The risks of mixing ayahuasca and SSRIs: 5 Questions for UCLA psychiatry professor Charles Grob

Grob discusses ayahuasca's risks, his research on the substance, and the growing need for new ayahuasca studies.

As ayahuasca retreats have become more popular, there have been several deaths among attendees in recent years. Those attendees reportedly died as a result of medical emergencies; details about cause of death are not always clear, but the incidents raise questions about the safety protocols in place at retreat centers, as well as the risk profile of ayahuasca.

The Microdose spoke with researcher Charles Grob about those risks, and the still-scant body of research about ayahuasca. Grob has been studying psychedelics for decades, and dreamed of doing so long before he was actually able to begin his research. After trying LSD as a college student at Oberlin in the 1960s, Grob dropped out and traveled; years later, he began working at a sleep and dream research lab in Brooklyn, where the primary investigator, Stanley Krippner, gave Grob full access to his extensive library. Grob gravitated towards his collection of psychedelics articles. He realized he wanted to study the compounds. When he told his father about his interest, his dad replied, “Well, son, there might be something to what you say, but no one will listen to you unless you get your credentials.”

So Grob did just that. He went back to college as a pre-med student at Columbia University, then went to medical school at the State University of New York. After an internal medicine internship in San Francisco and residency at Cedars-Sinai in Los Angeles, he completed child psychiatry fellowships at Cedars-Sinai and Johns Hopkins, then became the director of child and adolescent psychiatry at UCLA’s medical center in 1993. It was at UCLA where Grob finally got back to psychedelics, launching the first FDA-approved phrase 1 study of MDMA, and traveling to the Brazilian Amazon to study ayahuasca. He is now the cofounder and clinical director of the UCLA Ecological Medicine & Psychedelic Studies Initiative.

Tell me about your early ayahuasca studies. What did you find?

We went there in 1993, and we published several papers about our research between 1996 and 1999. We studied adults who had been members of the União do Vegetal (UDV) church for at least ten years, which meant they were long term ayahuasca users. In the UDV, they take ayahuasca on the first and third Saturday evenings of every month and sometimes on special holidays as well, so these were experienced users. They were very gracious and went all out to provide what we needed; we had full access to their religious temple to run our experimental sessions. First, we did interviews as well as medical screenings, labs, neuroscience testing, and personality testing of participants. We had a group of ayahuasca users, to whom we administered ayahuasca, as well as a control group that had never used ayahuasca, who did not receive ayahuasca.

We brought all of our samples back to the U.S — blood samples, urine samples and samples of the tea or the ayahuasca. Overall, we found some interesting results — there was an increased density of serotonin receptors in ayahuasca users. That’s the opposite of what you would expect to find in someone with, say, major depression or some types of substance use disorder. And in general, from our other data, we found that subjects seemed to be in very good shape, psychologically and physically.

We were invited back to Brazil in the early 2000 to do another study, because the Brazilian judiciary had just given approval for ayahuasca use within a religious context and they were concerned about minors who participated with their parents and grandparents in family ceremonies. We did interviews and testing with kids in the UDV community; some of them had even been exposed to the substance in utero because it’s believed to be healthy for the mother, and as babies, they were baptized with a tiny drop of ayahuasca, administered by an eyedropper, onto their tongue. Generally kids would not be invited to participate in ceremonies until they reached puberty. But long story short, we found that these were very healthy, high functioning kids who tested out as well or even better than the population-matched control group who had never taken ayahuasca.

What have we learned about ayahuasca since those 1990s studies?

I’m a little disappointed that the field of ayahuasca studies has not progressed to any great degree. There have been no clinical studies in the United States where ayahuasca has actually been administered to subjects; there have been some survey studies and brain scan studies, and Brazilian psychiatrists have done some interesting studies that suggest ayahuasca could be of value to people with chronic major depression, but those studies were not well controlled. It’d be good to see more elaborate, well-designed and methodologically strong studies.

There's a lot of ayahuasca use going on, not only from people flying to South or Central America, but also occurring in this country. There are two religions, the UDV and Santo Daime, which have received sanction from the courts for religious use. The UDV’s case actually went all the way to the Supreme Court, and I was an expert witness in that case. There are also a lot of informal, so-called neo-shamanic groups that hold ayahuasca sessions, so there’s really a need for more investigation into the range of effects of ayahuasca — the potential positive therapeutic effects as well as potential adverse effects.

What are the potential adverse effects?

In 1998, I published an article with James Callaway about the potential for severe adverse interactions between ayahuasca and SSRIs. We looked at three cases, all individuals in the U.S., who had negative effects during the course of ayahuasca, which is generally a four hour experience. They got very agitated, very confused, and had a great deal of sweating. They seemed to be spiking a temperature and had muscular rigidity. They were distressed and pretty out of it. In each case, they returned to baseline after the experience.

We thought that what might have been going on in these cases was serotonin syndrome, which can happen when you get a build up of serotonin in the central nervous system. The one commonality across the cases we looked at — as well as other cases I’ve heard of — is that they were all on an SSRI antidepressant. Those drugs block the reuptake of serotonin. Ayahuasca has two components: Psychotria, which contains the hallucinogenic DMT, and the Banisteriopsis vine, which contains harmala alkaloids. Those harmala alkaloids are monoamine oxidase inhibitors, or MAOIs — the MAOI inhibits the breakdown of DMT, so without that MAOI, the DMT would just be quickly metabolized by your body. So the MAOI allows the DMT to be absorbed through the gut and activates the nervous system. But when someone is on an SSRI, there's already a relative excess of serotonin in the central nervous system, and then if MAOIs are also blocking reuptake, you can have an excess of serotonin flooding your system.

What symptoms should people be looking out for if they suspect they might be experiencing an interaction effect, and what would you advise to prevent such interactions?

Like the case studies we wrote about in our paper, people might experience some degree of confusion and agitation; they might develop a high temperature, an elevation in blood pressure, or muscular rigidity. In severe cases, they could have seizures; that’s especially a risk if they have a history of seizures.

I’m generally very careful in advising people to go off their meds, but I would tell people to go off their SSRIs if they’re going to do ayahuasca because it can take up to 4 or 5 weeks for it to fully exit your system. As for other meds, like those affecting blood pressure or heart rhythm, I’m hesitant to give advice, because they may expose themselves to severe risks without those meds. This is one major deficit within the area of psychedelic research in general — most of the studies we’ve done are set up to minimize the risk of serious adverse events, but that means we don’t know a lot about interactions.

What kinds of studies would you like to see to help us better understand those risks?

For most of these studies, if you have a history of hypertension, you cannot be entered into the study. Many studies have an upper range limit of 60 or 65, at most seventy. I’m currently working on a study with Brian Anderson, Tony Bossis, and Alicia Danforth, where we’re studying demoralization at the end of life, and we're describing it as a pragmatic real world study, meaning we are lifting restrictions. We're lifting the upper age limit, which means we're going to get people with more medical problems. We’re doing that with help from our palliative care, oncology, and internist colleagues; we're going to have to figure out on a case by case basis whether or not it’s safe for people to go off their medications.

In general, this field really needs more investigation of older individuals, and particularly older individuals with medical problems. One alarming story I heard a few years ago was written in a letter to researchers by the daughters of a 74 year old man who arranged to take mushrooms with a reputable underground psychedelic therapist. He had never taken any psychedelics, and they met and discussed what his session might be like, and his intentions. They went over any potential risk factors and he had none to report. He took a moderate to moderately high dose of mushrooms and within two hours he had expired. The autopsy found he had a cardiac arrest, but his doctor said the guy didn't have any active medical problems. I suspect the guy had an underlying arrhythmia, which was exacerbated when he took mushrooms, and led to a fairly rare cardiac arrest. And I've heard of other cases, particularly in older individuals, where people who have underlying cardiovascular risk experience fatal events.

I think that also speaks to the underground. In the underground, you probably don’t have the resources to be screening for an underlying risk. And most of these underground therapists have no medical background. They don't coordinate with medically trained people, and a lot of medically trained people don't want anything to do with this because it’s still illegal.

This interview has been edited and condensed for clarity and length.