On Drugs and Fish: Contamination of Aquatic Environments and Drug Detection

I happened across an interesting article in Nature the other morning, titled "Human drugs make fish flounder". It explores the effects of two drugs, the antidepressant fluoxetine, and a sex hormone, estradiol.

At first glance it may seem odd to be concerned about the effect of human medications on aquatic wildlife. After all, fish are not typically known for travelling down to the local pharmacy. Rather, this article highlights a significant issue relating to the impact of humans and their behaviours on local ecosystems. A veritable cornucopia of drugs and drug metabolites are excreted via our urine and faeces, and though wastewater and sewage is typically treated,  these compounds end up in local waterways, and the aquatic homes of a range of fauna. The end result of this type of chemical pollution is not good, to say the least.

I won't go into significant detail on this specific issue, as the article in Nature is rather informative in itself. In short, researchers at the University of Wisconsin-Milwaukee's Great Lakes Water Institute have studied the effects of fluoxetine on fathead minnows. By exposing this species of fish to different levels of fluoxetine, including concentrations that have been detected in wastewater, a series of significant effects were found.

Though females appear unaffected by the lowest concentration of fluoxetine tested, male fish were found to spend more time building their nests. Increasing the concentration of fluoxetine further, to 10 times the highest detected level in waterways, resulted in the male fish "[becoming] obsessive, to the point they're ignoring the females".

Depression in fish. Simultaneously adorable and so, so sad...
Image by Thezules

Further research was also done by Dan Rearick, an aquatic toxicologist from St Cloud State University in Minnesota. In this research, it was found that exposing the larvae of the fathead minnow to estradiol, an estrogenic sex hormone occasionally used in Hormone Replacement Therapy (HRT) had a negative effect on fish populations. Namely, larvae exposed to estradiol were ultimately less capable of escaping or eluding predators, as their reaction times to external stimulus had been significantly lessened.

Moving away from the effects of two specific drugs on a single species of fish, the fact that drugs and drug metabolites may be detected in the effluent from sewer systems may come as a surprise. So prevalent are these compounds in aquatic environments, they are considered emerging environmental contaminants. As a consequence, the detection of these compounds has some rather significant implications for humans.

How?

Well, as most drugs and metabolites end up in the sewer system, this provides an excellent opportunity for chemists and toxicologists to analyse this effluent. Detection of these compounds may, in turn, allow for the analysis of drug use in local populations serviced by a section of the sewer system. Indeed, it is entirely possible to detect and compare illicit drug use in local populations through the collection and analysis of sewage, with the technique known as sewage epidemiology. As many drugs are metabolised to more polar compounds prior to excretion, much of this work revolves around the detection of drug metabolites, and using both their presence and relative concentrations to calculate drug consumption.

Though the following list is by no means exhaustive, it may provide you with a reasonable idea of the different drugs and respective metabolites reportedly detected in both wastewater and groundwater:

• Amphetamine-type substances (amphetamine, methamphetamine, ecstasy)
• Benzodiazepines (alprazolam, diazepam, lorazepam)
• Cannabis
• Cocaine
• LSD
• Opiates (heroin, morphine, methadone)

To date, a range of different populations and their apparent drug use/abuse has been studied. A quick read through peer-reviewed literature on this subject revealed the following areas that have been subjected to analysis via sewage epidemiology:

• Barcelona, Spain (Jurado et. al., 2012)
• Brussels, Belgium (van Nuijs, et. al., 2011)
• Correctional facility/prison, Catalonia, Spain (Postigo et. al., 2011)
• Ebro River basin, Spain (Postigo et. al., 2010)
• Paris, France (Karolak et. al., 2010)
• North-Eastern Spain (Huerta-Fontela, et. al., 2009)
• Three unnamed cities, Canada (Metcalfe et. al., 2010)

In addition to the above, a fascinating piece of research and collaboration, entitled "Comparing illicit drug use in 19 European cities through sewage analysis", sought to compare illicit drug abuse in a number of European cities. The range and number of cities selected in this study was rather impressive, and specifically sought to compare the usage rates of cannabis, cocaine and three amphetamine-type substances (amphetamine, methamphetamine, ecstasy). Perhaps the most incredible aspect of this manner of toxicological and chemical analysis is that this study allowed for the quantitative, non-intrusive and objective analysis of illicit drug use of approximately 15 million individuals, all over a one-week period.

An impressive feat, all things considered.
Image by Ssolbergj.

The general trends discovered in this work were quite fascinating. It would appear that cocaine use is more prevalent in more urbanised towns or cities within a set country. In terms of cannabis use, the data apparently indicated that the highest use was, unsurprisingly, in the Netherlands. In addition, the *ahem* highest reading recorded for cannabis use was in Amsterdam. Outside of the Netherlands, other high levels of cannabis use were detected in the Czech Republic, Spain, Italy and France. 

Moving on to the amphetamine-type substances, and in particular apparent methamphetamine use, it would appear that Finland, Norway and the Czech Republic collectively hold the dubious honour of having the highest methamphetamine usage rates in the cities studied. Meanwhile, for amphetamine, high apparent use rates were found in Northern Belgium and in the Netherlands. Ecstasy use, on the other had, was allegedly quite high in Eindhoven, Amsterdam and Utrecht (the Netherlands), and also in London (England). 

This method of assessing intra- and inter-community drug use may be considered rather contentious. On one hand, it allows for a non-intrusive method of assessing drug use, which may be of use for providing adequate health services and allow for the effective development of government policy. However, such techniques may also be construed as invasive. Indeed, some may well view with suspicion the position posed in an article by van Nuijs et. al., (2011), where the following point was made with respect to estimating drug consumption based on analysis of wastewater:

"The consumption of illicit drugs causes indisputable societal and economic damage. Therefore it is necessary to know their usage levels and trends for undertaking targeted actions to reduce their use... [and] could be used in routine drug monitoring campaigns"

That being said, Frost, Griffiths and Fanelli (2008), provide a fascinating editorial concerning detection of drugs of abuse in wastewater, and the ethical and political concerns therein. 

All in all, it is clear that the contamination of waterways with drugs and their respective metabolites may have a significant impact on aquatic wildlife. Though perhaps the fish are getting their own back, with it now possible to examine sewage and wastewater to monitor both licit and illicit drug use.

Until next time, 

Nathan