Galantamine May Reduce Illicit Opioid Use in Patients Treated With Methadone

Galantamine, which was found to reduce cocaine use in patients treated with methadone for opioid use disorder (OUD), may also be effective in reducing the use of nonprescribed opioids in this population, according to a study published in the American Journal on Addictions.¹

Concurrent use of opioids and cocaine in individuals maintained on methadone is a challenging issue without an approved pharmacotherapeutic solution. By inhibiting acetylcholinesterase, galantamine increases synaptic concentration of acetylcholine, the balance of which is thought to be implicated in substance use disorders.

This study is a secondary analysis of a randomized double-blind placebo-controlled trial conducted from 2009 to 2015 (Clinicaltrials.gov identifier: NCT0080935). The data from a total of120 adult participants (33% women; 52% white; 73% unemployed) who were maintained on methadone (mean baseline dose, 70.45 mg/day) for OUD and who were also dependent on cocaine were analyzed. Patients were randomly assigned to receive galantamine (n=55; 46%; maximum dose, 8 mg/day) or placebo (n=65; 54%) for a period of 12 weeks and were followed for 6 months afterward.

Urine and breath samples were collected semiweekly and tested using a 5-drug panel. Participants were assessed prior to starting treatment, every week during treatment, and at 1, 3, and 6 months posttreatment. Primary outcomes included the rate of opioid-negative urine screens and days of abstinence from illicit opioids.

The percentage of negative urine samples was greater in patients treated with galantamine vs placebo during the 12-week treatment phase (76.7% vs 62.4%, respectively; P =.027) as well as during the 6-month follow-up period (81% vs 59%, respectively; P =.001). In addition, urine samples positive for opioids were provided earlier by patients in the placebo vs galantamine group (median day: 14.5 vs 52.5, respectively), and participants who received placebo vs galantamine had fewer abstinence days (86.3% vs 92.5%, respectively; P =.03). Galantamine had an impact comparable to that of placebo on participants’ cognitive function and psychological symptoms.

Study strengths include a randomized and blinded design, high data availability, and verification of abstinence through urine toxicology screens. Study limitations include the use of 5-drug panels that may have missed some opioids and that as a secondary analysis, it was not principally meant to assess the effects of opioid use.

The authors of an accompanying commentary article estimated that the results of this analysis were clinically important in providing evidence that a cholinergic medication may be efficacious for the treatment of OUD.²

“If these results are supported in future trials, galantamine may hold promise across multiple drugs of abuse, including opioids,” noted the commentary authors. They recommended that future research assess the effect of galantamine in populations with other substance abuse issues.

Conflicts of Interest Disclosures

Dr Carroll is a member of CBT4CBT LLC, which makes validated forms of CBT4CBT available to qualified clinical providers. An approved management plan is in place with Yale University. The other authors have no disclosures.

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Reference

1. Carroll KM, DeVito EE, Yip SW, Nich C, Sofuoglu M. Double-blind placebo-controlled trial of galantamine for methadone-maintained individuals with cocaine use disorder: secondary analysis of effects on illicit opioid use [published online June 4, 2019]. Am J Addict. doi:10.1111/ajad.12904

2. Moeller SJ, Abi-Dargham A. Commentary: a novel therapeutic for opioid use disorder targeting the cholinergic system [published online June 4, 2019]. Am J Addict. doi:10.1111/ajad.12906