Brain
Expert Pharmacologist
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After years of struggling with treatment for worsening cancer, Kevin felt miserable — anxious, depressed and hopeless. Traditional cancer treatments had weakened him and it was unclear whether they would save his life.
But then Kevin got a spot in a clinical trial for an exotic drug. The drug wasn't meant to treat his cancer, but it was supposed to cure the terror and depression he constantly felt about his disease. And it worked. A few hours after taking the little pill, Kevin told the researchers: «Cancer is not important, the most important thing is love». According to the researchers, his fears of imminent death suddenly disappeared — and this state of mind lasted for at least a few months.
It wasn't traditional antidepressants like Zoloft or anxiety medications like Xanax that made Kevin rethink his life. It was a drug that had been banned for decades but was now at the center of a research revival: psilocybin, derived from hallucinogenic magic mushrooms.
But then Kevin got a spot in a clinical trial for an exotic drug. The drug wasn't meant to treat his cancer, but it was supposed to cure the terror and depression he constantly felt about his disease. And it worked. A few hours after taking the little pill, Kevin told the researchers: «Cancer is not important, the most important thing is love». According to the researchers, his fears of imminent death suddenly disappeared — and this state of mind lasted for at least a few months.
It wasn't traditional antidepressants like Zoloft or anxiety medications like Xanax that made Kevin rethink his life. It was a drug that had been banned for decades but was now at the center of a research revival: psilocybin, derived from hallucinogenic magic mushrooms.
Psychologists and psychiatrists have studied hallucinogens for decades — as a treatment for alcoholism and depression, and to stimulate creativity. But support for the research stopped in the 1970s, after the federal government placed many psychedelics on the list of Schedule 1 drugs. But now researchers are taking a new look at the drugs.
While stories like Kevin's are promising, we would need hundreds, perhaps thousands of other examples — rigorously tested, preferably in large randomized controlled experiments — to know that the effects claimed in the study are real and unbiased.
But this research is worth it. Psychedelics promise to alleviate some of the conditions that have proven to be the hardest to treat — addiction, obsessive-compulsive disorder, end-of-life anxiety and, in some cases, depression, notoriously resistant to treatment. For example, smoking relapse rates are estimated at 60-90% within one year, even though smoking kills hundreds of thousands of people each year.
There is still a lot we don't know and are just learning. So, to understand what we currently know about psychedelic drugs and psychedelic psychotherapy for treating some of the most persistent psychological conditions, we read over 50 studies analyzing their safety and efficacy and talked to the researchers involved.
We only looked at studies of classic psychedelics such as LSD, psilocybin from magic mushrooms, and DMT. These drugs have largely similar effects, activating certain serotonin receptors in the brain.
While stories like Kevin's are promising, we would need hundreds, perhaps thousands of other examples — rigorously tested, preferably in large randomized controlled experiments — to know that the effects claimed in the study are real and unbiased.
But this research is worth it. Psychedelics promise to alleviate some of the conditions that have proven to be the hardest to treat — addiction, obsessive-compulsive disorder, end-of-life anxiety and, in some cases, depression, notoriously resistant to treatment. For example, smoking relapse rates are estimated at 60-90% within one year, even though smoking kills hundreds of thousands of people each year.
There is still a lot we don't know and are just learning. So, to understand what we currently know about psychedelic drugs and psychedelic psychotherapy for treating some of the most persistent psychological conditions, we read over 50 studies analyzing their safety and efficacy and talked to the researchers involved.
We only looked at studies of classic psychedelics such as LSD, psilocybin from magic mushrooms, and DMT. These drugs have largely similar effects, activating certain serotonin receptors in the brain.
Chapter one. Research doesn't stand still.
The idea of using psychedelic drugs as medicine is not new. In 1943, Albert Hofmann was fortunate enough to discover the effects of LSD by taking it in his laboratory in Switzerland. This discovery sparked a wave of research into LSD and similar substances in the 1950s and 1960s.
Perhaps the most famous researcher of the time was Timothy Leary. He had experimented with drugs in college, becoming particularly fascinated with psychedelics. His interest led him, after he became a young faculty member at Harvard University, to begin a more formal study of drugs. This led to the creation of the Harvard Psilocybin Project, which administered psilocybin (usually found in magic mushrooms) to graduate students and several prominent artists of the time in a series of experiments to reveal the drug's effects on human consciousness.
Despite their strange origins, the research at the time was encouraging: dozens and dozens of studies — not just in Leary's lab, but in many others across the country — produced promising results suggesting that psychedelics could be used therapeutically to treat some of the most treatment-resistant conditions, such as addiction, anxiety and depression.
After a few decades, restrictions on psychedelic drugs began to loosen. Beginning in the 1990s, some researchers pushed to revisit psychedelic drugs as potential medical tools. With support from private groups such as MAPS, the Beckley Foundation, and the Heffter Research Institute, researchers overcame regulatory and financial obstacles to conduct small preliminary studies.
The idea of using psychedelic drugs as medicine is not new. In 1943, Albert Hofmann was fortunate enough to discover the effects of LSD by taking it in his laboratory in Switzerland. This discovery sparked a wave of research into LSD and similar substances in the 1950s and 1960s.
Perhaps the most famous researcher of the time was Timothy Leary. He had experimented with drugs in college, becoming particularly fascinated with psychedelics. His interest led him, after he became a young faculty member at Harvard University, to begin a more formal study of drugs. This led to the creation of the Harvard Psilocybin Project, which administered psilocybin (usually found in magic mushrooms) to graduate students and several prominent artists of the time in a series of experiments to reveal the drug's effects on human consciousness.
Despite their strange origins, the research at the time was encouraging: dozens and dozens of studies — not just in Leary's lab, but in many others across the country — produced promising results suggesting that psychedelics could be used therapeutically to treat some of the most treatment-resistant conditions, such as addiction, anxiety and depression.
After a few decades, restrictions on psychedelic drugs began to loosen. Beginning in the 1990s, some researchers pushed to revisit psychedelic drugs as potential medical tools. With support from private groups such as MAPS, the Beckley Foundation, and the Heffter Research Institute, researchers overcame regulatory and financial obstacles to conduct small preliminary studies.
In part because of the barriers to studying these drugs, new studies are preliminary and limited. Sample sizes are so small that it is difficult to say with certainty whether the results would hold true for larger, generalized populations. And some studies don't include control groups or placebos, the gold standard in science for ensuring that the observed effects are not caused by something else.
But the results are promising and complex. To the extent that these drugs may work, they appear to do so through a very unusual mechanism: inducing a mystical, spiritual experience.
Chapter Two. The hallucinogenic pattern of psychedelics give them therapeutic effects.
Here's a small sampling of how some participants in several studies since the 2000s have described psychedelic experiences:
But the results are promising and complex. To the extent that these drugs may work, they appear to do so through a very unusual mechanism: inducing a mystical, spiritual experience.
Chapter Two. The hallucinogenic pattern of psychedelics give them therapeutic effects.
Here's a small sampling of how some participants in several studies since the 2000s have described psychedelic experiences:
- «A sense of gratitude, a great (powerful) memory of humility...my experience of being, my experience of being in and within infinity»
- «Not religious at all, but important for motivating me to develop my spiritual life»
- «I believe that I have channeled the power of the Goddess and that I hold that power within myself. I believe she exists everywhere and I seek her out to add spark, life and joy to everyday, ordinary situations»
- «This experience has expanded my conscious awareness forever. It allows me to let go of negative ideas more quickly. It makes it easier for me to accept what is»
- «My conversation with God (golden streams of light) assures me that everything on this plane is perfect; but I don't have the physical body/mind to fully understand».
It may be easy to dismiss this experience. What do gods and golden streams of light have to do with medicine?
But the results of many studies, which can take months or years of follow-up, are promising, although not definitive. One very small study involving 15 smokers found that 12 of them (80%) were able to abstain from smoking for six months after psilocybin treatment.
A review of previous randomized controlled trials found that LSD helped alcoholics reduce their drinking, while a much smaller study found that psilocybin treatment helped people diagnosed with alcohol dependence reduce the number of days they drank alcohol. Another study found that psilocybin could help treat depression in patients who were resistant to other treatments.
But the results of many studies, which can take months or years of follow-up, are promising, although not definitive. One very small study involving 15 smokers found that 12 of them (80%) were able to abstain from smoking for six months after psilocybin treatment.
A review of previous randomized controlled trials found that LSD helped alcoholics reduce their drinking, while a much smaller study found that psilocybin treatment helped people diagnosed with alcohol dependence reduce the number of days they drank alcohol. Another study found that psilocybin could help treat depression in patients who were resistant to other treatments.
So how exactly do psychedelics accomplish this? Researchers readily admit that they don't have all the answers — or even complete certainty that it's solely about psychedelics. But based on current research, as well as studies from the '50s and '60s, they do have a theory: when people are dealing with debilitating mental disorders, psychedelics can trigger a powerful mystical effect. These experiences can then provide a psychological context that facilitates positive behavioral changes.
And here's what's really remarkable: in the studies, it turned out that one or two doses were enough to produce effects for several months. Unlike psychiatric drugs, which require regular, often daily doses, psilocybin treatment — if it really works — apparently requires only one or two sessions with a single dose of the drug to have an effect for several months.
«Spiritual experiences have been part of humanity for thousands and thousands of years. Instead of dismissing them, let's try to understand them. What's going on here? This is part of the human experience — a very relevant and meaningful part of the human experience. And now we have these tools to study how certain sacramental elements that occur in nature and can be synthesized...can be used for good» — said Samit Kumar, a physician closely following the research.
And here's what's really remarkable: in the studies, it turned out that one or two doses were enough to produce effects for several months. Unlike psychiatric drugs, which require regular, often daily doses, psilocybin treatment — if it really works — apparently requires only one or two sessions with a single dose of the drug to have an effect for several months.
«Spiritual experiences have been part of humanity for thousands and thousands of years. Instead of dismissing them, let's try to understand them. What's going on here? This is part of the human experience — a very relevant and meaningful part of the human experience. And now we have these tools to study how certain sacramental elements that occur in nature and can be synthesized...can be used for good» — said Samit Kumar, a physician closely following the research.
A new set of studies published in the Journal of Psychopharmacology, which used some of the largest sample sizes in psychedelic research to date, showed potential. The patients, totaling 80 in both studies, all had stage four cancer and end-of-life anxiety or depression, largely caused by their impending death. After a psilocybin treatment session, most patients (up to 80%) — in general — showed improvement in scores used to assess mood, depression and anxiety.
Although studies have not been able to test, due to small sample sizes and methodology, whether psilocybin itself leads to positive outcomes, research has shown that the depth of mystical experience, as measured by widely accepted scientific metrics for these types of experiences, correlates closely with how strong the patients' successes were. One study also found that a larger dose produced greater effects.
These new, larger studies confirmed the results of previous pilot studies that followed a similar model but had smaller sample sizes and therefore were less reliable for drawing more generalizable conclusions.
Johnson of Johns Hopkins University agreed, citing his research, «For both cancer-related end-of-life anxiety and smoking cessation treatments, we found that the degree of mystical experience predicted long-term positive effects — reduced anxiety and depression, and reduced cigarette smoking».
Although studies have not been able to test, due to small sample sizes and methodology, whether psilocybin itself leads to positive outcomes, research has shown that the depth of mystical experience, as measured by widely accepted scientific metrics for these types of experiences, correlates closely with how strong the patients' successes were. One study also found that a larger dose produced greater effects.
These new, larger studies confirmed the results of previous pilot studies that followed a similar model but had smaller sample sizes and therefore were less reliable for drawing more generalizable conclusions.
Johnson of Johns Hopkins University agreed, citing his research, «For both cancer-related end-of-life anxiety and smoking cessation treatments, we found that the degree of mystical experience predicted long-term positive effects — reduced anxiety and depression, and reduced cigarette smoking».
One way to understand this effect is to view it as the opposite of a traumatic experience, as explained in the smoking study:
We argue that, similarly, peak experiences triggered by psychedelic drugs may function as vivid, discrete events that produce PTSD-like feedback effects, i.e., persistent changes in behavior (and presumably in the brain) associated with lasting improvement. By the term «PTSD», we are not suggesting that these experiences necessarily share common biological mechanisms with PTSD.
Rather, we assume that these experiences are «PTSD-like» in the sense that a single discrete event can cause lasting behavioral (and presumably biological) changes, and «reversible» in the sense that these lasting changes are beneficial in nature, as opposed to harmful.
«We're not quite sure what it represents in the brain. The way they describe it often symbolizes what's going on in their head. Take the goddess leading you. Maybe it's a goddess leading you through your depression and out — if you take that metaphor» — said James Rucker, a clinical lecturer at King's College London who worked on the depression study.
We argue that, similarly, peak experiences triggered by psychedelic drugs may function as vivid, discrete events that produce PTSD-like feedback effects, i.e., persistent changes in behavior (and presumably in the brain) associated with lasting improvement. By the term «PTSD», we are not suggesting that these experiences necessarily share common biological mechanisms with PTSD.
Rather, we assume that these experiences are «PTSD-like» in the sense that a single discrete event can cause lasting behavioral (and presumably biological) changes, and «reversible» in the sense that these lasting changes are beneficial in nature, as opposed to harmful.
«We're not quite sure what it represents in the brain. The way they describe it often symbolizes what's going on in their head. Take the goddess leading you. Maybe it's a goddess leading you through your depression and out — if you take that metaphor» — said James Rucker, a clinical lecturer at King's College London who worked on the depression study.
Chapters 3-4 will be in the next issue and they are for especially interested readers.