My terrible plan for reducing opioid deaths

I have a terrible plan for reducing opioid overdose deaths. 

It would not reduce the number of people addicted to opioids; instead, it would ultimately increase it. It would not make opioids less attractive to addicts; instead, it would make them more attractive. It also would not make people less likely to try opioids; instead, it’d make newbies more likely to try opioids.

Now that I’ve stated why my plan is terrible, allow me to explain it. My terrible plan is to formulate GAL-021 into a nasal spray and sell it widely without a prescription. GAL-021, if you follow the link, is a drug that, when injected, inhibits the respiratory depression of opioids without inhibiting the active effects (i.e. pain control and euphoria) [1]. It’s an analog of almitrine, a formerly approved, now withdrawn drug which does the same but has nasty side effects. Given that respiratory depression is the reason people die when they overdose on opioids (i.e. they stop breathing), this means that this drug could save lives.

Think about a world in which this plan was followed through. Any opioid addict could take opioids without fear of overdosing, by simply taking GAL-021 soon after taking opioids. Given that overdoses usually take 1-3 hours after taking the drug, they’d have plenty of time to do so. Their friends could also administer the drug if they are concerned. If there was actually a danger of an overdose, this would save the addict’s life. If there wasn’t, there’d be no harm done, and it wouldn’t even ruin their high.

This would be an advantage over the current situation with Narcan, the nasal spray version of naloxone. True, Narcan/naloxone does stop an overdose. But, it does this by antagonizing the opioid receptors, which is basically like a reverse opioid high. Not only does it stop whatever opioid high you were feeling artificially, but it also stops any high from endorphins. As a result, Narcan feels terrible to the addict, making addicts unlikely to self-administer and making their friends less likely to administer unless they’re sure that they have to.

The disadvantage to making GAL-021 widely available, of course, would be that it could encourage people to take opioids because they see them as safer. However, this is the exact same issue as seatbelts encouraging people to speed or the availability of condoms encouraging teenage sex. As a society, we’ve generally come down on the side of “people are going to do dangerous things, so let’s make them safer”, and I don’t see any reason why this would be different.

You may be wondering how practical this plan is. I assure you that this plan, while terrible, is reasonably practical. First, turning an injectable into an intranasal is pretty easy. It only took Lightlake Therapeutics about a year to develop and test Narcan as an intranasal version of naloxone, and most drugs can simply just be crushed and snorted instead of injected, anyways.

The issue of price is also solvable. There’s no way of saying what the price of GAL-021 would be, as it never made it to market due to lack of commercial viability. We can get an idea, though, from the price of almitrine, which was about $115/dose before it was withdrawn from the market. Compare this to the price of Narcan, which is about $70 a spray, so not hugely different. Also, prices go down when drugs become generic. Generic naloxone is only about $30 an injection. I’d imagine the same would happen with this new drug.

A more serious concern would be the limited half-life of GAL-021, which, in the past, has limited the use of GAL-021 to infusion only. Extending the half-life would require some clever formulation or modification work of the sort I’ve discussed before in regard to semaglutide. Difficult, but not impossible.

Last, computer modeling suggests that severe opioid overdoses could not be reversed with GAL-021 alone. At that point, you’d probably need Narcan. However, that’s also the point at which the addict’s friends would also be willing to give Narcan, so the aforementioned reluctance would be less of an issue.

All in all, I think it’s clear that this is a terrible plan for solving the opioid overdose crisis, and I look forward to nobody following through with it. However, given that fentanyl, a synthetic opioid, is now the leading cause of death for ages 18-45, I thought I’d just throw this plan out there. 

[1] The science behind GAL-021 is described in this review, although it’s still not entirely clear. 

Essentially, our brain normally can detect hypoxia (a lack of oxygen) through the blockage of the specific potassium channels at the carotid arteries. Agonizing the opioid receptors, however, keeps those potassium channels open, so our bodies don’t notice hypoxia and don’t force us to hyperventilate.

GAL-021, almitrine, and related drugs artificially block those specific potassium channels anyways, which trips our body’s hypoxia sensors and forces us to breathe, without affecting the opioid receptors at all.