The study of psychoactive substances has faced a fundamental paradox since its inception: while physiological effects can be quantified with precise instruments, the user’s internal experience remains in a territory difficult to access with ordinary language. Evaluating what a person actually feels under the influence of a chemical compound is one of the most complex challenges in modern pharmacology. This article explores the scientific strategies designed to translate the subjective into objective data, allowing for a better understanding of how these substances interact with our biology and perception.
In brief
- Difficulty of verbalization: Psychedelic experiences often escape everyday language, requiring specialized tools for their measurement.
- VAS and Self-reporting: Visual Analog Scales and structured questionnaires are used to capture temporal changes in perception.
- Objective differentiation: Techniques like EEG allow for the distinction of hallucinogen effects from classic stimulants at the neuronal level.
- Ayahuasca vs. Amphetamines case: Clinical studies reveal unique brain activation patterns for each type of substance, debunking simplifications.
- Methodological rigor: Research with healthy volunteers under controlled conditions is essential to validate safety and real effects.
The challenge of the qualitative in pharmacology
In the field of clinical research, highly sophisticated methods exist to determine what a drug does to the body (pharmacodynamics) and how the body processes and eliminates the drug (pharmacokinetics). However, measuring the direct psychological experience is significantly more problematic. This obstacle is notably aggravated with substances of a psychedelic or entactogenic profile, whose effects are inherently resistant to conventional verbal description.
To address this limitation, psychopharmacology has developed three main strategies: the use of visual analog scales (VAS), self-report instruments, and the evaluation of reactions to emotional stimuli. This analysis focuses on the first two approaches, which are fundamental to understanding how we quantify what we normally consider a purely internal experience.
Objective measurements: beyond visible behavior
Before delving into subjectivity, it is crucial to understand what we can measure with precision. Drugs produce predictable physiological effects within their pharmacological categories. Psychostimulants, for example, tend to raise blood pressure and heart rate, dilate pupils, and reduce the sensation of fatigue. For these variables, we have advanced analytical instruments capable of measuring hormones, immune cells, or cardiovascular parameters with millimeter accuracy.
Furthermore, we can determine what the body does to the drug: its metabolism, excretion time, and degradation. There are also techniques to evaluate complex psychophysiological effects. The electroencephalogram (EEG) allows for the recording of brain electrical activity, while evoked potentials measure specific neuronal responses to stimuli. Modern neuroimaging techniques add an additional layer by allowing us to visualize which brain areas are activated and which receptors the drug acts upon.
These objective measurements not only characterize concrete effects but also help frame substances within precise pharmacological categories. An illustrative example comes from studies conducted with ayahuasca at research centers such as the Hospital de Sant Pau in Barcelona. In these trials, it was observed that the administration of this compound to healthy and experienced volunteers produced certain physiological effects similar to psychostimulants: activation, a slight increase in blood pressure, and pupil dilation.
From a purely scientific perspective, this might seem like a modest finding. However, from the point of view of the user conscious of these substances, it is evident that the subjective experience of hallucinogens differs radically from that of stimulants. Herein lies the necessity of science: to objectively characterize the effects so they are understandable even by those who have no intention of consuming them, based on hard, reproducible data.
The comparative study: Ayahuasca versus amphetamines
To resolve the discrepancy between the physiological and the subjective, researchers designed double-blind, placebo-controlled studies. In one of them, ayahuasca, d-amphetamine (a classic stimulant), and a placebo were randomly administered to healthy volunteers in separate sessions.
EEG analysis revealed a crucial difference: ayahuasca induced a specific effect on beta waves, which are associated with states of alertness and activation. Surprisingly, amphetamine did not differ significantly from the placebo in this specific variable. This led to the conclusion that there is a type of nervous system activation unique to hallucinogens, distinct from that produced by classic stimulants.
Although this finding may seem subtle from a strictly pharmacological perspective, it represents a significant advance in the understanding of how these compounds act on the brain. It allows for the distinction of mechanisms that are often confused in non-specialized discussions, avoiding esoteric speculation and relying on empirical evidence.
Translating the subjective: Visual Analog Scales
The real challenge arises when we ask ourselves how to measure what a person experiences internally. When a hallucinogen is taken, everyday language may lose its usual meaning or become insufficient to describe the perceived reality. Nevertheless, language remains our only tool for communication with the environment and researchers.
Therefore, in clinical research, two temporal strategies are used: asking volunteers about their effects while they are under the influence (requiring very simple questions) or conducting structured questionnaires once the experience has subsided. For the first strategy, Visual Analog Scales (VAS) have been developed.
VAS consist of lists of adjectives accompanied by a 100-millimeter graduated line. At one end is “not at all” and at the other “extremely.” Subjects must mark their current position regarding each adjective at different time points. This methodology allows for mapping the temporal curve of the effects, observing how they evolve from onset to resolution.
Detailed study with MDMA and amphetamines
A paradigmatic example of the application of these techniques comes from the Hospital del Mar Medical Research Institute (IMIM) in Barcelona. For more than a decade, this center has investigated the pharmacology of substances like MDMA under controlled conditions.
In a pioneering study, healthy volunteers were administered doses of 75 mg and 125 mg of MDMA, as well as 40 mg of amphetamine and a placebo. Each session was separated by one week to avoid cumulative effects or immediate tolerance, and the sequence was randomized.
For this study, a rigorous list of 28 adjectives was selected that covered various dimensions of the experience: general activation, changes in sensory perceptions (colors, lights, shapes), auditory alterations, bodily sensations, and emotional states. Measurements were taken at precise intervals: 15, 30, 45, 60, and 90 minutes post-administration, and subsequently every two hours up to 24 hours.
The results offered a clear view of subjective pharmacodynamics. The subjective effects of MDMA reached their maximum intensity between 90 minutes and 2 hours, returning to baseline around 4 hours. The highest dose (125 mg) was clearly differentiated from the placebo in terms of the sensation of being “high” and was better tolerated than the lower dose or the amphetamine.
It is interesting to observe how amphetamine, despite being a potent stimulant, did not generate the visual or auditory perceptual changes typical of hallucinogenic substances. Only the high dose of MDMA induced “changes in shadows” or lights and some confusion compared to the placebo and amphetamine. No treatment produced significant alterations in the perception of the environment as unreal, which confirms that, when administered acutely in a laboratory, these drugs do not possess dangerous psychotomimetic potential.
Critical reading and harm reduction
It is fundamental to distinguish between regulated clinical use in controlled environments and self-medication or recreational use without supervision. The studies described are conducted with healthy volunteers, under strict ethical protocols and specific doses that should not be extrapolated to high-risk contexts.
Scientific understanding of these effects is vital for harm reduction. Knowing that certain compounds produce specific activation in distinct brain bands (such as beta waves) helps predict adverse reactions or dangerous interactions with other substances. Likewise, knowing the duration and maximum intensity of the effects allows for the planning of safe situations.
Science does not seek to deny the subjective experience, but to provide it with an understandable framework for those who wish to be informed without needing to experiment directly. This is especially relevant in a culture where scientific concepts are often mixed with myths or unrealistic expectations about drugs.
Editorial closing
Psychonautics, understood as the conscious navigation through the sea of consciousness and pharmacology, requires precise tools to avoid getting lost in speculation. Measuring the subjective is an act of intellectual humility: recognizing that our internal experience is valid but difficult to communicate, and seeking scientific bridges to understand it.
Modest advances such as a differential response in a specific EEG band or the distinction between “stimulated” and “high” are the foundations upon which deeper knowledge is built. These data allow for the separation of evidence from hypothesis, and clinical use from dangerous fantasies.
Future installments will explore additional methods, such as detailed self-report questionnaires and responses to emotional stimuli. The ultimate goal is to foster an informed, prudent, and respectful relationship with these substances, always prioritizing the mental health and well-being of the individual.
