10/28/16

Fluctuations in the Heroin Market

© 4designersart | stcokfresh.com

© 4designersart | stcokfresh.com

The 2016 World Drug Report (2016 WDR) is a good-news bad-news source of information on global opiate statistics. The good news is that global opium production fell by 38% in 2015. The decrease was primarily the result of a decline in opium production in Afghanistan, which fell 48% compared to 2014. This was mainly because of poor yields in the country’s southern provinces. Despite this, Afghanistan was still the world’s largest opium producer, accounting for 70% of global opium production.

The bad news is that despite the drop in production, the global number of opiate users has remained relatively stable. And opium production in Latin America, mostly in Mexico, Columbia and Guatemala, more than doubled from 1998-2014. Central and South American production accounts for 11% of the estimated global opium production. Also, in North America, heroin use and heroin-related deaths have continued to rise. In both cases, the increases were roughly three times the 1999 levels. See the following chart from the 2016 WDR.

heroin-deathsIn 2014, the largest seizures of opiates were in South-West Asia, with Europe next in line. The Islamic Republic of Iran reported the largest opiate seizures worldwide, accounting for 75% of global opium seizures and 17% of global heroin seizures. The next largest heroin seizures were from Turkey (16% of global heroin seizures), China (12%), Pakistan (9%), Kenya (7%), the U.S. (7%), Afghanistan (5%), and the Russian Federation (3%). Iran is the first stop on the so-called “Balkan route” of opiate distribution. From there the route travels into Turkey, and onto South-Eastern Europe, where it is distributed throughout Western and Central Europe. “Seizure data suggest that the Balkan route, which accounts for almost half of all heroin and morphine seizures worldwide, continues to be the world’s most important opiate trafficking route.”

The massive decline in opium production of almost 40 per cent in 2015 is unlikely, however, to result in a decline of the same magnitude within a year in either the global number of opiate users or the average per capita consumption of opiates. It seems more likely that inventories of opiates, built up in previous years, will be used to guarantee the manufacture of heroin (some 450 tons of heroin per year would be needed to cater for annual consumption) and that only a period of sustained decline in opium production could have any real effect on the global heroin market.

In 2015 Bloomberg published an article with three maps of global drug smuggling routes. The major opiate producers are: Afghanistan, Myanmar, Laos, Mexico and Columbia. The opiate map illustrates the vast reach of the so-called Balkan route. The Americas are primarily supplied with opiates grown in Mexico and Columbia. More than 70% of all heroin and morphine seizures in the Americas were in the U.S. between 2009 and 2014. Seizures more than doubled from around 2 tons per year from 1998-2008 to 5 tons per year from 2009-2014. Heroin trafficking and use was seen in 2015 as the main national drug-related threat in the US, according to the 2015 National Drug Threat Assessment (NDTA).

The 2015 NDTA reported that heroin was available in larger quantities, used by larger numbers of people, and caused more overdose deaths than 2007. The increased demand and use of heroin is driven by greater availability and controlled prescription drug (CPD) abusers switching to heroin. Cheaper prices for heroin contribute to the switch as well.

Increases in overdose deaths are driven by several factors. The purity of heroin has increased in some areas. New heroin users switching from prescription opioids are used to the set dosage amounts potency of prescription drugs. Illicitly–manufactured drugs can vary widely in their purity, dosage and adulterants. Over the past few years the use of highly toxic adulterants like fentanyl (20 to 40 times stronger than heroin) in certain markets has also added to the increase in overdose deaths. Then there are heroin users who stopped using for a while (from treatment or incarceration) whose tolerance has decreased because of their abstinence.

Most of the heroin in the US today comes from Mexico and Columbia. Columbian heroin is still the predominant type available in the Eastern US. While Southeast Asian heroin, largely from Afghanistan dominates the global market, very little makes its way to the US. Southeast Asian heroin was the dominant supplier of heroin in the US at one time. But it no longer can compete with the transportation and distribution networks of the Mexican and Columbian drug cartels. Se the following chart from the 2015 NDTA.

heroin-seizuresThe Mississippi River has been a dividing line in the US heroin market for the past 30 years, with Mexican black tar and brown powder heroin west of the Mississippi and white powder heroin from South America in the East. There is increasing evidence that Mexican drug cartels are processing their own white powder heroin and mixing white heroin with Mexican brown powder heroin to create a more appealing product to the Eastern US markets. See charts 12 and 13 in the 2015 NDTA for further information on the availability of heroin types purchased in Eastern and Western cities.

The suspected production of white powder heroin in Mexico is important because it indicates that Mexican traffickers are positioning themselves to take even greater control of the US heroin market. It also indicates that Mexican traffickers may rely less on relationships with South American heroin sources-of-supply, primarily in Colombia, in the future. If Mexican TCOs [transnational criminal organizations] can produce their own white powder heroin, there will be no need to purchase white powder heroin from South America to meet demand in the United States. This would also reinforce Mexican TCOs’ poly-drug trafficking model and ensure their domination of all major illicit drug markets (heroin, cocaine, methamphetamine, and marijuana) in the United States.

Mexican TCOs have been increasing their cultivation of opium poppies, to an estimated 17,000 hectares in 2014. This can potentially produce up to 42 metric tons of heroin. Switching to opium cultivation from marijuana cultivation may be at least partly due to the lowered demand for illicit marijuana in the US because of the legalization movement. See “The Economics of Heroin” for more information.

The number of heroin users reporting they used heroin over the past month increased 80% between 2007 and 2012. Of the total number of heroin-related treatment admissions in 2012, 67.4% reported daily use and 70.6% reported their preferred route of use was by injection. Heroin treatment admissions were consistently highest in the New England and Mid-Atlantic states. There are also high rates of repeated treatment among heroin users. Eighty percent of the primary heroin users admitted to treatment in 2012 reported previous treatment; 27% had been in treatment five or more times.

Most opioid users in the 1960s began by using heroin. But that steadily changed until 75% of heroin-users in the early 2000s reported they began by using prescription opioids. The number of people using illicit prescription opioids who switched to heroin was a relatively small percentage of the total number of prescription drug abusers at 3.6%. But it represented 79.5% of new heroin users. Heroin use was 19 times higher among individuals who had previously used pain relievers non-medically.

The reformulation of OxyContin in 2011 is seen as helping to curb the abuse of the drug. In 2011 emergency department visits involving oxycodone declined for the first time since 2004. Overdose deaths from opioid analgesics also began to decrease in 2011. But remember, CPD abusers have been switching to heroin and seem to be contributing to the dramatic increase in overdose deaths from heroin.

The number of heroin overdose deaths increased 244% between 2007 and 2013. Keep in mind that heroin deaths are undercounted. This occurs because of the differences in state reporting procedures for reporting drug-related deaths; and because heroin metabolizes very quickly into morphine. A metabolite unique to heroin, 6-monoaceytlmorphine (6-MAM), quickly metabolizes into morphine erasing the biochemical evidence for heroin use. So many heroin deaths get reported as morphine-related deaths. So what does the future hold for heroin use in the US? The 2015 NDTA concluded the current outlook for the near future is more of the same.

Heroin use and overdose deaths are likely to continue to increase in the near term. Mexican traffickers are making a concerted effort to increase heroin availability in the US market. The drug’s increased availability and relatively low cost make it attractive to the large number of opioid abusers (both prescription opioid and heroin) in the United States.

The United Nations Office on Drugs and Crime (UNODC) publishes a yearly report giving a global overview of the supply and demand of various drugs and their impact on health.

11/30/15

The Seduction of Opioid Substitution

© Everett Collection Inc. | Dreamstime.con

© Everett Collection Inc. | Dreamstime.con

Heroin and prescription opioid abuse is a widely recognized public health crisis in the United States. In 2014, Attorney General Eric Holder referred to overdose deaths from heroin and other prescription pain-killers as an “urgent public health crisis.” The CDC reported that heroin use more than doubled among young adults between 18 and 25 over the past ten years. Forty-five percent of the people who use heroin are also addicted to prescription opioids.

A July 2015 “Morbidity and Mortality Weekly Report” report by the CDC recommended a comprehensive response to this public health crisis. The recommendations included: reducing inappropriate prescribing and use of opioids, stronger prescription drug monitoring programs, improved access to evidence-based substance abuse treatment—including medication-assisted treatment for opioid use disorders and greater access and training in the use of naloxone to treat overdoses. There have been several steps taken towards making these recommendations a reality. For example, on November 18, 2015, the FDA approved the first nasal spray version of naloxone hydrocloride: Narcan nasal spray. But not all of the proposals have the same potential to free the individuals caught up in the opioid health crisis.

And legislation has been introduced in the Senate to “combat the opioid crisis.” “The Opioid and Heroin Epidemic Emergency Supplemental Appropriations Act” would dedicate $600 million to this crisis. About $250 million would support programs related to prevention, treatment and recovery. Another $200 million would fund local and state law enforcement programs. Fifty million would go toward the CDC; and $35 million would go to NIDA to monitor prescription drug programs and do targeted research on drug addiction. “We are losing lives daily and our first responders, healthcare providers and criminal justice system are overwhelmed.”

I’m not a fan of increasing the use of opioid maintenance medications such as methadone and buprenorphine because they’re “treating” an opioid addiction with addictive opioids. And I’m concerned that in the midst of the existing health crisis, increased access to such treatment seems to be indiscriminately promoted as the most effective “treatment” approach. Sometimes the studies of medication-assisted treatment fail to consider the negative consequences to individuals when promoting opioid substitution treatment. And sometimes studies that suggest the “effectiveness” of opioid maintenance have a biased interpretation of their results. Often what emerges is a program for the social control of addicts rather than one that helps them establish and maintain a recovery-oriented lifestyle. Here is an example of one such study.

The National Institute on Drug Abuse (NIDA) turned a “Science Spotlight” on a new study that looked at intervention approaches for opioid dependent patients in emergency departments (ED). The idea is a good one—developing an intervention for ED medical personnel to help opioid-dependent patients get into treatment. But what it doesn’t make clear is that the “treatment” is primarily ongoing participation in opioid substitution treatment.

This study showed that patients who received buprenorphine, along with a brief intervention to discuss opioid use, and up to 12 weeks of buprenorphine maintenance, were more likely to get follow-up addiction treatment and had reduced self-reported illicit opioid use. In addition, they were also less likely to need inpatient addiction treatment services, saving treatment costs. This adds to the growing body of literature suggesting that opioid-dependent patients may benefit from immediate initiation of medication while awaiting more comprehensive substance use disorder treatment.

Let’s take a closer look at the study by D’Onofrio et al. to see if it truly lives up to the endorsement it received from NIDA.

The primary outcome was what the researchers called “engagement in treatment.” This was defined as being enrolled in and receiving formal addiction treatment on the 30th day following randomization. “Formal addiction treatment” could include a range of clinical settings such as an opioid treatment program, such as a methadone clinic, inpatient or residential treatment and outpatient services. The outpatient services could be intensive outpatient programs and “office-based physicians who prescribe buprenorphine or other forms of medication-assisted treatment.”

The patients in the buprenorphine group of the study received buprenorphine in the hospital and take-home doses of buprenorphine to last until a scheduled appointment in the hospital’s primary care center, which was within 72 hours of their placement in the group. The buprenorphine patients continued to receive office-based burprenorphine treatment for 10 weeks. At that time they were transferred to a maintenance treatment program or a clinician for ongoing treatment. If they preferred, they were offered a 2-week detoxification.

In the buprenorphine group, 78% of the patients were still engaged in treatment at the thirty-day follow-up. Only 37% of the referral only group and 45% of the brief intervention and referral group were engaged in treatment. But remember what the study considered as “treatment.” Any patient in the buprenorphine group who was still active in the free, office-based treatment after 30 days would have been counted as “still engaged in treatment.”  And they would have had another 40 days of free buprenorphine coming.

There was no information or data available on any of the groups beyond the thirty-day follow-up. So there was no clear indication if the patients in the buprenorphine group remained in treatment beyond the 10 weeks of the study’s subsidy of their substitution treatment. If the goal was to eventually engage individuals in more comprehensive treatment services, this “interim opioid agonist treatment,” should not have been lumped in with others as the outcome measure of “formal addiction treatment.” The failure of the researchers to distinguish this level of care from the others confounds the findings within the study’s primary outcome measure.

These patients had buprenorphine treatment initiated before they left the hospital. They also had an appointment scheduled within 3 days of their initial dose, with sufficient take-home medication to prevent any withdrawal until that appointment time. The other two groups did not receive any medication and so were on their own medically until they made an appointment and became engaged in treatment. They were sitting ducks for resuming the illicit opioid use that initially brought them to the ED. So the deck was staked in favor of the primary outcome measure.

Additionally, the buprenorphine care in the study was provided at no cost to the patients. The researchers dismissed this as a potential bias in their study, saying that 80% of the study’s patients had health insurance. However there are potential cost issues in health insurance despite the authors’ dismissal. Buprenorphine maintenance treatment is not always covered by insurance, as it is considered a “niche” medicine by insurance plans, as it is approved solely for the treatment of opioid dependence. Insurance companies predict that a limited number of their covered clients will need or use it. When there is coverage, there can be high co-pays. Insurance may pay for the prescription but not the office visits. Some Suboxone doctors don’t take insurance.

A secondary outcome measure for the study was self-reported use of illicit opioids. The buprenorphine group reported greater reductions in the mean number of days of illicit opioid use, from 5.4 days per week to .9 days per week. Patients in the referral group decreased from 5.4 days per week to 2.3 days; and the brief intervention group went from 5.6 days to 2.4 days. Remember that the buprenorphine group was treated with medication (buprenorphine) that forestalled withdrawal symptoms from the time they were placed in that treatment group while still in the hospital ED. Also, all three groups reduced their illicit opioid use over time. Comparing the buprenorphine treatment group to the others indicated that even with the medication, there were only 1.4 or 1.5 days less per week of illicit opioid use in the buprenorphine group.

Finally, the decreased use of inpatient treatment by the buprenorphine group was to be expected. The withdrawal symptoms that often precipitate detoxification or residential treatment were being addressed by the buprenorphine.

It has long seemed to me that the so-called harm reduction approach of opioid substitution treatment is more social control than actual treatment aimed at helping the individual addict to establish and then maintain sobriety. The positive outcomes and effects that are highlighted are typically things like lowered costs for residential treatment; lowered ED visits and costs; decreased drug-related crime.

There is proposed legislation, the Recovery Enhancement for Addiction Treatment Act, which would broaden the definition of a qualifying practitioner to include certain nurse practitioners or physician assistants and doctors with a board certification from the American Board of Addiction Medicine. The number of patients that a qualifying practitioner could dispense buprenorphine to within their first year would increase from 30 to 100. After one year, qualifying physicians could request approval to treat an unlimited number of patients under specified conditions. Writing about this proposed bill for the Huffington Post, James Charkis said:

The consensus among the medical establishment is that medically assisted treatments such as buprenorphine (and methadone), along with counseling, represent the best chance for addicts to gain a foothold on sobriety. Both medications can make withdrawal less painful and can significantly diminish further cravings for opioids — greatly reducing the chance of relapse.

One of the problems as I see it is that this “best chance” description is often mostly rhetoric. The “along with counseling” add-on becomes more window dressing than reality. Even where there is a tighter requirement for Suboxone patients to be active in some kind of counseling, individuals either fall through the cracks with counseling or just take up space because their presence in counseling is required for them to get what they really think will “treat” them—their Suboxone. Some individuals merely want Suboxone handy in case they can’t get any heroin or their opioid of choice to get high. Others want it to sell on the street to make some cash.

There is a place for opioid substitution treatment as we attempt to address the opioid health crisis. But the potential adverse consequences to the individual receiving the treatment need to be more clearly communicated. And studies of its “effectiveness” need to look beyond just the social benefits and the ability of opioid substitution treatment to seduce addicts into a more socially controlled form of opioid use.

08/24/15

Fake Heroin and Homemade Opioids

© zerbor | 123rf.com

© zerbor | 123rf.com

Okay, now there is a “fake” heroin on the market. What’s going on in the drug trade? There seems to be wanna-be “Walter White” biochemists trying to tweak opioid molecules for a bigger-and-better high. On July 17, 2015, the DEA issued a final order to temporarily schedule acetyl fentanyl into Schedule 1. This was said to be “necessary to avoid an imminent hazard to the public safety.” Before the action by the DEA, the drug was illicit, but still technically legal as long as it had a label that read “Not for human consumption.”

Paul Gaia, writing for The Fix, said acetyl fentanyl was first identified in 2013. A small amount can produce a euphoria like heroin or oxycodone. Because of the similar euphoria, acetyl fentanyl can be sold as heroin or mixed with heroin or oxycodone to produce a stronger high. Regularly buyers are unaware of the mixture or the added danger it brings. Acetyl fentanyl is said to be 5 to 15 times more potent than heroin. It has resulted in a series of ER visits and at least 39 overdose deaths.

Reporting for Vice News, Tessa Stuart said a Montreal supplier of acetyl fentanyl was busted with three kilograms. “Given that a typical dose of acetyl fentanyl is in the microgram range, a three-kilogram quantity could potentially produce millions of dosage units.” Because of its strength, it requires a larger dose of naloxone, perhaps double, to counteract overdoses. Its greater potency also means the difference between a recreational dose and a lethal dose of acetyl fentanyl is much smaller, leading to the increase in overdoses among individuals who are unaware they are not shooting pure heroin.

An editorial published in 2014, “The Potential Threat of Acetyl Fentanyl,” said that because it is an analogue of fentanyl, before the DEA action, drug distribution networks faced less severe legal penalties from cutting or replacing drugs like heroin or oxycodone with acetyl fentanyl. This legal grey area meant that as long as it was unregulated, there was a clear motivation for distribution networks to replace or mix heroin with it. Pressed into a pill form, acetyl fentanyl can be peddled as oxycodone. The author recommended the elimination of the loophole for products containing an analogue of a controlled substance when it is labeled “not for human consumption.”

Analogues regulated in this way present a challenge for law enforcement and prosecutors because products that are clearly intended for recreational use sidestep regulations of their marketed purpose is something else.

Fentanyl-laced heroin is not new. The CDC warned in a “Morbidity and Mortality Weekly Report” that 10 overdose deaths in Rhode Island in March-May of 2013 were from acetyl fentanyl. On June 27, 2013, the State of Pennsylvania Department of Drug and Alcohol Programs published a bulletin, “News for Immediate Release,” which noted that there were at least 50 confirmed fatalities and five non-fatal overdoses that year from fentanyl or acetyl fentanyl. The “Theraflu” overdose epidemic in the Pittsburgh area in January of 2014 seems to have been acetyl fentanyl-laced heroin.

Fentanyl-related deaths are also going global. Both The Fix and Vice News reported a 25% rise in overdose deaths attributed to fentanyl in British Columbia (BC) over the past three years. A Vice reference to a pill form known as “fake oxy” suggests that what is being sold is acetyl fentanyl. A survey by the BC Center for Disease Control found that 29% of drug users in the province had fentanyl in their system.

And the problem isn’t limited to BC, with a growing number of similar deaths happening across the country. In 2014, fentanyl was a factor in the deaths of 120 people in Alberta, and there have been 50 such deaths already this year. In Ontario, the drug is killing twice as many people as heroin. Across North American, fentanyl is rapidly becoming a drug of choice for many users.

Reporting for The Fix, Paul Gaia said that fentanyl has been a problem in countries such as Russia, the Ukraine and Sweden. Manufacturing labs have been seized in Mexico, Germany, Japan and China. A gas used in the 2002 assault on a Moscow theatre was based on fentanyl. A report from the European Monitoring Centre for Drugs and Drug Addiction, “Fentanyl in Europe” indicated there were an estimated 650 deaths in Estonia due to fentanyl between 2005 and 2011. Almost all the cases were IV drug users of illicitly produced fentanyl.

Not only is there fake heroin, there is the potential to produce a variety of different opiates from yeast. Lexi Pandell, reported for Wired how Stanford researchers have developed a method for replicating the poppy’s opiate-producing chemical pathways by genetically modifying yeast. John Duber, a bioengineer at UC Berkley said that you would need a background in synthetic biology and genetics to produce the right kind of yeast, so it’s not an imminent threat. “But if a strain made for licit purposes got out, then all that would be required is knowledge of brewing beer to ferment it into morphine.” Here is a link to the abstract of their article published in Science.

Dueber said that at this point, “the illicit danger is concrete.” But he also thinks the potential benefits are immense. He suggested that scientists and policymakers start now to consider the possibilities before the science gets ahead of the regulations—like what happened with acetyl fentanyl. Kenneth Oye, an MIT professor, suggested that developers could make yeast less appealing for illegal use by generating yeast strains that produce less-addictive drugs. Or they could make finicky strains that are hard to maintain outside of a lab. Oye also said regulators could require the yeast DNA be “watermarked,” so it could be traced back to specific labs.

In a May 2015 commentary published in Nature, Oye also said:

The synthetic-biology community, in tandem with regulators, needs to be proactive in evaluating the costs and benefits of such dual-use technologies. Here we lay out the priorities for discussions that are crucial to public health and safety, and to the progress of synthetic biology more broadly. These include restricting engineered yeast strains to licensed facilities and authorized researchers and technicians; reducing the attractiveness of engineered yeast strains in the illicit marketplace; and implementing a regulatory approach that is flexible and responsive to changes in understanding and capabilities.

Oye downplayed the high received from hydrocordone in a New York Times article, rightly earning the wrath of the addiction blogger, Guinevere, at Guinevere Gets Sober. She said she’d like to send him some of the mail she’s received over the years by individuals who have spent tens of thousands of dollars buying Vicodin (hydrocodone) through the internet and on the street. “I’d like to see Stanford, MIT, and other schools spend the money on researching effective treatment standards and educating medical students about how to recognize and treat this illness.”

Fake heroin is spreading globally. Hydrocordone and other opiates can be manufactured from yeast. And the FDA is getting ready to approve an antidepressant containing buprenorphine (See “The Coming Depression Apocalypse”). And then there are the heroin and prescription pain killer problems. What does the future hold for opioid addiction?