The Science and Shamanism of Psychedelics

Photo courtesy of Kacie Tomita

The Science and Shamanism of Psychedelics

Timothy Leary’s popular 1960s slogan “Turn on, tune in, drop out” is not hanging on many walls today. In fact, psychedelics, like LSD, MDMA, psilocybin, and ayahuasca, are now being reconsidered with a new weight. In what’s been dubbed “the psychedelic renaissance,” the scientific dossier on mind-expanding drugs has been reopened, building upon a massive body of research dug out from under decades of stigma, fear, and prohibition. Evidence suggests that used carefully under the guidance of shamans, licensed therapists, and other experts, psychedelics may be promising and powerful therapeutic agents. They’re being studied for their potential to address hard-to-treat mental health conditions like PTSD, treatment-resistant depression, even end-of-life existential anxiety.

Scientists like UCLA’s Charles Grob—one of America’s leading clinical researchers in the field of psychedelic-assisted therapy—have been on board for decades. “I think we’ve come a long way from the sixties,” Grob says. “We’re able to look at these compounds in a far more fair and objective way than in the past.” Minus the theatrics of counterculture psychologist Timothy Leary and the moral panic of the Nixon administration, the contemporary uptick in psychedelic research has been—and should continue to be—a boon to our understanding of the human brain, mental health, and pharmacology.

All that considered, Grob says, the science doesn’t stand alone. In order to fully understand these compounds, we need to understand their anthropological contexts. Certain psychedelics—ayahuasca and psilocybin included—come from shamanic traditions. And Grob argues that understanding their ritual use is vital to understanding the drugs themselves. “There are cultures that have been using these drugs for millennia,” he says. “They know how to use them.” That is to say: Don’t try this at home.

A Q&A with Charles Grob, MD

You’ve done research on psychedelics for over twenty-five years. Can you give us a primer on each of the substances you’ve studied and your work with them?

MDMA is a synthetic compound created in the laboratory, and it has structural similarities to both the classic hallucinogen mescaline and to psychostimulants, or amphetamines. MDMA was first discovered just prior to the beginning of the First World War. But it was not studied until the ’50s and ’60s, when the US military studied MDMA as part of its program examining the potential of mind-altering substances for the military’s purposes: interrogation, intelligence, and counterintelligence.

Individuals under the influence of MDMA have a remarkable facility to be able to articulate feeling states. So for people who are alexithymic1 —that is, they cannot express feelings verbally—it’s thought to be a very, very valuable adjunct to psychotherapy.

In the early ’90s, I conducted the first phase-one study of MDMA, examining the physiological and psychological effects of MDMA in normal volunteer subjects. And then over the last few years, I conducted a study using an MDMA treatment model for adults on the autism spectrum who have severe, incapacitating social anxiety. We were treating the social anxiety, not autism—it’s often difficult to treat social anxiety in people who are high-functioning on the autism spectrum using standard conventional treatment models. We had a good response. We had a strong drug effect, and we recently published our paper in Psychopharmacology.

There have also been some successful preliminary trials done by Michael Mithoefer in South Carolina using an MDMA treatment model for patients with chronic PTSD.

“For people who are alexithymic—that is, they cannot express feelings verbally—MDMA is thought to be a very, very valuable adjunct to psychotherapy.”


Psilocybin is one of the active alkaloids in the species of mushrooms that have hallucinogenic properties, particularly Psilocybe cubensis. So in the 1950s, an amateur mycologist named R. Gordon Wasson ventured to the highlands of North Central Mexico and made the acquaintance of a local indigenous healer named Maria Sabina, who introduced him to the use of mushrooms in healing ceremonies.

He sent specimens of the mushroom to the leading medicinal chemists in Europe and the United States, and the Swiss chemist Albert Hofmann was able to successfully isolate the active alkaloid, psilocybin. Hofmann was the same chemist who made the remarkable discovery of LSD in the early 1940s.

My work with psilocybin centers on the treatment of advanced cancer anxiety, depression, and demoralization—essentially, helping people who are in an existential crisis from the proximity of their demise. It’s not unusual for people with a terminal illness to become quite anxious and feel very demoralized, so this is a treatment specifically designed to address people in that difficult circumstance and improve their quality of life as they approach death.

“My work with psilocybin centers on the treatment of advanced cancer anxiety, depression, and demoralization—essentially, helping people who are in an existential crisis from the proximity of their demise.”


Ayahuasca is a concoction of two plants native to the Amazonian rain forest. The first, Banisteriopsis caapi, contains the harman alkaloids: harmine, harmaline, and tetrahydroharmine. And the other plant, Psychotria viridis, contains dimethyltryptamine, or DMT.

DMT is a very potent hallucinogen, but when it’s taken orally, nothing happens—monoamine oxidase enzymes in the gut deactivate it. But if you brew these two plants together for many hours in this special process, you get this synergy. The harman alkaloids in the Banisteriopsis inhibit the monoamine oxidase enzyme system, so it allows active DMT to enter circulation. It bypasses the blood-brain barrier and activates the central nervous system in such a way that you can get this four-hour-long, very profound visionary experience.

When we studied these plants in Brazil in the 1990s, it was with a religious group—the União do Vegetal2 , also known as the UDV. They had permission from the Brazilian government to take ayahuasca as part of religious ceremonies. We studied the short-term and long-term effects in adult members of this UDV church.

In the early 2000s, we were asked to come back by the Brazilian judiciary to do another study, this time looking at the functional status of adolescents whose parents were members of the UDV. In the UDV, adolescents are offered the option to attend and participate3 in occasional special family ceremonies with their parents.

So the Brazilian judiciary wanted to make sure there were no injurious effects of this on the teenagers, and our study gave them a very strong, clean bill of health. We compared fifty adolescents in the UDV with fifty matched controls who had never taken ayahuasca, and we found no difference between the two groups in terms of neuropsychological function. The only difference we found to distinguish one group from the other was that kids in the UDV who had been exposed to ayahuasca were far less likely to experiment with alcohol or other psychoactive drugs compared to the non-ayahuasca-exposed controls.

How is the shamanic tradition of psychedelics different from how scientists are researching them today?

In shamanism, psychedelics are taken only in ceremony under the guidance and supervision of the shaman, or the spiritual leader of the community. The shaman would administer these compounds only for very clear circumscribed reasons, such as an initiation rite or a healing ceremony to address individuals with severe medical or psychological problems. In the shamanic world, these compounds are never taken for frivolous reasons. That would be absolutely taboo. It would be a heresy to misuse these compounds for hedonic reasons.

There are also other traditional reasons for psychedelic use that are somewhat beyond our understanding. Anthropologists have reported some cultures use these compounds to find lost objects or to help find game for the hunt. Of course, I don’t quite understand how that works, but this is part of the anthropological record, which is I think very important for people in the contemporary world to study if we’re interested in understanding how psychedelics are used and how to optimally use them.

There are also often very strict rules, particularly with ayahuasca, that are part of indigenous and shamanic tradition. I think Westerners should at least examine these rules, because they come from the people that have used ayahuasca for millennia—we can presume they have learned how to optimize its use. In traditional ayahuasca ceremonies, they not only talk about avoiding intoxicants like alcohol and other drugs in the days or weeks leading up to the event but also talk about eliminating sugar, salt, and spices from one’s diet and prohibiting sexual activity in the few days leading up to the experience. It is thought that engaging in normative sexual activity leads to an energetic deficit that could make traversing the altered state induced by ayahuasca somewhat difficult and even perilous.

You were recently featured in Michael Pollan’s book How to Change Your Mind, where you described psychedelic therapy as “applied mysticism.” What’s the role of mystical experience in a therapeutic setting?

These compounds, under optimal conditions, have the remarkable potential to facilitate what appear to be genuine mystical-level experiences—profound psychospiritual epiphanies. What’s really interesting here: In the late ’50s, there was a Canadian researcher named Humphry Osmond who treated a large population of chronic alcoholics with LSD. He found that the best predictor of positive treatment outcomes (in what was generally a one-treatment process) was the mystical experience. Subjects who actually had a mystical experience4 during the many hours they were in this altered state of consciousness fared better than subjects who just had a powerful aesthetic experience or a powerful insight-oriented experience. In the late ’60s, Walter Pahnke and Stanislav Grof found similar results in the mood, quality of life, and existential anxiety level of terminal cancer patients.

That’s a very important finding: The mystical experience in and of itself seems to be predictive of a positive therapeutic outcome.

“The mystical experience in and of itself seems to be predictive of a positive therapeutic outcome.”

Mystical experience is kind of a sense of unity, a sense of oneness, a sense of merging with the divine—a perception of a transcendent level that puts individuals in connection with a plane where they have transcended their personal identities and are connected to the greater universe. It’s kind of a profound unitive experience often associated with a sense of awe and reverence. It’s also found to be ineffable and transient; it’s a time-limited phenomenon. There’s even the sense of paradoxicality—how things might appear isn’t exactly what they are.

Then we have some very interesting studies conducted at Johns Hopkins about ten to fifteen years ago. The Hopkins group was—again, under optimal conditions—reliably able to demonstrate that you can induce these mystical experiences in normal volunteer subjects, which means that you should be able to do that in your patient population, too, as long as you optimize the preparation, treatment conditions, and the post-treatment integration.

How else do you find that sense of “oneness” affects people?

One other interesting feature I’ll point out is from my observations down in Brazil—I spent some time down there conducting our ayahuasca studies. Quite a number of the people I knew who were members of the UDV religion were also environmental activists. And I’ve been reflecting on this: Over the last twenty-five years since we did the first study there, it’s been my observation that people who have had some experience with psychedelics often demonstrate a greater sensitivity and connectedness to nature and a greater awareness of the grave risks our planet is now facing in regards to environmental collapse.

Albert Hofmann, the Swiss chemist who discovered LSD and isolated psilocybin, talked a great deal about the value of psychedelics to open people up to not only the wonders and the beauties of the natural world but also issues addressing the survival of the natural world, which, by definition, would also involve the survival of the human species.

There are several different approaches researchers take to studying psychedelics. What are the primary ones?

The psychospiritual model:

The psychologic or psychospiritual model focuses on facilitating the goals of traditional psychotherapy with psychedelics. It’s about looking at our own lives and issues from a novel perspective and getting insight that we’re able to carry out and work with. The research in this area focuses on what psychological outcomes are achieved.

What often helps a great deal is some preparatory psychotherapy. When you look at your intentions for doing this treatment to begin with, why do you want to have this experience? Is there a particular kind of healing that you would like to facilitate? Are there questions you need to have answered about events in the past or decisions coming up in the future? Formulating and articulating clear intentions—you can have multiple intentions, you’re not limited to one—and doing so with a facilitator or therapist can really help create a focus for the experience. During the full-on altered state, you might not recognize or even recall that you went into it with a particular intention. But afterward, when you do your integrative work, suddenly the answers may be there or you realize that it’s facilitated some healing process.

The neurobiologic model:

Classic hallucinogens (including LSD, psilocybin and DMT) are believed to catalyze their perception-altering effects by acting on neural pathways in the brain that primarily utilize the neurotransmitter serotonin. Serotonin has an important function in regulating mood, aggression, impulsivity, sexual behavior, appetite, pain, thermoregulation, circadian rhythm, sleep, cognitive function and memory. Some of the most pronounced effects induced by these drugs occur in the prefrontal cortex of the brain, where they can have a profound impact on perception, mood, and cognition.

There are other neurotransmitter systems involved, including the dopaminergic system, but primarily we’re looking at a serotonergic phenomenon.

The default mode network hypothesis:

There are some new suggested models, including one by a team at Imperial College London who have posited the role of the so-called default mode network. The idea is that the part of the brain that’s responsible for our sense of ego temporarily goes offline during a mystical experience. And this allows for kind of a rebooting of the system and a re-equilibration of mental processes. It’s an appealing suggested mechanism. However, within the brain-imaging community that has done neuroimaging work with psychedelics, there’s still some controversy as to what exactly is going on and what the implications are.

It’s intriguing, but for findings to become accepted within science and medicine, there has to be replicability. From one research program to another, they should be finding similar phenomena. And I’m not quite sure that’s been demonstrated yet with psychedelics and the default mode network. But be that as it may, it’s an appealing model, and it’s certainly catalyzing a lot of interesting discussion.

What’s on deck in the field of psychedelic research and therapy?

One hopeful outcome would be getting these compounds out of their Schedule I status and reclassifying them to Schedule II, possibly Schedule III. A Schedule I drug is defined as one with no safe use and no clinical treatment potential. But we know that certain psychedelics can be used safely when you carefully control set and setting and all of the study’s other features. And we know, even going back to the research of the 1960s, that under optimal conditions, we can clearly identify positive therapeutic outcomes.

But you know, I don’t think this will ever be the kind of substance that a doctor will write a prescription and say, “Here, have the pharmacy fill this. Take it during the week, and then when we meet next week, tell me how it went.” That’s never going to happen. I think what we’re most likely to see is a process where facilitators get credentialed—that there’s some kind of oversight in making sure facilitators fully understand both how to establish strong safety parameters and also that the facilitators demonstrate strong ethical principles, and so it’s safety and ethics that have to be demonstrated.

“I don’t think this will ever be the kind of substance that a doctor will write a prescription and say, ‘Here, have the pharmacy fill this. Take it during the week, and then when we meet next week, tell me how it went.’”

There’s also this controversial question: Should facilitators be licensed health professionals or licensed mental health professionals? Do you want or need that extra level of ability? And that’s controversial because over the last half-century, there’s been an underground network of facilitators who do not necessarily have these kinds of credentials or professional licenses, but who are highly skilled and follow ethical practices. So how should they be involved? That’s going to have to be worked out. What we may come down to is a system whereby at least one professional in the room has necessary credentials and licensure. I think that would be advisable.

One other thing that I think is important: During the ’50s and ’60s and even now, the field of psychedelic research has been heavily dominated by men. And I think it’s going to be very important for more women to become involved in the field and assume leadership positions. I also think that when you’re looking at facilitation, it’s important to utilize male-female dyads, both for clinical and safety reasons. That will help to ensure that strong ethical standards5 are established and maintained.

There’s a lot at stake as we move forward. My hope and my expectation is that when people are carefully prepared and researchers adhere to safety parameters and the highest ethical standards, we will continue to demonstrate the usefulness of psychedelics, particularly for the mental health of patients who don’t respond well to conventional treatments. Hopefully, this work can have an impact on the health professions and the world we live in.

Charles Grob, MD, is a professor of psychiatry and biobehavioral sciences and pediatrics at the David Geffen School of Medicine at UCLA and the director of Harbor-UCLA Medical Center’s Division of Child and Adolescent Psychiatry. Grob has been involved in psychedelic research for over twenty-five years, focusing on psychedelics as novel psychopharmacological therapies for substance abuse, mood disorders, and anxiety disorders.

This article is for informational purposes only, even if and to the extent that it features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment and should never be relied upon for specific medical advice. The views expressed in this article are the views of the expert and do not necessarily represent the views of goop.

1Alexithymic means “without words for feelings.” From Greek roots “lexis,” meaning speech, and “thümós,” meaning soul, as the seat of emotion and thought.
2União do Vegetal” is Portuguese for “Union of the Plants.”
3For adolescents to participate in these special family ceremonies, they have to have hit puberty. Preadolescents are not allowed to participate. In the UDV, women will attend ceremonies during pregnancy, consuming small amounts of ayahuasca. They sometimes take a small amount of ayahuasca during labor and delivery, and babies are baptized with one or two drops of ayahuasca deposited on their tongue from an eyedropper.

From baptism to the onset of puberty, kids do not participate in any use of ayahuasca in ceremony.

4To objective observers, the mystical experiences from use of these drugs were indistinguishable from classical mystical experiences from nondrug causes.
5Male-female dyadic teams, compared to teams composed of only male facilitators, may have a preventive effect on the emergence of any inappropriate (and potentially injurious) sexual boundary violations.
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