:Since the effects of psilocybin persist, is it a possible cure for depression?
Dr Griffiths:The acute pharmacological effects of psilocybin, the visuals and the distortion and thinking or moods, are really gone by the end of the session. That's consistent with what we know about the elimination half-life of psilocybin. But the curious feature is that the impact of these experiences endures; how long probably depends on the clinical condition. In studies that we ran in people with depression and anxiety secondary to a life-threatening cancer diagnosis, we saw very little relapse to those conditions 6 months afterward. And we have talked to volunteers years after the experience who claim to have been changed permanently. Some people who formerly smoked have remained abstinent for at least a year.In our depression trial, we've gone out over a year with some volunteers and shown sustained remission from depression symptoms. However, it appears that there is going to be more variability in response among volunteers with depression. Some don't respond particularly well to psilocybin. None get worse, but some have rather minimal responses, and some respond initially and then have a recurrence of symptoms.I want to underscore that we're in the very early phases. As we know from investigation of different types of pharmaceuticals, you're prone initially to get a strong treatment effect with a lot of enthusiasm. Those effects seem to disappear as the sample sizes increase, and we start to understand the limitations of the therapy. We don't want to oversell it. Nonetheless, this is an enormously exciting new paradigm for some of these conditions.
JAMA:Psilocybin has been decriminalized in Denver and in Oakland, California, and Oregon voters might be asked in 2020 whether they want to legalize it. Do you have concerns about that?
Dr Griffiths:I have concerns about getting ahead of ourselves in terms of exposing people to unwarranted risk. I'm interested in working through existing regulatory mechanisms to prove or disprove safety and efficacy. I have concerns that overuse of these substances by people who are not carefully screened and prepared and supported is going to result in significant adverse events. What I most want to avoid is the cultural backlash that we got in the 1950s and 1960s.These drugs on a relative basis are considered quite safe, and they don't have classic addiction potential. That doesn't mean they're safe for everybody and under all circumstances. People who have vulnerability to psychotic illness may get exposed to these compounds and end up with a diagnosis of schizophrenia, and that would be awful. We also know it is almost certain that some people who take these substances under unconstrained conditions are going to become frightened and engage in behaviors that put themselves or others at risk. That all being said, I'm not a fan of criminalization of substances, but this really is a policy debate that is outside of my field of expertise.
JAMA:Why is “consciousness” part of your center’s name?
Dr Griffiths:We had some debate about whether we should put consciousness in the title because there is something called the hard problem of consciousness. And that problem is really whether consciousness is ever going to be explicable in terms of the methodologies that we use to peer into that question.I think there is something unique about these experiences with psychedelics that shines a bright light on the nature of consciousness, the existential question of what it is to be sentient. That's a profound question to ask. It comes out of meditation practices, contemplative practices, and the use of psychedelics. We're very interested in the neural underpinnings of consciousness, so we are doing some interesting imaging work, looking at brain structures that have been alleged to be seats of consciousness. We'll see how activity in those centers corresponds to some of these other effects that we have seen and that we think are so critical to the power of these substances.
Rubin R. Philanthropists Fund Johns Hopkins Center for Study of Psychedelics. JAMA. Published online October 31, 2019. doi:https://doi.org/10.1001/jama.2019.17126
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