Is opiate pain medication safe for addicts? Part I

A recent user question on VYou (see my response here) addressed the issue of prescribing addicts with opioid pain medication. Since prescription medication abuse and addiction is on the rise and getting more and more attention in the media every year, the question of whether addicts in recovery, or people who have dealt with substance abuse and addiction problems in the past, should be prescribed these medications is a very relevant one.

Chronic pain affects a substantial portion of the population worldwide (as many as 30%, see here). Opiate medications are one of the most commonly used approaches to treating such pain, which if untreated can cause serious disruptions to sufferers’ lives. Even when treated, chronic pain can be pretty debilitating. Some research (1) brings up good questions about the true effectiveness of opiate therapy for chronic pain, especially among long-term opiate users (like heroin and prescription pain medication addicts) but also among other drug using populations.

So how common is the practice? What sort of results do drug addicts usually get from these opiate therapies? And finally, how many of the addicts or drug abusers who receive these therapies end up abusing them and can we identify those people early so we can stop prescribing to them? In this three-part series of articles we’re going to cover these questions in-depth.

Prescription pain medication use in addict populations

Clinicians treating chronic back pain choose from a range of options, including opioid medications, exercise therapy, nonsteroidal anti-inflammatory medications, tricyclic antidepressants, acupuncture, and electrical stimulation. One study (1)  found wide variability in the percent of chronic pain patients prescribed opioids (from 3%-66%) although the studies varied widely in their size and population served – some even looks at general back pain and not chronic pain alone (they tended to have much lower opioid prescription percentages). Among chronic pain clinic patients, chronic opioid pain medication use was estimated at 19% (2).

Among addicted populations, concerns about tolerance, withdrawal, and abuse tend to cut prescription rates for opioid pain medications. However, past drug abuse can exacerbate pain issues, especially for people who abuse, or have abused, opiates in the past. For this reason, it can sometimes be difficult to properly manage pain in people with a history of addiction. One study (3) found that as many as 67% of patients in a Methadone Maintenance Program and 52% of patients in short term residential treatment programs were being prescribed opiates for pain. It’s important to note that these numbers are higher than those reported in other studies but that populations in treatment do generally show prescription rates higher than the general population. A study in Finland (a country that has great medical record data) found that opiate prescription rates in substance abuse populations were equivalent (not higher or lower) to those in the general population. The College of Problems on Drug Dependence itself had released an official statement noting that a balance must be reached between fear of opioid prescriptions for pain and the usefulness of opioid pain medication for chronic and severe pain (4).

Interestingly, it seems that of all opioid pain medication prescriptions, the largest increases in troubling use has been around oxycodone (Oxycontin), which gets mentioned as often in emergency departments (ED) around the country even though it is prescribed about one-third as often as hydrocodone (Vicodin). This is less surprising when you consider the fact that many addicts report using oxycontin in different ways including smoking, snorting, and injecting the stuff, which is stronger and does not have the same amount of fillers as most hydrocodone preparations. The fact that oxycodone is stronger also means it is more effective for pain relief through higher activation of the opioid system that is relevant for addiction.

In our next piece we are going to explore whether opiate pain medication is helpful in controlling pain among addicts and substance abusers, see you then!

Citations:

1. Martell, O’Connor, Kerns, Becker, Morales, Kosten, Fiellin. (2007). Systematic Review: Opioid Treatment for Chronic Back Pain: Prevalence, Efficacy, and Association with Addiction. Annals of Internal Medicine, 146, 116-127.

2. Chabal, Erjavec, Jacobson, Mariano, Chaney (1997). Prescription Opiate Abuse in Chronic Pain Patients: Clinical Criteria, Incidence, and Predictors. Clinical Journal of Pain, 13, 150-155.

3. Rosenblum, Joseph, Fong, Kipnis, Cleland, and Portenoy (2003). Prevalence and characteristics of chronic pain among chemically dependent patients in methadone maintenance and residential treatment facilities. The Journal of the American Medical Association, 289, 2370-2378.

4. College on Problems of Drug Dependence taskforce on prescription opioid non-medical use and abuse: position statement.

U.S. Drug overdose deaths are increasing

The second leading cause of accidental death in the US is drug overdose (JAMA 2007). Prescription painkiller overdose deaths (opioid analgesics like OxyContin, Vicodin and methadone) account for nearly half of the 36,450 total fatal overdoses with 15,000 deaths that have claimed a number of celebrity lives including famous actor Heath Ledger (CDC 2011).

With so much concern over illegal drugs, it seems silly not to focus on a problem that is at least as deadly but far more accepted.

Drug overdose deaths increasing quickly

Drug overdoses are normally considered accidental and they're on the riseWe’ve reported on this phenomenon before, so for the regular A3 readers this report might not seem new. But what’s staggering is just how quickly these numbers are moving up.

In 2004 there were 19,838 total accidental overdose deaths, with about 9,000 caused by prescribed drugs, and 8,000 more caused by illegal drugs like cocaine, heroin, and methamphetamines (Paulozzi, LJ, Budnitz 2006). That signals a near doubling in about 7 years, and when you look at numbers from 1999, we’re talking about triple the accidental drug overdose deaths in just over a decade! Fastest growing cause of death in our country ladies and gentlemen.

SAMHSA Reports that use of prescription pain relievers (opioid analgesics) have increased since 2002 from 360,000 to 754,000 people in 2010. That means that people are twice as likely to use these drugs now, which would be fine if 5% of the users weren’t dying every year.  A study I talked about on ABC’s Good Morning America earlier this year (see here) reported that people taking heavy doses are especially likely to die and that this might be at least partially due to additional opioid use over and above the prescribed regimen.Time to get this under control prescribers!!!

This increase in usage opioid analgesics like Oxycontin, Vicodin, and methadone has made them the some of the most deadly drugs in the USA (Paulozzi, LJ, Budnitz 2006). In 1999 to 2004 prescription overdose related to opioid analgesics increased from 2,900 to at least 7,500, this equates to 160% increase in just 5 years (Paulozzi).

A JAMA study conducted between 1999 to 2004 reported that white women showed a relative increase in unintentional drug related deaths of 136.5% followed by young adults aged 15-24 years (113.3%). But the latest report from the CDC suggest that Men and middle aged individuals are most likely to be affected by this growing epidemic. The bottom line is this problem is either moving around or is universal enough affect essentially every major group of Americans. One of the scariest findings from this most recent CDC study may be the conclusion that states are generally unprepared to deal with this growing epidemic.

What can we do about overdose deaths?

First of all, it is seriously time that we had more consistent state and federal computer systems keeping track of prescriptions for heavily controlled drugs in this country. We can keep track of packages moving across state lines with no problem, why is it so damn hard to watch pills that lead to 35,000 deaths? Most states have them in place but they’re not heavily used and there’s nothing at all that looks at cross federal prescription patterns.

Second, we wrote about some harm-reduction methods to reduce overdose deaths, things like intranasal naloxone, safe injection sites, and more. As far as I’m concerned, we need to get off our national moral horse and start acting responsibly when it comes to saving lives. If we have simple solutions that have been shown to reduce deaths while not increasing abuse, I say let’s implement!!! Anything else is simply wrong.

Citations:

Paulozzi, LJ, Budnitz, DS, Xi, Y. Increasing deaths from opioid analgesics in the United States. Pharmacoepidemiology Drug Safety 2006; 15: 618-627. (originally published in 2006 and recently updated)

Saving lives made easy – Treating opiate overdose with intranasal naloxone

oxycodone-addiction-big1Contributing co-author: Andrew Chen

Imagine that you and your friend have been using heroin (or another opiate). A few hours go by and you notice your friend is progressively becoming more and more unresponsive. You check on him and find that his breathing is shallow, his skin is cold, and his pupils are constricted. You recognize these as signs of opiate overdose and call for help. Now what?

Well… If you had some naloxone around, you might be able to treat the overdose and save your friend’s life before the paramedics even arrive.

Naloxone hydrochloride (naloxone) is the standard treatment for opioid overdose. Naloxone works by blocking opioid receptors, thereby removing opioid agonists, such as heroin or oxycodone, from those same receptors. As a result, the overdose is reversed and death is prevented.

What makes naloxone great is that it has no potential for abuse. In fact, it makes the user feel pretty crappy.

Naloxone is typically delivered through an injection, which makes it pretty much useless in many situations. However, it can also be delivered using an intranasal spray device. This intranasal form of naloxone is getting lots of attention recently because it is relatively easy to administer.

In 2006, The Boston Public Health Commission (BPHC) implemented an overdose prevention program, providing training and intranasal naloxone to 385 individuals deemed likely to witness an overdose. These individuals were often family members of opiate users or drug-using partners.

15 months later, the BPHC conducted a follow-up:

  • Contact was made with 278 of the original participants.
  • 222 reported witnessing no overdoses during the 15-month span.
  • 7 had their naloxone stolen, lost, or confiscated.
  • 50 reported witnessing at least one overdose during the 15-month span. Together, these 50 individuals reported a total of 74 successful overdose reversals using intranasal naloxone!

The BPHC program is not the only example of successful use of naloxone in opiate overdose prevention programs. Similar programs have popped up in Chicago, New York, San Francisco, Baltimore, and New Mexico.

Unlike injections, using a nasal spray isn’t rocket science. All of the participants in the BPHC program were trained by non-medical public health workers, which makes the idea relatively cheap. As the data shows, the participants were able to effectively recognize an opiate overdose and administer intranasal naloxone. By targeting at-risk populations and providing proper training, distribution of intranasal naloxone can help in saving lives.

For more information, check out our post Addiction and the brain part IV – Opiates

Citation:

Doe-Simkins, M., Walley, A.Y., Epstein, A., & Moyer, P. (2009) Saved by the nose: Bystander-administered intranasal naloxone hydrochloride for opiod overdose. American Journal of Public Health. 99(5)

Conversation with an addiction expert – Chris Evans, opiate master

Here at A3 we have already armed you with over 400 articles’ worth of knowledge on a wide variety of topics such as sex, gambling, and alcohol addictions. Our articles have in the past been written mostly by the team members at A3 (with a few notable guest pieces) based upon research findings and personal experience. Now we decided to expand our reach and get a different kind of perspective, broadening the knowledge we are able to provide to you and providing you expert opinion on commonly asked questions that the public often has about addiction.

Chris Evans, Ph.D.Our first expert is Christopher J. Evans (PhD) who is a professor in the David Geffen School of Medicine at UCLA. In addition to his work at the school of medicine, Evans is also a part of the UCLA Opioid Research Center, and Shirley and Stefan Hatos Center for Neuropharmacology. Evans is particularly interested in opioid drugs and is currently working on discovering the differential signaling at opioid receptors. Some of his past work has touched on withdrawal and on the theory of opponent processes involved in withdrawal, a counter to the theory that a rebound from over-activation is the whole story in the withdrawal process.

11 answers from an addiction expert

1 ) How did you become interested/specialized in addiction research?

Following my PhD studies in protein chemistry where I studied enkephalins and endorphins – opioids in our brains.

2 ) If you had to sum-up your “take” on substance use disorders in a few sentences, what would those be?

A sad disease where an obsession develops for an abused substance that creates fluctuating hedonic states. Increasingly there is decline to a negative hedonic state that can only be relieved by the abused drug.

3 ) What have been the most meaningful advances in the field in your view over the past decade?

The development of genetic models and imaging to begin to tease out circuits involved in liking a drug, withdrawal from a drug and drug craving.

4 ) What are the biggest barriers the field still needs to overcome?

Resolving the interaction of genetics and environment in creating phenotypes such as depression and anxiety leading to susceptibility to substance abuse.

5 ) What is your current research focused on?

Opioid drugs and the differential signaling at opioid receptors.

6 ) What do you hope to see get more research attention in the near future?

Inhalants and genetic studies aimed at behavioral phenotypes relevant to obsessive substance use .

7 ) How do you think the Health Care reform recently passed will affect addiction treatment?

It appears that there will be more attention paid to substance use disorders.  With increased access to health services the treatment of substance disorders is likely to become more of a focus.

8 ) What is your view regarding the inclusion of behavior/process addictions in the field?

They should be included.  Many of the process addictions have the same co-morbidities with substance use disorders and these are what need to be understood.

9 ) What is your view on the relative importance of Nature Vs. Nurture?

They are intertwined ? the interaction of nature with nurture directs our behaviors so neither should be considered more important than the other.  Either nature or nurture can be a disaster for a life.

10 ) In your view, what are some of the biggest misconceptions that the public still holds about addiction?

That addiction is driven solely by the acute rewarding effects of the drug and not by subsequent adaptations induced by the drug including dysphoria or memories of drug action.

11 ) What is the most common question you get from others (public?) when it comes to addiction?

Is marijuana harmful for you?

And there you go, a set of untouched, unedited answers about addiction and addiction research diretly from one of the masters. We hope you’ve enjoyed this and that you’ll look forward to more as All About Addiction continues a monthly exposure of what addiction research looks like from within.

Is marijuana addictive? You can bet your heroin on that!

marijuana“Is marijuana addictive?” seems to be the ultimate question for many people. In fact, when discussing addiction, it is rare that the addiction potential for marijuana doesn’t come up.

Some basic points about marijuana:

The active ingredient in marijuana, THC, binds to cannabinoid receptors in the brain (CB1 and CB2). Since it is a partial agonist, it activates these receptors, though not to their full capacity. The fact that cannabinoid receptors modulate mood, sleep, and appetite is why you get the munchies and feel content and why many people use it to help with sleep.

But how is marijuana addictive? What’s the link to heroin?

What most people don’t know is that there is quite a bit of interaction between the cannabinoid receptor system (especially CB1 receptors) and the opioid receptor system in the brain. In fact, research has shown that without the activation of the µ opioid receptor, THC is no longer rewarding.

If the fact that marijuana activates the same receptor system as opiates (like heroin, morphine, oxycontin, etc.) surprises you, you should read on.

The opioid system in turn activates the dopamine reward pathway I’ve discussed in numerous other posts (look here for a start). This is the mechanisms that is assumed to underlie the rewarding, and many of the addictive, properties of essentially all drugs of abuse.

But we’re not done!

Without the activation of the CB1 receptors, it seems that opiates, alcohol, nicotine, and perhaps stimulants (like methamphetamine) lose their rewarding properties. This would mean that drug reward depends much more heavily on the cannabinoid receptor system than had been previously thought. Since this is the main target for THC, it stands to reason that the same would go for marijuana.

So what?! Why is marijuana addictive?

Since there’s a close connection between the targets of THC and the addictive properties of many other drugs, it seems to me that arguing against an addictive potential for marijuana is silly.

Of course, some will read this as my saying that marijuana is always addictive and very dangerous. They would be wrong. My point is that marijuana can not be considered as having no potential for addiction.

As I’ve pointed out many times before, the proportion of drug users that become addicted, or dependent, on drugs is relatively small (10%-15%). This is true for almost all drugs – What I’m saying is that it is likely also true for marijuana (here is a discussion of physical versus psychological addiction and their bogus distinction).

Citation:

Ghozland, Matthes, Simonin, Filliol, L. Kieffer, and Maldonado (2002). Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors. Journal of Neuroscience, 22, 1146-1154.

Addiction-brain effects – Tolerance, sensitization, and withdrawal

If you’ve been with us for any length of time, you’ve already read about the addiction-brain effects for specific drugs. I think it’s important to understand some of the more general changes that occur in the addicted brain regardless of the specific drugs used.

One of the most common effects of long term drug use is something called tolerance, or the reduced effect of a drug dose. A lot of people know about this one, especially if they’re users and have found themselves needing to use more and more to get the same effect. However, while this is the most known, it is not the only change in the body, or brain’s, response to drugs with repeated use. The other effect, known as sensitization, is characterized by the exact opposite reaction – an increase in the response to the drug.

Tolerance & Withdrawal in the addicted brain

toleranceThe exact mechanism by which tolerance occurs is different for each drug, but the overall concept is the same. With repeated drug administrations, the body adjusts its internal processes in an attempt to return to its initial level of functioning. Drug use normally causes greater quantities of neurotransmitters like dopamine, serotonin, the opioids, and adrenaline to be present in the drug user’s synapses (see here for a review). The body counters this by reducing its own release of these chemicals, reducing the numbers of receptors that can be activated by the neurotransmitters, and increasing functions known as “opponent processes” that are meant to counter their activity.

The interesting thing about tolerance is that by reducing the level of these important neurotransmitters, addicts are left with another, possibly more important effect, which is the loss of the addicted brain’s ability to respond to any reward, including natural ones like food, sex, enjoying a good football game, or anything else. Essentially, this sort of cross-tolerance leaves the addict less able to respond to rewards in general.

The reduced response to drugs, and the corresponding changes in the body and brain’s own functioning, have long been thought to be a major cause of addiction. The withdrawal that results once drug taking stops is closely linked to the development of tolerance. Still, we now know that tolerance and withdrawal are not necessary, and certainly not sufficient for the development of addiction. Nevertheless, they are referred to as the physical dependence portion of addiction and are often are part of the overall picture.

Sensitization

Sensitization is the term used for an increased response to the same dose of a drug. That might sound a little oxymoronic after the tolerance discussion we just had, but bare with me.

Tolerance commonly develops when drug use is constant, or ongoing. It’s an aspect of chronic, long-term, use. On the other hand, sensitization is likely to occur when a user engages in intermittent, binge-like, drug use happening either once daily, or with even greater spacing (as in once every few days) and in large quantities. When you combine chronic use with binge behavior, you can actually get both responses.

Sensitization to drugs has been shown for physiological responses like heart-rate, blood pressure, and movement in animals and humans. More importantly, sensitization plays a part in increasing the motivation for drug use. Just like sensitization increases the physical response to drugs, there is a corresponding increased response in the addicted brain in areas important for motivation (like the NAc and VTA for instance). If an addict responds more to their drug of choice after repeated use, it should come as no surprise that sensitization has also been hypothesized to play an important role in the addiction process.

Drugs cause brain changes that drive addiction

opponent processesWhen both tolerance and sensitization develop in someone who has been using drugs, they’re left with a reward system that is less responsive to rewards in general while being more responsive to the drugs they’ve been binging on and to cues (or triggers) that are associated with those drugs. If that sounds like a recipe for disaster, it is. If you’re an addict yourself, you don’t have to imagine this, you’ve lived it – A state where nothing seems rewarding without being high.

The problem is that both tolerance and sensitization are examples of changes in response to drugs that are completely outside of the control of the user. There’s no doubt that the average drug user doesn’t think about, or even recognize, that as they continue to use drugs, their body adjusts in multiple ways that can make it that much harder for them to stop use at a later point. It should be clear that this is not an issue for everyone – both tolerance and sensitization require repeated administration of drugs that are pretty close together. But they don’t require hundreds of uses, a few days with continuous, or intermittent use, are often enough to bring about these changes in the addicted brain.

We often hear that even the first hit of a drug can cause someone to be addicted. While there’s little doubt that even a single drug administration can change brain response in important ways, I can say with absolute certainty that using a drug repeatedly cause long-lasting changes in the brain chemistry that make future drug use more likely.

Salvia, a popular hallucinogen that is much shorter-acting than LSD

Co-authored by Jamie Felzer

If I were a betting person (I’m not really), I’d bet that most of you have been to YouTube before. For some of us the video site provides good information and for others it’s an endless source of comedy.  Either way, YouTube has also become a hallmark of the youngest generation of computer users – they love to post funny videos of their friends for the whole world to see. Some of those young YouTube users have been posting videos of themselves using Salvia.

Salvia, Salvinorin A, and YouTube

For those unaware, Salvinorin-A (note Salvanorin by the way) is the active, hallucinogenic drug in Salvia, a plant that is legal for those above 18 in the United States. Salvinorin A is a very potent hallucinogen that unlike LSD and many other hallucinogens, does not act on serotonin circuits, but instead acts on opioid receptors to produce short term effects.  The range of effects include surfacing of past memories, uncontrollable laughter, sensations with various motor properties and becoming one with an inanimate object.

Salvia’s usage has long been documented among South American Shamans for visions and healing purposes. However, shamans use it only through extraction into tea or through chewing and modern methods of use include smoking or ingestion sublingually. Smoking the drug produces a much faster onset. Chewing Salvia leaves results in a much smaller amount of the drug, allowing the shamans to use the plant therapeutically.  Large doses, such as those that are used now aren’t shown to have therapeutic effects.

Interestingly, the opioid receptor Salvia acts on (the Kappa opioid receptor-type) is not the same one that morphine and heroin act on (called the mu opioid receptor). This can leave Salvia users with a dysphoric effect (like depression) that makes for a miserable experience and a desire for the trip to end.  Good thing it is a quick trip!!  However, Salvia is known to produce different effects in different users, so dysphoria is not always present.

Recently, researchers looked into YouTube videos people posted of themselves or their friends using Salvia. Since Salvia is a fairly short-acting drug, lasting an average of 6 minutes, they were able to see many of the full experiences in their natural environment.  Some of the observed effects of salvia included uncontrollable movements, changes in visual perception, laughter and “separateness” of body.

Salvia, addiction, and long term effects

As far as we know right now, Salvia use doesn’t seem to produce many long-term, severe, consequences and it’s addictive properties are not yet known. Still, the experience during use can be quite harsh. The number of hits, as to be expected, closely correlated with the amount of functionality problems exhibiting themselves in diction and fluency of movements.  As noted earlier, although usage in low doses may be used for holistic healing purposes, smoking of Salvia does not seem to have any sort of healing powers.

Like many other legal drugs, Salvia use should be undertaken with caution, understanding the potency of the drug, its effects, and the possible consequences. Just because a drug is legal doesn’t mean it’s completely safe – Make sure you know what you’re doing before trying it out.

Citation:

Lange, Daniel, Homer, Reed, Clapp. Salvia Divonorum: Effects and Use Among YouTube Users. Drug and Alcohol Addiction. May 4 2009