The investigators are proposing a randomized pilot feasibility study to evaluate the effects of galantamine versus placebo on preventing relapse to opioid use following tapering from methadone or buprenorphine maintenance (Medication Assisted Treatment, or MAT) among adults with opioid use disorder, with additional behavioral therapy (web-based cognitive behavioral therapy) provided across all conditions to help individuals successfully transition from MAT to a drug-free state.

This is a randomized pilot study to examine the potential use of galantamine as an adjunct to the standard buprenorphine or methadone taper in the context of behavioral support. Early abstinence from opioids is associated with high relapse rates and there is a great need to develop interventions that will prevent relapse to opioid use.

In this randomized pilot, 30 adults enrolled in the methadone or buprenorphine maintenance programs at the APT Foundation and who have sought a medically supervised, voluntary taper from these medications will be offered participation in a double-blind, placebo controlled, randomized trial of galantamine as an adjunct to standard tapering procedures at this clinic along with the combined approach utilizing concurrent behavior therapy. Primary outcomes will be: (1) successful completion of taper (achieving a methadone/buprenorphine dose of 0), (2) opioid withdrawal symptoms, and (3) opioid use, assessed by self-report and urine samples during and up to 3 months after the end of opioid taper. The investigators will also closely monitor patient comfort and safety (assessed by opioid withdrawal symptoms, adverse events, with measures of stress, sleep and pain) as well as cognitive function (assessed by the CANTAB).

Inclusion Criteria:

• Are male and females, between the ages of 18 and 65
• Are enrolled in the APT methadone or buprenorphine program, have been stabilized for at least one year, and who voluntarily wish to taper off MAT.
• For women of child-bearing age, have a negative serum pregnancy test at screening, agree to adequate contraception to prevent pregnancy, and agree to have monthly urine pregnancy tests at the clinic.
• Are fluent in English and have a 6th grade or higher reading level.
• Can commit to at least 12 weeks of treatment and are willing to be randomized to treatment

Exclusion Criteria:

• Are undergoing administrative (non-voluntary) tapering (e.g., example due to non-payment of program fees, program rule infractions).
• Meet DSM-V psychiatric classifications for lifetime schizophrenia or bipolar disorder, or have a depressive or anxiety disorder with current use of a prescribed psychotropic medication that cannot be discontinued;
• Current DSM-V diagnosis of drug or alcohol use disorder (other than opioids or tobacco);
• Demonstrate significant medical conditions, including asthma or chronic obstructive lung disease, history or current gastrointestinal ulcer, hepatic or renal impairment and cardiac rhythm disturbances or any other medical conditions that the study physician deems contraindicated for galantamine treatment;
• Use of other medications including a) drugs that slow heart rate (e.g., beta-blockers),which may increase the risk of bradycardia and AV block and b) NSAIDs; increased potential for developing ulcers/active or occult gastrointestinal bleeding;
• Have a screening liver function test (AST or ALT) greater than 3 times normal;
• Known allergy or adverse reaction to galantamine

10 weeks of taper