The health threat of new synthetic as adulterants of classic drugs of abuse e107

Letter Clin Ter 2020; 171 (2):e107-109. doi: 10.7417/CT.2020.2198

The health threat of new synthetic opioids as adulterants of classic drugs of abuse R. Rinaldi1, F. Negro1, A. Minutillo2

1Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, Rome; 2Centro Nazionale Dipendenze e Doping, Istituto Superiore di Sanità, Rome, Italy

Abstract tic or additive effects with illicit drugs on the central nervous system and cardiovascular system (4). In addition, foreign Extensive scientific evidence shows that there is a broad spec- substances or contaminants may be created through a che- trum of substances used as adulterants, whose effects on the user’s mical reaction during processing, or added though acciden- health may be extremely harmful. The degree of purity of the drugs tal contamination during storage. The term “adulterant” most commonly abused is highly variable depending on the region generally refers to the addition of substances with some or epidemiological context. Practices of drug adulteration have been psychoactive effects, such as caffeine or ephedra. Such substantially evolving over the years: a significant trend has been adulterants are cheaper than the main substance, but may observed in the last decade indicating a decline in the average purity produce similar or complementary effects when added, thus of most drugs. Although the most frequent adulterants of common helping to conceal the fact that the desired substance has street drugs have long been well known, the rise of synthetic opioids been cut or diluted (5). Substances without psychoactive has inevitably entailed gaps in knowledge in terms of the substances properties such as lactose, other sugars, or talc, are added being used and their composition, which constitutes an even greater to a drug primarily to increase the volume or weight of the threat to public health. Clin Ter 2020; 171 (2):e107-109. doi: 10.7417/ illicit substance, or for aesthetic purposes in order to deceive CT.2020.2198 the user. The most commonly adulterated illicit drugs are , cocaine, methamphetamine, ecstasy and cannabis. Key words: New Synthetic Opioids, adulterants; drugs of abuse Heroin is sometimes cut with phenobarbital, quinine, clen- buterol, , caffeine, procaine, paracetamol, strychnine. Cocaine has been found to be adulterated with Dear Editor, lidocaine, hydroxyzine, antihistamine, phenactin, levami- The proliferation of dangerous adulterated drugs has sole, caffeine, procaine, strychnine. Methamphetamine may reached alarming proportions. Deaths from unintentional be cut with Methylsulfonyl, caffeine, or be contaminated by overdose are almost globally endemic, and not limited lead, possibly a manufacturing residue. Ecstasy could be to impoverished countries and communities. Overdoses added with , amphetamine and/or meth- from adulterated heroin, cocaine, prescription opioids or amphetamine, paramethoxymethamphetamine and/or ecstasy have been recorded throughout demographics and paramethoxyamphetamine, caffeine. Recently, even GHB socioeconomic segments, and the incidence is not biased has been adulterated with sildefanil (6) or more commonly by race, income or geographical location. In this letter, the substituted with its precursor GBL (7). Furthermore, GHB/ authors will be briefly describing the dangers posed by new GBL, mephedrone, and other synthetic cathinones synthetic opioids used as adulterants and the process and are at times used in conjunction with illicit opioids in high- trends involved. risk “chemsex” practices (8). The “cutting” or “adulteration” Illicit drugs are often found, at the point of purchase, to of street drugs is common practice at the manufacturing, contain substances in addition to the active ingredient (or distribution, and selling stages; the main purpose is undoubt- named drug); these adulterants can have serious, sometimes edly to maximize profits. Some adulterants, on the other fatal, health consequences. Substances may be added as hand, are simply the by-product of the particular drug bulking agents (i.e. to increase volume) or for the purpose manufacturing process. For example, illicitly manufactured of diluting the drug, to enhance the effects of the active methamphetamine is frequently contaminated by non- ingredient, or to make drug administration easier, for in- stimulant impurities such as lead or mercury (extremely stance in powdery drugs such as heroin and cocaine (1, 2). toxic heavy metals), or by carcinogenic solvents used in the Lidocaine, caffeine (3) and dextromethorphan are well synthesis. The local anesthetic lidocaine is often added to known adulterants that have been associated with synergis- cocaine, since both drugs are fast-acting local anesthetics.

Correspondence: Raffaella Rinaldi. E-mail: [email protected]

Copyright © Società Editrice Universo (SEU) ISSN 1972-6007 e108 R. Rinaldi et al.

The case of antiparasitic medication levamisole appears to crisis and the issue of drug adulterants has gained growing be particularly significant in that regard: according to the attention in the United States, which led to the authorities United States Drug Enforcement Administration (DEA), focusing on the potential role of such factors when assessing 60%-89% of seized street cocaine contains levamisole (9). and treating patients with addiction issues, involved in drug Levamisole appears to be partly metabolized into an am- abuse, or overdose deaths (26). In conclusion, new syn- phetamine-like compound, which could increase dopamine thetic opioids certainly represent a daunting threat to public concentration in the mesolimbic pathway,thus activating health. Given the large number of casualties caused by such endogenous opioids: it can replicate the effects of cocaine compounds, it is essential to improve the identification and at a much lower cost. Levamisole has been linked to various detection processes involving biologic matrices in order to types of severe blood disorders, including leukopenia, implement adequate therapies and tackle severe complica- agranulocytosis, multifocal inflammatory leukoencephal- tions such as respiratory depression and cardiovascular and opathy, and neutropenia; pulmonary vasculitis has also been neurological fallout caused by -related adulterants. It observed in abusers of levamisole-adulterated cocaine (10); is important for specialists treating intoxicated a common presentation is vasculitis resulting in loss of limbs. patients to consider the possibility of fentanyl-analogue Thus, a real danger in adulterants such as levamisole is their adulteration as well. Hence, synthetic opioids ought to be toxicity beyond those of the drug to which they are added, covered by toxicological screening methodologies, along causing numerous medical consequences – including death. with analysis of alternative matrices, whenever available; To further complicate the overall scenario, new synthetic that would be greatly helpful in detecting poly-drug use and opioids such as fentanyl have emerged: such adulterants are possible opioid tolerance. In order to effectively address certainly a new trend in the landscape and pose a serious such a pressing public health issue, it is necessary to build threat to public health (11), and can be extremely harmful broader and more comprehensive international collaboration, even in very small amounts (12). In March 2015, the DEA targeted legislation, reliable investigative procedures, and a issued a nationwide alert on fentanyl as a threat to health closely-focused oversight of online forums and markets, and public safety in the United States (13, 14). Fentanyl particularly those operating in the “deep web”, underground analogues are commonly abused, posing major health con- version; furthermore, in light of the issue’s social pervasive- cerns, in addition to other opioid sub-categories of novel ness, all communities need to get involved with raising psychoactive substances (NPS) such as , awareness and spreading knowledge throughout societies. , , , and its Doctors should make sure at all times that the resources analogue (15). Given the elusive nature of such available are effectively harnessed, while ensuring that the substances, progressively coordinated reporting systems evolving right to health is upheld with no discrimination focused on pharmacovigilance would be vital in order to (27). identify new trends of NPS adulteration (16). In fact, over the last 3 years, the availability of illicitly manufactured References fentanyl, often used as a heroin adulterant (17), has caused an unprecedented rise in overdoses and deaths(18). In 2016, 1. Solimini R, Rotolo MC, Pellegrini M, et al. Adulteration 75% of overdose-related fatalities in the state of Massachu- Practices of Psychoactive Illicit Drugs: An Updated Review. setts had fentanyl in their system, a significant rise from 57 Curr Pharm Biotechnol. 2017; 18:524-530 percent in 2015 (19). The DEA has also warned that the 2. Kudlacek O, Hofmaier T, Luf A, et al. Cocaine adulteration. 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