Psilocybin research at Johns Hopkins

Psychiatry Grand Rounds started on Monday, Oct. 7, 2019, as they do every Monday at Johns Hopkins, with the department chair interviewing a patient.

The patient told James Potash, MD, that he had suffered with depression for many years and that medications were only a partial fix. His participation in a psilocybin trial at Johns Hopkins in Baltimore was different, and 3 months after the second, and final, treatment, he felt remarkably better. The treatment had quieted the self-deprecating script that had looped through his thoughts for years. “It was nothing like what I was expecting,” the patient said. “I didn’t feel out of control. And now I’m not fighting with myself all day.”

Grand Rounds at Hopkins are different from those at other institutions in that the rounds are given by departments’ full-time faculty members; psychiatrists from other institutions are invited to come speak at other times during the week. But Grand Rounds are reserved for the faculty to present their own research. The patient interview was followed by a lecture by Roland Griffiths, PhD, on “Psilocybin: A potentially promising treatment for depression.” Dr. Griffiths has been studying the effects of psychedelic drugs for the past 40 years; he’s been at Hopkins since 1972. The Grand Rounds presentation came just weeks after it was announced that Dr. Griffiths would be heading the Johns Hopkins Center for Psychedelic & Consciousness Research, funded with $17 million in private donations.

Dr. Griffiths began by talking about the history of psychedelic drug research and the fact that research had been dormant for several decades. “There was – and still is – concern about potential adverse reactions, including panic reactions and the possibility of precipitating psychosis,” he said.

Originally, he conducted several studies in healthy volunteers with no history of psychedelic use. Participants had one or more day-long sessions with staff members who would then serve as monitors when psilocybin was administered; these preliminary meetings were designed to build trust and rapport with the team and to decrease the risk of adverse reactions. On session days when psilocybin was administered, participants were told to eat a low-fat breakfast and then were given a high dose of psilocybin in a capsule. The next 6 hours were spent with the volunteer lying on a couch with an eye mask, headphones with soft music, and two monitors in the room. “The room is decorated like a living room. We created a container for people to explore their inner experience.”

Dr. Griffiths talked about the experiences people reported.

“There were large increases in personally meaningful and insight-type experiences. People reported a sense of unity and interconnectedness of all things, accompanied by a sense of preciousness or reverence, and by the sense that ... the experience was more real or true than everyday waking consciousness. Although the acute effects of psilocybin resolved by the end of the session day, the memories remain and people reported enduring changes in mood, attitude, and behavior.”

The data were remarkable. One month after these high-dose psilocybin sessions, 78% of the volunteers rated the experience as among the top five most personally meaningful experiences of their lives, 94% said they had an increased sense of well-being with improved life satisfaction, and nearly 90% endorsed positive behavior change. Six months after the last session, participants still endorsed having more positive relationships, feeling more love, tolerance, empathy and compassion, friends, family members, and others. Family members and work colleagues who were interviewed noted these positive changes as well.

At this point in Grand Rounds, I was ready to volunteer. My best estimate (tongue in cheek, with no corroboration) is that about half of the audience was waiting on free psilocybin samples, while the other half was remembering Timothy Leary, PhD, bad trips, and psychosis. “We’ve been down this road before,” the gentleman next to me commented.

Dr. Griffiths went on to talk about trials of psilocybin in clinical populations. In one study, the effects of psilocybin were examined in cancer patients with depression and anxiety. Of the 51 cancer patients, half previously had been treated with psychotropic medications before coming to the study. This randomized, double-blind crossover study compared high-dose psilocybin with an extremely low dose of psilocybin used as the placebo. As with studies in healthy participants, the results were striking – 6 months after administration of psilocybin, 78% of patients reported a significant decrease in their cancer-related distress.

Another study looked at patients with major depression who, like the patient interviewed, had not had full resolution of symptoms with conventional antidepressants. Of the 24 participants in that group, 69% reported clinically significant improvement 12 weeks after the treatment. Just over half of participants reported a full remission to normal.

Dr. Griffiths ended by concluding that the positive experiences people have with psilocybin are associated with “enduring positive trait changes in attitudes, mood and behavior, spirituality, and altruism ... and that such experiences are now amenable to systematic prospective scientific study.”

J. Raymond DePaulo, MD, chair of the National Network of Depression Centers and former chair of psychiatry at Johns Hopkins, noted that he used to be skeptical. He has been impressed that Dr. Griffiths has listened to criticism and addressed concerns others have raised. “When it was suggested that this was the result of delirium, he started giving people cognitive tests while they were using psilocybin and he showed it wasn’t the case.”

“I have always objected to words like ‘psychedelic’ and ‘hallucinogen,’ ” said Dr. DePaulo. “They are confusing and inaccurate. No one takes these medications because they want to hallucinate. They take them to change their mood. That said, I am thrilled that we are on the precipice of being able to use this to treat depression.”

Since 1999, the Johns Hopkins Psilocybin Research Project has conducted more than 700 sessions with 369 participants. When might psilocybin be available to patients outside of a research protocol? Two companies have obtained approval from the Food and Drug Administration to initiate registration in trials for treatment of depression. Dr. Griffiths estimates that it could be another 5 years before psilocybin will be available for medical use.

The new center with its generous funding will allow for more studies with more patient populations. The center’s projects will look at using psilocybin as a treatment for opioid use disorder, comorbid depression and alcohol use disorder, anorexia nervosa, depression in Alzheimer’s disease, posttreatment Lyme disease syndrome, and PTSD.

Scott Aaronson, MD, is a mood disorder expert and director of clinical research at the Sheppard Pratt Health System in Towson/Baltimore. Dr. Aaronson, who also studies psilocybin as a treatment for depression, noted: “The problem with the development of psychedelics is that we are not really prepared to capture the improvement we see with their use, as the main changes are not in the classic markers of depression like the Montgomery-Åsberg or the Hamilton Depression rating scales, but [rather] in the patient’s perception of who they are, how they fit in with the world, and what is most important. We need to develop ways to capture those critical changes and work with the FDA to develop an entirely new vision of what constitutes improvement in psychiatric illness. My overall take is that it is a terrific time to specialize in treatment-resistant mood disorders!”
 

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Psychiatry Grand Rounds started on Monday, Oct. 7, 2019, as they do every Monday at Johns Hopkins, with the department chair interviewing a patient.

The patient told James Potash, MD, that he had suffered with depression for many years and that medications were only a partial fix. His participation in a psilocybin trial at Johns Hopkins in Baltimore was different, and 3 months after the second, and final, treatment, he felt remarkably better. The treatment had quieted the self-deprecating script that had looped through his thoughts for years. “It was nothing like what I was expecting,” the patient said. “I didn’t feel out of control. And now I’m not fighting with myself all day.”

Grand Rounds at Hopkins are different from those at other institutions in that the rounds are given by departments’ full-time faculty members; psychiatrists from other institutions are invited to come speak at other times during the week. But Grand Rounds are reserved for the faculty to present their own research. The patient interview was followed by a lecture by Roland Griffiths, PhD, on “Psilocybin: A potentially promising treatment for depression.” Dr. Griffiths has been studying the effects of psychedelic drugs for the past 40 years; he’s been at Hopkins since 1972. The Grand Rounds presentation came just weeks after it was announced that Dr. Griffiths would be heading the Johns Hopkins Center for Psychedelic & Consciousness Research, funded with $17 million in private donations.

Dr. Griffiths began by talking about the history of psychedelic drug research and the fact that research had been dormant for several decades. “There was – and still is – concern about potential adverse reactions, including panic reactions and the possibility of precipitating psychosis,” he said.

Originally, he conducted several studies in healthy volunteers with no history of psychedelic use. Participants had one or more day-long sessions with staff members who would then serve as monitors when psilocybin was administered; these preliminary meetings were designed to build trust and rapport with the team and to decrease the risk of adverse reactions. On session days when psilocybin was administered, participants were told to eat a low-fat breakfast and then were given a high dose of psilocybin in a capsule. The next 6 hours were spent with the volunteer lying on a couch with an eye mask, headphones with soft music, and two monitors in the room. “The room is decorated like a living room. We created a container for people to explore their inner experience.”

Dr. Griffiths talked about the experiences people reported.

“There were large increases in personally meaningful and insight-type experiences. People reported a sense of unity and interconnectedness of all things, accompanied by a sense of preciousness or reverence, and by the sense that ... the experience was more real or true than everyday waking consciousness. Although the acute effects of psilocybin resolved by the end of the session day, the memories remain and people reported enduring changes in mood, attitude, and behavior.”

The data were remarkable. One month after these high-dose psilocybin sessions, 78% of the volunteers rated the experience as among the top five most personally meaningful experiences of their lives, 94% said they had an increased sense of well-being with improved life satisfaction, and nearly 90% endorsed positive behavior change. Six months after the last session, participants still endorsed having more positive relationships, feeling more love, tolerance, empathy and compassion, friends, family members, and others. Family members and work colleagues who were interviewed noted these positive changes as well.

At this point in Grand Rounds, I was ready to volunteer. My best estimate (tongue in cheek, with no corroboration) is that about half of the audience was waiting on free psilocybin samples, while the other half was remembering Timothy Leary, PhD, bad trips, and psychosis. “We’ve been down this road before,” the gentleman next to me commented.

Dr. Griffiths went on to talk about trials of psilocybin in clinical populations. In one study, the effects of psilocybin were examined in cancer patients with depression and anxiety. Of the 51 cancer patients, half previously had been treated with psychotropic medications before coming to the study. This randomized, double-blind crossover study compared high-dose psilocybin with an extremely low dose of psilocybin used as the placebo. As with studies in healthy participants, the results were striking – 6 months after administration of psilocybin, 78% of patients reported a significant decrease in their cancer-related distress.

Another study looked at patients with major depression who, like the patient interviewed, had not had full resolution of symptoms with conventional antidepressants. Of the 24 participants in that group, 69% reported clinically significant improvement 12 weeks after the treatment. Just over half of participants reported a full remission to normal.

Dr. Griffiths ended by concluding that the positive experiences people have with psilocybin are associated with “enduring positive trait changes in attitudes, mood and behavior, spirituality, and altruism ... and that such experiences are now amenable to systematic prospective scientific study.”

J. Raymond DePaulo, MD, chair of the National Network of Depression Centers and former chair of psychiatry at Johns Hopkins, noted that he used to be skeptical. He has been impressed that Dr. Griffiths has listened to criticism and addressed concerns others have raised. “When it was suggested that this was the result of delirium, he started giving people cognitive tests while they were using psilocybin and he showed it wasn’t the case.”

“I have always objected to words like ‘psychedelic’ and ‘hallucinogen,’ ” said Dr. DePaulo. “They are confusing and inaccurate. No one takes these medications because they want to hallucinate. They take them to change their mood. That said, I am thrilled that we are on the precipice of being able to use this to treat depression.”

Since 1999, the Johns Hopkins Psilocybin Research Project has conducted more than 700 sessions with 369 participants. When might psilocybin be available to patients outside of a research protocol? Two companies have obtained approval from the Food and Drug Administration to initiate registration in trials for treatment of depression. Dr. Griffiths estimates that it could be another 5 years before psilocybin will be available for medical use.

The new center with its generous funding will allow for more studies with more patient populations. The center’s projects will look at using psilocybin as a treatment for opioid use disorder, comorbid depression and alcohol use disorder, anorexia nervosa, depression in Alzheimer’s disease, posttreatment Lyme disease syndrome, and PTSD.

Scott Aaronson, MD, is a mood disorder expert and director of clinical research at the Sheppard Pratt Health System in Towson/Baltimore. Dr. Aaronson, who also studies psilocybin as a treatment for depression, noted: “The problem with the development of psychedelics is that we are not really prepared to capture the improvement we see with their use, as the main changes are not in the classic markers of depression like the Montgomery-Åsberg or the Hamilton Depression rating scales, but [rather] in the patient’s perception of who they are, how they fit in with the world, and what is most important. We need to develop ways to capture those critical changes and work with the FDA to develop an entirely new vision of what constitutes improvement in psychiatric illness. My overall take is that it is a terrific time to specialize in treatment-resistant mood disorders!”
 

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Psychiatry Grand Rounds started on Monday, Oct. 7, 2019, as they do every Monday at Johns Hopkins, with the department chair interviewing a patient.

The patient told James Potash, MD, that he had suffered with depression for many years and that medications were only a partial fix. His participation in a psilocybin trial at Johns Hopkins in Baltimore was different, and 3 months after the second, and final, treatment, he felt remarkably better. The treatment had quieted the self-deprecating script that had looped through his thoughts for years. “It was nothing like what I was expecting,” the patient said. “I didn’t feel out of control. And now I’m not fighting with myself all day.”

Grand Rounds at Hopkins are different from those at other institutions in that the rounds are given by departments’ full-time faculty members; psychiatrists from other institutions are invited to come speak at other times during the week. But Grand Rounds are reserved for the faculty to present their own research. The patient interview was followed by a lecture by Roland Griffiths, PhD, on “Psilocybin: A potentially promising treatment for depression.” Dr. Griffiths has been studying the effects of psychedelic drugs for the past 40 years; he’s been at Hopkins since 1972. The Grand Rounds presentation came just weeks after it was announced that Dr. Griffiths would be heading the Johns Hopkins Center for Psychedelic & Consciousness Research, funded with $17 million in private donations.

Dr. Griffiths began by talking about the history of psychedelic drug research and the fact that research had been dormant for several decades. “There was – and still is – concern about potential adverse reactions, including panic reactions and the possibility of precipitating psychosis,” he said.

Originally, he conducted several studies in healthy volunteers with no history of psychedelic use. Participants had one or more day-long sessions with staff members who would then serve as monitors when psilocybin was administered; these preliminary meetings were designed to build trust and rapport with the team and to decrease the risk of adverse reactions. On session days when psilocybin was administered, participants were told to eat a low-fat breakfast and then were given a high dose of psilocybin in a capsule. The next 6 hours were spent with the volunteer lying on a couch with an eye mask, headphones with soft music, and two monitors in the room. “The room is decorated like a living room. We created a container for people to explore their inner experience.”

Dr. Griffiths talked about the experiences people reported.

“There were large increases in personally meaningful and insight-type experiences. People reported a sense of unity and interconnectedness of all things, accompanied by a sense of preciousness or reverence, and by the sense that ... the experience was more real or true than everyday waking consciousness. Although the acute effects of psilocybin resolved by the end of the session day, the memories remain and people reported enduring changes in mood, attitude, and behavior.”

The data were remarkable. One month after these high-dose psilocybin sessions, 78% of the volunteers rated the experience as among the top five most personally meaningful experiences of their lives, 94% said they had an increased sense of well-being with improved life satisfaction, and nearly 90% endorsed positive behavior change. Six months after the last session, participants still endorsed having more positive relationships, feeling more love, tolerance, empathy and compassion, friends, family members, and others. Family members and work colleagues who were interviewed noted these positive changes as well.

At this point in Grand Rounds, I was ready to volunteer. My best estimate (tongue in cheek, with no corroboration) is that about half of the audience was waiting on free psilocybin samples, while the other half was remembering Timothy Leary, PhD, bad trips, and psychosis. “We’ve been down this road before,” the gentleman next to me commented.

Dr. Griffiths went on to talk about trials of psilocybin in clinical populations. In one study, the effects of psilocybin were examined in cancer patients with depression and anxiety. Of the 51 cancer patients, half previously had been treated with psychotropic medications before coming to the study. This randomized, double-blind crossover study compared high-dose psilocybin with an extremely low dose of psilocybin used as the placebo. As with studies in healthy participants, the results were striking – 6 months after administration of psilocybin, 78% of patients reported a significant decrease in their cancer-related distress.

Another study looked at patients with major depression who, like the patient interviewed, had not had full resolution of symptoms with conventional antidepressants. Of the 24 participants in that group, 69% reported clinically significant improvement 12 weeks after the treatment. Just over half of participants reported a full remission to normal.

Dr. Griffiths ended by concluding that the positive experiences people have with psilocybin are associated with “enduring positive trait changes in attitudes, mood and behavior, spirituality, and altruism ... and that such experiences are now amenable to systematic prospective scientific study.”

J. Raymond DePaulo, MD, chair of the National Network of Depression Centers and former chair of psychiatry at Johns Hopkins, noted that he used to be skeptical. He has been impressed that Dr. Griffiths has listened to criticism and addressed concerns others have raised. “When it was suggested that this was the result of delirium, he started giving people cognitive tests while they were using psilocybin and he showed it wasn’t the case.”

“I have always objected to words like ‘psychedelic’ and ‘hallucinogen,’ ” said Dr. DePaulo. “They are confusing and inaccurate. No one takes these medications because they want to hallucinate. They take them to change their mood. That said, I am thrilled that we are on the precipice of being able to use this to treat depression.”

Since 1999, the Johns Hopkins Psilocybin Research Project has conducted more than 700 sessions with 369 participants. When might psilocybin be available to patients outside of a research protocol? Two companies have obtained approval from the Food and Drug Administration to initiate registration in trials for treatment of depression. Dr. Griffiths estimates that it could be another 5 years before psilocybin will be available for medical use.

The new center with its generous funding will allow for more studies with more patient populations. The center’s projects will look at using psilocybin as a treatment for opioid use disorder, comorbid depression and alcohol use disorder, anorexia nervosa, depression in Alzheimer’s disease, posttreatment Lyme disease syndrome, and PTSD.

Scott Aaronson, MD, is a mood disorder expert and director of clinical research at the Sheppard Pratt Health System in Towson/Baltimore. Dr. Aaronson, who also studies psilocybin as a treatment for depression, noted: “The problem with the development of psychedelics is that we are not really prepared to capture the improvement we see with their use, as the main changes are not in the classic markers of depression like the Montgomery-Åsberg or the Hamilton Depression rating scales, but [rather] in the patient’s perception of who they are, how they fit in with the world, and what is most important. We need to develop ways to capture those critical changes and work with the FDA to develop an entirely new vision of what constitutes improvement in psychiatric illness. My overall take is that it is a terrific time to specialize in treatment-resistant mood disorders!”
 

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.