Giving drugs to humans, the whys and wherefores

Late last week, the esteemed Drugmonkey pointed me toward an article that came out in the Washington Examiner. The Drug Czar of the Bush administration expressed shock and outrage when he suddenly found out that drug researchers give addictive drugs to human addicts as part of studies on human addiction. Shock me, shock me, shock me, with that deviant behavior. I think Drugmonkey expressed it best when he said

It is harmful to our Nation’s public policy on drug control and substance abuse to run roughshod over the scientific information in this way. It is specifically harmful to drug abuse science to misrepresent the studies in this way.

No kidding. But, issues of politics aside, there are ethics issues associated with giving drug addicts drugs. Janet has done an excellent job (as usual) of explaining the ethical implications of giving drugs to drug addicts. But there’s a third topic that needs to be addressed. We do lots of animal studies with addictive drugs, why do we need to be giving it to humans?


Well, the fact is that rats can’t tell us everything. People who use animals self-administering addictive drugs can learn a lot of things. They can find out how often animals self-administer the drug in specific doses, which can help us to figure out how long the subjective effects of a drug last. We can know the biochemical half-life of a drug without knowing what that means to the animal, and self-administration can teach us which drugs you feel only for 15 minutes (like cocaine), and which you feel for hours (like MDMA), before you have to take another hit.
Self-administration studies can also show which drugs are preferable, by giving an animal a choice and seeing which one they go for. This is different from drug self-administration in humans, when the drug of choice is often a matter of price or availability, and may not actually be the more rewarding or reinforcing choice. Researchers can also use this drug discrimination ability to see how new drugs may act neurochemically, by asking the animal which drug it feels closest to.
Drug research in animals can tell us a LOT about the neurochemical activity of drugs, how they act, where they act, and what acute and chronic effects in the brain look like. These are effects we often can’t see in humans.
Finally, animal research studies can show which drugs are more likely to be addictive, based on whether an animal will self-administer it. Animals will rapidly and reliably self-administer cocaine, morphine, or heroin. Alcohol is more difficult, as it tastes bad, and most rodents don’t have a gag reflex. Drugs like LSD are almost never self-administered, which can tell you a lot about the addictive potential.
But animal studies simply can’t tell you everything there is to know about drug abuse and addiction. First of all, drug dependence is a disease that is characterized primarily by its symptoms, not by a cause. We know you are addicted to drugs because you crave them, can’t quit them, feel withdrawal when you’re not on them, etc. But there’s nothing we can really look for in your body as an underlying cause of addiction. No virus, very little in the way of particular genetic codes.
And the fact is, drug dependence in society depends on far more factors than you could ever simulate in a lab animal. People with drug dependence often have comorbid psychiatric disorders, which themselves are extremely difficult to model in an animal. People are often dependent on more than one drug, or abusing more than one drug, and no person’s drug cocktail of choice, or their drug history, is exactly the same. While we use animal models to figure out the specific effects of certain drugs, effects are sometimes different when we look in humans with variable drug histories.
Additionally, while we may be able to figure out a drug that might help drug addiction by testing in the laboratory, we need to to know HOW it’s stopping drug intake. An animal will stop intake when exposed to certain drugs, but it can’t tell you why. We need to perform studies in humans to find out whether their craving is decreased, their withdrawal symptoms are decreased, or whether they just don’t feel very good. Animal studies can only tell us these things in a very limited way.
Not only that, WHY people start taking addictive drugs is something that is very hard to model in the lab. Some people may take addictive drugs due to stress, which is something we can model, but other are self-medicating for underlying conditions. Each person’s underlying condition is different, and not all of them can be modeled well in animals. While a drug might help to reduce drug administration in laboratory animals, it needs to be tested on humans to determine whether it will work with a given person’s underlying conditions. And it needs to be tested on humans in the presence of drug, to look for potential interactions.
Rats certainly can tell us a lot about cue-induced drug responding, changes in the brain in response to chronic drugs, etc. But only a human can tell us what a drug really FEELS like. Only a human can tell us WHY they are taking what they are taking. Only a human can describe the feeling that goes along with tolerance, and only a human can tell us how other drugs compare in terms of how good or bad they feel. The bottom line is, only a human can talk. Until we can get a rat that can tell us about his bad day at work and how he just wanted ONE drink, we will have to be doing at least some drug addiction research on humans.

15 Responses

  1. Thanks for picking up on this scicurious. Something very odd is afoot what with Walters engineering a media campaign in DC. The claims in the Examiner article are so patently ridiculous that one wonders. Clearly the misdirection worked, if you look through the comments on the original article.

  2. Is that the same Bush Administration that was gung-ho on forcing addictive drugs (which were never clinically tested on children) on ADD/ADHD children?

  3. Whoa, Sci–something of an error here. The article appeared in the Washington Examiner, which is not even close to the Washington Post. Well, maybe they’re both in the Washington area, so they kind of close… The Examiner is a free weekly paper that was created from a combination of several suburban weekly papers. Wikipedia describes it as “conservative,” and that bias clearly shows in the editorial that accompanies the cited article http://www.washingtonexaminer.com/opinion/Need-a-fix-Call-the-feds-for-a-line-of-cocaine-42284892.html

  4. how is a human study on drug addicts different than a human study on any other condition we seek to treat and/or prevent? unless he doesn’t view drug addiction as a problem of actual physiology…

  5. Leigh,
    It’s a big deal because drug addicts could be considered a “vulnerable” population, which would make their participation, even consensually, an ethical grey area.

  6. Brian-
    how so, say, compared to terminal cancer patients? children? minority populations? graduate students in it for the cash? i’m not a clinical researcher, so i am not experienced in this area.

  7. Oooh. Thanks Dad.

  8. Brian –
    I really don’t see much of a gray area here. I would tend to think that a factor in making it ethical, would be ensuring those involved in such a study would receive top notch treatment at the conclusion of their participation. I have every reason to assume that this actually happens. While I have yet to take the time (spare time?) to look into it, I do recall reading about this several years ago and that was a requirement to even get the DEA license to perform such research.
    There are a hella lot of addicts who would happily give up certain body parts for an opportunity like this. To whit, they get to take their drug of choice under clinical conditions and in a pure form for a little while. They get to help advance teh science of drugs with high dependency rates and addiction. And they get the opportunity to get help quitting.
    Contrary to what many might think, even getting into a decent rehab program is not easy and it isn’t cheap. Most addicts are not keen on being addicts – they just aren’t afforded the opportunity to get the help they need.
    So beyond the general ethical concerns about using human subjects, I am not seeing something special about this one.

  9. Sci –
    Something that I really have a hard time understanding (not an argument against clinical human tests, I get the why of that) is why there seems to be such a profound disconnect between the hard research end of this discussion and those who are actually working with addicts, the addicts themselves and those developing and researching new clinical treatment methodologies. (hows that for a runon sentence?) I realize that this is probably a better question for DM, but I thought I would throw it out here too. Because it really seems to me that folks on every side of this equation would be well served with better interaction and understanding of the others.

  10. Nice Empire Records shoutout!

  11. DuWayne, there are actually a diversity of approaches to therapy in these settings. Some studies involve subjects who are seeking treatment and some involve individuals who are not actively seeking treatment. By intent. (You can see why this might be an important difference in the subject pool characteristics and give you different answers to particular questions). Also, some studies involving human users are specifically testing therapeutic approaches and some are not.
    If I am not mistaken (and I am not steeped in the minutia) even studies which do not do therapy and use non-treatment-seekers involve at least a little bit of post-study counseling on health risks, why they should seek to decrease use and where to get help. However, you can also appreciate how excessive levels of intervention, trying to induce someone to quit or seek therapy, would also run afoul of ethical considerations of subject autonomy (see Janet’s post for the autonomy issue).
    This is why local IRB consideration and balancing of the issues related to the best protection of specific user populations is so important.

  12. Erin: I LOVE Empire Records. I think I use the comment “shock me shock me shock me with that deviant behavior” at least ten times a day in my head.
    DM: Thanks for getting on DuWayne’s comment. DuWayne, DM’s totally right. I know of studies using both treatment and non-treatment seeking addicts.
    As to your next comment about interactions between research and clinical settings…it’s a difficult issue, and Sci doesn’t pretend to know everything about it. Sci is super-tired right now, but she’ll try and give you her take.
    Many of the drug addiction researchers that I am acquainted with work with addiction research is a very abstract way. They look into things like mechanisms of reward and reinforcement, the mechanisms of sensitization and tolerance, and receptor and brain area changes. All of this is, of course, toward the eventual end of finding a cure. But there is a lot of research being done simply for the understanding of the system. I think, in the day-to-day research with levels of receptors in specific sub-regions of the brain, many researchers feel they don’t have anything new to say to clinicians. The communication comes when the research gets to the translational level, with clinical trials for drugs or treatments, but those can often be decades away from the initial research into the mechanism.
    I know that NIDA (the National Institute on Drug Abuse) in particular has called for more translational research avenues, and I think this is a very positive thing. Many researchers, honestly, get caught up in the minutiae. To some researchers, the system is what they are interested in, and “clinical relevance” is only something you write in to get the grant funded. Obviously, many researchers are NOT this way, and have help for patients as their goal, but there are still some that are more interested in the basic science than the clinical outcome. That’s fine, we need the basic information in the interest of developing a clinical outcome. But some pressure toward a translation angle WILL help us link the basic mechanisms to the clinic and facilitate the development of new treatments.
    And in the same way, while researchers need to reach toward the clinic, it’s important that clinicians show an interest in the latest developing research. New insights into what is changing in addiction and how those changes occur could help them tweak what to prescribe, not to mention what kind of therapy is necessary. And their insights which they gain from their patients could be of a great deal of value to us bench-people.
    Basically, there’s not as much reach in both directions as there should be, but I think people are coming to understand that, and starting to realize that changes need to be made.

  13. However, you can also appreciate how excessive levels of intervention, trying to induce someone to quit or seek therapy, would also run afoul of ethical considerations of subject autonomy…
    That actually is an important consideration that I hadn’t really considered, but totally agree with. But at the same time, I would almost see this as even less ethically ambiguous. If you are dealing with an addict that expresses a desire not to quit, then you are also dealing with someone who is going to be using regardless and ability to consent becomes rather moot in my mind. Especially given that I very much would doubt that everyone who participates is getting the dosage levels that they would normally use on the street – in a sense, some of them at least, are likely actually giving up something to take part in those sorts of studies.
    Also, some studies involving human users are specifically testing therapeutic approaches and some are not.
    I was honestly unaware that they were clinically testing therapeutic approaches that allowed addicts to continue taking their substance of abuse, here in the U.S. I know of therapists who encourage their patients to take smaller steps to quitting, or to simply take control of their use, but I didn’t find anything that involved actually clinical work, except in the Netherlands, Sweden and one or two in the UK.
    Sci –
    To some researchers, the system is what they are interested in, and “clinical relevance” is only something you write in to get the grant funded.
    Honestly, I really don’t have a problem with that, because whether they think it is or not – the work in the lab will probably be a net positive anyways. The problem I have is that even for those doing very specific research that may or may not be translational would be well served in having an underlying understanding of the real world in conjunction with what they are researching.
    And in the same way, while researchers need to reach toward the clinic, it’s important that clinicians show an interest in the latest developing research.
    I couldn’t agree more and have pissed off a couple of specific clinicians by pointing this out. I by no means meant that to be a comment that was criticizing lab researchers alone – I am very much interested in seeing clinicians from every treatment methodology pay attention to whats coming out of the labs. And unfortunately, it is often the very people who are revolutionizing addiction treatment who are the least interested in the lab.
    Thankfully I haven’t pissed anyone off enough that they don’t want to continue supporting me and the research project and presentation I am working on. And I have gotten some agreement. But one of the people who is most interested in the direction I am going with my linguistics approach got rather snitty with my suggestion that clinicians pay more attention – in a “why the fuck should I listen to you” sort of way. He did apologize for it later, I suspect when he considered the irony of that statement in conjunction with his major support of the approach I am trying to develop…
    I will admit though, that I mainly got focused on this line of reasoning, because of several discussions that have occurred at DM’s and what I see as a significant disconnect between the hard science in the lab and the reality of what clinicians are dealing with. But even on that count, I place as much blame on clinicians for providing very poor tools – most notably the DSM for addiction and substance abuse.

  14. Hi,
    Thanks for writing such a great article. It’s really good to know about drug rehab in such a detail. It all begins with the idea to try how it feels when you take a sip of alcohol. It was not only depends a mouthful, so that increases the desire of some of the drink. And that is how we become dependent, and soon will need Alcohol Detox and rehabilitation.
    People like the use of alcohol as a fashion and show their position in principle and is now a drug for them. Sad is that some are not able to achieve. But some are not able or their bad habit or you decide not able to stop what they do with themselves. People who have an addiction to alcohol can do Alcohol Detox. And place that can facilitate the Addiction Treatment is Treatment Solutions Network or http://www.treatmentsolutionsnetwork.com. By doing Alcohol Detox, alcohol addicts will understand how to overcome the desire to drink alcohol again. And with the desire to recover, usually will accelerate recovery for the patient’s own self. In addition, Opiate Detox can also be done to remove toxins from the body, this can be done if the patient has both alcohol and drugs dependence.
    Thanks,
    – Andrew Morales

  15. Getting rid of addiction to alcohol isn’t an overnight magic. Rehabilitation in itself is a long term battle, especially when the person has been affected by alcohol addiction previously. The backslide is greater if the post-rehabilitative scenario consists of a neighborhood that can affect the newly rehabilitated individual. This is the assessment of how efficient the treatment has been in the alcohol facilities. The real thing with alcohol happens soon after one has been discharged from the center and the real test of how powerful remedy would occur upon offers of the substance once again.’

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