• 02 AUG 16

    Synthetic Antidepressants are harming the Earth

    By Robert Gorter, MD, PhD, et. al.

    Robert Gorter is emeritus professor of the University of California San Francisco (UCSF)

    Dr. Robert Gorter: For a long time, the effects on the eco-system of medications for human use and their metabolites that end up in the eco system, have been ignored by scientists, public health officials and by politicians alike.

    Although the devastating effects hormones have on the environment were known since the early 1970’s, little has been done to look into other medications and their metabolites on human health and the eco-system man is part of.

    Some medications (and their split products) are much worse than others; one can say that hormones and SRIs are among the worst ones, next to heavy metals.

    Many argue that the pharmaceutical industry makes a lot of profit from there drugs and hence, should be kept (at least in part) accountable for the devastating effects.

    Still unclear is what the long term evolutionary effects will be on future generations in triggering mutations, deformations, etc. But all scientists with knowledge in these fields agree that a time bomb is ticking……


     

    Synthetic Antidepressants are harming the Earth

     

    Synthetic Antidepressants

     

    Many are aware of the harm that taking synthetic antidepressants, namely serotonin reuptake inhibitors (SRIs), can cause on a personal level. Few, however, are aware of the harm it can do on a large scale. All life forms on earth, including the very earth itself, are negatively impacted by antidepressants, as they disrupt adaptive processes regulated by serotonin. For example, serotonin is found in plant tissues and, just like it is in humans, it is responsible for various functions crucial to a plant’s quality of life. Because they are not very biodegradable, excretion of SRIs impacts all organisms that use serotonin to function properly, including plants, the animals that eat those plants, and therefore all humans – not just those who directly take antidepressants. When looked at from this perspective, it becomes clear that the decision of whether or not to take SRIs is a much larger one than we thought, as the choice to do so provokes a negative ripple effect on the planet as a whole.

     

    Serotonin in plants

    Serotonin has various functions in plants, including but not limited to reproduction, protection of plant cells, growth, free radical scavenging and the development of root systems – aka a plant’s predominant neural network. 5-HT1a and 2a receptors in the neural networks of plants interact with serotonin similar to the way they do in animals. 5-HT1a receptors, for example, interact with serotonin to create intracellular stability in a plant’s cytoskeleton. In response to environmental stress, 5-HT2a receptors interact with serotonin in the internal cytoskeleton of a plant by inhibiting old patterns of neural networks that are having difficulty adjusting to environmental changes and create new ones that are more adaptable.

    How the use of synthetic antidepressants can harm plants

    Over fifty synthetic serotonin reuptake inhibitors (SRIs) are excreted by urine mainly into the earth, and not a single organism that uses serotonin to function is exempt of paying the harmful repercussions. SRIs are highly active even in trace amounts and are found in virtually all waste water streams in industrial nations, thereby interfering with reproduction, germination and root development in every system on the planet affected by serotonin. All forms of SRIs come equipped with the same destiny of collectively working with one another to deregulate the neuronal networks of the planet. The extent to which any specific type of SRI proves harmful varies, though, with some causing more destruction than others. For example, only 20 uM of Prozac reduces root development from 15-20 per nodal segment to only 4. Worsening the picture is the fact that these SRIs are not very biodegradable. By not very, I mean they take four months to degrade in streams – in the best case scenario. If they manage to sink to the sediment at the bottom of rivers and ponds before degrading they do not seem to biodegrade at all.

    The intricate relationships among animals and plants that make up an ecosystem depend upon a certain balance. Therefore the question that haunts Black, Armbrust and others is: What happens to those organisms — and to us — if that balance is upset?

    “We used to think that only compounds in the water would harm humans, and only through direct exposure,” Black said. But scientists have come to realize that the harm may occur indirectly by disrupting ecological biodiversity.

    Chemicals Out of Place

    Up to 90 % of many prescription drugs that humans consume ultimately find their way to sewage-treatment plants. While treatment plants that process drinking water remove these chemicals and their metabolic byproducts, these compounds pass through sewage-treatment facilities, which are designed to remove solids and bacteria but are not equipped to screen for pharmaceuticals. Armbrust, who is also the state chemist for Mississippi, was particularly taken aback by a 1999 paper in the journal Environmental Health Perspectives that documented a steady stream of pharmaceuticals — including Prozac and other selective serotonin re-uptake inhibitors, or SSRIs — being passed into the nation’s waters. SSRIs are among the 200 most-prescribed medications in the United States; the number of adults taking antidepressants has nearly tripled since Prozac was first introduced to the market in 1987, according to the USA Centers for Disease Control and Prevention.

    In some people who have depression, the brain doesn’t produce enough of the neurotransmitter serotonin — a natural chemical that helps transport electrical impulses by shuttling back and forth across the spaces between neurons. So SSRIs are deployed to keep the chemical’s concentration high. In animals, serotonin also performs a critical role of “regulating a broad spectrum of behaviors, ranging from mating to feeding,” said Christian Daughton, chief of the Environmental Chemistry Branch of EPA’s National Exposure Research Laboratory and a co-author of the 1999 paper that first piqued Armbrust’s and Black’s interest.

    Soon after that study was published, Black and Armbrust teamed up to investigate the possible ecological impact of these new contaminants. The two scientists secured a three-year grant for $522,000 from the U.S. EPA to determine what happens to SSRIs in the water and what effect, if any, they have on frogs, fish and other aquatic life.

    Black, who came to UGA in 1995, first examined water-quality issues as a graduate student at the University of Tennessee. Her focus on the biological aspects of contamination — the impacts of pollutants on aquatic life — neatly complements Armbrust’s interest in the chemistry of contaminants. While Black (who serves as principal investigator on the EPA grant) and her group observe the effects of SSRIs on aquatic invertebrates, fish and frogs, Armbrust’s team analyzes the chemical behavior of the drugs — what’s getting through the wastewater-treatment facilities, how quickly the SSRIs biodegrade once they’re in the environment, what they break down into and how long all these chemicals persist. Basically, said Armbrust, “we’re measuring exposure and they’re measuring effects.”

    Provactive Results

    When Black and Armbrust first conducted an extensive review of the scientific literature to see what was already known, they found evidence to suggest that Prozac affected the reproductive systems of clams. Was it possible that other forms of aquatic life were affected as well?

    Early results in Black’s lab suggested that SSRIs may indeed cause problems for a range of organisms. For one thing, fish and frogs exposed to SSRIs were lethargic, which could leave them easy targets for predators. But on a deeper biological level, Black and UGA post-doctoral fellow Theodore Henry, now on the faculty at the University of Tennessee, observed that relatively low concentrations of Prozac in mosquito fish led to developmental delays, particularly in the formation of reproductive tissue. Because reproductive success in fish depends heavily on timing, even modest delays could leave them unable to generate new broods and ultimately lead to population declines. Henry also found increased mortality and lower reproductive rates in daphnids, tiny crustaceans commonly used to evaluate a compound’s toxicity in aquatic environments.

     

    Daphnia, a genus of small planktonic crustaceans, are 1–5 millimeters (0.04–0.20 in) in length. Daphnia are members of the order Cladocera, and are one of the several small aquatic crustaceans commonly called water fleas because their saltatory (Wiktionary) swimming style resembles the movements of fleas. Daphnia live in various aquatic environments ranging from acidic swamps to freshwater lakes, ponds, streams and rivers

    Daphnia, a genus of small planktonic crustaceans, are 1–5 millimeters (0.04–0.20 in) in length. Daphnia are members of the order Cladocera, and are one of the several small aquatic crustaceans commonly called water fleas because their saltatory (Wiktionary) swimming style resembles the movements of fleas. Daphnia live in various aquatic environments ranging from acidic swamps to freshwater lakes, ponds, streams and rivers

     

    The group’s most provocative results so far have involved amphibians. Serotonin is believed to affect thyroid function, which is particularly important in frogs because thyroid hormones are thought to trigger their metamorphosis. In one set of experiments, Black and doctoral student Emily Rogers discovered that exposure to Prozac slowed this essential process. “The delay’s biggest problem is that it can leave frogs totally vulnerable for much longer periods,” said Black, and not only with respect to predation. Many tadpoles undergo metamorphosis while nestled in small pools of ephemeral waters on land. If their developmental timing is off, the water could dry up before the immature frogs complete this stage.

    Studies by Armbrust and post-doctoral fellow Jeong Wook Kwon also are yielding interesting findings, particularly on Prozac’s environmental persistence in water and sediment. “If it’s in water,” Armbrust said, “it’s not going to break down quickly – the half-life there is about four months. And in sediment, it doesn’t seem to biodegrade at all.”

    Despite their early results, Black and Armbrust are not yet prepared to sound any alarms on SSRIs in the environment. They suspect that the degree of impact depends not so much on short-term concentrations, even if relatively intense, but on long-term exposures to constant environmental levels of the drugs. The latter occurrence is likely, given that people who take SSRIs usually do so for long periods of time. But because that cumulative effect on populations of aquatic life has not been demonstrated, it is what the researchers plan to explore next.

    “From an ecological standpoint, the preservation of biodiversity is so important,” Black said. “The loss of one species may not seem that critical, but could be very critical if it was the sole food source for another species.”

    In the past, a lack of technology and information may have limited scientists’ ability to see the big picture on water quality, but research advances over the past few decades may be changing the situation, Black suggested. “Perhaps now that we’re looking more holistically at watersheds,” she said, “we’ll see things we missed before.”

    When Black and Armbrust first conducted an extensive review of the scientific literature to see what was already known, they found evidence to suggest that Prozac affected the reproductive systems of clams. Was it possible that other forms of aquatic life were affected as well?

    Early results in Black’s lab suggested that SSRIs may indeed cause problems for a range of organisms. For one thing, fish and frogs exposed to SSRIs were lethargic, which could leave them easy targets for predators. But on a deeper biological level, Black and UGA post-doctoral fellow Theodore Henry, now on the faculty at the University of Tennessee, observed that relatively low concentrations of Prozac in mosquito fish led to developmental delays, particularly in the formation of reproductive tissue. Because reproductive success in fish depends heavily on timing, even modest delays could leave them unable to generate new broods and ultimately lead to population declines. Henry also found increased mortality and lower reproductive rates in daphnids, tiny crustaceans commonly used to evaluate a compound’s toxicity in aquatic environments.

    The group’s most provocative results so far have involved amphibians. Serotonin is believed to affect thyroid function, which is particularly important in frogs because thyroid hormones are thought to trigger their metamorphosis. In one set of experiments, Black and doctoral student Emily Rogers discovered that exposure to Prozac slowed this essential process. “The delay’s biggest problem is that it can leave frogs totally vulnerable for much longer periods,” said Black, and not only with respect to predation. Many tadpoles undergo metamorphosis while nestled in small pools of ephemeral waters on land. If their developmental timing is off, the water could dry up before the immature frogs complete this stage.

    Studies by Armbrust and post-doctoral fellow Jeong Wook Kwon also are yielding interesting findings, particularly on Prozac’s environmental persistence in water and sediment. “If it’s in water,” Armbrust said, “it’s not going to break down quickly – the half-life there is about four months. And in sediment, it doesn’t seem to biodegrade at all.”

    Despite their early results, Black and Armbrust are not yet prepared to sound any alarms on SSRIs in the environment. They suspect that the degree of impact depends not so much on short-term concentrations, even if relatively intense, but on long-term exposures to constant environmental levels of the drugs. The latter occurrence is likely, given that people who take SSRIs usually do so for long periods of time. But because that cumulative effect on populations of aquatic life has not been demonstrated, it is what the researchers plan to explore next.

    “From an ecological standpoint, the preservation of biodiversity is so important,” Black said. “The loss of one species may not seem that critical, but could be very critical if it was the sole food source for another species.”

    In the past, a lack of technology and information may have limited scientists’ ability to see the big picture on water quality, but research advances over the past few decades may be changing the situation, Black suggested. “Perhaps now that we’re looking more holistically at watersheds,” she said, “we’ll see things we missed before.”

     

    The Gorter Model

     

    Potent pharmaceuticals flushed into the environment via human and animal sewage could be a hidden cause of the global wildlife crisis, according to new research. The scientists warn that worldwide use of the drugs, which are designed to be biologically active at low concentrations, is rising rapidly but that too little is currently known about their effect on the natural world.

    Studies of the effect of pharmaceutical contamination on wildlife are rare but new work published on Monday reveals that an anti-depressant reduces feeding in starlings and that a contraceptive drug slashes fish populations in lakes.

    “With thousands of pharmaceuticals in use globally, they have the potential to have potent effects on wildlife and ecosystems,” said Kathryn Arnold, at the University of York, who edited a special issue of the journal Philosophical Transactions of the Royal Society B.” Given the many benefits of pharmaceuticals, there is a need for science to deliver better estimates of the environmental risks they pose.”

    She said: “Given that populations of many species living in human-altered landscapes are declining for reasons that cannot be fully explained, we believe that it is time to explore emerging challenges,” such as pharmaceutical pollution.

    Research published in September revealed half of the planet’s wild animals had been wiped out in the last 40 years. In freshwater habitats, where drug residues are most commonly found, the research found 75% of fish and amphibians had been lost.

    A few dramatic examples of wildlife harmed by drug contamination have been discovered previously, including male fish being feminised by the synthetic hormones used in birth-control pills and vultures in India being virtually wiped out by an anti-inflammatory drug given to the cattle on whose carcasses they feed. Inter-sex frogs have also recently been found in urban ponds contaminated with wastewater.

    Vultures in India were virtually wiped out by an anti-inflammatory drug given to the cattle on whose carcasses they feed. Photograph: Adrian Page/Alamy

    But because the pharmaceuticals are not designed to kill – unlike pesticides – the damage caused to wildlife can be more subtle.

    In one of the new studies, Tom Bean at the University of York and colleagues showed that the common antidepressant fluoxetine, at the low levels expected in the environment, led starlings to feed less often during the key foraging times of sunrise and sunset. “Importantly, fluoxetine is not the only pharmaceutical, or indeed the only antidepressant, to be detected in the environment,” he said. “Mixtures of pharmaceuticals could potentially be more potent.”

    Another new study, led by Karen Kidd at the University of New Brunswick, showed synthetic estrogen used in the birth control pill not only wiped out fathead minnows in lakes used for experiments in Ontario, but also seriously disrupted the whole ecosystem. The lakes’ top predator – trout – declined by 23-42%, due to the loss of the minnow and other prey, while insects increased as they were no longer being eaten by the minnows.

    Amphibians are suffering the hardest in the global biodiversity decline and Cecilia Berg, at Uppsala University, and colleagues reported that a number of hormonally active pharmaceuticals harm reproduction in amphibians at concentrations that occur in natural waters.

    The most environmentally dangerous drugs are identified in a paper by Anette Küster and Nicole Adler, both at Germany’s Federal Environment Agency. “For human medicinal products, hormones, antibiotics, [painkillers], antidepressants and [anti-cancer drugs] indicated an environmental risk,” they said. For veterinary drugs, hormones, antibiotics and parasiticides were highlighted.

    Pharmaceuticals can contaminate the environment through discharges from drug factories, as well as through sewage. Professor Joakim Larsson, at the University of Gothenburg, found that drug levels in effluents can even exceed those found in the blood of people taking medication.

    Larsson cited antibiotic pollution coming from factories in China, India, Pakistan, Korea, Denmark, Norway and Croatia. “Although pollution from manufacturing is less widespread, discharges that promote the development of drug-resistant microorganisms can still have global consequences.” He also documented antidepressant pollution from factories in Switzerland, Israel and Spain and “narcotic opioid” pollution in the US.

    The use of pharmaceuticals is rising with increases in the human population and the livestock it keeps. Environmental exposure is also rising as sewage is increasingly used to irrigate or fertilize farmland. In the US, for example, about 4m tons of dry sewage biosolids are applied to land each year.

    Sally Gaw, at the University of Canterbury, and colleagues warned that even less is known about the effect of pharmaceutical pollution in the oceans. “This is a critical knowledge gap given the significant increase in coastal human populations around the globe and the growth of coastal megacities, together with the increasing importance of coastal [fisheries] around the world.”


    Resources

    • Whitlock Kelli. “Casting Prozac upon the waters.” University of Georgia Research Magazine, Summer 2005.
    • P. Andrews et. al., “Primum non nocere: An evolutionary analysis of whether antidepressants do more harm than good”
    • Ramon Pelagio-Flores et al., “Serotonin, a tryptophan-derived signal conserved in plants and animals, regulates root system architecture probably acting as a neural auxin inhibitor in Arabidopsis thaliana,” 490
    • Buhner, Stephen. Plant Intelligence and the Imaginal Realm: Into the Dreaming of Earth. Vermont: Bear & Company, 2014.