We were interested in developing a new rating scale to more accurately assess the subjective effects induced by DMT, a powerful, short-acting hallucinogen. To this purpose, 19 experienced DMT smokers were interviewed, mostly by telephone, to provide a relatively detailed description of the physical, perceptual, emotional, and cognitive effects of smoked DMT free base. If there was any overriding framework within which these initial interviews were conducted, it was from a descriptive, phenomenological and non-judgmental perspective. Additionally, the items I began with involved what might be called the "mental status" approach, learned by all third year medical students during their psychiatry rotations. This approach takes a systematic view of mental phenomena and breaks mental experience down into several categories: perceptual, emotional, cognitive, interoceptive/somatic (that is physical sensations), and volition. Interviews ranged from 1-2 hours and were at first loosely structured; they became more focused toward the later stages of this process.
A draft of a new scale, the Hallucinogenic Rating Scale (HRS), was developed and administered in approximately 25 non-blind low (0.05 mg/kg) and high (0.4 mg/kg) dose DMT sessions. The HRS was modified based on the experiences reported during these sessions, and upon suggestions of the subjects. The final questionnaire contained 126 questions, many of which were repeated in a "Stage" format, so that subjects were requested to answer 238 questions. There was a "Beginning" stage, the first 30-60 seconds, corresponding to drug onset; a "Middle" stage, the period from 1-5 minutes post-injection, when effects peaked or plateaued; and an "Ending" stage, corresponding to the 5-15 minute post-injection "resolution" phase. A final stage, "Wrap-up," allowed a global assessment of certain general features of the session, such as degree of liking, desire to repeat the experience, how high subjects were relative to other hallucinogenic experiences, and to guess at what dose they received that day.
Questions were all posed retrospectively; i.e., subjects were asked to recall their experiences from the immediately preceding session. The brief duration of the drug effect and incapacitating nature of the higher doses precluded subjects answering the questionnaire during the acute intoxication. The first time filling out the HRS took about 35-40 minutes. Once subjects became familiar with it, 20 minutes or less were required. Nearly all questions were coded 0-4: 0 = "Not at all;" 1 = "Slightly;" 2 = "Moderately;" 3 = "Quite a bit;" 4 = "Extremely." Some questions were coded 0-2. For example, "Were you unconscious during any part of the session?" was coded 0 = "Definitely no;" 1 = "Not sure;" and 2 = "Definitely yes." Finally, several questions were scored in a "bipolar" fashion; i.e., -2 to +2. For example, "Was there an effect on your sense of bodily weight?" was coded in the following manner: -2 = "Much lighter;" -1 = "Somewhat lighter;" 0 = "No effect;" 1 = "Somewhat heavier;" and 2 = "Much heavier."
A tremendous amount of "number crunching" has gone into analyzing the data from this questionnaire. The data base we are using consists of responses from 11 subjects given drug or placebo 5 times each; this results in over 13,000 responses. Most of the statistical analyses have been performed on PC's; however, our final approach to some of the problems will require a mini-computer recently installed in the Clinical Research Center's computer room.
The immediate concern that comes to mind is, "How can 238 questions be turned into a manageable number of factors?" One cannot publish results of analyzing 238 questions 55 times. The process by which "shrinking down" a lengthy questionnaire occurs is called "factor analysis." Two methods of factor analysis were preformed to create a more manageable number of "clusters" of questions. The first method for developing factors was the "empirical" method. Based upon our initial interview with DMT smokers, and the narrative accounts of our subjects of their experiences, we arrived at six factors that appeared to "hang together" conceptually. They also were appealing from a descriptive, phenomenological, "mental status" perspective. These factors were:
The second method of developing clusters was based on purely statistical issues, allowing the computer to choose which questions belonged in which categories. We told the computer to generate six factors, the number we chose in our "empirical" approach. Our computer program, SAS (from Cary, NC), provides a procedure called Principal Factor analysis, which creates relevant factors, using what is called a "Varimax rotation," which allows the responses of questions to "rotate in space" in such a way as to maximize the relationships among all questions.
We then analyzed the ability of each of these sets of factors to discriminate among doses of DMT and placebo. As you may recall, we gave 0.05, 0.1, 0.2 and 0.4 mg/kg intravenous DMT fumarate, or saline placebo, in a double-blinded manner to our subjects. That is, neither I nor the subject knew what substance he/she was getting any particular session, and there was no set order in which any of the substances were given.
We found that either of these methods of clustering questions provided greater ability to separate doses of DMT than any of the biological effects of DMT (blood pressure, heart rate, pupil diameter, body temperature, §-endorphin, adrenal stimulating hormone, prolactin, growth hormone, cortisol or pineal melatonin). Surprisingly, but gratifyingly, we found that the "empirical" factors provided a greater ability to distinguish among doses of DMT, particularly between the lowest dose (0.05 mg/kg) and saline placebo than the computer-derived factors. This is of note because many subjects mistook the 0.05 mg/kg dose with placebo; and the questionnaire provided data that could statistically separate responses from the 0.05 mg/kg dose and placebo based on the total number of responses. Furthermore, the empirical "Intensity" factor is the only one among all 12 factors (six "empirical" and six "computer-derived") which provides a clear separation among all 5 doses. Thus, we retained our empirical factors in lieu of the computer derived factors.
It may be of interest to briefly describe each dose effect, realizing that subjects differed widely in their experiences at any particular dose.
0.4 mg/kg: Subjects were almost uniformly overwhelmed at the intensity and speed of onset of this dose, given for the first time, non-blind.
All described an intense, rapidly developed, and generally transient anxiety-provoking "rush" throughout their body and "mind." This was described as a "freight train" by several subjects. It immediately and totally disrupted normal mental function, replacing it with the hallucinogenic effects of DMT. Most subjects lost awareness of their bodies at this point, and many were not cognizant of being in the hospital, or participating in an experiment, so completely compelling, arresting and overwhelming were the initial two minutes of the experience. Interestingly, the three subjects with experience smoking DMT free base all described the effects of the IV drug as more overwhelming and rapid in onset than the smoked form.
Visual effects, at the peak, included concrete, formed, more or less recognizable visual images with eyes open or closed. Examples of these types of images are: "a fantastic bird," "a tree of life and knowledge," "a ballroom with crystal chandeliers," human and "alien" figures (such as "a little round monstrous creature with one big eye and one small eye, on nearly invisible feet"), stairways, etc. At the other end of the visual effects spectrum, some subjects described kaleidoscopic geometric patterns that were not obviously representational. In between these two poles were discrete visual images of novel phenomena. For example, some subjects saw "the inside of a computer's board," "tubes," "ducts," "DNA double helices," "a pulsating diaphragm," " a spinning golden disc off to my left," " a huge fly eye bouncing in front of my face," etc. Subjects generally described the colors as brighter, more intense and more deeply saturated than any colors they had ever seen in normal consciousness, and some found the visual images more intensely constituted than those seen on other hallucinogenic drugs. Subjects' visual phenomena were qualitatively quite similar for the two 0.4 mg/kg doses ( non-blind and double-blind). As the effects resolved, subjects would open eyes and note that the visual field was overlaid by geometric patterns, with undulating movement and intensification of colors of external objects.
Auditory effects were consistent from one high dose to the other, if they were noted at all. Auditory hallucinations were not formed (e.g., music or voices) but were usually high pitched, "whining," "chattering," "crinkling/crunching," or at times comical, such as the "boing, sproing" sounds heard in cartoons.
Somaesthetic effects were generally of a highly stimulating "fear response" nature, although all subjects recognized a curious distinction between their physical reaction to the drug and the less emotional subjective response to this reaction. Phrases such as "my body was afraid but I wasn't" were relatively common. As effects resolved, the physical sensations became quite pleasant and relaxing. However, one subject, the least experienced of the group, began to uncontrollably shiver during the resolution phase of his non-blind high dose. This responded to verbal reassurance and brief massage of his chest and abdomen. Some subjects described a sexual effect of the highest dose; a hot and pleasurable sensation developing in their genital area. No subjects experienced orgasm or ejaculated.
Emotionally, most subjects were initially anxious as the "rush" developed. However, they quickly settled into the experience within 15-30 seconds post-injection. The majority of subjects described the high dose as exciting and uplifting, euphoric and highly positively charged. These qualities were often associated with the visual hallucinatory display. However, most paradoxically also described the emotional "valence" as "bland," "unemotional," and "journalistic" in nature. That is, the experience developed and resolved so quickly that there did not seem to be time for subjects to react to it one way or the other; subjects just "held on" and dispassionately watched the experience unfold. For some, however, the rapidity of the experience was not the primary reason for a lack of emotional response: one subject "tried to get myself worked up over what I was seeing, but I just wasn't able to respond emotionally." Some, however, found the experience emotionally quite unsettling. For example, a non-practicing Catholic found himself "face to face with God," and "saw how insignificant and stupid mankind is, and how non-moral and basically uninterested God is." He was "blown away; my foundation for religion has been destroyed." He subsequently began an interest in and practice of another, non-Western religion, that "fit my needs more realistically."
Cognitively, most subjects found the high doses to not necessarily be "novel" or "insightful." Only a few emerged from the intoxication with new perspectives on their personal and/or professional lives (as in the subject described in the preceding paragraph). Neither was there much distortion of normal thinking processes. Subjects almost uniformly remarked at how unchanged their thinking processes were. Some subjects compared this phenomenon to that of a dream; in which their total involvement and belief in the certainty of what was unfolding coincided with an unimpaired ability to observe.
Nearly every subject found the high dose to cause an almost total loss of control. They felt extremely regressed, more or less completely helpless and unable to function either physically or psychologically in a normal manner. They did not seem able to affect the hallucinatory phenomena in any way during the earliest stages.
The first non-blind high dose was usually more anxiety ridden (particularly for the first 30 seconds post-injection) than the subsequent high dose. That is, subjects were prepared to "lose control" and be swept away after having been in that state once before. Furthermore, their understanding that the drug experience was essentially safe, that they "would live" and not "lose their minds" was strengthened by having had the high dose before. Finally, their confidence in the research team to unobtrusively support their regressed state grew as their participation in the study progressed.
0.2 mg/kg: For most subjects, this was the threshold dose for hallucinogenic effects. The majority of subjects had some visual hallucinations, but auditory ones were rare. Some found this to be their "dose of choice," being less disorienting and frightening than the 0.4 mg/k dose, but generating enough perceptual and affective effects to be interesting, novel and pleasurable. The "rush" was difficult to distinguish, at the onset, from the 0.4 mg/kg dose, but it soon became apparent that the intensity of the experience would be less than the highest dose.
0.1 mg/kg: This dose was generally not enjoyed by many subjects. They felt the somaesthetic sensations of excitation and the "drive to discharge" were more striking than the perceptual or affective changes induced. Thus, they were physically expecting an hallucinogenic effect, but were left only with uncomfortable physical tension. One subject remarked, "You'll never sell this dose. It has all of the physical effects without any of the mental ones."
0.05 mg/kg: Several subjects mistook this dose for placebo. Those who were able to distinguish this from saline remarked on its uniformly relaxing, comforting and warm physical effects. One former heroin user likened it to the "soft cotton batting" of heroin. There were no perceptual (auditory or visual) effects at this dose.
Subjects were relatively consistent in their style of reacting to all doses of DMT. That is, those who began speaking early did so on all doses; those who preferred a longer period of silence with eyes closed did so on all doses, too. At the high dose, subjects varied widely in their capacity to and interest in beginning to interact with the research team. Some subjects would open eyes and make a brief remark at 2-3 minutes after the injection was complete, commenting that the experience was beginning to fade; others could not speak or open eyes for 10 minutes or more. Many, even if they were able to speak early on, chose to remain silent with eyes closed so as to be able to follow carefully the progression of effects.
In summary, we have developed a rating scale for the effects of DMT that is not based on any particular theoretical framework except one of a descriptive nature; that is, it is based on the effects reported by a group of experienced DMT users who also have a wide range of exposure to other hallucinogenic drugs. The Hallucinogen Rating Scale is more capable of distinguishing among doses of DMT/placebo than any of the biological effects of DMT; furthermore, our "empirical" factoring of the questions into a manageable number of sub-scores is more sensitive to dose effects than the factoring on a purely statistical basis. There are several major areas that we believe this rating scale will now help in the conduct of future hallucinogenic drug studies, both with DMT and with other drugs.
First, studies designed to modify the effects of DMT, either by blocking certain receptor subtypes that might mediate its effects, or by strategies designed to enhance its effects, will have that much greater power to carefully tease apart what effects are actually being modified by the experiments. That is, if one particular subtype of serotonin receptor is blocked, will that change the "Perceptual" effects more or less than the "Volitional" effects? If dietary manipulations enhance the effects of DMT, are its effects enhanced across the board, or only in "Affective" or "Somaesthetic" areas?
Second, a careful comparison of hallucinogenic drug effects in humans can now be accomplished, using this rating scale. Animal experiments often equate phenethylamine hallucinogens such as DOM, DOB, and DOI with tryptamine compounds such as psilocybin, DMT, and 5-methoxy-DMT and with the lysergamide LSD. However, there are clearly subtle differences when humans take these drugs, subtle differences which are not discernible using animal behavioral models. Thus, applying the HRS to a gamut of hallucinogenic drugs in humans will begin the necessary and important process of categorizing compounds in terms of their human effects. For example, is psilocybin more "Perceptual" than LSD? Is LSD more "Affective/Emotional" than DMT? How similar to the "classic" hallucinogens are the effects of MDMA in humans? These questions can be given quantitative answers using the Hallucinogenic Rating Scale.
A third, somewhat peripheral, but potentially important corollary of this work is that regarding potential therapeutic applications. If certain psychological disorders can be determined to show defects or dysfunction in certain areas that are affected by certain hal-lucinogenic compounds, this would strengthen the rationale by which these drugs could be applied to certain psychological disorders.