02/12/16

A Double-Edged Drug

© arkela | 123f.com

© arkela | 123f.com

Dee Roberts referred to Suboxone (buprenorphine) maintenance as “withdrawal avoidance” while describing her journey from Vicodin to Suboxone to tapering off of Suboxone. The truth of the statement stung. She said she developed a “deeply rooted” fear of not having the medication with her. Does that sound familiar? Tellingly she said: “My behavior on Suboxone and while using had some alarming similarities.”

In “Kicking Suboxone: The Last Milligram” she described her efforts to break free from what had initially promised her freedom from the Vicodin-vodka cocktail that had stopped working for her. She said she was one of the first to try Suboxone when it became available in 2003. But “not one doctor who saw me suggested I consider going off of the drug. I stayed on it for 10 years until the side effects added up, motivating me to make the final jump.” She spent over $50,000 dollars out of pocket on doctor’s visits and drug co-pays.

If it weren’t for an adrenal imbalance that developed, she thinks she might well have continued taking it for many more years. But that wasn’t her only adverse effect. After a couple of years, she noticed personality changes. She felt like she was watching someone else’s story unfold. She wasn’t able to put words to the experience at the time. “The fighter in me had retired without notice.” She developed a skewed appetite, going from sugar fix to sugar fix. The final straw was when she noticed her hair falling out.

She tried several consultations before she found a doctor willing to help her taper off of buprenorphine (Suboxone). “As if waving a voodoo doll, I was warned multiple times about tempting relapse.” It had been 11 years since her last illicit prescription. She said she found it difficult to separate real withdrawal symptoms from psychosomatic ones in her tapering process. I’d suggest that a better distinction would be between acute withdrawal symptoms (her sense of “real” withdrawal symptoms) and post acute withdrawal symptoms (what she called psychosomatic ones).

Dee’s journey is described in more detail in her original article for The Fix. It involved off-and-on sleep deprivation, bouts of depression, stomach pains, hot and cold flashes, an emotional rollercoaster ride, and the help of a Border Collie mix who became her personal trainer. She had to find her own way out of her withdrawal avoidance disorder, “Since there have been no long-term use studies on Suboxone, side effects are often downplayed or ignored by the medical community.” She referenced a doctor in Boca Raton Florida, Steven Scanlon MD, who wrote a helpful article on “Detoxing from Suboxone.” He said:

 Patients, the first question you need to ask your current Suboxone doctor is whether he has ever taken anyone completely off Suboxone or Subutex.  If he says that he just tapers a patient down after they have been on it long-term and they are fine, then he is disingenuous or at least ill-informed.  If he tells you that he is going to put you on 16mg sublingually for six months while your brain stabilizes and heals and then taper you off it he is purposely or unknowingly misleading you.  How can your brain heal if you are still taking an extremely potent opioid that is classified as a pain medication and approved by the FDA as a medication to treat severe pain? On the other hand, if he tells you about the symptoms I discuss below and has previously helped people get off Suboxone when they are ready, then stick with this doctor and do what he says. When I detox patients off Suboxone I follow them for approximately 5 or 6 months and see them once a week during that time.  I make sure to follow them for at least two months after we stop the Subutex.  I do not use Suboxone, only Subutex, and I will explain why not.

Dawn Roberts suggested that to get a sense of the scope of the problem with recovering addicts who are desperate to get off of Suboxone, type “get off Suboxone” into a search engine. I found over 16,000 results. Then I tried “Suboxone taper” and had over 8,000 results. “Suboxone withdrawal tips” garnered 47,900 results. “Suboxone withdrawal help” had 184,000 hits; and “Suboxone withdrawal symptoms” had 410,000 hits. Writing for The Fix, Roberts investigated why there was no official protocol to detox addicts off Suboxone in “So You Thought You Could Get Off Suboxone?

She provided a brief history of the process that Reckitt Benckiser Pharmaceuticals (RBP) used to bring Suboxone to market and turn it into a blockbuster drug. They spent ten years and millions of dollars to cultivate the buprenorphine formula and another 13 years to bring Suboxone to the market in 2002. They lobbied Congress to create the Drug Addiction and Treatment Act of 2002 (DATA). Then RBP worked with NIDA and the FDA to lay the foundation to introduce Suboxone to the market. Their efforts garnered RBP $1.23 billion in sales in 2011 and $1.35 billion in sales in 2012. According to RBP’s annual report, Suboxone sales were $1.2 billion in 2013, ranking it at #39 of the top 100 drugs prescribed in the US. Oh, and Genetic Engineering & Biotechnology News ranked Suboxone as the second most abused drug of 2013.

Roberts then related how Reckitt Benckiser told her they were not aware of an established guideline or protocol for titration (tapering) off of Suboxone. A RBP spokesperson said:

Patients seeking to discontinue treatment for opioid dependence should be advised to work closely with their healthcare provider on a tapering schedule and should be apprised of the potential to relapse to illicit drug use associated with discontinuation of opioid agonist/partial agonist medication-assisted treatment.

Roberts concluded that RBP outright refuses to study the long-term effects of buprenorphine maintenance. And it seemed that the company was intolerant of buprenorphine patients who decide they want to discontinue Suboxone substitution treatment. I’m beginning to hear a line from the Eagles song, “Hotel California” in my head: “You can check-out any time you like, but you can never leave.”

Guinevere, on Guinevere Gets Sober, a great recovery blog, came to the same conclusion.  In “Suboxone Detox Redux,” she noted that Tim Baxter, the global medical director for RBP, told her: ”We don’t promote detox” from Suboxone. She decided RBP wants you to stay on the drug. Guinevere also recommends Dr. Scanlon’s paper, “Detoxing from Suboxone.” Read her article for good advice if you are considering any attempt to taper or titrate off of buprenorphine.

It seems that RBP has been trying to build a clientele that will continue using their Suboxone products for extended periods of time. Here is an article describing in some detail the gamesmanship of RBP over the years that Suboxone was under patent. RBP lost their exclusivity rights to Suboxone in 2009. However, they submitted a New Drug Application to the FDA for a sublingual film version of Suboxone in October of 2008. It was approved in August of 2010 with patent exclusivity until 2023. In their 2011 annual report, RBP said that competition from generics could take up to 80% of the revenue and profit of the Suboxone tablet business in the US. But they expected “that the Suboxone film will help mitigate the impact.”

Then in September of 2012, RBP announced that they were voluntarily withdrawing the tablet form of Suboxone from the market, citing data they had received from the US Poison Control Centers indicating high rates of pediatric overdose on the tablet formulation. But they were manipulating the market by offering discounts on the sublingual film version while raising the price of the tablets. Hours after announcing their plan to take the tablets off the market, RBP announced they had filed a “citizen’s petition” urging the FDA to require all manufacturers of buprenorphine-containing products to implement safeguards to prevent pediatric exposure, etc. They also asked the FDA to reject any new drug applications for buprenorphine (generic Suboxone) tablets. The FDA didn’t bite and approved generic tablet versions of Suboxone. Janet Woodstock, the Director of the FDA Center for Drug Evaluation and Research, said:

The timing of Reckitt’s September 2012 announcement that it would discontinue marketing of the tablet product because of pediatric exposure issues, given its close alignment with the period in which generic competition for this product was expected to begin, cannot be ignored.

Writing for The New York Times, Deborah Sontang published two articles on the pros and cons of Suboxone: “Addiction Treatment With a Dark Side” and “At Clinics, Tumultuous Lives and Turbulent Care.” The doctor running a clinic near Pittsburgh was quoted as saying, “I know on the surface it might look like a pill mill. . . . We’re seeing a fair number of patients, and they’re primarily receiving a prescription.” But he added they encourage, support and don’t judge. “There’s a kind of love.” Read the article to get a clearer picture of his bedside manner. After his “recovery” and entrance into the Suboxone clinic business, Ohio revoked his medical license in 2011 because he had forged signatures verifying his attendance at 12-Step meetings. Pennsylvania suspended his license in 2010 for failing to submit to three unannounced drug tests while he was on vacation.

So getting on Suboxone maintenance is like checking into the Hotel California:

Last thing I remember, I was
Running for the door
I had to find the passage back
To the place I was before
“Relax, ” said the night man,
“We are programmed to receive.
You can check-out any time you like,
But you can never leave!

If you want to hear the entire Eagles song, listen here.

IRETA, the Institute for Research, Education & Training in Addiction, seemed to disparage Sontang’s portrayal of buprenorphine as a “double-edged” drug. They concluded their reflections with the following: “Singling out buprenorphine as ‘the’ double edged drug seems an inaccurate and potentially stigmatizing view of it.”  I’m not buying their rhetoric. From what I’ve seen, buprenorphine really IS a double-edged drug.

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?