Thursday, July 13, 2006

A Question of Terminology: How Do We Describe LSD?

When discussing psychoactive substances, terminology can be an occasionally touchy subject. To pull an example out of a hat, although it is useful to describe a class of drugs by their effect--such as the class of 'stimulants'--it lacks utility in other settings. For instance, if we're sitting down and having a conversation about stimulants, it can make a huge difference which chemical class we're talking about: are we talking about alkaloids, such as , , or (my personal favorite) ? Or are we talking about a such as ? Perhaps we wish to limit ourselves to abused stimulants, or to the class of stimulants that act on : but then we still have to distinguish between the amphetamine-like drugs, which releases DA by opening the transporter, and , which simply blocks the transporter and thus inhibits DA reuptake.

Hopefully, you can see how this might make our conversation confusing were we to fail to be quite specific in our statements. However, to the best of my knowledge, there's no ongoing controversy to classification of stimulants (feel free to correct me if I'm wrong). But there is some disagreement over another group, one which seems as though it should be fairly easy to identify.

So, a simple question for the audience: what do , , and all have in common? If you answered that they are chemically similar, you'd be wrong. Psilocybin and LSD are both , whereas peyote is another phenethylamine. The difference between them is clear, hopefully even to the untrained eye:


LSD


Psilocybin


Mescaline

Fortunately, these drugs all have a common pharmacological target which is believed to be responsible for their common effect: they are all agonists of the 5HT2A/C subtype of receptors. This target is common to most drugs with a similar effect. So we have a class of drugs whose primary effects are decently described in both popular and scientific literature--albeit with an absence of precise characterization of long-term and secondary effects--with a common pharmacological target. So when we want to bring them up in polite conversation, how do we refer to them?

One obvious answer would be to call them "serotonergic agonists of the 2A/C receptor subtype," or something similar. This has many drawbacks, just to name a few: I can't expect anyone who isn't a neuroscientist to remember that for more than five minutes. Of course, it could still be usable in the scientific literature: but believe it or not, even scientists generally prefer to have non-clunky, non-confusing terminology to refer to things by when possible. So that's right out, at least for our general purposes.

Now, this debate's been going on for something like fifty years, and we have four main terms that still get tossed around (each of which seems to still be used right now by at least a few people):
  • Psychotomimetic (a word I am very sad to see does not have a wikipedia entry)

  • Hallucinogen (ditto)




A true psychotomimetic drug would be one which causes a state mimicking psychosis or schizophrenia in an individual. This was one of the first terms applied to LSD when it first appeared, as it was thought that LSD was in fact bringing on a psychosis-like state in the subject. For a short time, researchers attempted to use it as a chemical model until it became apparent that something entirely different was going on. These days, very few people would argue that this term is useful to describe the class of drugs we're talking about; but certainly there are still some out there

Hallucinogen is, at this point, the most commonly used term. But there is a dissatisfaction with it, which seems--at least, to me--to have been growing over the years. The problem is that it, too, seems to be an inaccurate description of the effect of these drugs based on a poor understanding of the effects. Despite the archetype of acidheads tripping out and staring at the pretty colors or interacting with things that aren't there, only a small percentage of users seems to actually report hallucinations. Although many do report some form of altered perception, it is far from universal and generally limited to distortions of actually present objects--and the user can generally recognize both what the object really is and that their senses are altering it. A hallucination, on the other hand, is ideally something which literally isn't there. As such, many have suggested that the term is better used to refer to tropane alkaloids such as or , which can induce visions that seem to be unrelated to one's actual surroundings. As such, those drugs are often referred to as the "true hallucinogens" to distinguish them from the more common and broader use of the term. Another reason why it might be useful to limit the term is demonstrated by this page on eMedicine, the second site to come up after a google search for "hallucinogen"; here, the category is applied so broadly that it might be more simply referred to as "all non-opiate illegal drugs."

Entheogen is a term that was coined in the late 70s specifically to counter the use of hallucinogen--disliked because of its negative connotations with insanity--and psychedelic (which we'll cover next)--disliked because of its association with 1960s drug culture. It translates roughly as "causing the god within." Honestly? As the term's use is currently advocated, it's awful. If reeks of having been developed as an attempt to improve PR for recreational use of a class of drugs (even if that wasn't the intent). The problem is it's a use-based term: any drug someone wishes to take for religious purposes can be viably deemed an entheogen. The problem, of course, is that there are an endless variety of human religious practices: ultimately, in one context or another any drug could be an entheogen. Attend a UDV ceremony, and consume the classic entheogen ayahuasca. Then go over to your local reservation--and depending on where you are, you may be able to sample the entheogen peyote or the entheogen tobacco. Perhaps you feel like starting a new religion dedicated to the Roman gods Pan & Bacchus? If so, then at your bacchanalia you may wish to promote use of your group's own entheogen, Viagra. I hope you can see the dilemma: the term seems to be quite useful in an anthropological or archaeological context, but has little use when trying to refer to a class of drugs based on their pharmacological properties.

And finally, we have the last entry: psychedelic. Although the term is still much less frequently used in the literature than hallucinogen (for instance, I just did a PubMed search and got a single result for "psychedelic LSD 2006" vs. 56 for "hallucinogen LSD 2006"), I've seen a number of people--both in and out of the scientific arena--advocating for its use. Consider, for instance, the existence of MAPS: the Multidisciplinary Association for Psychedelic Studies. The Heffter Research Institute also refers to the drugs they study as psychedelics. The only problem with the term that critics usually point to is its negative associations with 1960's & 1970's-era drug culture. To my mind, this isn't a very good argument. Psychedelic also has the advantage of being the most useful description of the state evoked by these drugs: "mind-manifesting."

I admit that this debate is in certain respects almost entirely political. Nonetheless, the terms one chooses to use do have a certain power to them, especially the power to guide how the public thinks about them. In that respect, all of these terms have major drawbacks: but nonetheless, research into many of them is starting to pick up some serious momentum. So the scientific community may either be ultimately forced to recover one of these terms in the public eye, or come up with yet another term to describe them--and hope that it's both accurate and that it doesn't immediately become associated with drug culture.

26 Comments:

At 13 July, 2006 13:37, Anonymous Anonymous said...

Surely if you're willing to write that much about it, you're capable of writing the wikipedia entry, yes?

 
At 13 July, 2006 13:42, Anonymous Plant Master Flash said...

it was thought that LSD was in fact bringing on a psychosis-like state in the subject. For a short time, researchers attempted to use it as a chemical model until it became apparent that something entirely different was going on.

If "something completely different" is going on in psychosis as compared to in the use of one of these drugs, why then do they screen out people who have had a psychotic episode, or history of schizophrenia and bipolar disorder when using them in anthropologically medical settings (I say "anthropologically medical" to include indigenous uses)?

I'm obviously nudging in the use of DMT (via ayahuasca) here, which I'm not sure is valid. But I have definitely seen this as the case for recent studies in psilocybin. OCD? Depression? Anxiety disorders? Sure thing, we're even gonna try to treat 'em with psilocybin. Psychotic disorders? Fuggetaboutit.

 
At 13 July, 2006 13:53, Blogger The Neurophile said...

Surely if you're willing to write that much about it, you're capable of writing the wikipedia entry, yes?

For me, there is a large confidence gap between being confident enough to write about something on my blog, confident that I'm getting the gist of things right if not necessarilly portraying the history and context of the arguments entirely accurately; and writing an entry for an encyclopedia that I am willing to commit to as being accurate and lacking in bias. Maybe someday I'll feel confident enough to do that sort of thing, but for now I still don't.

 
At 13 July, 2006 13:55, Blogger The Neurophile said...

If "something completely different" is going on in psychosis as compared to in the use of one of these drugs, why then do they screen out people who have had a psychotic episode, or history of schizophrenia and bipolar disorder when using them in anthropologically medical settings (I say "anthropologically medical" to include indigenous uses)?

I've tried several times, but I'm completely and utterly failing to parse what you're trying to say here. Can you try again, only this time with feeling? Mostly I have no idea what you mean by "anthropologically medical settings."

 
At 13 July, 2006 16:09, Anonymous Plant Master Flash said...

By "anthropologically medical" I mean a medical treatment that may or may not be considered valid by doctors in our own culture, but that is considered valid by a doctor in some other culture. Ayahuasca usage is one such example. Depending on who you ask, other examples could be herbalism, homeopathy, acupuncture, or reiki.

 
At 13 July, 2006 16:37, Blogger The Neurophile said...

So your question is, if psychedelics do not in fact induce a state similar to psychosis or schizophrenia, why is it that amazonian shamans don't administer it to people who have had psychotic episodes or who are schizophrenic?

I'm not really sure why that question needs to be asked: there are a million possible answers. The most obvious of which is: it doesn't have to induce psychosis or schizophrenia to be something one shouldn't give to psychotics or schizophrenics. There's no real reason why the latter requires the former.

 
At 14 July, 2006 08:30, Anonymous Plant Master Flash said...

Then you have to admit it begs the question why someone would think that using these substances for OTHER mental illnesses is seen as valid. Granted, they are probably not all spawned the same way mechanistically, but why e.g. would someone think it's a good idea to send someone with an anxiety disorder on a trip, considering people often have anxiety-inducing trips? I really don't see what the difference is.

 
At 14 July, 2006 08:53, Blogger The Neurophile said...

I don't know of anyone who IS proposing using these drugs to treat people with anxiety disorders. A pubmed search for "hallucinogen anxiety", scrolling through to 2004, doesn't find a single article discussing a possibility of treatment. The closest we get is this article which proposes a possible anxiolytic role for endogenous DMT.

And furthermore, I really can't see how you can argue that it would be BETTER to give the drug to someone with a mental disorder if the drug really DID induce psychosis or schizophrenia.

 
At 14 July, 2006 13:37, Anonymous Erin Oakman said...

LSD leads to a 5-HT2A receptor-mediated arachidonic acid, which blocks the A current in thalamocortical and corticothalamic neurons. As a result, depersonalization (what we might also refer to loosely as psychosis) occurs. Unpredictable behavior may result, just like any time that the ego is challenged and familiar routines are crumbling.

the interesting thing is that LSD seems to mimic the learning process. An LSD trip is salience detection, or detection of change, to the max. We often find ourselves in situations where routine behaviors do no suffice, at which time the detection of change is necessary to modify the routines in the brain. When the A current is strong, the brain may operate predictably, but LSD or other hallucinogens may block the A current, leading a situation where neurons become highly sensitive to sensory stimuli. Ultimately, the detection of change facilitates learning about the immediate environment, which can modify the predictable brain.

Said another way, hallucinogenic drugs may lead to a diminishment of rhythmic inhibition and a simultaneous increase in stimulus EPSPs in cortex, since rhythmic inhibition normally limits neuronal excitability by reducing stimulus EPSPs.  Normally, open high-voltage K+ (Kv) channels shunt synaptic GABA currents through open somatodendritic K+ channels in pyramidal (corticothalamic) cells.  In contrast, hallucinogenic drugs would increase the impact of EPSPs which reach the soma by closing many Kv channels via 5-HT2aR-mediated arachidonic acid signaling.  Hallucinogens may alter
rhythmic inhibition, thereby disinhibiting the formation of sensory constraints and diminishing stereotyped behaviors.  PLA2 inhibitors and 5-HT2AR antagonists appear to block hallucinogenic effects, implying an critical role for AA signaling.

 
At 14 July, 2006 14:05, Blogger The Neurophile said...

Well, you've certainly got me beat hands down. Is this an actual field of research for you?

 
At 14 July, 2006 18:44, Blogger Chris Chatham said...

Erin, like the Neurophile, you have got my intense interest. Are you equating maintenance of the ego with this "A current"?

Also, given your "salience detection" interpretation of hallucinogens, isn't it surprising that (according to Neurophile's account) they work on serotonin, as opposed to dopamine, given that thalamocortical dopamine projections are thought to underlie the "gating" or "updating" processes in working memory (loosely analogous to salience detection)?

 
At 17 July, 2006 14:49, Anonymous Plant Master Flash said...

And furthermore, I really can't see how you can argue that it would be BETTER to give the drug to someone with a mental disorder if the drug really DID induce psychosis or schizophrenia.

I have no idea how you pulled that out of what I said. The only thing I was trying to imply was that there is probably a closer relationship between psychosis/schizophrenia and the hallucinogen experience than you are allowing for in your original post. (And maybe also how unfair the universe is that I can't empirically test this hypothesis for myself. :p )

As for current studies on hallucinogen use for treatment of mental issues...go read your back issues of MAPS. There has, at the bare minimum, been a study on treating OCD with mushrooms. I would also suggest doing a more comprehensive search than "hallucinogen anxiety," considering that you yourself used the original post to point out how problematic it is to call these compounds by anything but their chemical names. Quick example? "Psilocybin anxiety" brings ten hits. And damn, but I wish I had time to read 'em all. :)

 
At 17 July, 2006 16:53, Blogger The Neurophile said...

The only thing I was trying to imply was that there is probably a closer relationship between psychosis/schizophrenia and the hallucinogen experience than you are allowing for in your original post.

Then you completely failed in your attempt at implication, because the only thing you've stated in that regard is pointing out that no one has proposed treating psychotics or schizophrenics with psychedelics. Which is still a pretty big leap to assuming that they're psychotomimetic in my mind, since no one has--for instance--proposed using penicillin for treatment of psychosis to the best of my knowledge, and schizophrenics are probably screened out of most studies involving mifepristone. But I don't think either of those are psychotomimetic, either.

If you'll look at the hits for "Psilocybin anxiety" (which I did previously but didn't mention because there were so few), you'll notice that the closest any of them comes to being about the treatment of an anxiety disorder is the case report about a man whose body dysmorphism lessened when he took mushrooms. Hallucinogen, as I pointed out in the post, is the term usually used in the literature, which is part of why it gets 40x as many hits.

 
At 17 July, 2006 16:54, Blogger The Neurophile said...

Also, why couldn't we have had this conversation while you were in town for the last three days?

We'd BE DONE BY NOW.

 
At 21 July, 2006 11:49, Blogger Simon Kornblith said...

However, to the best of my knowledge, there's no ongoing controversy to classification of stimulants (feel free to correct me if I'm wrong).

There is, at least to a limited extent, some controversy. The question is, where do drugs such as modafinil and the (not yet approved) ampakines fit in? It's been proven that neither works through the same dopaminergic pathway as amphetamines and cocaine (ampakines work through glutamatergic pathways, while modafinil's mechanism of action is still unclear). Neither raises heart rates or prevents sleep to the same degree as classical stimulants. Especially in sports, however, classification of these substances is a major issue.

 
At 24 July, 2006 10:31, Blogger Daniel Poynter said...

Fascinating post, Jonathan.

I also, like 'plant master flash', have to stear clear of psychedelics. Both of my genetic parents had schizophenia.

When I *really* got high on marijuana for the first time, I was left spell bound. How in the *world* can the act of smoking this change my soul so profoundly?

Thus began an obsession with altered states, psychedelics, the mind, the brain, existence...

I kept extensive accounts in my notebooks of each time I smoked marijuana. The more reseach I did, the more I realized my accounts sounded very similar to other accounts--but from people on stronger psychedelics like LSD or psilocybin.

Each time I smoke, my awe in the face of the mystery of existence is reignited, no, atomically-supernovally-exploded.

But smoking marijuana with an unstable mind is like jumping on ice. Why do we tempt Fate?

 
At 18 August, 2006 16:36, Blogger daksya said...

A recent EMCDDA paper(PDF) had a sidebar on the terminology:

------
Issues related to hallucinogenic drugs have aroused vehement discussions and often controversy among both concerned experts (psychiatrists, psychologists, psychopharmacologists etc.) and people using them. At different times, these drugs have been called 'psychedelic' (mind opening, mind
expanding), 'psychotomimetic' (resembling psychosis), 'psychodysleptic' (mind disrupting), 'hallucinogenic', or the less familiar - 'phantastica', 'oneirogenic' etc. All these names depend on the purposes and starting premises of those using them and bring different positive or negative connotations (Gossop, 1993). The scientific community has largely adopted the term 'hallucinogens', however inaccurate it might be, whereas most of the users naturally prefer the term 'psychedelic'. In practice, the two terms are being used interchangeably.

The term 'hallucinogens' refers to the hallucinogen-producing properties of these drugs. However, the hallucinations are not the only effects caused by these drugs and often occur only at very high doses. The hallucinations are most often visual, but can affect any of the senses, as well as the individual's perception of time, the world, and the self (Jacob and Fehr, 1987).

The term hallucinogens. However, is misleading as these drugs do not generally cause true hallucinations (i.e. sensory perceptions in the absence of external stimuli). The effects could be more accurately described as perceptual distortions than hallucinations, though the effects also extend beyond perceptions. Changes of thought, mood, and personality integration (self-awareness) are all important effects (Gossop, 1993; Pechnick and Ungerleider, 2005).

------

What would I recommend? 'Psychedelic' seems apt. 'Psychotropic' seems closer, but has a broader connotation that can't be yoked off now.

 
At 17 February, 2007 15:50, Anonymous tribble said...

Hi,

i have interviewed Jonathan Ott also on the question how they got the term "entheogen".

True, it is the use.

But "the use" has nothing to do with religion. You have misunderstood something very important.

The basis of entheogen use is the context, in which the drug is used. It is like you do something in an ritual.

Rituals have nothing to do with religion. Some make a ritual out of morning coffee and the newspaper. If the user knows about the drug coffein and that he/she can better concentrate and is aware of the "morning ritual", this could be entheogen use.

 
At 17 February, 2007 19:14, Blogger The Neurophile said...

Tribble:

If that's really what he's telling people, then I'm forced to bluntly admit that that's a pretty poor claim.

First off, the entire problem with the term is that it's contextually use-dependent. If the term can be expanded that easily to apply to any pharmacologically active substance, then it has no pharmacological use; it can only be used in an anthropological or ethnographic context. Furthermore, if they intended the term to be used in that broad a sense of "ritualistic" context, they should have developed a term that less explicitly referred to divinity and religious concepts. And finally, the definition of the term from wikipedia (presumably quoting from Ruck et al 1979, published in Journal of Psychedelic Drugs):

In a strict sense, only those vision-producing drugs that can be shown to have figured in shamanic or religious rites would be designated entheogens, but in a looser sense, the term could also be applied to other drugs, both natural and artificial, that induce alterations of consciousness similar to those documented for ritual ingestion of traditional entheogens.

So even in the looser version of the definition, it seems to apply explicitly to drugs with effects similar to those used in shamanic or religious contexts.

 
At 19 February, 2007 01:08, Anonymous Vic from O-hi-o said...

As mentioned earlier, it depends on the purpose someone has for consuming the substance, what they hope to achieve out of it. LSD, PCP, psylocybin, peyote, ecstasy, even marijuana can have similar effects in that perception is altered. If someone is taking it ceremoniously then sure, call it an 'ethogen'(I've never heard this term before); but in other contexts it wouldn't be accurate. It's just misleading calling something a 'hallucinogen' when the only 'true hallucinogens'(and not for everybody who's experienced it, since most people still have external sensory) is.. what, LSD? Personally I have a colloquial leaning towards 'psychadellic' despite it's "60's drug connotation" for the mere fact that it is usually appropiate, and is exclusive to all other drug categories. daksya hit the nail on the head, "… 'Psychedelic' seems apt. 'Psychotropic' seems closer, but has a broader connotation that can't be yoked off now."
And then there's the fact that these different 'psychotopic' drugs or what have you, work in slightly different ways.
Wikipedia has a convenient big master venn-diagram of ALL the types of drugs (pharmaceutical, street, et cetera), as per their 'categories'. Unfortunately, I cannot seem to find the url atm...
Btw, on a sidenote, I turn 16 tomorow^ __ ^

 
At 23 March, 2007 13:41, Anonymous Derek Snider said...

As the term "psychedelic" was specifically coined by Dr. Humphry Osmond to refer to mescaline-like substances, I do not see any problem with using that term. There are far more negative implications surrounding the drug "LSD" than surrounding the term "psychedelic". I don't see how different terminology will make any difference in that respect.

The only real issue with the term "psychedelic" is that so many people have used it to refer to so many different substances, including cannabis, MDMA, PCP, ketamine and DXM (the cough suppressant).

Some clarification of what is included under the "psychedelic" blanket would be beneficial.

For now, I suppose one could use "serotonergic psychedelic" or "classic psychedelic" to refer specifically to substances such as LSD, mescaline and psilocybin.

 
At 14 July, 2008 18:26, Blogger komteidan said...

Phenethylamines would be appropriate. keep it at the chemical level. it is hard to name a wide range of drugs with one term, especially when each one of them is going to do something completly different then the last.

 
At 16 August, 2008 18:15, Anonymous Anonymous said...

Inability to accept the mystic experience is more than an intellectual handicap, lack of awareness of the basic unity of organism and environment is a serious and dangerous hallucination.—Alan Watts

 
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