What are the relevant dimensions of drug effects?

“Does it make you stupid? Does it make you hallucinate? Gosh, I don’t know what else to ask!”

– Moms everywhere, worrying about the latest Research Chemicals

It is hard to keep up with all of the new research chemicals (RCs). When a substance comes onto the scene, it is hard to predict whether first adopters will experience fascinating, terrifying or just plain weird effects from the drug. Largely, one thing is certain: Most psychonauts agree that describing subjective effects is brutally difficult. Without a principled framework for pinning down the nature of a drug experience, we will continue to misunderstand and misjudge the states of consciousness disclosed by brains on RCs.

What should we know about the subjective effects of a drug? In what way are drugs different? And in what way do they produce similar effects? This post will present a general conceptual framework for discussing drug effects in a principled fashion. This will be done by analyzing the responses of a recent survey on drug effects. The major axes of variance are obtained using factor analysis, and the dimensions are interpreted and discussed.

The Survey

About a month ago I asked people to fill out an anonymous survey about the subjective effects of psychoactive substances. The survey was advertised in many Facebook groups (Hedonistic Imperative, Stanford Transhumanist Association, etc.), subreddits (r/LSD, r/drugs, r/opiates, etc.), online forums and via email.

The survey asked participants to either choose a substance from a list of 36 (with options including LSD, Salvia, Piracetam and even Tobacco), or to specify a drug by writing it down in the “other” section. After asking basic questions such as age and number of times the drug has been used, the survey presents 52 5-points Likert items: Participants had to rate on a scale from -2 to +2 how much a given word or brief phrase describes their experience with the drug. Examples of such words or phrases are: “subtle”, “irritating”, “intense”, etc.

An example review: Imagine that you are answering the survey and chose to review the effects of MDMA. The first Likert item has the word “energetic.” You remember that your MDMA experiences have been uplifting but not really full of energy, so to speak; you give it a 1. The second item has the phrase “anxiety producing” and right away you recall that MDMA has made you feel more at ease with yourself, rather than placing you in weird or anxious situations. Hence you give it a -2, meaning that MDMA is the opposite of “anxiety producing”. And so on.

The survey was filled out a total of 442 times. The top 10 most reviewed substances in the survey are: LSD (74), Marijuana (64), MDMA (45), Psilocybin (39), Alcohol (34), Heroin (20), DMT (17), D-Amphetamine (12), Salvia (10) and Cocaine (10).

The cleaned and anonymized dataset, as well as the analysis presented here, can be found here. Feel free to conduct your own analysis and add to the discussion in any way you want. My analysis here focuses on general features of the responses and on the interpretation of dimensions. There is a lot more that can be said about this data. If not me, I hope someone takes advantage of it sometime in the future.

6 Dimensions of Experience

Given that the total number of different drugs reviewed by survey participants (46) is smaller than the number of items (53), I decided to use each submission as an observation. I performed a varimax factor analysis on the 442 observation rows X 52 subjective properties columns.

The cumulative variance explained for one, two, etc. number of factors looks like this: 25%, 37%, 42%,  45%, 49%, 52%, 53%, 54%… The jump between 5 and 6 factors adds 3% of variance explained, and from 6 to 7 this percentage increases only by 1%. Adding extra factors after the 7th barely increases the variance explained.

I inspected the factor loadings for each dimension, and it does seem that using six factors results in semantically meaningful dimensions. Using less than 6 results in factors that have semantically mixed elements (for example, a factor that includes both cognitive impairment and arousal). Six seems to be the sweet spot. Let’s see what the factor loadings are:

Trivia: Which words have both a large loading on significance and slow euphoria?

Answer: “Love” and “Blissful”! :*

Where do the drugs live?

The six dimensions outlined above define a rudimentary (but informative) state-space of subjective drug effects. In this state-space, we can estimate the centroid region where responses about a given drug tend to fall. Below I plot the estimated location of such means. The color scheme represents the number of survey responses for each compound. For that reason you should calibrate your trust in the shown location as a function of how far up the rainbow the color of the substance is.

Three Varieties of Euphoria

Three out of the six dimensions directly involve our general sense of wellbeing. Our sense of wellbeing seems to have three components here, rather than being a single homogenous feeling. Think of this as three faces of a cube that share a corner. Let’s call this the Euphoria Cube:

Navigating through this map can be fun. As you can realize, MDMA/MDA are rock-solid-wonderful in all three euphorias. Perhaps that’s why people have such a strong trust in its effects – it has a little of everything that is good (experience-wise). Acid is wonderful, yes, but it has unreliable slow euphoria… could we improve an acid experience with phenibut? These kinds of questions pop up when you examine the state-space.

You may see now why Salvia gets such a bad rap. It is clearly mystical and spiritual in its own way. But it has no hint of either slow or fast euphoria. Salvia is a very tricky compound to handle, but may still be very worthwhile. Since spiritual bliss tends to be so much deeper and long-lived than the other two kinds of bliss, salvia can still be of significant therapeutic value.

Within the class of psychedelic compounds themselves we also see differences. For example, 2C compounds seem to generally have more fast euphoria than other psychedelics. Perhaps a better choice than shrooms for a melancholic depressive?

I suspect that there are several other ‘natural kinds’ of euphoria. (Well, natural kind sounds ontologically very strong – I’m only using this as an intuition pump). And there seems to be a definite and finite set of euphoria flavors I’m aware of. If I am pressured to guess what a good taxonomical account of euphorias would look like, I would use the following one:

The bliss of safety

The bliss of intimacy

The bliss of social coordination

The bliss of loving-kindness

The bliss of understanding

The bliss of wonder and intuition

The bliss of enlightenment

But this would sound awfully cultish. Moving right along.

The existence of three euphorias is foreshadowed by the rough legal and educational classification of ‘street’ drugs into one of three categories: Stimulants, depressants and hallucinogens. Drug education, unfortunately, fails to convey the message that hallucinogens not only affect your senses, but induce spiritual euphoria.

The location of substances in the Euphoria Cube also has a straightforward relationship with the receptor types implicated in the mechanism of action of these drugs. Slow euphoria comes with modulation of GABA and Opioid receptors (with Oxytocin also being a likely player). Fast euphoria is related to dopamine, and to a lesser extent to: norepinephrine, glutamate and the cholinergic system. The axis of significance, or spiritual euphoria (to give it a name), implicates both specific serotonin receptors (such as 5HT2A) as well as, strangely, the kapa opioid receptor.

In a limited sense, this is also a ballpark replication of the Lövheim cube of emotion. It is exciting to think that surveys like this can readily provide actual quantitative estimations of these experiential qualities. And this may be helpful for researchers and users alike.

What about the other three dimensions?

Is it worth it? Does it impair you? Will I enjoy food?

What the euphoria cube tells you is how a drug can be used for fun, spiritual growth and solace. What that cube does not tell you is whether, all things considered, taking the drug is a good idea to begin with. Perhaps a particular compound gives you a reliable buzz and a little relaxation, but don’t forget to ask whether it also make you dumb and confused! These three dimensions provide a context for the euphoria values.

We can see that nootropics seem to have their main action on the dimension of clarity. What is clarity? A good guess might be that clarity refers to the signal-to-noise ratio that a mind experiences at the time of doing mental operations. The sort of mental activity that you perform does not tell you how noisy the mind is while attempting to do it. Some drugs may somehow diminish your ability to filter and eliminate noise. Others, may enhance those processes. Stimulants for the most part activate the inhibitory control involved in thinking about implications of premises. Thus clarity is experienced: Strong and robust symbolic manipulation of implicit ontologies and concepts. This, although generally good, may incidentally make the mind be locked in a state with fixed ontologies and background assumptions. Thus, the mind can get in conceptual prisons by getting lost in the implication of ontologies. Taking a strong cholinergic nootropic in the morning may result in a whole day of a mind fixated on a given problem. Thus too much clarity can be a problem, too.

What about the dimension of cost benefit? An unfortunate red flag is that tobacco does not seem to have a particularly low value in the cost-benefit dimension. The way I interpret this is that participants understood items such as “dangerous” and “worth-it” to refer to the immediate window time around of a drug’s acute effects (which includes hang-over and after-effects, but does not include long-term negative health effects). This interpretation would explain as well why MDA and MDMA are ranked very highly for cost-benefit, given the (controversial) neurotoxic effect associated with more than casual use.

Stimulus seeking is a weird dimension. It seems to be largely dominated by marijuana-specific effects, which somehow contrast with the anorexia induced by stimulants in general. An interesting way of interpreting this factor is in terms of the source of one’s bliss. Drugs with a high stimulus seeking value make us appreciate external influences such as music and food. Drugs with low stimulus seeking create a sort of euphoria that makes people temporarily self-sufficient. Outwardly focused interests versus inwardly focused interests is a neat, though somewhat speculative, interpretation of this factor. Any other ideas?

Why physicists are not into consciousness and monks are not into spaceships

A particularly interesting cross-section of the data is the interaction between Spiritual euphoria and Clarity. Why? Because, on the one hand, Spiritual euphoria, in a way, comes when one gains a certain sort of awareness and imaginative capability that enables the conception of entirely new ontologies. Hence, one’s models of personhood, morality, wellbeing and even logic can break down and be reconstructed during a psychedelic experience. On the other hand, conceptual clarity of the sort shown here happens when pre-existing ontologies are navigated and used efficiently, effortlessly and robustly. Hence, it is not hard to see why states of consciousness in which both conceptual clarity and conceptual revolutions are happening are very uncommon. More so, no known drug induces states of consciousness with those two qualities at the same time. This is made evident by the empty upper right quadrant of this space:

Will we ever discover a substance high on Spiritual euphoria and Clarity at the same time? Perhaps if we use a Generalized Wada Test: Just inject amphetamines in one hemisphere and DMT on the other More seriously, this may be a fundamental limitation of the mind: It can’t both see the problem with its current ontologies at the same time as using them to think by believing their implications. Maybe we just need bigger brains.

That said, the flip-side of the question is just as valid: Is there any substance that makes you dumb, both spiritually and cognitively at the same time? Wait, looks like we are lucky this time! The answer is Alcohol! Probably, though, a finer analysis may find that small amounts of alcohol have mild mind-expanding effects – unfortunately the sweet spot that accomplishes this, it seems to me, is very delicate.

The orthogonality of these two functions of the mind (thinking rationally and efficiently; having spiritual or philosophical insights) may explain why it is hard to find people who are passionate about (and good at) math at the same time as passionate (and good at) exploring different states of consciousness. This may give us hints of an explanation for why it has taken this long to develop computational models of psychedelic experiences! A drug that enhances both facets of consciousness at the same time, though, would be truly revolutionary (and part of me thinks micro-dosed LSD may already be doing this).

The full dimensional table

Here I present the full table of mean factor loadings for each substance. Use this wisely. Perhaps future introductory psychonautic programs will study state-space maps and tables like the one below, and develop navigation strategies. For example, the map can be used to infer that DMT induces extremely profound experiences, but that at the same time it lacks direct slow or fast euphoric effects. LSD, as the map shows, is more stimulating than shrooms, so it may be better suited than psilocybin for certain tasks (say, for micro-doses or productive creativity enhancement). And so on. One can even imagine a psychiatrist and patient in 2025 looking at these maps while choosing a psychedelic that satisfies the patient’s therapeutic needs. A small personal difference in proclivity to panic attacks could make one choose MDA over, say, 2C-E.

Discussion

The current survey and methodology has the potential to ground a lot of high level discussion about drug effects. Similar methodologies and datasets could be used to infer many other properties that are hard to talk about anecdotally. The dimensions surfaced may be helpful for harm reduction (allowing people to minimize risks while maximizing possible benefits) and even transhumanism. Although here I found three axis related to euphoria, otherwise talked about as hedonic tone, I suspect that future iterations of this sort of analysis will reveal a finer map of conscious bliss. Hopefully we will someday soon discover the biomolecular signatures and qualia preconditions for all of the forms of bliss, so that we once and for all find a method to abolish experiences not worth having.

I predict that follow-up research will find many verifiable and useful dimensions that describe the “core” differences between states of consciousness. The words and phrases used in this survey are limited in scope, so they do not help us differentiate properly the singular characteristics of specific psychedelic compounds. Hypothetically, there could be a reliable cluster of unique phenomenologies produced by certain class of phenethylamines. This difference may not affect the response given to any of the survey items, and thus remain undiscovered.

For example, perhaps 2C-T-X compounds produce visual hallucinations that involve more diagonal drifting than what is common for all other 2C-X compounds. Given the broad focus of the current survey, we can predict it will not detect any difference of this subtle sort, unfortunately. Nevertheless, this is the first step: We currently work on the low hanging fruit that makes very different drugs different, so that we can later go on to measure the more subtle differences between similar drugs.

I am currently refining the survey so that finer phenomenological differences can be discovered. I am also incorporating some of the work on authenticity by Matthew Baggott and other scales for altered states of consciousness. Feel free to email me if you have any suggestions or would be interested in collaborating on this research project.

Thank you for reading!

---

Transparency about errors:

There were a few mistakes in the execution of the survey. First, I wrote “Heroine” when I should have written “Heroin”. Second, the word “constructive” is found twice on the survey (the correlation between participant’s answers to both “constructive” items is .86, showing a high consistency of responses). And third, during the first 30 submissions of the survey the “Other” option did not work properly. This was corrected immediately and the participants who submitted after that had no problem sending reviews about “Other” drugs.