Pill to Gill: Antianxiety Drugs Flushed into Water May Be Making Fishes Fearless

Levels of human drugs commonly found in the world's waterways may be altering the way fishes behave















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Levels of human drugs commonly found in the world's waterways may be altering the way fishes behave. Image: Flickr/Saspotato

Antianxiety drugs may be making fish more aggressive. New laboratory tests reveal that even extremely low concentrations of the calming drugs benzodiazepines—more commonly known as Valium and Xanax, among others—cause fish to become less timid and to feed faster, among other effects.

"This is an essential drug that is used around the world," said chemist Jerker Fick of Umea University in Sweden at a press conference preceding publication of the research in Science. Benzodiazepines calm people with anxiety by stimulating the GABA receptor, enhancing the sedative effect of that neurotransmitter. The drugs are then excreted in urine, often as the compound oxazepam—a compound that is produced when the body breaks down some benzodiazepines as well as a drug in its own right. Then there are all the compounds are flushed down the toilet.

But humans are not the only animals with GABA receptors. "It is present in almost all vertebrates. All fish have these," Fick added.

A previous survey revealed that low levels of such antianxiety drugs contaminated Sweden’s waterways, reaching levels as high as 0.58 microgram per liter. Oxazepam in particular proved long-lasting because even sunlight failed to break it down. As a result, the compound built up in the tissue of wild-caught perch, reaching levels of 3.6 micrograms per kilogram—or more than six times higher than in the surrounding waters. So the Swedish researchers decided to run some experiments to see how these low levels of drugs might be affecting fishes.

The researchers used 90 juvenile European perch, Perca fluviatilis—the same fish whose levels in the wild had been measured. They tested their behavior in clean water: recording how active they were; their risk-taking behaviors such as entering an unknown and open stretch of water; how they interacted with their fellow perch; and even how quickly they fed on prey.

The researchers then either kept some of the fish in clean water for a week, exposed them to low levels of oxazepam (1.8 micrograms per liter, or three-times environmental levels) or high levels of the drugs, 910 micrograms per liter. The effect was obvious, says ecologist Tomas Brodin of Umea University, who led the research. "They became more active, they became asocial and they became risk-taking," Brodin explained at the press conference. "We do daily care on these fish. On day three, without knowing [which fish was in which group], I could tell which fish were exposed."

That's because the unexposed fish would cower in dark corners or swim around nervously whereas exposed fish quickly explored new, but possibly dangerous aquatic territory. The exposed fish also ate prey faster—it took 75 seconds for unexposed fish to decide the coast was clear enough to eat zooplankton, as compared with 25 seconds for fish exposed to low levels of the drug and just two seconds for fish with the highest levels.

Drugged fish are not likely to impact humans: "You'd have to eat four [metric] tons of perch from the river to get one tablet of the drug," Fick explained at the press conference. "It's not a human health issue, it's an aquatic issue."

And it may be that the levels actually found in water—about one third of the exposure levels in the lab—are low enough that no impact is seen. "We need to reduce the exposure concentration to see where we don't have any effect," Fick admitted. But "we can see profound effects at low levels, at levels that correspond to levels we actually find in surface waters."



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  1. 1. sandragon 12:02 PM 2/16/13

    I suppose this sort of behavior change could lead to increased spread of organisms into new territories. Not just naturally, but also by helping them move boldly into the new environment when moved by humans. Perhaps similar testing on other animals is called for.

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  2. 2. vapur 12:03 PM 2/16/13

    Why is untreated sewer water making it into rivers? I thought people were told by the FDA to dispose of their old and unused medications down the sink or toilet.

    quote, "When you dispose of these patches and certain other powerful medicines down the sink or toilet you help to keep others safe by ensuring that these medicines cannot be used again or accidentally ingested and cause harm."

    So, the most harmful things can be disposed of in such a manner to remove its immediate harm to humans or pets, but who cares about the environment!

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  3. 3. sandragon 12:21 PM 2/16/13

    vapur, the current recommendation for disposal is to take unused meds to a designated collection facility or back to the pharmacy. If this is impossible, tightly seal and wrap the drugs and put in the trash. I trust that someone will post the exact quote. I never thought about what you would do with used patches.
    Of course the big problem here is that the drug is present in human urine and current wastewater treatment doesn't remove it.

    To add to my previous post, I particularly wonder if this has had an effect on creatures like the "flying" carp in the midwest or even the mollusks and worms which have invaded our lakes. Perhaps similar studies could be done on zebra mussels?

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  4. 4. tomgarven in reply to vapur 02:14 PM 2/16/13

    Where I live in Arizona we have collection days for unused drugs. Thousands of pounds of old drugs are routinely collected and disposed of by various methods including incineration at high temperatures. I am also quite sure that thousands of pounds of drugs are still being flushed or dumped instead of being collected. But we diffidently discourage flushing or dumping down the toilet or sink since after sewer treatment that water is either re-injected into the aquifer or feed into a nearby lake. Neither would be a good place to put a cocktail of drugs, yuk.

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  5. 5. Bops in reply to vapur 01:23 AM 2/17/13

    I do...a lot of other people too.
    We have a fish tank, 30 years now, I know a little about different fish.
    We have to feeder gold fish that zoom around the tank and eat everything.
    We put up a barrier to let the other fish eat. I want t give them the boot... but our cat love them because they come to greet her and spit water. She like to watch them any way.

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  6. 6. Bops in reply to Bops 01:31 AM 2/17/13

    Sorry about the spelling. I should have my glasses on.
    I always keep the fish that are nice, the ones that aren't have a new home in my friends aggressive fish tank.
    These two gold fish are not like any of the other gold fish we have had. These are over active, very playful, they are so nuts they try to jump out when I clean the tank.

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  7. 7. Oldineluctable 05:19 PM 2/20/13

    This can be a serious issue. We need to find a way to make it easy to get rid of our drugs or return them without just tossing them in to the garbage. My father passed and I wanted to return an order. No dice, they didn't know what we did to the drugs, even though they were un opened. So, we have some logistic problems not to mention attack perch.

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  8. 8. ssm1959 07:53 PM 2/21/13

    I have to call BS on this one. Granted in this short review it is not possible to provide all the rationale behind the study. However please explain why 3x the highest recorded environmental concentrations ever found was used as the minimum in this study, and where did the 910ug/l come from? I am far more interested the effects at 0.58ug/l, a condition that actually exists in the real world. I suspect only the higher levels were reported because there was no demonstrable effect at the lower concentrations.

    My second issue is the phrase "the effect was obvious". Was that at the lowest concentrations, the highest, or both. The implication clearly suggests the latter but is that really what was seen.

    The authors are directing their investigation to support a straight line dose-response curve. Mountains of research clearly show this is not the case with any drug or other pollutant for that matter. There is a concentration of benzodiazepine below which there is no observable effect.

    Even if the authors are correct their research does not replicate the real world. Fish living every day in Valium water will develop a tolerance to the drug just as humans do. Taking non-exposed fish and providing a drug will most definitely produce an effect just as if I inject 5mg of this same drug into your vein. If I do that daily to you, very quickly the effect will become muted and ultimately you will need 10 mg or more to get an effect equivalent to the first dose. In other word the drug becomes part of the normal milieux.

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  9. 9. Steven 11:36 PM 2/21/13

    Probably the most important information would be tissue levels of the drugs, (benzo's) in the fish's tissues. If the low environmental levels resulted in accumulated drug residues in the brain, then they may be onto something by investigating the effect on the fish.
    Usually the most important environmental contaminants are hormonal mimics or estrogen blockers, which may have the potential to be carcinogens, and also alter embryonic and probably further development, possibly even leading to hormonally stimulated tumors such as breast, or prostate cancer, possibly even testicular cancer, so disposing of drugs without environmental contamination is important.
    It is pretty hard to dispose of drugs, even taking them back to pharmacies, although this is actually the way control drugs such as narcotics are to be disposed of, with documentation of destruction.
    It is interesting how feeding behavior is stimulated. Alcohol, which also is mediated through GABA receptors, may have a similar effect on relieving inhibitions and possibly could have a similar effect on fish.
    I don't think alcohol accumulates in the water like the drugs however, which apparently accumulate in the environment to some degree.
    Certainly alcohol has similar effects in other vertebrates, including humans, relieving inhibitions and getting people into risky situations.
    I don't know what levels would be necessary to stimulate feeding behavior in fish.
    Perhaps the GABA receptors stimulate feeding frenzies in sharks, which are apparently set off by blood in the water. If the benzodiazepines and their break down products are bioconcentrated, such as when bigger fish eat the smaller fish, the drug residues might accumulate in large predators, such as sharks.
    If feeding behavior and aggressiveness is stimulated in sharks by accumulated tissue residues, it might explain some shark attacks on humans.
    Checking the tissue levels of sharks and other large predators for accumulated drug residues might be important to understand the potential of environmental contamination through bioaccumulation through the food chain, similarly to that which occurs with mercury, which may accumulate in large predator fish such as tuna to some degree.

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  10. 10. rlh2012 11:55 PM 2/25/13

    Interesting

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