REVIEW OF: Kheirabadi GR et al, J Clin Psychopharmacol 2021;41(1):45–48

STUDY TYPE: Randomized controlled trial

Methamphetamine (meth) addiction is notoriously difficult to treat. There are no FDA-approved medications, and even the most promising trials have mixed results. People withdrawing from meth experience dysphoria, anxiety, mood instability, sleep disturbances, and intense drug cravings. In this study, researchers chose to investigate whether treating drug cravings could decrease participants’ meth use, and secondarily, whether this would lead to improvements in the depression, stress, and anxiety experienced during withdrawal. Targeting cravings seems intuitive, but the researchers made the unusual decision to use buprenorphine (bup), the mu-opioid partial agonist, as their anti-craving agent.

Bup is best known as a treatment for opioid use disorder (OUD), but it is hypothesized to have the potential for more general anti-craving effects by inducing dopamine release from the nucleus accumbens. While we don’t have any convincing human data yet, animal studies have shown that bup alters the dopamine neurotransmission brought about by meth that is thought to correlate with drug craving (Pereira FC et al, Neurotox Res 2011;19(1):94–101). The researchers in this study therefore theorized that bup’s potential anti-craving effect might be applicable to patients addicted to meth.

The researchers conducted a randomized, double-blind, placebo-controlled trial of 40 participants (30 men and 10 women), with an average age of 32.3 years and an average meth-addiction duration of 2.49 years. Half were assigned to receive bup (2 mg daily for one week, 4 mg daily for six weeks, then 2 mg for one week) while half received placebo. All participants enrolled in the same 16-week intensive multimodal psychotherapy program.

Over the study’s 24 weeks, those taking bup did better on all outcomes. Drug cravings were measured weekly for the first eight weeks and monthly thereafter, and the intervention group had modestly but significantly lower drug cravings at all time points after the first two weeks. Consistent with the hypothesis that treating cravings might improve sobriety, the intervention group had fewer meth-positive urine tests, with a mean of 5.80 positives in the bup group versus 7.80 in the placebo group (p < 0.001). Secondary endpoints of depression, anxiety, and stress were also slightly better in the treatment group versus the placebo group, at least at the two-month time point, which was the only time point reported in the study.

The small number of trial participants is a limitation, but not unusual for a study of this nature. However, several other key questions are left unanswered. Whether participants had a period of sobriety at the time of enrolling in the trial was not addressed. Neither was the authors’ choice to use unusually tiny doses of bup. And while outcomes reached statistical significance, the clinical utility of this approach remains questionable.

CATR’s Take
Bup did reduce cravings and abstinence in people with meth addiction in this small study, but lots of question marks remain about prescribing an unusual dose of a controlled substance for a non-FDA-approved indication. This approach is promising, so keep an eye out for future developments, but prescribing bup for meth addiction should remain in the realm of research until we have better clinical data. In the meantime, see the May/June 2021 CATR for a Q&A and clinical update on treating stimulant use disorders.