However, experiments in rodents, such as those outlined above, are insufficient to model human reward based behaviors and to predict the addictive potential of drugs. Thus the present results provide the first unequivocal demonstration that URB597 lacks THC-like reinforcing properties, and suggest that this FAAH inhibitor might be used in therapy without anticipated risk of abuse or triggering relapse to drug use. Exogenous anandamide exerts potent reinforcing effects in monkeys . Thus, it may be surprising that the ability of URB597 to potentiate brain anandamide signaling does not translate into overt rewarding properties. However, there are two plausible reasons why URB597 does not support self-administration responding. First, exogenous and endogenous anandamide might each access distinct sub-populations of CB1 receptors in the brain. In particular, systemic administration could allow anandamide to reach a receptor pool that is normally engaged by 2-AG. In this context, the observation that treatment with URB597 decreases 2-AG levels in the monkey brain suggests the existence of a compensatory mechanism aimed at reducing 2-AG signaling in the face of enhanced anandamide signaling. Such a mechanism might account, at least in part, for the inability of URB597 to serve as a reinforcer. Consistent with this idea, a recent report suggests that pharmacological or genetic disruption of FAAH activity causes a down-regulation of 2-AG production in acutely dissected rodent striatal slices, which is reportedly due to vanilloid TRPV1 receptor activation . However, rolling benches for growing we were unable to replicate this observation in live animals even when using doses of URB597 that completely suppressed FAAH activity and significantly increased anandamide levels . Another possibility is that the kinetics of CB1 receptor activation may differ between anandamide and URB597 administration, as the former is likely to produce a more rapid recruitment of CB1 receptors than the latter.
It is well established that effectiveness of drug reinforcement in monkeys depends on a rapid drug distribution throughout the brain . Irrespective of the mechanism involved, the impact of 2-AG down-regulation on the broad pharmacological properties of URB597 in primates remains to be determined. In conclusion, our findings with URB597 unmask a previously unsuspected functional heterogeneity within the endocannabinoid signaling system in the brain, and suggest that FAAH inhibitors such as URB597 might be used therapeutically without risk of abuse or triggering relapse to drug abuse. Big cities produce a lot of sewage, which often contains pharmaceuticals, illicit drugs, and caffeine. These flushed pollutants can remain in wastewater even after processing by a wastewater treatment plant, and may have negative effects on marine organisms and ecosystems if introduced into the marine environment. California is home to Los Angeles, San Diego, and San Jose—three of the ten most populous cities in the United States.1 All three are located in coastal counties2 and utilize wastewater treatment plants 3 that discharge treated wastewater effluent directly into the Pacific Ocean.4 As our cities grow, municipal wastewater is expected to contain increasing concentrations of flushed pollutants, posing a heightened threat to the health of our coasts and the marine environment more broadly. However, monitoring and regulation of flushed pollutants is currently insufficient, allowing them to be introduced into the marine environment undetected. This raises serious concern that flushed pollutants may devastate the marine environment beyond repair. The precautionary principle, a central tenet of environmental law and policy, “asserts that regulators and decision makers should act in anticipation of environmental harm, without regard to the certainty of the scientific information pertaining to the risk of harm.”In the face of great uncertainty as to the amounts of flushed pollutants being introduced into the marine environment and the effects they will have on marine organisms and ecosystems, a precautionary approach is necessary to ensure adequate protection.
This Article advocates for policy reform to increase monitoring and regulation of pharmaceuticals, illicit drugs, and caffeine in wastewater, and to ultimately minimize the amounts of these flushed pollutants that are discharged into California’s coastal waters. Part I provides an overview of the wastewater life cycle as a pathway for flushed pollutants to enter the marine environment. This is followed by a discussion of the effects that pharmaceuticals, illicit drugs, and caffeine may have on marine organisms. Part II discusses the current legal and regulatory landscape for managing pollutants in municipal wastewater and its inadequacies in preventing flushed pollutants from harming marine organisms and ecosystems. Part III proposes various legislative tools that can be used to address this issue and suggests topics for future research.In addition to their contributions to tourism and the economy, coastal ecosystems offer unique recreational and educational opportunities, hold important cultural value, and provide a variety of ecosystem services. California’s ocean economy produced over $44 billion in 2013 and its coastal counties are home to almost three-quarters of the state’s population, despite comprising less than a quarter of the state’s land area.Coastal ecosystems can be incredibly complex and marine organisms vary in their sensitivity to pollutants. The discharge of treated wastewater effluent containing pharmaceuticals, illicit drugs, and caffeine into coastal waters raises concerns for the health of these ecosystems and humans alike. This Part introduces three categories of flushed pollutants that are of particular abundance and concern and provides an overview of the means by which flushed pollutants are discharged into the marine environment. It then discusses the potentially devastating effects that these pollutants may have on marine organisms and ecosystems. When humans consume pharmaceuticals, illicit drugs, and caffeine they excrete a portion of these substances as waste. In turn, this waste is flushed down toilets. Flushing is also a common means of disposal of unwanted pharmaceuticals and illicit drugs. In the context of large cities, flushed wastewater is generally transported through a network of sewers to a POTW.These facilities employ a variety of technologies and processes designed to remove solid waste, bacteria, and other pollutants from municipal wastewater.The levels of pharmaceuticals, illicit drugs, and caffeine that remain in treated wastewater effluent largely depend on the technology used.
POTWs located in coastal regions, such as the Hyperion Treatment Plant in Los Angeles, the Point Loma Wastewater Treatment Plant in San Diego, and the San José/Santa Clara Water Pollution Control Plant in San Jose, often discharge treated wastewater effluent directly into coastal waters.This makes POTWs the last safeguard to prevent flushed pollutants from reaching coastal waters. Although POTWs reduce the concentrations of pharma ceuticals, illicit drugs, and caffeine in wastewater, some measure of these pollutants still remains in wastewater after treatment and is thus introduced into the marine environment. A recent study in Southern California tested effluent from four large POTWs that discharge into coastal waters through marine outfalls.The study found pharmaceutical hormones such as estradiol, testosterone, progesterone, and estrone in 63–100% of effluent samples.Another alarming study detected cocaine in 36% of mussel tissue samples collected along the California coast and caffeine in 19% of the samples.As more research is conducted to determine the levels of pharmaceuticals, illicit drugs, vertical cannabis grow and caffeine in POTW influent and effluent, concern is growing over the effects these pollutants may have on marine organisms and ecosystems. Pharmaceuticals, illicit drugs, and caffeine have been detected in California’s coastal waters, but little research has been done to determine the rate at which these pollutants are being introduced into the marine environment. The persistence of these pollutants and the effects they have on marine organisms and ecosystems are also largely unknown. If these pollutants prove to be harmful and persistent, exposure and bio accumulation could threaten the collapse of ecosystems already imperiled by climate change, overfishing, and other anthropogenic impacts. This section introduces pharmaceuticals, illicit drugs, and caffeine, and summarizes what is known about the concerning effects these pollutants may have on marine organisms and ecosystems. Pharmaceuticals include both prescription and over-the counter medications. Antibiotics, antidepressants, and repro ductive hormones are a few examples of particular concern. In a 2012 study, almost half of Americans reported using at least one prescription medication in the past 30 days,and pharmaceutical use in the United States continues to rise.The body absorbs only a portion of pharmaceutical compounds that are consumed and excretes the remainder as waste.With prescription drug abuse and overdose rates on the rise,16 unused pharmaceuticals are also commonly flushed as a method of disposal. Pharmaceutical pollution has been detected in treated wastewater effluent and in surface waters throughout the nation,and has been documented in detail along the South Florida Coast.In fact, according to the National Centers for Coastal Ocean Science, pharmaceutical pollution may be as common in the marine environment as agricultural pollution.However, as compared to agrochemicals, far less research has been conducted on the effects of pharmaceuticals on marine organisms and ecosystems. Pharmaceutical antibiotics, antidepressants, and reproductive hormones are endocrine-disrupting chemicals that have been detected in treated wastewater effluent.EDCs interfere with “the production, release, transport, metabolism, binding, action, or elimination of natural hormones in the body responsible for the maintenance of homeostasis and the regulation of developmental processes.”EDCs have been linked to reproductive and developmental toxicity, carcinogenesis, immunotoxicity, and neurotoxicity in humans,and research indicates EDCs may have similar impacts on wildlife.Exposure to pharmaceutical EDCs has been shown to have devastating consequences for freshwater organisms and preliminary research indicates marine organisms may be similarly affected.Appropriately, there is growing concern in the environmental community over the introduction of pharmaceutical EDCs into coastal ecosystems through treated wastewater. For the purposes of this paper, illicit drugs are those for which non-medical use or possession is prohibited by federal law.
A 2013 report prepared by the Substance Abuse and Mental Health Services Administration estimated roughly 9.4% of Americans aged 12 or older had used at least one illicit drug in the past month.Similar to its treatment of pharmaceuticals, the human body does not absorb a large portion of illicit drugs that are consumed. Illicit drugs thus “enter the wastewater network . . . by human excretion after illegal consumption or by accidental or deliberate disposal.”A variety of illicit drugs have been detected in surface waters and treated wastewater effluent from POTWs across the United States, including cannabis,cocaine, MDMA,methadone, and methamphetamine.However, the effects of illicit drugs on marine organisms and coastal ecosystems are not well studied. Research indicates that exposure to illicit drugs could produce devastating effects in freshwater organisms, including genetic damage and mutation.Illicit drugs may have similarly disastrous consequences when introduced into the marine environment.The consumption of caffeine, which is found most notably in coffee and tea, has been linked to reduced fatigue and heightened mental alertness.Caffeine is widely enjoyed throughout the United States, with roughly 85% of Americans consuming at least one caffeinated beverage daily.Caffeine originating in human waste has been detected in coastal waters across the United States, including Puget Sound,Boston Harbor, and the Oregon coast.The ubiquitous nature of caffeine in our nation’s surface waters and treated wastewater effluent is well-documented and concern over the continuous discharge of caffeine into coastal waters is tempered as compared with concerns over pharmaceuticals and illicit drugs. However, the effects of caffeine on marine organ isms and coastal ecosystems have not been well-researched and are largely unknown. One laboratory study indicated that a seven-day exposure to environmental concentrations of caffeine induced a stress syndrome in Mediterranean mussels, causing the mussels to undergo detoxifying processes.Bioluminescence inhibition, fertilization impairment, algal bleaching, and mortality have also been observed in marine species as a result of exposure to high concentrations of caffeine.Although current environmental concentrations of caffeine are thought to be too low to significantly affect the survival, growth, and reproduction of marine organisms, there is concern that higher concentrations of caffeine released into the marine environment may have devastating effects. This Part provides an overview of the primary state and federal laws that address pollutant flushing, wastewater treatment, and discharges of treated wastewater effluent into the marine environment. When it comes to flushed pollutants, the Clean Water Act and Porter-Cologne Water Quality Control Act provide the most effective protection for the marine environment through the regulation of discharges of pollutants by hospitals and other large-scale flushers into the sanitary sewer system, as well as discharges of effluent from POTWs into the ocean. The Controlled Substances Act and California Uniform Controlled Substances Act help to reduce household flushing of unwanted pharmaceuticals by providing alternative mechanisms for safe and legal disposal.