This story is part of When the Drugs Hit, a Motherboard journey into the science, politics, and culture of today's psychedelic renaissance. Follow along here.
We’ve all seen the YouTube videos.
They usually start with someone taking a hit from a pipe while their friend laughs behind the camera. Within seconds, the subject loses motor control and any sense of where—or who—they are. As the high peaks a minute later, they are seized by laughter or succumb to terror as their hallucinations devour reality. Perhaps they have traveled to space, struck up a conversation with the salvia gods, or experienced eternity in some ineffable psychedelic landscape. Regardless of where the high takes them, however, the journey is always a short one. Just a few minutes after dosing they’re back in reality, sober as a judge, and a little curious as to how they ended up hanging upside down off the couch.
This is salvia divinorum—arguably the strangest and least understood naturally occurring hallucinogen ever discovered.
In 2008, a report by the New York Times pointed to an abundance of online videos of people experimenting with salvia as “exhibit A” in the push to make the substance illegal throughout the United States. But it wasn't just the videos. The stigma around salvia is also due to the nature of the trip itself, which is characterized by its vivid hallucinations and intense dissociative effects. Almost everyone I know has either tried salvia or knows someone who has, but I’ve yet to meet anyone who enjoyed the experience.
Although I’ve had several unpleasant salvia experiences myself, I recently volunteered to be a participant in the first-ever brain imaging study on salvinorin A, the main psychoactive compound in the salvia plant. Only a handful of salvia studies have ever been conducted on human subjects and this study was the first time that researchers were able to watch the brain as it was tripping on salvinorin.
“This is the first step off the cliff into the void,” Fred Barrett, a cognitive neuroscientist at Johns Hopkins University and the lead researcher on the salvia trial, told me. “This will essentially be setting the roadmap of where future [salvia] research will take us.”
WHY STUDY SALVIA DIVINORUM?
Salvia divinorum grows wildly in the cloud forests of southern Mexico, where the Mazatec people have consumed the plant ritualistically for centuries. Although the ritual use of salvia by the Mazatec was first described by American ethnobotanists in the early 60s, it wasn’t until the mid-90s that scientists identified salvinorin A as the main psychoactive compound that produces salvia's hallucinogenic effects.
In the past 25 years, only a handful of human research trials on the effects of salvia have been conducted. The lack of research on such a potent psychedelic is odd, especially because it is legal in many US states. Barrett said he thinks the lack of research on salvia likely has to do with the fact that salvia trips often suck.
“Salvia’s not a typical drug of abuse,” Barrett said. “It’s a very powerful drug and it can have very dysphoric effects, but when people encounter salvia, the normative response is ‘that was terrible, I’m never going to do that again.’ There’s no salvia crisis, so frankly I don’t think the community of scientists who typically study drugs of abuse has really cared."
Starting in the late 90s, concentrated extracts of the salvia divinorum plant started cropping up in smoke shops throughout the United States. These extracts are rated based on concentration of salvinorin A relative to natural levels (e.g., 10x concentrate, 20x concentrate, 30x concentrate, and so on.) These ratings are only an approximation, however, since the salvinorin content of the leaves and the preparation methods of extracts can vary drastically.
Salvinorin A is unique in both the effects of its high and the chemical’s mechanism of action in the brain. The drug is infamous for its rapid onset, dissociative effects, and intense visual and auditory hallucinations. Although the subjective effects of salvinorin A are wide ranging, past surveys of salvia users have identified a number of recurring features of salvia trips.
“People are still consciously aware of something while they're experiencing salvia, it's just something completely different than what everyone else in the room is experiencing."
In 2015, a team of Spanish researchers collaborated with Johns Hopkins to produce a study on the subjective effects of salvinorin A at various doses. Among the experiences frequently reported by users were “tunnel or window-like visions…geometric patterns…other worlds of multiple colors…objects were felt as being associated with the body…and a perceived inability to interact with one’s body and surroundings.” One user reported an encounter with “magical beings…wearing garish dresses, similar to the clothes of a royal court jester.” As the researchers noted, carnival-themed imagery had also been reported in several other studies on the subjective effects of salvinorin A.
“With a high enough dose you have a clean break from what we would consider consensual reality,” Barrett said. “People are still consciously aware of something while they're experiencing salvia, it's just something completely different than what everyone else in the room is experiencing. Really strong and reversible manipulations like this are of huge interest in the basic neuroscience of consciousness.”
Salvinorin A also has a highly unusual mechanism of action in the brain: It targets the kappa opioid receptor, one of four types of opioid receptors and arguably the least understood. In this respect, salvinorin A is much different from “classic” psychedelics, such as LSD, mushrooms, mescaline, and DMT, which all act on the 2A serotonin receptor. Salvinorin A, however, bypasses the 2A serotonin receptor entirely.
“These two classes of drugs work in completely different ways, but they both lead to these profound alterations in consciousness,” Barrett said. “If you have two drugs that can give you similar strengths of change in consciousness, but a different character of change in consciousness, then you have a really interesting research question: How can we use these compounds to better understand changes in consciousness and the therapeutic effects of those changes?”
For Barrett, one of the most interesting neurological questions about salvia is how it interfaces with the claustrum. As detailed in a 2005 study, the “enigmatic” claustrum is a “thin, sheet-like neuronal structure…that is remarkable in that it receives input from almost all regions of the cortex and projects back to almost all regions of the cortex,” the wrinkly outermost region of the brain that plays a fundamental role in consciousness. According to Barrett, another notable feature of the claustrum is that it has the highest density of serotonin 2A and kappa opioid receptors in the brain, and both of these receptors are targeted by two very different classes of consciousness-altering hallucinogens.
“One of the things we expect is there to be pretty vast changes in the way the claustrum communicates with different brain regions,” Barrett told me. “We're also going to look for differences in the activity and connectivity of the default mode network, the executive control brain network, and the brain network involved in reward and emotion processing.”
Barrett and his colleagues see the unique effects of salvinorin A as a promising way to learn more about some of the most fundamental aspects of neurobiology. In this respect, my participation in the salvia study was a small contribution toward a greater understanding of consciousness, memory, and embodied experience.
WHAT IT’S LIKE TO SMOKE SALVIA FOR SCIENCE
I was first introduced to salvia when I was a freshman in high school, and by the time I graduated I had smoked it about a dozen times. In retrospect, I would not describe a single one of those experiences as “pleasant,” “enjoyable,” or “fun.” The last time I used salvia was almost a decade ago, and during that trip I became convinced that I had been irreversibly transformed into a suspension bridge. Good times.
Despite a history of bad experiences with the substance, I volunteered for the Johns Hopkins salvinorin A study out of a suspicion that salvia probably had more to offer than what I experienced in high school. As a teen, each of my salvia experiences was under less than ideal conditions—usually at a party or in a park after curfew. These sorts of situations lend themselves to paranoia and anxiety, which don’t mix well with a strong dissociative hallucinogen. I figured if the settings were changed to a relaxed environment where I was surrounded by medical professionals, perhaps the nature of the trip would as well.
In the weeks leading up to the study, however, I began to feel a little anxious about where the trip would take me. I’ve had strong psychedelic experiences previously while taking ayahuasca and mushrooms, but on each of those occasions the negative parts of the trip were offset by the positive aspects. Not so with salvia. Each time I’d tried salvia the experience had been uncomfortable at best and terrifying at worst. At the end of a trip I never felt as though I had gained some profound insight or mental clarity, but I did often feel as though I’d been through hell and back.
Ahead of my visit to Johns Hopkins, I asked about the dose strength I’d receive during the trial so that I could mentally prepare myself for the experience. Due to the study protocols, however, Barrett and his colleagues were unable to give me much information. All they could tell me was that I’d be smoking a “moderately high dose” of pure salvinorin A and that it couldn’t really be compared to the salvia extracts sold in smoke shops because it was the pure molecule, not plant matter.
Read More: Stop Policing Psychedelic Science
When I arrived at Johns Hopkins for the first day of my clinical trial, I was ushered into one of the two session rooms at the hospital. These rooms are furnished so that they resemble a living room to allow study participants to feel relaxed when they’re tripping. There was a couch against one wall flanked by a coffee table that held a lamp and a small mushroom statue. The walls are decorated with tasteful, vaguely psychedelic artworks and a Tibetan prayer flag hung in the corner. If it weren’t for the small camera pointed at the couch and workstation in the back of the room, one could almost believe that this was a living room rather than a laboratory.
The first day of the study was mostly just to establish a baseline health profile and make sure I was qualified for the trial. Participants in the study were required to be in good health, experienced with using psychedelics, and with no personal or family history with a psychotic disorder. Screening for this involved a routine physical exam, an extensive psychiatric interview, and several of the most interesting questionnaires I’ve ever completed (sample questions: “Have you ever had encounters with intelligent entities during previous psychedelic experiences?” “ Did they tell you anything about the future? ” and so on).
The following day, I met with John Clifton, a Johns Hopkins research assistant, and Manoj Doss, a postdoctoral researcher who specializes in memory. Clifton and Doss were going to be my trip sitters during my salvia sessions, so for about an hour and a half before my first dose we talked about our lives to get a bit more familiar with each other.
For the first salvia session I laid on the couch and donned an eye mask while Doss sat at the far end of the room with the smoking apparatus. The simple device consisted of a small glass bulb with a plastic hose connected to the top and was described to me as an “FDA-approved crack pipe.” Along the bottom of the bulb was a barely noticeable residue of a white crystalline substance, which I was informed was one dose of 99.9% pure salvinorin A.
I was given one end of the hose and instructed to begin a 45-second long inhale as Doss vaporized the salvinorin A with a butane torch. At the same time, Clifton began to play a new age soundtrack through speakers and came to put his hand on my leg to ground me during the trip. When the 45 seconds were up, I exhaled and felt the effects of the salvia almost immediately.
The first thing I noticed was the feeling of my body dissolving. Shortly after I began feeling the physical effects, the hallucinations began. I felt as though my head had split in two and a patterned stream began flowing from both sides of my face. This stream was a “harlequin pattern” of large brown and white diamonds that flowed away from me and began to form the “boundary” of an infinite three-dimensional space. These diamonds continued to tessellate to an infinite point and I felt as though I were suspended above this expanse, hanging like a figure head hangs off the bow of a ship.
Throughout the trip, I remember being overcome by the profound beauty of the scene I was witnessing. If I tried to focus, I could remember that in base reality I was in a room in Johns Hopkins, but that didn’t alleviate the feeling of being in an entirely separate reality, as though I were sitting in a container that cordoned me off from the ‘normal’ world. Overall, the experience was quite pleasant. I only had a brief moment of panic when it seemed like one of the notes in the new age soundtrack had been held for far too long. I began to worry that time was dilating and that I might be trapped in this space for eternity. When the music progressed to the next note, however, the panic quickly subsided and time resumed its normal cadence.
A structural scan of the author’s brain. Image: Johns Hopkins University/Motherboard
This entire experience only lasted for about three minutes. The return to base reality was as abrupt as when I left it. At a certain point, the diamonds in the harlequin pattern began to stretch larger and larger until the entire world was brown, which eventually faded to black. At the same time I began to be aware of my body again and could feel Clifton’s hand resting on my leg. I didn’t feel any sort of panic or unease, but I found myself taking long, deep breaths as I came down.
This first trip was a sort of test run to make sure that I could handle the highest dose I would receive the following day in the MRI machine. The most important thing, however, was to make sure that I remained absolutely still during the trip since even slight movements in the MRI machine can ruin the brain scan. Fortunately, one of the more common effects of salvia is a sense of not having a body, which renders users immobile. According to Clifton and Doss, I stayed still as a rock throughout the trip.
The following day, I met Doss and Clifton in the basement of the main Johns Hopkins Hospital, where MRIs are done. Magnetic resonance imaging basically involves putting your body inside a very powerful magnet and creating an image of your internal organs by studying how the magnetic field interacts with your body. After being warned that the NFC chip I have implanted in my hand might act as a conductor and get burning hot during the scan, I was strapped into the machine for a structural brain scan. After this was completed, I would be given two doses of salvia. One dose would be as strong as the day before and the other could be anything from a placebo up to a dose as powerful as the one I experienced the day before. I wouldn’t be told in advance which dose was which.
I had never been in an MRI machine before and it didn’t take long to realize that it wasn’t exactly the best environment for tripping. For starters, MRI machines are very narrow—there’s hardly any room to move your body, but that’s because you’re not supposed to. Since this was a brain scan, however, it meant that I would also have to wear a tight, full face helmet on top of my eye mask.
I also learned that MRI machines are very, very loud. They sound like a huge laser firing dozens of times per second. It sounds absolutely terrible and I grew concerned about how it would affect the trip. To make the noise a little less awful, I was provided with a pair of MRI-safe headphones that would play loud new age music during my trip to partially drown out the sound of the machine.
During my first dose of salvia in the machine I didn’t feel anything at all. This meant that it may have been a placebo, a very low dose of salvinorin A, or that I had made some error during inhalation. (If you swallow during the 45-second inhalation, for example, it can result in air being pushed back in the tube and the salvinorin A won’t be delivered.)
During the second dose, however, the effects once again began almost as soon as I had finished my 45 second inhale. After feeling my body dissolve from my chest outward, I began to see two pinwheels form in front of my eyes. These pinwheels began moving away from me and morphing together into a rotating tunnel. I remember feeling an intense desire to go into the tunnel and a sense of frustration at being unable to move toward it. After I accepted that I wouldn’t be going in the tunnel that day, however, I spent the remainder of my trip watching a harlequin pattern—green and yellow this time—flow across its surface. As the trip wound down, the tunnel began floating over the back of my head. I tried to tilt my head back to keep following it, only to realize that I still couldn’t move. Once the tunnel had disappeared, however, I regained feeling in my body and once again was in base reality. I was glad to find that my chip had not become blistering hot during the experience.
Compared to the day before, the trip in the MRI machine was slightly less intense. The reason, I think, was that the loud and persistent sounds of the MRI machine kept me tethered to the outside world and I was unable to fully immerse myself in the world that the salvia was generating. Still, I would describe it as a pleasant and visually striking experience. Now all that remains to be seen is what Barrett and his colleagues saw in my brain as I was chasing psychedelic tunnels.
After my trip, I met with Doss and Clifton to discuss the experience and do an exit questionnaire. I was told that I would likely be the twelfth and final participant in the study and that over the next few months Doss, Barrett, and their colleagues would begin the arduous task of analyzing brain images. According to Barrett, they will be comparing images of my brain on salvia to images of my sober brain to look for any differences in neural activity between these two states. My brain image will then be compared with the images of the 11 other volunteers to see if any patterns of activity emerge through the comparison.
“This is a basic roadmap,” Barrett said of the study. “We’re shooting a flare out in the desert in the dark to get a general idea of where the road is. Then we can point our car in the direction of the road and start to look for the road signs we need to pay attention to.”
The decision to volunteer for the study was a small contribution toward a better of understanding of one of the world’s strangest hallucinogenic drugs, but it also ended up being one of the most beautiful experiences of my life. After a few weeks of reflection on the experience, it’s made me realize the importance of considering the context when discussing the regulation and use of psychedelic substances.
In 2009, the Maryland government considered a bill that would have outlawed the possession of salvia divinorum. If it had passed, getting the necessary approval to run the study I participated in would be prohibitively difficult and likely would never have happened. In fact, it was only due to the passionate defense of salvia presented by Roland Griffiths and Matthew Johnson, both pioneers of psychedelic research at Johns Hopkins, to the Maryland senate that the plant remains legal in the state.
Like all the other anti-salvia legislation that was passed in the early 2000s, the Maryland bill was a product of reactionary fear over a misunderstood substance. We’ve all seen the YouTube videos, of course, but salvia has much more to offer. Like the other “classic” psychedelics, it may provide a deep insight into the nature of consciousness or prove to be a potent medicine for a variety of psychiatric illnesses. We’ll never know, however, unless we are allowed to take that plunge into the deepest regions of our psyche—if only to see what we might find.