Joe Biden, Hunter Biden, Stimulant Use Disorders and ARPA-H

There was a press release issued by NIDA today, trumpeting a report of a Phase III trial of medication for methamphetamine use disorders. As a very brief recap, we have no approved medications to assist with methamphetamine (or any psychostimulant) use disorder and the distressing health consequences for addiction to cocaine, methamphetamine and some other related drugs are very severe. According to 2019 data from SAMHSA (Table 5.14A), some 534,000 folks over age 25 were in treatment for cocaine use disorder, 566,000 for methamphetamine and this contrasts with 594,000 for heroin, 552,000 for marijuana and 1,957,000 for alcohol. Table 5.1A points out that some 756,000 of folks in this range probably had a cocaine use disorder, 904,000 had a methamphetamine use disorder and 10,959,000 had an alcohol use disorder.

Not everyone who needs treatment gets it. Not even close.

Hunter Biden, the President’s second (and still living) son has recently published a memoir detailing his struggles with addiction to cocaine and alcohol. Joe Biden, the President, issued a recent press release calling for a $6.5 billion launch of an Advanced Research Projects Agency for Health (ARPA-H) within the National Institutes of Health.

With an initial focus on cancer and other diseases such as diabetes and Alzheimer’s, this major investment in federal research and development will drive transformational innovation in health research and speed application and implementation of health breakthroughs.

Notably missing is any prominent mention of substance use disorder in ARPA-H.

On the relative scale of progress in treating cancer and diabetes, and yes even Alzheimer’s, I would argue that treatments for substance use disorders have been woefully under researched. Funding has lagged for the development of treatments and medications both in the public and private sectors. This means novel discovery, of course, but the real glaring deficit is in the routine churning of clinical trial after clinical trial for evaluating pretty run of the mill stuff. As they did in this recent Phase III trial.

Methamphetamine, as they say, is a helluva drug. From Brecht and Herbeck, 2014, we see the following relapse survival curve for a sample of methamphetamine users admitted to the Los Angeles County substance use treatment system. the followup period ranged from 22-90 months over which 23% maintained abstinence from methamphetamine. That means 77% relapsed, with a range of 0-79 months until relapse. As you can see from the below, 36% returned to methamphetamine use immediately upon discharge (Nb, this is not a sample selected for desire to quit), 14% more relapsed by 6 months and a total of 61% had relapsed within a year of entry. The good news, if there is any, is that this should be low hanging fruit. Anything, anything at all, that seems to work will be a huge gain versus the situation at present.

The new trial conducted by Trivedi et al. found that depot injection of naltrexone combined with daily oral buproprion (a cathinone-derivative, aka “bathsalt”) was effective, versus placebo control, in treating methamphetamine use disorder.

“Effective”.

Meaning that within a population of methamphetamine users with “moderate to severe” use disorder who intended to quit, 11.4% responded. Where a response was 3 out of four urine samples negative for methamphetamine during weeks 11-12. Only 1.8% in the placebo group had this “response”. Let’s round that out to 10% efficacy.

Now, the glass is most emphatically half full. Ten percent is not very impressive sounding but it is something. It is some improvement for some folks. Ten percent of the ~904,000 estimated with a methamphetamine use disorder is a lot of people and their families that have improved lives. We are moved by the stories of single individuals- like Hunter Biden, and Nic Sheff and William C. Moyers. Let us apply that same empathy we feel for these men and their relative success at recover to each and every other person with a stimulant use disorder.

And we have nowhere to go but up, with discovery of any additional strategies that, btw, likely will also help with cocaine use disorder.

Do we need DARPA-like innovation? of course. Anti-drug vaccines (something I’ve worked on, for disclosure) have been languishing in a twilight of basic biological efficacy but need a big kick in the pants to advance to real-world efficacy. Wearable technology has several immediately imaginable future uses. Deep brain stimulation. TMS. Individualized therapy based on genotyping. There is no reason to think that we could not go big with ARPA-H for substance use.

It is more than a little bothersome that Joe Biden, who so explicitly ties his interest in Cancer Moonshots and the like to the fate of his older son, does not exhibit the same motivations for the trials of his younger son. Who, btw, is not dead and is at continual risk of relapse given his history.

Trivedi MH, et al. Trial of Bupropion and Naltrexone in Methamphetamine Use Disorder. New England Journal of Medicine. January 14, 2020.