All Our Favorite Toxins

April 17, 2008 3:30 AM

The Drug Addiction Paradox "The plants should never have developed toxins that reward animals for eating them, and humans should never have developed a reward mechanism for toxic plants"... De-evolution or Idiotic Design?

If this turns out to be as bogus as the German Kid vs. NASA story, I promise I will never do science posts again, OK?

posted by wendell (65 comments total)

Not bogus, is based on a real paper (free pdf can be downloaded here).
posted by kisch mokusch at 3:52 AM on April 17, 2008

Hmm... but that's co-evolution, isn't it? Like, we develop a rural-agrarian society, and then suddenly it becomes in a plant's best interests to have humans addicted to it, because we'll work to cultivate it at the expense of its competitors. Sure we ingest most of it at the end of the process, but we're still collecting and replanting the seeds, and growing it on a far larger scale than it would have ever managed naturally. 'Paradox' solved?
posted by RokkitNite at 3:55 AM on April 17, 2008 [1 favorite]

And let's not forget the capsiacin in chili peppers. How'd that evolutionary misstep happen?
posted by PM at 4:01 AM on April 17, 2008 [3 favorites]

Bizarre.

Considering that plants originally developed these toxins to deter herbivorous predators

Maybe these compounds are spandrels and not arches. More than that, intense-use methods such as injecting refined extracts of the putative prinicipals have become popular only in the last 150 or so odd years. Historical forms of most of the common street drugs don't confer much increased risk of acute mortality, as opposed to long-term mortality (after having progeny). The drugs that have a narrow therapeutic window are more unpopular. As far as addiction goes, it depends on how debilitating the dependence is. A tobacco habit, in itself, doesn't stop young people from having jobs and having kids, so there's no fitness problem there either.
posted by daksya at 4:05 AM on April 17, 2008

I mostly call bullcrap.

Is it de-evolution that we have receptors in our brain that let our own bodies reward us variously? Is it then de-evolution that plants happened to evolve with toxins, nay, let's say compounds that also bund to those receptors?
posted by opsin at 4:07 AM on April 17, 2008

This doesn't seem to be much of a paradox to me at all. The toxins may only reward a subset of animals, including a subset that no longer exists. Also, having the traits of a plant that humans would like to cultivate is an awesome selective advantage. The fact that cows taste good to humans is partially responsible for the large numbers of cows on the planet.
posted by grouse at 4:09 AM on April 17, 2008 [1 favorite]

Let me add a sentence...

It sounds awfully like some of the arguments in favour of intelligent design to me (while clearly not supporting that theory very well either), i.e. removing chance from the way the world works and has formed over millions of years.
posted by opsin at 4:09 AM on April 17, 2008

opsin, I didn't see anyone use the word "de-evolution" besides wendell.
posted by grouse at 4:10 AM on April 17, 2008

I really am missing the 'paradox' here. Is it me or do people forget all the horrific and random missteps evolution makes along the way to survival. Shit does happen; sometimes good, sometimes bad, and sometimes a little of both. At any given period in history, evolution won't guarantee that all is best in the best of all possible worlds. To throw in with grouse, why not ask: Why did cattle evolve to be a tasty source of protein and energy when clearly that would be to their disadvantage?

-or-

The plants are plotting to create mindless, drug-addled slaves to care for their offspring. I for one welcome our new plant overlords.
posted by Avelwood at 4:31 AM on April 17, 2008 [1 favorite]

Michael Pollan's The Botany of Desire examines the evolutionary symbiosis between plants and humans. One chapter is devoted to Cannabis sativa L.

"But officer, I was only smoking this pot to protect myself from hookworm infestation. . . "
posted by rdone at 4:56 AM on April 17, 2008

Hmm... but that's co-evolution, isn't it? Like, we develop a rural-agrarian society, and then suddenly it becomes in a plant's best interests to have humans addicted to it, because we'll work to cultivate it at the expense of its competitors.

Exactly. Those addictive properties have been huge boons for those plants.

And let's not forget the capsiacin in chili peppers. How'd that evolutionary misstep happen?

It's not a misstep at all. Capsiacin has no affect on birds, so birds still eat those peppers, while mammals avoid them, and the seeds get spread much father by birds then they would by mammals.
posted by delmoi at 4:56 AM on April 17, 2008 [1 favorite]

opsin, I didn't see anyone use the word "de-evolution" besides wendell.

Well, I was calling bullcrap on his addition to it then.
Certainly the article didn't evoke those kinds of reactions from me, but I don't see where the paradox lies.
posted by opsin at 4:58 AM on April 17, 2008

It sounds awfully like some of the arguments in favour of intelligent design to me (while clearly not supporting that theory very well either), i.e. removing chance from the way the world works and has formed over millions of years.

And let me add a few words: evolution is not chance.

The plants should never have developed toxins that reward animals for eating them

If, indeed, that is why plants produce such chemicals. It's a leap of faith. (But a leap of faith seemingly common to evolutionary biology.)

Evolution is not so clean and tidy and the causal relationships are vastly more complicated than that.
posted by three blind mice at 5:12 AM on April 17, 2008

Insects eat the most plants; there are coincidences in the limited shambles of amino acids.
posted by Samuel Farrow at 5:15 AM on April 17, 2008 [1 favorite]

And let me add a few words: evolution is not chance.

OK, perhaps (as Samuel Farrow just used the word) coincidence is a better choice for what I mean than chance.
I don't necessarily buy that THC and cannibinols existing in marijuana, for instance, has co-evolved to help the plant spread based on it having the effect it does on humans. Most evidence seems to judge that the way it grows trichomes of these compounds is to ward of insects and herbivores. That it's then coincidence that the brain has various receptors that can bind these compounds seems as likely, if not more, than that the plant has co-evolved with the human race to help propogate it's existence across the planet.

As you say, evolution is not clean and tidy, and the idea that anything in this article makes any definitive sense just seems completely bogus to me.
Trying to formulate, based on the behaviour of our species over the last couple of hundred years in particular, as someone pointed out, how a few compounds from various plants affect us, just seems to be treating our species like we're more important or unique in the overall picture of the planet than I think we are.
We are just another creature roaming the face of the earth, essentially nothing more special than that to the biosphere.
posted by opsin at 5:32 AM on April 17, 2008

And let's not forget the capsiacin in chili peppers. How'd that evolutionary misstep happen?

Peppers want to be eaten by birds so that the seeds get wide dispersion (I think their digestive tract does something helpful to the seed too). Capsai...capsi...that spiciness chemical doesn't affect birds but (supposedly) keeps other animals away. Of course, humans are crazy.
posted by DU at 5:51 AM on April 17, 2008

Well, I was calling bullcrap on his addition to it then.
Just a reminder: most of wendell's posts have a JOKE attached to them.
posted by wendell at 5:54 AM on April 17, 2008

Well I welcome any and all research into the sham athiest science of "Darwinism", and I'm glad that people are finally starting to recognise that the intelligent design of toxic plants, malaria, leprosy, flesh-eating bacteria and ravenous sharks proves once and for all what a complete prick God really is.
posted by the quidnunc kid at 5:58 AM on April 17, 2008 [5 favorites]

For clarification, since the linked article doesn't explain it as succinctly as the actual paper, and from the comments in this thread, I'm not sure how many of you actually understand the point trying to be made:

Evolutionary biologists studying plant–herbivore interactions have convincingly argued that many plant secondary metabolites, including alkaloids such as nicotine, morphine and cocaine, are potent neurotoxins that evolved to deter consumption by herbivores ( Karban & Baldwin 1997; Roberts & Wink 1998). On the other hand, neurobiology’s reward model sees interactions between drugs and the nervous system as rewarding and reinforcing. Hence, in their current forms, neurobiology’s reward model and evolutionary biology’s punishment model appear to be incompatible. We term this incompatibility the paradox of drug reward.

The authors are arguing that the plant-herbivore evolutionary argument is the more convincing one, and that the drug reward model operates under a number or (flawed) assumptions. The assumption that the authors take biggest issue with is the idea that these toxins/drugs a having a "novel" effect on the brain. i.e. that we've never seen the drugs before and when we get exposed to them, they hotwire into a reward-reinforcement system. To the contrary, they provide evidence that we've been exposed to neurotoxins throughout our evolutionary history.

So it's not some novel coincidence - these drugs are toxins and our brains and body (at least initially) treat them as such. So why do we keep taking them? Because this is the crux of the matter. Another assumption they take issue with is that the current reward model assumes that drugs of abuse are intrinsically rewarding. My drug use experience is pretty limited, but has anybody ever spoken to a smoker that actually liked their first cigarette?

So the new question is why do we search out and take drugs that don't reward us?*

*Note that this is not the talking about the processes of dependence that occur later.
posted by kisch mokusch at 5:59 AM on April 17, 2008 [1 favorite]

Aristocrats!
posted by Balisong at 5:59 AM on April 17, 2008

Just a reminder: most of wendell's posts have a JOKE attached to them.

Indeed, apologies. I did actually kind of wind up defending my 'that article is bullcrap' statement in my longer post... I was too tired to spot the sarcasm this morning, and I transfer bullcrap to the article deciding it's a 'paradox'.
posted by opsin at 6:00 AM on April 17, 2008

So the new question is why do we search out and take drugs that don't reward us?

Because they do... It's not news that many of these drugs bind to receptors in the brain that are reward systems for the brain.
Just because you didn't like smoking that first cigarette doesn't mean the effect of the nicotine on the brain wasn't such that it rewarded you for having smoked it.

The compounds in drugs all exist within the body, or at least compounds enough like them to be able to use the same receptors. Opiates work as pain relief because our bodies use compounds very similair or the same as them to dull pain without injecting any foreign substances.
posted by opsin at 6:05 AM on April 17, 2008

Let me state this: Evolution is not only chance, it is nothing but chance. Plants and animals do not "want" anything in the sense that this "want" might drive evolution. The OP seems ridiculous because it completely misunderstands how evolution occurs.

Mutations occur randomly. They are the result of transcription errors, radiation and chemical damage, and lately the random shuffling of genes in sexual reproduction. If the completely random mutation increases the chances that the organism will reproduce, it tends to be expressed by a larger and larger population. If the completely random mutation decreases the organism's survival chances, it dies out.

Over time -- vast amounts of time -- this accumulation of beneficial traits creates the appearance of determinism, but that is an illusion. Four billion years of so high-grading our chemical underpinnings has left the biosphere with a vast and ever-growing library of wonderfully interactive molecules. Not one of these molecules was "designed" or was the directed result of any quest for a useful trait. They are, every single one of them, the outcome of billions of random errors piled one upon another. For every one of the elegant molecules that make life possible, a billion more have been tried and found lacking and thus aren't regularly made by living things.

Sometimes you can sort out that a particular chemical clearly gives its creator a specific advantage in a specific situation, but more often it's a great big muddy mess why organisms operate the way they do, and very often the only "why" in operation is that evolution hasn't sorted it all out. Humans in particular are a very new species and we are relating to the world very differently today than we did 10,000 years ago, and evolutionary pressure hasn't had time to sort that out at all.
posted by localroger at 6:09 AM on April 17, 2008 [5 favorites]

delmoi writes "seeds get spread much father by birds then they would by mammals"

Well, considering that rodents chew and digest the seeds while birds just pass them through the GI tract undamaged (and deposit them in a pile of handy fertilizer at the end), yeah. I'd say that birds do offer a wider dispersal potential than mammals.

Tests have been done using non-hot peppers (bell varieties) vs. spicy ones, and it's pretty clear that rodents are not a viable dispersal vehicle for the seeds.
posted by caution live frogs at 6:12 AM on April 17, 2008

Humans (with big brains) are not old enough to explain this in evolutionary terms. Small brained animals would probably avoid drugged plants because it would make them, well, happy meals. Also most of the drug plants are from the new world where humans did not evolve (much).
posted by stbalbach at 6:16 AM on April 17, 2008

The paper is also missing the most obvious explanation: Those plants just happened to have chemicals in them that just happened to bind to receptors in the brain as a coincidence. There are only so many receptor/binder shapes and often 'near' shapes will also bind to receptor sites.
posted by delmoi at 6:25 AM on April 17, 2008 [1 favorite]

delmoi writes "seeds get spread much father by birds then they would by mammals"

clearly you haven't watched Michael Pollan's talk on how we're all evolutionary slaves to agriculture. If I were a plant species I'd certainly consider it advantageous to have people planting me (even if clandestinely) all over the place and saving the strongest of my seeds to get more high next year.
posted by datacenter refugee at 6:30 AM on April 17, 2008 [1 favorite]

clearly you haven't watched Michael Pollan's talk on how

Clearly I was talking about non-human mammals who would avoid eating spicy peppers, while birds don't have that problem.
posted by delmoi at 6:32 AM on April 17, 2008

Proof that God wants us to be happy.
posted by LordSludge at 6:34 AM on April 17, 2008

Toxins evolved very long ago. The selective advantage gained from them was that certain herbivores would no longer eat those plants. It is unlikely that the toxins evolved to keep humans (or their evolutionary ancestors) from eating them. It would therefore seem likely that the effects of the toxins in humans are by accident. For instance you could imagine a situation in which a toxin binds a certain protein in an herbivore to act as a poison. Perhaps the homologous human protein has evolved to serve a different funciton such that the toxin still binds to and inhibits that proteins function, but at a physiological level the effects are quite distint. Or perhaps the homologous protein in humans could still bind the toxin, but with a much reduced affinity such that you see effects, but the lethal dose of the toxin becomes extemely high. Caffine for instance is lethal at much lower doses in dogs and cats than in humans. (Note: This is only an example, I am by no means suggesting plants evolved a pathway for the production of caffine to keep dogs and cats from eating them.)

From the abstract:

By contrast, emerging insights from plant evolutionary ecology and the genetics of hepatic enzymes, particularly cytochrome P450, indicate that animal and hominid taxa have been exposed to plant toxins throughout their evolution. Specifically, evidence of conserved function, stabilizing selection, and population-specific selection of human cytochrome P450 genes indicate recent evolutionary exposure to plant toxins, including those that affect animal nervous systems.

The first part is true, animals have been exposed to plant toxins throughout evolution. Cytochrome P450s generally modify non-polar molecules making them more polar such that they can be excreted by the kidneys. However, they have a very broad sustrate specificity. There are not enzymes for modifying a certain toxin. The claim that this suggests exposure to the toxins that have pleasant neurological effects (nicotine, morphine, cocaine) is unfounded. One could make a similar claim about most modern small molecule drugs as they are modified by these same cytochrome P450s.
posted by batou_ at 6:41 AM on April 17, 2008

Evolution is not only chance, it is nothing but chance.

localroger: You overstate that particular perspective to the point of being wrong. Evolution isn't random, though some of its components are. Natural selection isn't random - that's why it's called 'selection' and it is, of course, the reason why useful mutations propagate, giving the illusion of design. It's a non-random filter. If mutations are random sized objects and the environment is a mesh of a certain size then it's not random which objects pass through the mesh. Evolution should be said to occur to populations within environments - not individuals.

Mutations, though, are random. But mutations in themselves are not evolution.

I know you probably know all this, but it bears repeating.
posted by Sparx at 7:10 AM on April 17, 2008

Evolutionary biologists studying plant–herbivore interactions have convincingly argued that many plant secondary metabolites, including alkaloids such as nicotine, morphine and cocaine, are potent neurotoxins that evolved to deter consumption by herbivores ( Karban & Baldwin 1997; Roberts & Wink 1998). On the other hand, neurobiology’s reward model sees interactions between drugs and the nervous system as rewarding and reinforcing. Hence, in their current forms, neurobiology’s reward model and evolutionary biology’s punishment model appear to be incompatible. We term this incompatibility the paradox of drug reward.

Maybe these neurotoxin filled plants were the killer versions reserved by the species to out survive their eaters, or even wipe out the eaters entirely, which then left the herbivores who were less prone to dying from it (but had enough reactions to stop eating after a few).
posted by Brian B. at 7:12 AM on April 17, 2008

Maybe these neurotoxin filled plants were the killer versions reserved by the species to out survive their eaters

No, the species does not make decisions about which of its offspring evolve in certain ways.
posted by grouse at 7:14 AM on April 17, 2008

Because they do... It's not news that many of these drugs bind to receptors in the brain that are reward systems for the brain.
Just because you didn't like smoking that first cigarette doesn't mean the effect of the nicotine on the brain wasn't such that it rewarded you for having smoked it.

The compounds in drugs all exist within the body, or at least compounds enough like them to be able to use the same receptors. Opiates work as pain relief because our bodies use compounds very similair or the same as them to dull pain without injecting any foreign substances.


You know, I don't have a dog in this fight. I was just trying to explain the point of the paper, since everybody was talking about there being some kind of benefit for the plant to be addictive (which is covered in the paper, but ruled out for some, nicotine being one). The authors are making a pretty big claim, but it's not a bad argument (if you bother to read it, which you clearly haven't, since it addresses all of the points you've raised so far).

On the cigarette example, are you trying to claim that all the non-beneficial effects that occur alongside first-time drug use are outweighed by effects in the CNS? I don't believe this. And your example is a euphoric drug mechanism, while the question in the paper is concentrated on non-euphoric drugs (but again, if you'd read it...).

Personally, I don't think the argument being made is completely incompatible with the drug-reward-reinforcement theories, but it does point out, at the very least, that the behaviour surrounding addiction isn't as simple as some of those same models would suggest.
posted by kisch mokusch at 7:26 AM on April 17, 2008

No, the species does not make decisions about which of its offspring evolve in certain ways.

I was anthropomorphizing for effect, it would have been a minor genetic trait waiting to explode.
posted by Brian B. at 7:36 AM on April 17, 2008

I was anthropomorphizing for effect

Evolution doesn't like it when you anthropomorphize it, so please don't. Even if it was just "for effect," what you are saying still makes no sense.
posted by grouse at 7:47 AM on April 17, 2008

Masturbation.


That is all.
posted by CynicalKnight at 7:48 AM on April 17, 2008 [1 favorite]

De-evolution or Idiotic Design?

False dichotomy. It is evidence of a loving God who wants you to get high.
posted by Meatbomb at 8:03 AM on April 17, 2008

Sparx, it's obvious that the result of evolution isn't random, any more than the shape of a quartz crystal is random. But when I see people writing of what a species "wants," what "drives" evolution, and even thinking a silly thing like that the existence of psychoactive drugs is in any way a paradox, I see the kind of mushy thinking that makes Young Earth Creationism possible. Yes putting it that way is more dramatic, but it is also fundamentally wrong.

Yes there is a mesh which high-grades the random effects of mutation, but that mesh itself was created by the random effects of mutation. Other than the relatively simple and obvious effects from the laws of physics and mineral and energy availability, the mesh that sorts life out is itself made mostly of life that got sorted out. People tend to think, largely because of mushy thinking like this, that there is some overall bias toward greater complexity, power, size, perfection, or whatever. There is no such bias. The only bias is toward whatever works, and not even whatever works best but whatever works adequately.

What drives evolution is random change; nothing more. This is in fact so important that one of those random changes, the introduction of sexual reproduction, became nearly universal because it increases the frequency of random changes. That increases the rate at which evolution occurs, and therefore the rate at which beneficial changes are "discovered," which is itself a selective advantage in the long term. But I put "discovered" in quotes because there is no force that "wanted" this, no "evolutionary pressure" which drove toward or created sexual reproduction; it was a thing that originally happened by pure, blind, random chance, probably as the botched result of one bacterium trying to cannibalize another, and lo and behold it turned out to be useful. That is all there is to it. It is foolish and misleading to suggest that there is any more to it, just as it would be foolish and misleading to suggest that atoms of silicon and oxygen "want" to make a six-sided prism with a point.
posted by localroger at 8:06 AM on April 17, 2008 [5 favorites]

Sparx: Who or what does the selection in natural selection? Nature? It seems to me that nature doesn't have the capacity to pick and choose what propagates and what doesn't. I think you're using that term a little too literally.

On preview: localroger says it best.
posted by jstef at 8:19 AM on April 17, 2008

There is no goal in evolution. Evolution is always forward, never backwards. Nothing is more evolved than something else.
posted by ozomatli at 8:29 AM on April 17, 2008

the introduction of sexual reproduction, became nearly universal because it increases the frequency of random changes

That's not really why sexual reproduction is important. There are asexual organisms that mutate far more quickly than ourselves. The biggest advantage that sex brings is a way to mix and match adaptive alleles and especially to eliminate deleterious alleles. It keeps us from getting into a Muller's ratchet situation.

Saying that evolution is "nothing but chance" really overstates the case. While mutation is a stochastic process, other mechanisms of evolution are really anything but random.
posted by grouse at 8:31 AM on April 17, 2008 [2 favorites]

Who or what does the selection in natural selection? Nature?

Nature absolutely is the selector. localroger is correct that evolutionary changes are basically random, but nature rewards beneficial changes and punishes detrimental changes. It is merely a system of efficiency (for lack of a better word).
posted by Benny Andajetz at 8:42 AM on April 17, 2008

localroger: Agreed on all points - although I suspect you and I would place different emphasis on the importance of the 'relatively simple and obvious effects' of physics, in terms of climate, atmosphere, geology, vulcanology, energy availability, etc In the longer term, I feel those environmental elements are every bit as important (although perhaps not as dynamic) as the aspects of the environment that are themselves evolutionarily derived. You are unlikely to evolve squid on land - for example, which might happen in a truly random process.

Jstef: I would say that nature selects - I just wouldn't subscribe any intentionality to it.

grouse and benny: Word.
posted by Sparx at 8:53 AM on April 17, 2008

ascribe, dammit
posted by Sparx at 9:00 AM on April 17, 2008

It is very, very hard to avoid anthropomorphisms when talking about evolutionary theory. Even the word "reward", which everyone in the thread has been using, strikes me as an anthropomorphism.
posted by creasy boy at 9:02 AM on April 17, 2008

kisch mokusch: To the contrary, they provide evidence that we've been exposed to neurotoxins throughout our evolutionary history.

The authors base this on the presence of P450 and that their "xenobiotic-metabolizing function is conserved".

First, not all neurotoxins need be psychoactive, and also the particular psychoactive neurotoxins in wide circulation today may not have been in sufficiently wide favor much earlier to be relevant to this argument. As they later say, there's lot of variation in the profile of detox enzymes among closely-related species: "A comparison of the human genome with the initial sequence of the chimpanzee genome similarly found rapid evolutionary divergence in xenobiotic-metabolizing genes".

Finally, they say, "Second, modern euphoric drugs, like heroin, might represent a genuine evolutionary mismatch—drugs that are vastly more pleasurable than any neurotoxins occurring naturally in ancestral environments", So is there no paradox for modern euphoric drugs? Never mind that heroin is for the most part a more potent version of morphine which is a plant toxin and also endogenously produced in the human body. The key difference is the typical kinetics of drug induction today. Also, never mind that heroin produces euphoria in only some of its subjects and dysphoria or nothing prominent in others, and the same is true of the ancestral drugs as well.

these drugs are toxins and our brains and body (at least initially) treat them as such.

From the paper:

The unpleasant consequences of PNS-binding sites are shared by all of the most commonly used plant drugs (e.g. tobacco, betel nut, khat, cola nut, coffee, tea, coca, cannabis) such as tremor, face flushing, sweating, changes in heart rate and blood pressure, salivation, nausea and broncoconstriction.

That's funny because I don't remember most of these effects happening when having the occasional caffeine kick. Do they present any surveys elsewhere on the prevalence and relative prominence of these negative effects?

In particular they seem to be railing against the MDS theory of drug reinforcement. They seem to define euphoria as the only metric for reward instead of including stimulation and other pleasant/useful outcomes as reward as well, and thus ending up defining many drugs as non-rewarding. Of course, the whole thing rests on their premise that these drugs were indeed toxic and recognized as such long ago.
posted by daksya at 9:17 AM on April 17, 2008

And your example is a euphoric drug mechanism, while the question in the paper is concentrated on non-euphoric drugs (but again, if you'd read it...).

I did read it. Doesn't change the fact that I think it's a valid example regardless.
I don't think there's a difference between the way the brain chemistry works whether it's a euphoric or non-euphoric drug (what does that mean anyway, other than you supposedly won't notice it's effects on the brain - which is bullshit too, considering the noticable stress relief and muscle relaxing effects of nicotine). A large part of why I don't buy into this paradox of which they speak.
posted by opsin at 9:39 AM on April 17, 2008

It also bears mentioning that drug enjoyment is a complex phenomenon. In my personal experience, only about 1 in 10 people truly enjoy the experience of smoking pot; most other people find it interesting but not particularly amazing, and another quarter or so actively dislike the experience. Genetic variation in a population is the mechanism that allows evolution to happen, just as natural selection is the engine that drives it forward.

Additionally, the positive effects of drugs are in many ways a social phenomenon, in that the infrastructure of our societies and culture allows drugs to be a positive experience. Imagine being a lone subsistence-level hunter surrounded by dangerous animals and on the edge of starvation. Now, imagine there's a plant that will get you high as a fucking kite. Do you eat it? What feels good in your apartment with Ween blasting from your stereo system is very different from what feels good in the wild.
posted by freedryk at 10:02 AM on April 17, 2008 [1 favorite]

daksya: these effects do certainly exist -- for some more than others, as in all things for sure. Caffene can certainly raise your heart rate (giving you that "kick") and after more than you might be used to, getting shakey can totally happen. And you got it with the more obvious examples, like the vomiting/nausea that goes along with heroin use.
I'm still interested to see where human's use of tools enter the picture. It takes 30kg of poppy seeds to get 1 gram of morphine. That's close to half the mass of an "average" human. And when we would ingest those seeds, we'd be ingesting all that fiber along with it (and then explode and never make it close to 30 kg). It's in the use of tools that we can transform potency from something the mass of a 9 year-old to that of a Smartie. So I'm not sure we can compare our "everyday" experiences, because we've become quite good at distilling drugs. How many of us chew coca leaves during our lunchbreak? Or instead go for that diet soda.
And though, yes, I used an example of a "euphoric" drug, I think the concept holds well enough. I'm also unsure of the disagreement Opsin. Kisch mokusch pointed out that the original article does talk about both nicotine and morphine. Which, granted, I haven't read yet, as I've been too busy reading everyone's comments. And am now convinced it's worth a glance at. (TY yet again MeFi)
posted by Sweetdefenestration at 10:22 AM on April 17, 2008

Theory 1: God is lonely.
Theory 2: God is bored.
posted by flotson at 10:25 AM on April 17, 2008

Who or what does the selection in natural selection? Nature?

Who does the section?

Darwin's observation was that evolution is based on reproductive fitness. Selection is done by sexual partners. Scary huh?
posted by three blind mice at 11:19 AM on April 17, 2008

three blind mice: Natural selection can apply even in cases of asexual reproduction or random mating. In some simple models, fitness is measured by the probability of surviving to reproductive maturity.
posted by grouse at 12:18 PM on April 17, 2008

I think God clearly designed pot to be awesome, and wants us all to smoke it as much as possible. Why else would he design it that way?

Cause clearly he designed it.

Intelligent design, right guys? Right? Bueller? Anyone?
posted by Caduceus at 12:41 PM on April 17, 2008 [1 favorite]

Damn it, that last sentence was supposed to be small. *shakes fist at Metafilter html rules*
posted by Caduceus at 12:43 PM on April 17, 2008

Sweetdefenestration: these effects do certainly exist -- for some more than others, as in all things for sure.

I'm not denying that negative side-effects don't occur. The authors are making a stronger claim:
Most commonly used plant drugs are correctly and unsurprisingly ‘recognized’ as toxins by most new users, both physiologically and affectively, and the physical and affective responses are accurate warnings of fitness costs.

In other words, the first time around, =most= users have an overall negative experience. That's news to me. As support, they cite a study on tobacco, implying nicotine. But nicotine has long been a dark horse as far as psychoactive drugs go. Its effects are subtle and depends on its delivery within smoked tobacco. To support their case, they would have to show that the normal reaction to first use is negative on balance and not just a no-show. They already concede the case for "modern" drugs, since they seem to be "vastly more pleasurable".
posted by daksya at 1:20 PM on April 17, 2008

..do occur
posted by daksya at 1:21 PM on April 17, 2008

A plant only needs to be poisionous to that which would otherwise be its greatest threat. An evolutionarily-recent tool-using giant monkey that isn't eating it for food, but instead tried it as a spice and discovered it had psychologically pleasant side effects? That's extremely recent, in an evolutionary sense. And then we're cultivating it, causing those plants to be propogated- and that is the only definition of "success" evolution is capable of creating. We're seeing to it that there are more of them, so they stand.

Alcohol's a little different. It's a side effect, rather rare as anything but the waste products of decomposition- or fermentation, if you prefer. Plenty of animals actively seek out fermented fruit for about the same reasons humans do, as far as biologists have been able to determine. And it's not something the plants are producing- it's something bacteria are producing, partially to limit their own population.

So why do we get intoxicated by toxic things? Most of these toxic things are or are similar to chemicals the body already uses to regulate itself. Incoming doses of them confuse all the systems that those chemicals refer to. Some of these systems regulate pleasure, tranquility, lack of pain- all the "positive" effects of drugs. But why are they poisonous even though we rely on them? Because we rely on the right amount, and too much throws a system way out of whack.

It's just that what's way too much for a little rodent trying to eat a flower is just enough to get a human high.
posted by Kistaro at 2:06 PM on April 17, 2008 [1 favorite]

daksya, I don't really have any good answers against your criticisms (it's good to see a good critical analysis, though, they are rare in the scientific paper threads).

I completely agree that the P450 line of argument, while sound as evolutionary evidence of our exposure to neurotoxins, does not necessarily prove that these drugs are not having novel effects.

On the euphoric drug use, it's interesting that some (most?) first-time users of heroin have a dysphoric or non-euphoric response. That of course fits well with their argument, even if they hadn't mentioned it. On that note, the paradox doesn't exist when it's a novel effect, right? So a genuine "mismatch" is a novel effect, and can be excluded from the list. At least that's how I'm reading it. Keep in mind that it also has to be immediately rewarding in some way for the MDS argument to hold.

On the anecdotal side of caffeine, I certainly remember hating everything about coffee as a kid. It's something I think we acquire a taste for. It's effects on the heart are well described, and besides the last three symptoms (salivation, nausea and broncoconstriction.), I think their list holds for caffeine.

The argument is against the MDS theory, but only for the early stages of drug-seeking behaviour, which is why I don't have such a problem with this paper as, say opsin, who really seems to hate it (and, I'm pleased to see, finally read it). Using nicotine as an example, it's perfectly conceivable to me that an individual could develop the habit of smoking before they became addicted. The authors are saying that those smokers didn't start the habit because it was rewarding, but don't exclude the role for the MDS system later. And yes, there are different measures of reward, but they are only interested in disparaging the theory that these drugs, right from the word go, are short-circuiting our existing reward systems, and that that is the reason for the early stages of drug-seeking behaviour.

I think you're getting closer to the truth of the matter when you talk about prevalence. The arguments on both sides are quite cut and dry with regards to how our brains work. Among other things, they tend to ignore the variation within the human population, which can't be dismissed so easily.
posted by kisch mokusch at 2:31 PM on April 17, 2008

see also Michael Pollan's talk at TED The Herbivore's Next Dilemma, on how grass and corn have manipulated us in their quest for world domination.
posted by MiltonRandKalman at 2:45 PM on April 17, 2008 [1 favorite]

I can only guess that the authors of the paper fail to realize just how strongly conserved neurotransmitter receptors are. For example, dopamine receptors, which seem to be at the heart of the rewarding effects of drugs in mammals, are also found in C. elegans, a tiny roundworm.

So the effects of these plant chemicals in man are probably irrelevant. None of them are major human foodstuffs, so the plants have no need to discourage human predation--and, conversely, there was no evolutionary pressure for humans to develop defenses against such toxins. Maybe there is today, but evolution takes many generations. And in fact, it is notable that humans do something very odd. Cocaine is so rewarding that virtually every mammal ever tested will take cocaine if given the opportunity, pretty much to the exclusion of any other activity. Yet humans do something quite odd--some humans, even after having been exposed to cocaine, choose not to take it. So it may well be that humans have, to some extent, evolved genetic defenses against drug abuse, even if those genes have yet to spread completely through the human population

So the valid question is, what did these chemicals do to the organisms that were the major predators at the time when plants evolved the ability to produce them? It could be very different from what they do to humans?

And we have a clear example in front of us: tobacco. Tobacco is not a food, and people would probably have little interest in it if it didn't have nicotine. But nicotine is a quite potent toxin, and very effective at killing insects--to the point that it is still used as an insecticide, where it acts on receptors very similar to the ones that humans have. So there is little doubt what advantage nicotine provides to the plant. It is probably pure accident that nicotine--at lower doses than those at which it causes respiratory paralysis, convulsions, and death in man--happens to release dopamine in midbrain reward systems.
posted by trrll at 5:15 PM on April 17, 2008 [1 favorite]

Sparx, it's not that physical processes are unimportant; of course it would be ridiculous for a squid to evolve in a land-based environment, for example. It's that, compared to living processes, environmental processes are relatively simple. That's why it's pretty obvious why squids don't live on land, but it takes some thought to ask why Cannabis Sativa L. produces a molecule of such interest to humans.

The thing is, it doesn't take much for life to survive in an otherwise mostly life-free environment. What drives the ever-increasing spiral of complexity is the competition of life with other life. On an otherwise sterile but nutrient-rich world you wouldn't need squid to survive in the ocean or anywhere else either; single-celled micro-organisms would be fat and happy and unprone to "invent" new and clever means of production. But the world is finite and it is competition for those relatively simple but limited resources that causes living things to constantly test themselves and weed out the less successful, often simpler designs and create what appears from too far away to be a kind of striving for complexity, power, and utility.
posted by localroger at 5:19 PM on April 17, 2008 [1 favorite]

Do I jinx the thread by saying that it's been awesome and noise-free? It has. Thank you.
posted by Durn Bronzefist at 8:04 PM on April 17, 2008

localroger: you're preaching to the converted. My complaint was in your terming evolution as "nothing bit chance" - specifically in describing the environmental influence as such, while still maintaining that "the result of evolution isn't random".

If the result of evolution (non-random) plays a part in the process of evolution, then evolution cannot be entirely chance/random.

I know we're quibbling over semantics here. To what extent should we call the environment random? The meteorite that killed the dinosaurs - random? A particularly long winter that halves a species' population - random? An ice age that halves the number of species - random? A mutation that over a thousand years bred a faster predator - random? It's an intersting question and argument could be made for each case (I have discovered a wonderful proof for each, but this comment box is insufficient to contain it).

Mutations obviously fuel evolution, and play their part in creating the environment - but the environment itself is acting in the here and now in the process of selection and, to my mind, cannot be considered a random influence. I suspect this is where we part company, but I also suspect it's just a matter of perspective.
posted by Sparx at 2:58 AM on April 18, 2008

Thanks, delmoi and DU. I'll put my question in the "Case Closed" file.
posted by PM at 4:23 PM on April 23, 2008