Buprenorphine IV: What about Cocaine and Methamphetamine?

I have been thinking about buprenorphine, naltrexone and the stimulants cocaine and methamphetamine.

An issue which came to my mind recently and which I think it worth discussing is that cocaine is often cut and replaced with fentanyl to hide the over-dilution. This is sometimes done sloppily leading to fentanyl overdoses of people who did not know they were consuming opiates.

This is another reason to provide naltrexone to all who request it — it can protect against the temptation to use opiates and can also protect from opiates that people don’t even know are there (so this is a harm reduction use of naltrexone not an addiction treatment use).

Similarly buprenorphine also blocks opioid receptors. This is an additional benefit of DAT of OUD for people with combined opioid and stimulant addiction.

The other issue is a literature suggesting that buprenorphine is also useful for reducing cravings for and use of cocaine and methamphetamine. This is an unproven hypothesis. Much of the evidence comes from animal studies (that is one of a really large number of publications most of whose abstracts I haven’t read).

There was a strange randomized controlled trial (see also here) in which it was tested whether buprenorphine provided additional benefits if combined with naltrexone (I don’t even see how this could work). The result was that there was not a significant effect on the principal outcome measure but additional statistical analysis showed a statistically significant benefit. This sort of data analysis is not at all well received in the medical literature and does not convince the FDA. But how was it supposed to work with an opioid antagonist included ?

There is a newer literature with promising results regarding methamphetamine addiction (oddly much of the research done in Iran). “Conclusions: Buprenorphine augmentation, in comparison with the placebo, significantly reduced the craving to use METH during treatment with the Matrix program.”

“Comparing the effect of buprenorphine and methadone in the reduction of methamphetamine craving: a randomized clinical trial” “All 40 patients completed the study. Both drugs were effective in decreasing methamphetamine craving during methamphetamine withdrawal. Reduction of craving in the buprenorphine group was significantly more than in the methadone group (P < 0.05).”

Or how about Buproprion (welbutrin) ? “Both medications were effective in the reduction of methamphetamine cravings. Reduction of craving in the buprenorphine group was significantly more than the bupropion group (P = 0.011). Overall, a significant main effect of day (P <0.001) and group (P = 0.011) and a non-significant group-by-day interaction (P >0.05) were detected.”

For those who want a more prestigious journal, here is a trial of bupropion and naltrexone published in the very top New England Journal of Medicine. “Bupropion and Naltrexone in Methamphetamine Use Disorder”

A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone–bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone–bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone–bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone–bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone–bupropion during the trial.


Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo.”

“The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2”

Not great but statistically significantly better than nothing.

Oh and a new trial is recruiting

This is plenty for me to support drug assisted treatment of cocaine and methamphetamine addiction, but I am a fanatical enthusiast, and I don’t propose that Joe Biden insist on it.