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The Genesis of a Critical Environmental Concern: Cannabinoids in Our Water Systems
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Navid B. Saleh, Onur Apul,* and Tanju Karanfil
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pproximately 192 million people worldwide aged 15−64 (i.e., 3.9% of the global population, per 2016 estimates) regularly use Cannabis, more commonly known as marijuana. The estimated market share of this widely used drug will surpass $22 billion by 2022. On June 28, 2018, the United States Food and Drug Administration approved Epidiolex, a cannabinoid-based drug developed for the treatment of a rare form of epilepsy. Sales of Epidiolex in the U.S. are expected to exceed $1.1 billion by 2022, reflecting a 1100% increase in consumption in less than a decade.1 The burgeoning demand for cannabinoid-based pharmaceuticals such as Epidiolex has shifted the perception of the “marijuana problem” from the use of an illicit substance (marijuana continues to be a Schedule I controlled substance) to the use of approved pharmaceuticals. Though the movement in public discourse may not necessarily change environmental release of recreationally consumed marijuana, its approval as a pharmaceutical will increase the release of cannabinoid-based drugs; due to predicted expansion of its market share as high as 700% by 2020. The annual development and release of pharmaceuticals and personal care products continue to expand the list of emerging contaminants (EC) every year. Similar to many pharmaceuticals, cannabinoid molecules are known to transform in both natural and engineered systems and thus render a higher-level uncertainty and toxicity. Predicted toxicity indices (i.e., −log LC50 for 48 h exposure to D. magna) for cannabinoids and their halogenated byproducts are orders of magnitude higher than those for the toxicity of brominated and chlorinated disinfection byproducts (DBPs) i.e., regulated trihalomethanes (THMs) and haloacetic acids (HAAs).2 Therefore, under© XXXX American Chemical Society
standing the fate, transformation, and removal of cannabinoids in environmental systems is of great importance. Unfortunately, despite their widespread availability, uncertainty-in-point and mass production projections, adverse effects on the nervous system and increased pharmaceutical use, cannabinoids remain the most understudied class of ECs within aquatic systems. The transformation of these products, which are often more toxic than the parent compounds, encourages understanding the reaction processes that cause their development.3 Indeed, new organic contaminants or ECs that are created by the transformation processes in water and wastewater systems have been detected in waste and surface waters, which means that treatment processes must evolve accordingly.4 Halogenated methanesulfonic acid (HMAs), a new class of organic micropollutant produced from an approved drug, is now prevalent in the water cycle and is one of the latest addition to the EC list. As with HMAs, cannabinoids will likely introduce similar compounds during their passage through engineered treatment systems. Δ9-tetrahydrocannabinol (THC) is the primary psychoactive constituent within the cannabinoid class. THC is metabolized and excreted as 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC−COOH) as its main urinary metabolite.5 This metabolite has been detected in untreated, treated, surface waters, and tap water up to 2500, 750, and 500 ng/L, and 1 ng/L, respectively.4 The molecular structure of THC and its metabolite(s) includes a heteroaromatic structure with an alkane chain. Although THC is the predominant psychoactive chemical in Cannabis sativa, there are other natural and synthetic cannabinoid-like chemicals. Cannabidiol (CBD), the main nonpsychoactive cannabinoid constituent, is such a compound that is biogenerated from the same parent precursor (i.e., cannabigerolic acid) with a very similar molecular structure. THC/THC−COOH and CBD molecules have a strong tendency to undergo chemical transformation when entering our treatment systems. The transformation of cannabinoids is particularly significant because of the presence of a phenolic group that undergoes electrophilic substitution with halogen atoms (e.g., chlorine and bromine) during disinfection. The chain-shortening and ring opening reactions and halogen-substitution during oxidation and disinfection need to be systematically evaluated for these emerging heteroaromatic molecules to assess their fate and removal in the treatment systems. THC/THC−COOH and CBD chemical structures bring unique reaction possibilities, when compared to common drug molecules. The most heavily excreted pharmaceuticals in our treatment systems are antibiotics, anticonvulsants, antidepressants, beta-blockers, analgesics, anti-inflammatory drugs, Received: January 10, 2019
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DOI: 10.1021/acs.est.8b06999 Environ. Sci. Technol. XXXX, XXX, XXX−XXX
Viewpoint
Environmental Science & Technology
(5) Huestis, M. A., Pharmacokinetics and metabolism of the plant cannabinoids, Δ 9-tetrahydrocannibinol, cannabidiol and cannabinol. In Handbook of Experimental Pharmacology, 2005; Vol. 168, pp 657− 690.
hormones, and psycho-stimulants. The chemical structures of most of these drug families generally include single or multiple aromatic groups with carboxyl or hydroxyl, amino, and in some cases methyl or ether moieties. On the other hand, common cannabinoids have an aromatic ring and a cyclohexene with attached methyl and phenolic groups and joined by a pyranlike structure. The aromatic ring in CBD is not joined with a cyclic structure but rather with a single C−C bond. The presence of both aromatic and aliphatic components on these molecules makes these unique, with CBD likely being more reactive with additional π-electrons in its structure and lack of rigidity due to the cyclic group in the center, and their reaction with iodine and bromine may encourage formation of halogenated heteroaromatic structures, iodo/bromo-trihalomethanes, iodo/bromo-haloacetic acids, and haloacetaldehydes. Marijuana farming and its recreational use have released cannabinoid molecules into the natural aquatic environment for decades. What is different today is the recent increase in legalization of medicinal marijuana use as well as the approval of CBD-based epilepsy drugs with an expected surge in pharmaceutical market. It is thus timely and important for the environmental engineering and science community to engage in an assessment of the fate, transformation, and removal of cannabinoids from engineered and natural water systems. Although elucidating the transformation of these compounds in natural and built aquatic systems is likely the most effective approach of study, understanding the interaction of cannabinoids and their transformation products within the other unit processes in water and wastewater treatment systems is also relevant. Their fate in these engineered processes are intertwined with the physicochemical properties of the compounds and the nature of their interaction. For example, while parent THCs are removed upon strong partitioning onto biosolids, the oxidized or halogenated byproducts of these compounds may remain in higher concentrations downstream in the treatment train and escape classical removal processes. Understanding the transformation pathways of cannabinoids and relevant compounds will provide the environmental engineering and science community with methods to develop similar drugs with less detrimental effect to our engineered and natural water systems.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Navid B. Saleh: 0000-0001-6092-5783 Onur Apul: 0000-0002-2964-8279 Tanju Karanfil: 0000-0003-0986-5628 Notes
The authors declare no competing financial interest.
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REFERENCES
(1) Brodwin, E., There’s a sea change coming for the $1 billion marijuana-based industry you’ve never heard of. Business Insider 2018. (2) EPA Toxicity Estimation Software Tool. (3) Shen, R.; Andrews, S. A. Demonstration of 20 pharmaceuticals and personal care products (PPCPs) as nitrosamine precursors during chloramine disinfection. Water Res. 2011, 45, 944−952. (4) Mackie, A. L.; Park, Y. R.; Gagnon, G. A. Chlorination Kinetics of 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol: Effects of pH and Humic Acid. Environ. Sci. Technol. 2017, 51 (18), 10711−10717. B
DOI: 10.1021/acs.est.8b06999 Environ. Sci. Technol. XXXX, XXX, XXX−XXX
