Skeptical Raptor's Blog hunting pseudoscience in the internet jungle

Drug can block heroin addiction! Scientists didn’t actually say that.

Here we go again. The popular press rewrites a press release that overstates the result of a published paper. The press repeats the story everywhere. We now think that it’s the truth, but it hasn’t been proven in a clinical trial and the original published paper says nothing even close to what’s being written. And, it’s left to a couple of bloggers to walk back the exaggerations to the real scientific conclusions published in the real paper.

According to an article in Science Daily, Scientists can now block heroin, morphine addiction:

In a major breakthrough, an international team of scientists has proven that addiction to morphine and heroin can be blocked, while at the same time increasing pain relief.

The results — which could eventually lead to new co-formulated drugs that assist patients with severe pain, as well as helping heroin users to kick the habit — will be published August 16 in the Journal of Neuroscience.

“Our studies have shown conclusively that we can block addiction via the immune system of the brain, without targeting the brain’s wiring,” says the lead author of the study, Dr Mark Hutchinson, ARC Research Fellow in the University of Adelaide’s School of Medical Sciences.

“Both the central nervous system and the immune system play important roles in creating addiction, but our studies have shown we only need to block the immune response in the brain to prevent cravings for opioid drugs.”

Before we even start looking at the original paper, I need to refer you to a couple of articles I wrote before. First, always dig down to the original sources, and second, always ignore press releases (and I suppose any news article that relies upon press releases, like Science Daily seems prone to doing these days). It’s so important to clear away the hype from the reality, whether it’s some obscure article claiming that some vitamin cures cancer (when it’s just a minor pilot study that has limited evidence that may or may not show anything) or a broad pivotal double blind clinical trial that provides actual statistical evidence of of a result.

Back to heroin addiction. The original article by Hutchinson et al.Opioid Activation of Toll-Like Receptor 4 Contributes to Drug Reinforcement, was recently published in the Journal of Neuroscience. And there conclusion is:

Thus, the discovery of TLR4/MD2 recognition of opioids as foreign xenobiotic substances adds to the existing hypothesized neuronal reinforcement mechanisms, identifies a new drug target in TLR4/MD2 for the treatment of addictions, and provides further evidence supporting a role for central proinflammatory immune signaling in drug reward.

No, that does not say “we found a cure for opioid addiction.” It doesn’t even presume to find one in the future.

But I don’t profess to be a neuroscientist (nor am I going to presume to be one with just a few hours of research on the internet), so I’ll defer to a great review of the Hutchinson et al. articleSTOP THE PRESSES! We cured heroin addiction by Scicurious (a Scientific American blogger). Before I pull out some relevant points, let’s jump to a general overview. Hutchinson’s paper is a good one. It’s an important one. It will lead to advances in addiction research. But it is not a pivotal study that will give us a new drug to cure heroin addiction.

So, before we continue, let’s quickly describe what causes opioid addiction:

Opiates, including drugs like morphine, heroin, and oxycodone, are drugs that act via the receptors of your (aptly named) endogenous opioid system. When activated, the receptors of this system (the most famous being the mu-opioid receptor) reduce pain. Activation of these receptors will also indirectly increase dopamine in reward-related areas of the brain, resulting in the highs associated with opiate use (opiate receptors are also in other areas of the body, so there are side effects including some fun ones in your gastrointestinal tract). So opiates are highly addictive drugs, producing long lasting and tough addictions to treat. Treatments include things like naloxone, an inverse agonist of the opioid receptors which can reverse overdoses, and drugs like methadone, which are long and slow acting drugs that replace the morphine and heroin and allow someone to function without being high.

But. Opiates are also the most effective pain medications available. There really is nothing else that compares. So scientists are constantly looking for ways to develop new opiate drugs that could relieve pain, but without the addictive side effects. And of course we’re always looking for new drugs to treat addiction.

Hutchinson et al. are examining a new drug called (+)-naloxone, which is a synthetic mirror isomer of naloxone, that  has no significant affinity for opioid receptors, but instead has been discovered to act as a selective antagonist of Toll-like receptor 4. This has some nice effects on the drug-addiction-related effects of opiates. Incidentally, a number of California opioid addiction treatment centers and detox facilities all over the country have been offering Naloxone as an antidote for opioid overdose for some time now.

Scicurious goes on to discuss the results of the Hutchinson et al. article, which surprisingly focuses more on pain relief than addiction, which you can read in detail. His conclusion is very pertinent and completely different from what was written in the press releases:

So not only could toll-like receptor 4 have effects in the rewarding properties of opiates, blocking toll-like receptor 4 (with, say, (+)-naloxone) could help to potentiate pain relief.

It’s a good study, and the implications are there for both the addiction-related findings and the pain, but I actually think the press-release took the wrong tack, here. (+)-naloxone has not cured addiction. But it could do great things with pain. Because it appears to have no addictive properties itself (it produces no place preference, but I would like to make sure its not self-administered, though I don’t think it would be), but it potentiates the pain relief from opiates, it could be given as a combination medication with traditional opiate painkillers. This means that we could use much lower doses of opiates than we current do, and use (+)-naloxone to make up the difference, hopefully reducing the possibility of people becoming addicted to their painkillers.

This is HUGE. There have been very few recent breakthroughs in pain pharmacology, and a drug like this has a lot of potential.

And the addition of toll-like receptor 4 is a nice new mechanism, it’s nice to see the new immune focus bear interesting fruit. I would be glad to see drugs targeting this receptor get tested and see what they might do on their own.

My question is, why did the press release focus on the drug addiction? While the drug addiction angle is interesting, the pain angle seems to have more immediate therapeutic use. I suppose heroin is always sexier than pain. But keep in mind: this paper is really interesting. There’s a lot of good stuff here, some new mechanisms and new therapeutic angles. But we haven’t “blocked addiction” yet.

I agree. This is a wonderful new drug that could be a blockbuster for medicine. A painkiller that may not be addictive (though I’d want to see more on psychological addiction before considering it some sort of miracle). It could replace a lot of drugs that are abused because they are used initially for pain then become addictive. Reading the article, I’m not even sure that (+)-naloxone has any relevance in treating addiction, because I’m unconvinced that the study was using “addicted” animals (just trained ones), and Scicurious seemed to have the same bit of skepticism. The pain killing angle was much more important.

Once again, you’ve got to read beyond the headlines. We haven’t got anything here that would definitely be another tool in treating heroin addiction. Maybe down the road if other studies can show that it might help. But we might have a really great drug to treat pain. That’s really cool. 

Key citations:

  • Hutchinson MR, Northcutt AL, Hiranita T, Wang X, Lewis SS, Thomas J, van Steeg K, Kopajtic TA, Loram LC, Sfregola C, Galer E, Miles NE, Bland ST, Amat J, Rozeske RR, Maslanik T, Chapman TR, Strand KA, Fleshner M, Bachtell RK, Somogyi AA, Yin H, Katz JL, Rice KC, Maier SF, Watkins LR. Opioid activation of toll-like receptor 4 contributes to drug reinforcement. J Neurosci. 2012 Aug 15;32(33):11187-200. PubMed PMID: 22895704; PubMed Central PMCID: PMC3454463.
Comments (1)
  • Chugs 1984

    +Naloxone is Naloxone with Ibudilast.

    Hutchinson discovered that Ibudilast, a simple anti-inflammatory, reduces heroin withdrawals & tolerance whilst improving the analgesic affect of opiates.

    The root of all this is that he discovered that opiates induced glial activation,which participates in the mediation of pain including neuropathic pain, due to release of neuroexcitatory, proinflammatory products – it this process that causes opiate withdrawals.

    Basically the withdrawals have nothing to do with pleasure, conditioning or a failure of character to get off of heroin.

    Instead the individual is primed at birth to be a drug addict. Hutchinson proved this by purposely damaging rats in pre/post natal development and saw that these rats proved to be all the more addicted to heroin then rats that weren’t damaged.

    Furthermore he could reverse the withdrawals with the use of ibudilast . See previous Addiction Medicine orthodoxy thought that addiction and withdrawals were caused by the other. What is now being realised is that people are born with addictions.

    See tomorrows drug addict is right now feeling sick as the brain produces inflammatory molecules that target the glia. Not in huge amounts but enough to encourage the individual to engage in risky activities thus flooding the brain with dopamine, adrenaline and endorphins. Eventually the individual is exposed to opiates and the rest is history. Their forever tied into using this drugs in a sub-concious form of self-medication.

    Drug addiction is not a weakness of character but rather brain damage. What is amazing is that ibudilast has been found to work with Meth addicts and in theory should work with any drug that causes classical withdrawal symptoms that we see with opiate users.

    Hutchinson claims Naloxone is required to:

    “Additionally, this nonstereoselectivity provides a means of specifically blocking opioid-induced glial activation by using drugs such as (+)-naloxone. This would allow (-)-opioids to act neuronally to suppress pain via their actions on classical opioid receptors, while preventing (-)-opioids from simultaneously activating glial TLR4, which causes the release of pain-enhancing proinflammatory cytokines that oppose or counter-regulate the pain suppressive effects of opioids.”

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