This was commonsense advice. If the DMT brought on intense nausea, it was best to have an empty stomach. However, it wasn’t worth bringing on a coffee-withdrawal headache.
I dated the note in DMT-22’s chart and wrote: “Low dose tolerated without incident. Patient sent home on overnight pass from the hospital. Will return tomorrow a.m. for high dose.”
Alex returned the next morning. We followed the same preliminary routine until it was time for the injection. I looked over at Laura, on the other side of the bed, and noted that there was a vomit basin close enough for her to pick up, just in case. Tossing the used alcohol swabs and their wrappers into the nearby wastebasket, I began, “It comes on just as fast, but it’s a lot stronger. It may startle you. Don’t bother trying to resist, because it’s usually impossible.”
“Okay.” Alex smiled thinly but determinedly.
“What do you normally do when you find yourself overwhelmed in a psychedelic experience?”
“I usually breath deeply and slowly. That’s something I learned from my years of meditation. Or I may touch these,” he said, fingering his necklace of Tibetan prayer beads.
Other volunteers might hold a fetish, a rock or piece of wood. Some might hum, sing, or chant. A few evoked the image of a teacher, friend, or loved one. Those with a deep and sustained meditation practice started meditating before the DMT went in and tried to maintain that mental balance throughout the session.
I said, “Sometimes people think they’ve died, or are dying, or that we’ve overdosed them. So far, no one’s been injured. This is a physically safe dose, although your blood pressure and heart rate will probably take a nice jump. We can respond if there are problems.
“If you think you’ve died, there’s two ways I tell people they can deal with it. One is ‘Man, I’m dying, and I’m going to kick and scream and try and stop it.’ The other is ‘Okay, I’m dying, now let’s see what this is like. Very interesting.’ Easier said than done, of course.”
“I know what you’re talking about.”
“You probably won’t notice the first blood pressure reading at 2 minutes. You’ll most likely be down enough at 5 minutes to feel that one.”
I was done marking my notepad: DMT-22, date, protocol number, dose. Blood pressure and heart rate columns.
When all was said and done, we three—Alex, Laura, and myself—looked at each other. If a plane were flying overhead, we paused, waiting for it to pass. As the time for the injection approached, the air in the room and on the ward took on a certain density. There was little more to say.
Alex put on the eyeshades, and we lowered the head of the bed. I prepared all the syringes and moved my chair closer. Laura warmed up her hands, getting ready to hold Alex’s if he needed a loving touch.
“Are you ready?” I asked.
“Yes.” Barely audible.
Laura said, “Good luck. We’ll be here waiting.”
I watched the second hand of my watch as it approached the 9. I said, “I’ll start in about 5 to10 seconds.”
Then, as the second hand hit the 12, I told him quietly, “I’m beginning the injection now. . . .”
Ten, 20, 30 seconds, slowly emptying the drug into Alex’s vein. My feelings at this point were always intense and contradictory: jealousy of his impending fantastic experience, sadness for any pain he might undergo, doubt mixed with certainty regarding the wisdom of what I was doing.
“The DMT’s in.”
Time was speeding up and slowing down at the same time. My movements felt quick, but also leaden. Was Alex going to be all right? Could he manage his trip? I felt my heart beating in my chest. Could we manage his trip?
There was no turning back.
“Here’s the flush. . . .”
Before I could finish my sentence, Alex murmured,
Here it comes. . . .
He took in an enormous breath, then sighed it out loudly, just as I finished saying, “The flush is done.”
I knew he probably had not heard the end of my sentence. Nor would he likely remember his loud exhalation.
Leaning back into my chair, I sighed, too, although silently, looking over at my nurse colleague, then gazing down at Alex, his body motionless. One minute. Ninety seconds. It was almost time for the first blood pressure check. He would be peaking and wouldn’t feel the iron grip of the cuff.
His words echoed in my head and my heart.
Here it comes. . . .
8
Getting DMT
Twelve subjects participated in the original dose-response study, which took most of 1991 to perform. They each received non-blind low and high doses of DMT and subsequently got the same doses double-blind. Two intermediate doses and a saline placebo completed this series of injections.
Once we had thoroughly characterized DMT’s effects in the doseresponse study, the first follow-up project investigated whether it was possible to develop tolerance to repeated injections of DMT.
Tolerance occurs when the same dose of a drug produces smaller effects when taken repeatedly. LSD, psilocybin, and mescaline all produce rapid and nearly complete tolerance after three or four daily doses. In other words, an amount that had quite profound psychedelic effects on the first day, given every day, would be barely noticeable on the fourth.
DMT appeared unique in that tolerance was quite difficult to demonstrate, even in animals given full doses every two hours around the clock for twenty-one days in a row. The only published human study couldn’t elicit tolerance when researchers gave full intramuscular doses twice a day for five days.1
“Field” reports among recreational DMT users were inconsistent. Some believed they could smoke DMT all night with no diminishing effects, while others described being able to use it only three or four times in a row before they seemed immune to it. However, an important factor in these field stories is fatigue—it’s difficult to inhale large volumes of DMT vapor time and time again at one sitting. Maybe this “tolerance” was the result of not getting enough DMT into the lungs after the second or third trip.
DMT’s lack of tolerance development also was one of the factors making it a likely naturally occurring schizotoxin. If tolerance to endogenous DMT did develop, psychotic symptoms of schizophrenia, for example, would last only as long as it took for tolerance to build up. Since psychotic symptoms are usually chronic and constant, demonstrating that DMT could not elicit tolerance would be powerful evidence that it could play a role in these disorders.
There were other reasons a tolerance study intrigued me. The brevity of DMT’s action seemed to limit its usefulness as a tool for any inner psychological or spiritual work. All one could do was hold on tight through the rush. By the time volunteers got their bearings, they were already coming down. Repeated entrance into the DMT state might provide better conditions for applying its incredibly profound psychedelic properties.
Another less clearly articulated reason for performing this study right after the dose-response one was that it was a “pure” DMT study. Protocols following up the tolerance project would start investigating mechanisms of action by modifying brain serotonin and other receptors using various drugs in combination with DMT. Something in me knew that these studies, which attempted to replicate animal laboratory experiments in humans, would be difficult. In retrospect, I think that I wanted to delay getting on with those types of projects as long as possible.
I proposed that DMT’s short duration was the reason previous studies failed to demonstrate tolerance. LSD, psilocybin, and mescaline tolerance experiments all used once-daily doses. However, their effects last 6 to 12 hours, while those of DMT were much shorter. This suggested the need to give DMT at much shorter intervals, every 30 to 60 minutes, in order to demonstrate reduced responses over time.
The other option was a continuous intravenous infusion, a “drip” of DMT into volunteers’ veins. However, I liked the idea of people “coming down” after each injection so we could hear what had happened. With a continuous dr
ip, communication would be problematic.
After two months of trial and error, I determined that the best regime was four injections of 0.3 mg/kg DMT given at 30-minute intervals. This dose, while highly psychedelic, was just below our highest, 0.4 mg/kg. One man, Cal, was able to manage four 0.4 mg/kg injections at half-hour intervals. However, his wife, Linda, was completely spent after three doses and refused the fourth and final one during this preliminary work. Remembering the harrowing nature of giving too much DMT to Philip and Nils, I backed off without argument and settled for one notch less. Better safe than sorry.
We enrolled thirteen volunteers in the tolerance study, many of whom had already participated in the dose-response project. New research subjects went through the same screening and received their non-blind low and high doses.
While the tolerance experiment was double-blind and saline-placebo-controlled, the “blind” became apparent within a few seconds of the first injection. It was either a big dose of DMT or saline. And, if it was DMT, there would be three more big trips before the morning was over.
We drew blood samples similar to those for the dose-response project and gave a shortened version of the rating scale that took only about five minutes to fill out. The timing was split-second but worked perfectly. Volunteers began talking at about 10 to 15 minutes, and then filled out the rating scale. We’d have a chance to process their trip and get ready for the next one over the ensuing 5 to 10 minutes. If it were four injections of saltwater, we spent the morning in more casual conversation.
This study showed that there was no tolerance to the psychological effects of repeated DMT injections. The experience was as intensely psychedelic the fourth time as it was the first. Because of this, and as I had hoped, subjects were much more able to process and do something with the repeated high dose than with a single isolated experience. Many of the most moving tales from DMT volunteers in the following chapters derive from this study.2
After demonstrating what DMT did, the biomedical model requires determining how those effects occur. These are mechanism-of-action studies. As our research was pharmacologically based, these follow-up experiments would attempt to establish which brain receptors mediated DMT’s effects.
The first of these was the pindolol project. Pindolol is a drug used in medical practice to lower high blood pressure. It does this by blocking certain adrenaline receptors. Another property of pindolol is that it obstructs one particular type of serotonin receptor in the brain, the serotonin “1A” site. Since DMT attaches firmly to 1A receptors in animal brains, this site might be involved in DMT’s effects. If, for example, blocking the 1A site with pindolol made for a “less emotional” experience relative to DMT alone, we would propose that the 1A site regulated the emotional responses brought on by DMT. As it turned out, pindolol markedly enhanced the psychological and blood pressure effects of DMT.
Eleven volunteers participated in the pindolol study, several of whom were veterans of the dose-response and tolerance ones. This protocol yielded less dramatic examples of inner work than did the tolerance study, although there were remarkably powerful single experiences.
The next serotonin receptor blockade study used cyproheptadine, an antihistamine drug with additional anti-serotonin properties. In this case, cyproheptadine prevents drugs from attaching to the serotonin “2” site, the receptor researchers believe is the most important in controlling how psychedelics work.
This protocol was identical in design to that of the pindolol study in that volunteers received cyproheptadine several hours before DMT. Eight volunteers completed this study. Most were new recruits.
There appeared to be some suppression of effects, so we gave the high dose, 0.4 mg/kg, with and without the serotonin blocker. Because cyproheptadine clearly did not magnify DMT’s effects, we hoped that using this large dose would give us the best chance of establishing a significant level of DMT suppression. However, the sedating properties of the drug were so pronounced that they complicated interpretation of the data. It was difficult to tell how much was specific DMT blockade, and how much was general tranquilization.
At this juncture, it was becoming difficult to bring in first-time research subjects, or to induce experienced ones to return. Who wanted to take a drug that would suppress the effects of DMT? I could draw people in to this study by emphasizing that they would get two unadulterated high doses: one on the first screening day, and the other in combination with placebo-cyproheptadine. However, I heard myself sounding apologetic for this project, a bit like a used-car salesman.
I initiated several other experiments that received university and FDA approval. However, they did not receive enough funding to perform full-scale investigations.
One of these, the naltrexone study, continued with mechanism-of-action experiments designed to determine brain receptors regulating DMT effects. In this case, naltrexone blocks opiate receptors, and for that purpose it is helpful in treating heroin addiction. Animal data showed some interaction between opiates and psychedelics, and naltrexone might help us find out more about that relationship in humans.
We began preliminary work in three volunteers for this project. However, one fellow felt so bad on naltrexone alone that he dropped out after his first session. In the other two men, we saw little effect one way or the other, and so we went no further.
Another pilot project was to assess if the phase of the menstrual cycle in women affected the DMT response. Many women report cyclical variations in their sensitivity to psychedelics. In addition, animal studies clearly indicated that sex hormones influenced responses to psychedelic and other serotonin-active drugs.
We divided the cycle into early, middle, and late in one woman, Willow, who usually had quite deep and insightful DMT experiences. In this sole volunteer, no obvious differences in psychological effects emerged. Since we didn’t have funding to pursue this fascinating line of DMT research, we brought in no more volunteers for it.
We also turned some high technology onto the DMT state. Three men received 0.4 mg/kg DMT doses at the Research Center while we recorded their brain waves using an EEG, or electroencephalogram. We hoped this would show us which brain areas were more or less active during the DMT intoxication.
These were difficult studies, as the EEG machine was extraordinarily bulky and noisy and required constant adjustments. As well, there were eighteen electrodes firmly attached to volunteers’ scalps, glued in place by some of the strongest-smelling contact cement I have ever encountered. While all three subjects had “full” responses to DMT, the setting was terribly unpleasant. I recruited no more volunteers than these three, wanting first to be sure the data were so impressive as to justify the discomfort. The results were not especially striking, and we ran no more EEG experiments.
Finally, I took advantage of some state-of-the-art brain-imaging research taking place at the University of New Mexico. This was “functional magnetic resonance imaging,” a modified MRI head scan that measures brain metabolism, rather than just its structure. For example, we might be able to show that the brain areas involved in vision were using more sugar after a visual DMT experience.
To an even greater extent than the EEG equipment, the MRI equipment absolutely dominated the setting. This scanner, support equipment, and staff required their own building on the other side of campus. These were the only DMT studies ever performed outside the Research Center.
The MRI machine generates intensely high energy magnetic fields, and there can be no metal anywhere in the room, or in the person’s body. Otherwise, that metal gets instantly and irresistibly pulled into the machine. To accommodate the scanner, the room is cavernous, and it is kept quite cool because this reduces the power necessary to maintain the magnetic fields.
The space into which we slid volunteers for their scans was a very narrow shiny metallic tube. I knew many people suffered their first panic attack during an MRI scan because of the cramped quarters into which one has to fit for the procedure. I now saw why.
Worst of all was the noise. The machine contains a massive coil that swings back and forth, much like a washing machine, only ten times as fast and hundreds of times as loud. The “BANG-BANG-BANG-BANGBANG- BANG-BANG” of the coil reminded me of a jackhammer. Anyone in the scanner, or the room, had to wear earplugs. Even so, the tumult set one’s teeth on edge.
Nevertheless, some of our research subjects were unbelievably robust. They liked DMT, they wanted to help with the experiments, and they were interested in knowing what the scans would show. I was alone with them in the MRI room while four or five other researchers sat on the opposite side of a thick “soundproof” window, in front of the instrument panels, adjusting dials, flipping switches, and keeping in contact through the intercom system. The scan began; I injected the DMT and stayed in the room throughout the session, checking blood pressure and providing moral support. During the trip, my colleagues took scans every few minutes.
For all of the effort, stress, and expectations, these data, too, were not especially revealing. The MRI team believed that major and expensive modifications to the scanner might have helped in increasing its ability to reveal DMT-induced brain changes. However, I didn’t like the machine, and I didn’t want to expose any more volunteers, or myself, to its deafening sound, claustrophobic quarters, and powerful magnetic fields.
While it may sound as if I had lost all modesty, or common sense, regarding what sort of studies I enrolled volunteers in, I did draw the line at radioactivity. Positron emission tomography (PET) scans provide very nice color photographic images of brain activity using what I thought were negligible amounts of radioactivity. I located some colleagues who were interested in a DMT PET scan study. PET scans would most certainly provide a more refined analysis of where DMT was acting in the brain. However, after learning about the amount of radiation involved, I decided against it.
DMT: The Spirit Molecule: A Doctor's Revolutionary Research into the Biology of Near-Death and Mystical Experiences Page 15