Does cannabis availability help prevent opioid overdoses?

There’s been lots of chatter about the cannabis-opioid substitution question.

Newsweek headlines, “Can Legal Marijuana Solve the Opioid Crisis?”  while Dr. Jeff Sessions opines that cannabis is “only slightly less awful” than heroin.

People whose background is medical research tend to distrust anything that’s not a randomized controlled trial. They point to the positive correlation between cannabis use and opioid use at the individual level, and the fact that opioid deaths continue to rise even where cannabis is most freely available. Their position is, “We don’t know anything about this. Let’s due the clinical studies before taking action.”

But “not taking action” now means continuing to criminalize even the possession of cannabis. If cannabis substitutes for opioids, those laws cost lives: lives that can’t be regained ten years from now, after the clinical-trial results are in.

Moreover, the relevant clinical trials can’t actually be done in the U.S. The DEA-imposed University of Mississippi monopoly on the production of cannabis for research means that the cannabis available for research bears little resemblance to the products available in California dispensaries or Washington or Colorado cannabis stores. It’s lower in potency; it’s all flower rather than extract; it doesn’t embrace the wide variety of strains - each with its own chemical composition - now available commercially. It’s entirely possible that “Mississippi mud” doesn’t effectively substitute for opioids, but that the average dispensary product does, or that the average dispensary product doesn’t but some do. That’s one reason clinical trials with cannabis are so hard: cannabis isn’t one thing, it’s thousands of different mixtures of hundreds of different active chemicals.

Fortunately, there are other valid means of inquiry. You can look at the pattern of opioid prescriptions, treatment admissions, and overdose deaths before and after the passage of “medical marijuana” or full-legalization laws, and also study what happens as the number of outlets. the number of registered users, or the volume of product sold grows, and also what happens when a state reins in a previously wide-open “medical marijuana” system.

To a clinical researcher, these are all merely “ecological studies,” just one step up from chiromancy. But in fact econometricians have developed enormously sophisticated techniques of time-series analysis that allow solid causal inferences to be drawn from non-experimental data.

Rosalie Pacula and her team at the RAND Drug Policy Research Center have been doing such studies. Here’s their summary of the findings, which are consistent with studies done by other researchers:

* The relationship between medical marijuana laws and reductions in opioid overdoses is complex.

* Medical marijuana laws vary in their effect on reducing opioid overdoses.

*States with medical marijuana dispensaries experienced reductions in opioid-related overdoses.

* As states have become more stringent in regulating dispensaries, the protective value of medical marijuana laws generally has fallen.

* These findings suggest that broader access to medical marijuana facilitates substitution of marijuana for powerful and addictive opioids.

Is that a definitive finding? No.

Does it specify a mechanism? No.

Perhaps some patients find they can use cannabis instead of opioids for pain relief (which, it’s worth remembering, means not just reducing pain perception but making the experience of pain less stressful). Perhaps others find that they can use cannabis to get the same level of pain relief with lower doses of opioids. Perhaps some non-medical users use cannabis, when it’s available, instead of opioids. In still other cases cannabis might substitute not for the opioids themselves, but for the alcohol or benzodiazepines that, used in combination with the opioids, enhance the experience but also multiply the risk of fatal overdose by potentiating opioid respiratory suppression. Or cannabis might make withdrawal from opioids more bearable. Any or all of those effects could be at work.

Nonetheless, with these results in hand, if you asked me to bet on whether easing access to cannabis in a given state was likely to reduce the rate of increase in opioid overdoses in that state, I’d want very long odds to bet on “No.” Since, if the substitution effect is real, waiting costs lives, I think that’s a strong argument for going ahead with liberalizing cannabis access, whether under the guise of “medical marijuana” or (as I’d now prefer for other reasons) with frank legalization for adult use.

Of course that potential benefit needs to be weighed against the costs of liberalization in the form of increased prevalence of Cannabis Use Disorder. (Those costs could be minimized with well-designed legalization, but that’s not the legalization we’re actually getting.)

So it’s not irrational to remain a cannabis-policy hawk in the face of the opioid substitution findings. But it’s no longer reasonable to say, “We don’t know anything about whether cannabis substitutes for opioids.” We know enough to have a strong hunch.

I should add that these findings came as a complete surprise to me. Naturally, I can invent explanations for the fact of substitution now that there’s evidence for it, but I didn’t predict it. I did predict substitution for alcohol - that seemed to me among the strongest arguments for cannabis legalization, even back when I was mostly against it - but that prediction turned out to be wrong. The study that convinced me that there wasn’t substitution for alcohol - part of Rosanna Smart’s thesis work - also provided the first convincing evidence I’d seen of opioid substitution. That wasn’t something Smart had been looking for; it just popped out of the data.

The world is a complicated place. We should be prepared for surprises, and willing to learn from the findings of more than one research tradition.