Heroin: a worsening problem and a challenge for testing

The recent high-profile deaths of actors Philip Seymour Hoffman and Cory Monteith due to heroin overdose and the flurry of news coverage that followed have brought to light the rise in heroin use and fatal overdoses in the United States.

 Depending on the report you read and the exact question being asked, anywhere from 600,000  to 1.5 million Americans use heroin.^1,2 The rate of unintentional overdose on heroin remained fairly stable from 1999 to 2007, the latest date for which we have national statistics. But individual states are reporting significant spikes in heroin overdoses in more recent years.³ Michigan reported heroin overdose deaths jumped by more than 200% from 1999-2002 and 2010-2012, while New Hampshire deaths from heroin rose by 55% from 2012 to 2013. North Carolina deaths nearly doubled from 2011 to 2012 (77 to 148), and West Virginia reported a more than threefold increase in deaths from 2007 to 2012 (22 to 70).

 What is the reason for this increase in heroin use? The generally accepted theory is that new heroin abusers are or have been abusers of prescription painkillers, specifically opioids such as Vicodin, Percocet, and Oxycontin, who turn to another source to supply their addiction. In 2010, two million people reported using prescription painkillers non-medically. Among the 14,800 deaths from prescription painkillers in 2008, roughly 1% were known or admitted abusers of or people who were dependent on prescription painkillers.^4-6 This led more than 30 states to implement Prescription Drug Monitoring Programs that track both the prescribing and dispensing of controlled substances. Further restrictions, such as stronger prescribing controls, reducing the number of allowable refills, and reclassifying painkillers containing hydrocodone as Schedule II instead of Schedule III, are being considered. Prescription pain medications that are abused are often obtained from a friend or relative, secondarily obtained by valid prescription, or acquired on “the street.” 

 Why the turn toward heroin? It is believed that heroin has become a readily available and cheap opiate substitute for prescription drug abusers as the street supply of prescription opioids diminishes. Heroin from Mexico (generally found west of the Mississippi River) is referred to as “black tar,” whereas heroin from Colombia (supplier for east of the Mississippi River) is referred to as “white heroin,” and the supply is plentiful.⁷ The Washington Post and other sources have repeated the statistic that along the border with Mexico, U.S. authorities seized a record 2,162 kilos of heroin in 2013 compared to 367 kilos in 2007. 

Moreover, as the supply of heroin increases, the price continues to fall. South American heroin dropped from $1.75 per milligram  pure in 2010 to $1.18 in 2011. During the same period, heroin from Mexico decreased from $2 to $1.35 per milligram pure.⁷ Even with “street market mark-up,” this compares favorably with the price, per pill, for opioids such as hydromorphone, oxymorphone, methadone, oxycodone, and morphine.

Why is it so easy for users to overdose? Statistics show that new heroin users tend to be young adults from ages 18 to 25. Risk factors for fatal overdoses include being male, being single, being unemployed, having a history of heroin dependence, not being in treatment for heroin dependence, intravenous use, and the concomitant use of alcohol or benzodiazepines.^8-10 It is generally accepted that fatal heroin overdoses result from induced depression of respiration with resulting hypoxia and death. Heroin’s mechanism of action, like that of all other opiates and opioids, is interaction with opioid receptors (primarily μ) in the CNS to reduce pain. This class serves as agonists of the opiate receptor. Heroin is rapidly hydrolyzed to morphine in the brain, and the user experiences a short-lived sensation or “rush” of euphoria. Heroin’s fast action in the brain is thought to be responsible for its highly addictive nature. Tolerance builds up quickly, requiring the addict to use more and more heroin to get the same rush, which leads to addiction.

Unfortunately, determining a “dose” of heroin is complicated by the fact that the purity of the heroin is often unknown, as it is common practice to “cut” heroin with inactive adulterants and bulking agents such as sugar, starch, powdered milk, or quinine. More dangerous active adulterants include cocaine, amphetamine, methamphetamine, fentanyl, clenbuterol, diphenhydramine, and acetaminophen. 

A significant contributor to the ease of overdose is the fact that the purity of heroin is improving. South American heroin samples exhibited the highest average purity at 31.1%, an increase of 5.2 percentage points from 2010. Average purity of heroin from Mexico increased slightly in 2011 to 16.8%, up 2.1 percentage points from 2010.⁷

Heroin testing is usually performed on urine, although both blood and urine samples may be utilized as part of a forensic autopsy. The parent, diacetylmorphone, is rapidly metabolized to 6-monoacetylmorphine (6-MAM), which is then metabolized to morphine. Because codeine metabolism also proceeds through morphine as an intermediate, it is the presence of 6-MAM that must be used to substantiate heroin use. There are many rapid/screening testing platforms to detect opiate and opioid use, but few are able to single out heroin use from use of other opiates/opioids. Most liquid-phase immunoassay tests utilize antibodies raised against and specific for morphine, although some assays do target 6-MAM specifically or have significant cross-reactivity to 6-MAM. In general, however, most immunoassays still suffer from varying degrees of specificity for 6-MAM and cannot be used to confirm or substantiate heroin use. 

Confirmation testing of any screening result using gas-chromatography mass-spectrometry and liquid-chromatography mass-spectrometry remains the gold standard to detect 6-MAM specifically and quantify levels of this specific heroin metabolite. Such detection and quantified values are essential in order to comply with many employment and probationary drugs-of-abuse testing requirements. But, more importantly, they allow us to impart specific information to our clinical colleagues. 

References

1. SAMHSA, Center for Behavioral Health Statistics and Quality, National Survey on Drug Use and Health, 2010 and 2011. http://www.samhsa.gov/data/NSDUH/2011SummNatFindDetTables/NSDUH-DetTabsPDFWHTML2011/2k11DetailedTabs/Web/HTML/NSDUH-DetTabsSect1peTabs1to46-2011.htm#Tab1.1A.Accessed May 27, 2014.
2. Kilmer B, Everingham S, Caulkins J, et al. What America’s Users Spend on Illegal Drugs: 2000-2010. Office of National Drug Control Policy, Office of Research and Data Analysis.  http://www.whitehouse.gov/sites/default/files/ondcp/policy-and-research/wausid_results_report.pdf. Accessed May 27, 2014.
3. The Associated Press on April 05, 2014. http://www.nola.com/crime/index.ssf/2014/04/snapshot_of_heroin_use_deaths.html. Accessed May 27, 2014.
4. Substance Abuse and Mental Health Services Administration, Results from the 2010 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-41, HHS Publication No. (SMA) 11-4658. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2011. http://oas.samhsa.gov/NSDUH/2k10NSDUH/2k10Results.htm. Accessed May 27,2014.   
5. CDC. Vital Signs: Overdoses of Prescription Opioid Pain Relievers—United States, 1999-2008. MMWR.2011;60:1-6.
6. Substance Abuse and Mental Health Services Administration. Drug Abuse Warning Network: selected tables of national estimates of drug-related emergency department visits. Rockville, MD: Center for Behavioral Health Statistics and Quality, SAMHSA; 2010.
7. 2011 Heroin Domestic Monitor Program, Drug Intelligence Report, DEA Intelligence Division, Office of Intelligence Warning, Plans and Programs, March 2013.
8. National Institute on Drug Abuse. Epidemiologic Trends in Drug Abuse, in Proceedings of the Community Epidemiology Work Group, Advanced Report 2013. U.S. Department of Health and Human Services, National Institutes of Health, Division of Epidemiology, Services and Prevention Research, National Institute on Drug Abuse, Bethesda, Maryland
9. Pollini RA, Banta-Green CJ, Cuevas-Mota J, Metzner M, Teshale E, Garfein RS. Problematic use of prescription-type opioids prior to heroin use among young heroin injectors. Substance Abuse and Rehabilitation. 2011;2:173-180.
10. Warner-Smith M, Darke S, Lynskey M, Hall W. Heroin overdose: causes and consequences. Addiction. 2001.96;1113-1125.