Can Wellbutrin (bupropion) be used to treat methamphetamine cravings?

Bupropion for Methamphetamine Craving: Limited Evidence with Modest Benefit in Select Patients

Bupropion (Wellbutrin) shows modest efficacy in reducing methamphetamine cravings and subjective effects in laboratory settings, but clinical trial data demonstrate it is only effective for increasing abstinence in males with low-to-moderate baseline methamphetamine use—not as a broad treatment for methamphetamine dependence. 1, 2

Evidence for Efficacy

Laboratory and Preclinical Data

• Bupropion significantly reduces acute methamphetamine-induced subjective effects, including ratings of "any drug effect" (p<0.02) and "high" (p<0.02) following methamphetamine administration 1
• Cue-induced craving is reduced with bupropion treatment, showing a significant bupropion-by-cue exposure interaction on craving scales (p<0.002) and behavioral intention to use (p<0.001) 1
• Animal models demonstrate dose-dependent reduction in methamphetamine self-administration, though effects are only somewhat specific to methamphetamine versus other reinforcers 3

Clinical Trial Results: Mixed and Limited

• A large randomized controlled trial (n=151) showed no statistically significant overall difference between bupropion 150 mg twice daily and placebo in achieving methamphetamine-free weeks (p=0.09) 2
• Subgroup analysis revealed benefit only in males with low-to-moderate baseline methamphetamine use (p<0.0001), not in heavy users or females 2
• A head-to-head trial comparing bupropion 300 mg daily versus buprenorphine 8 mg daily found buprenorphine significantly superior in reducing methamphetamine cravings (p=0.011), though both showed some effect over time 4
• Recent case series data (n=4) suggest potential benefit in patients with comorbid PTSD and methamphetamine use disorder, showing greater PTSD symptom reduction and lower relapse rates (25% vs 48.8%) compared to serotonergic agents alone 5

Practical Dosing and Monitoring

Initiation Protocol

• Start bupropion at 150 mg once daily, increasing to 150 mg twice daily after 3-7 days if tolerated, with maximum dose of 300 mg/day 6
• Avoid taking the second dose after 3 PM to minimize insomnia risk 6
• Studies used sustained-release formulations at 150 mg twice daily (total 300 mg/day) 4, 2

Critical Safety Monitoring

• Absolute contraindications: Active seizure disorder, brain metastases, stroke history, eating disorders (anorexia/bulimia), or any condition increasing seizure risk 6, 7
• Bupropion carries 0.1% seizure risk at therapeutic doses, which increases with higher doses 6
• Monitor blood pressure and heart rate regularly; contraindicated in uncontrolled hypertension 6, 7
• Black box warning: Monitor closely for suicidal ideation and behavioral changes, particularly in patients under 24 years old 6, 7
• Avoid concurrent MAO inhibitor use or within 14 days of discontinuation 6
• Dose reduction required in moderate to severe hepatic impairment; avoid in end-stage renal disease 6

Clinical Decision Algorithm

Best candidates for bupropion trial:

• Males with low-to-moderate (not heavy) baseline methamphetamine use 2
• Patients with comorbid depression, as bupropion addresses both conditions 7
• Patients with comorbid PTSD and methamphetamine use disorder 5
• Those attempting to quit smoking or reduce alcohol intake concurrently 7
• Patients describing addictive behaviors or cravings (based on obesity literature showing benefit for food cravings) 7

Poor candidates:

• Heavy methamphetamine users (no demonstrated benefit) 2
• Patients with seizure history or risk factors 6, 7
• Those with uncontrolled hypertension 6, 7
• Patients with eating disorders 7, 6
• Those on opioid therapy (if considering naltrexone-bupropion combination) 6, 7

Critical Limitations

The evidence base is weak: the largest clinical trial showed no overall benefit, with efficacy limited to a narrow subgroup 2. Bupropion is inferior to buprenorphine for methamphetamine craving reduction 4. The mechanism—dopamine and norepinephrine reuptake inhibition—provides theoretical rationale 1, but clinical translation is limited. This is not a first-line or broadly effective treatment for methamphetamine dependence.