What is the recommended gabapentin dosing schedule for an adult with cannabis (Δ9‑tetrahydrocannabinol) use disorder to reduce cravings, including titration, renal dose adjustments, and monitoring?

Gabapentin for Cannabis Use Disorder: Dosing and Management

Gabapentin 1200 mg/day (divided into three doses of 400 mg) is the evidence-based regimen for reducing cannabis cravings and withdrawal symptoms in adults with cannabis use disorder, based on the only positive randomized controlled trial demonstrating significant reductions in cannabis use and withdrawal severity. 1

Evidence Base and Efficacy

The recommendation is anchored in a 12-week randomized, double-blind, placebo-controlled trial of 50 cannabis-dependent adults that demonstrated gabapentin 1200 mg/day significantly reduced:

• Cannabis use measured by urine toxicology (p=0.001) 1
• Self-reported cannabis use via Timeline Followback (p=0.004) 1
• Withdrawal symptoms on the Marijuana Withdrawal Checklist (p<0.001) 1
• Executive function deficits associated with cannabis dependence (p=0.029) 1

However, the broader evidence remains limited. A 2025 Cochrane systematic review found insufficient evidence to recommend gabapentin routinely, noting that pharmacotherapies for cannabis use disorder should still be considered experimental. 2 A 2015 review identified gabapentin as one of only four medications with positive trial results but concluded there is no indication for routine off-label prescription. 3

Dosing Protocol

Target dose: 1200 mg/day divided into three doses (400 mg three times daily) 1

Titration schedule (extrapolated from neuropathic pain guidelines, as the cannabis trial did not specify titration):

• Start: 100-300 mg at bedtime 4
• Increase by 50-100% every few days 4
• Target: 900-1200 mg/day in 2-3 divided doses 4
• Maximum studied dose for cannabis: 1200 mg/day 1

Renal Dose Adjustments

Dose adjustment is required for renal insufficiency 4:

• CrCl 30-60 mL/min: Reduce dose by 50%
• CrCl 15-30 mL/min: Reduce dose by 75%
• CrCl <15 mL/min: Reduce dose by 85-90%
• Hemodialysis: Supplemental dose after dialysis

Clinical Context and Patient Selection

Gabapentin should be considered experimental and reserved for patients who have failed psychosocial interventions, which remain first-line treatment. 5, 2

Brief psychosocial support (5-30 minutes) incorporating motivational principles and individualized feedback is the cornerstone of cannabis dependence management and should be attempted first. 5 Cognitive behavioral therapy (4-14 sessions) yields superior outcomes with benefits maintained at 9-month follow-up. 5

Immediate specialist referral is mandatory for: 5

• Failure to respond to brief psychosocial intervention within 2-3 weeks
• Significant comorbid mental health disorders (anxiety, depression, psychosis)
• Polysubstance use
• Severe withdrawal symptoms requiring close monitoring

Monitoring Requirements

Withdrawal symptom timeline: 6, 5

• Onset: 24-72 hours after cessation
• Peak: Days 2-6
• Duration: 1-2 weeks (up to 3 weeks in heavy users)
• Cannabis craving may persist for months or years

Monitor for: 5

• Withdrawal symptoms using Cannabis Withdrawal Scale
• Worsening depression or emergence of psychosis (requires immediate specialist referral)
• Somatic symptoms: irritability, anxiety, insomnia, decreased appetite, restlessness, abdominal pain 6, 5

Follow-up schedule: 5

• Structured assessments at 2-3 weeks and 12 weeks after therapy initiation

Critical Contraindications and Warnings

Never use dexamphetamine for cannabis use disorder—this is explicitly contraindicated. 5

Avoid opioids entirely as they worsen nausea, carry high addiction risk, and do not address underlying pathophysiology. 6, 5

Do not taper or cease cannabis within 24 hours of surgery due to increased risk of withdrawal syndrome. 5

Cannabinoid Hyperemesis Syndrome (CHS) Differentiation

Critical distinction: Cannabis withdrawal syndrome (CWS) occurs after cessation, while CHS occurs during active use. 6, 5

CHS diagnostic criteria (all required): 6

• Stereotypical episodic vomiting ≥3 times annually
• Cannabis use >1 year before symptom onset, frequency >4 times/week
• Resolution after ≥6 months continuous abstinence

CHS acute management: 6, 5

• First-line: Lorazepam 0.5-2 mg IV/PO every 4-6 hours
• Second-line: Haloperidol or droperidol
• Adjunctive: Topical capsaicin 0.1% cream
• Never use opioids

CHS long-term management: 6, 5

• Cannabis cessation (only definitive cure)
• Amitriptyline 75-100 mg at bedtime (start 25 mg, titrate weekly by 25 mg)

Preclinical Support and Mechanism

Preclinical data support gabapentin's biological plausibility: in mice, gabapentin ≥10 mg/kg reduced somatic withdrawal signs (paw tremors, head twitches) and restored withdrawal-suppressed responding on progressive ratio schedules, though it did not normalize stress-induced corticosterone elevation. 7 This suggests gabapentin may treat somatic and affective symptoms independently of endocrine stress pathways. 7

Common Pitfalls

• Expecting rapid response: Gabapentin requires titration over days to weeks; immediate symptom relief is unlikely
• Using as monotherapy: Psychosocial support must accompany any pharmacotherapy 5, 2
• Inadequate dose: The 1200 mg/day target from the positive trial is higher than typical starting doses 1
• Confusing CWS with CHS: These require opposite management strategies (supportive care vs. cannabis cessation) 6, 5
• Slower titration for elderly or medically frail patients is essential 4