What medications can help manage symptoms in a patient experiencing marijuana withdrawal?

Medications for Marijuana Withdrawal Symptoms

For patients experiencing cannabis withdrawal syndrome (CWS), consider nabilone or nabiximols (synthetic cannabinoid agonists) as the primary pharmacological treatment, particularly in heavy users consuming >1.5 g/day of smoked cannabis or >20 mg/day of THC oil, with referral to psychiatry or addiction medicine for initiation and guidance. 1

Identifying Patients at Risk for Cannabis Withdrawal

Cannabis withdrawal syndrome occurs in approximately 50% of regular and dependent cannabis users after abrupt cessation, with symptoms appearing 24-72 hours after stopping and peaking in the first week. 2

High-risk patients include those consuming: 1

• More than 1.5 g/day of inhaled cannabis
• More than 20 mg/day of THC-dominant cannabis oil
• More than 300 mg/day of CBD-dominant oil
• Cannabis products with unknown THC/CBD content more than 2-3 times per day

DSM-5 diagnostic criteria require abrupt cessation of prolonged/heavy cannabis use plus three or more of: irritability/anger, anxiety, insomnia, decreased appetite, restlessness, altered mood, and physical symptoms (abdominal pain, tremors, sweating, fever, chills, headache). 1

Primary Pharmacological Treatment: Cannabinoid Agonist Replacement

Nabilone (Synthetic THC Analogue)

Nabilone is the most appropriate first-line medication for CWS, functioning as cannabinoid agonist replacement therapy similar to nicotine replacement for tobacco withdrawal. 1

Mechanism and properties: 1

• Synthetic analogue of Δ9-THC with anxiolytic, anti-emetic, and analgesic properties
• 96% oral bioavailability with 2-hour elimination half-life
• Reduces withdrawal symptoms and cannabis craving in persons with cannabis use disorder

When to prescribe nabilone: 1

• Patients with active CWS symptoms who were consuming >1.5 g/day of high-THC (>20%) smoked cannabis
• Patients with active CWS symptoms who were consuming >20 mg/day of THC oil
• Not appropriate for patients consuming less than these thresholds or minimal THC content products

Important prescribing considerations: 1

• Optimal dosages for CWS treatment are not established in the evidence
• Do not exceed already-accepted dosages for nabilone's approved indications
• Requires expert guidance from clinicians familiar with prescribing cannabinoids (pain specialists, psychiatrists, addiction medicine specialists)

Common adverse effects to monitor: 1

• Drowsiness, dizziness, vertigo
• Postural hypotension
• Dry mouth

Nabiximols (THC/CBD Combination Spray)

Nabiximols is an alternative cannabinoid agonist with similar efficacy to nabilone for reducing CWS symptoms and cannabis craving. 1, 3

When to consider nabiximols: 1

• As substitution therapy for patients with active CWS symptoms
• Same usage thresholds as nabilone (>1.5 g/day smoked cannabis or >20 mg/day THC oil)
• Requires same expert guidance for prescribing

Evidence Base for Cannabinoid Agonist Therapy

Systematic review evidence demonstrates that dronabinol, nabilone, or nabiximols show promise in reducing cannabis withdrawal symptoms, likely with dose-dependent effects, and are considered safe with good tolerability and few adverse effects. 3

However, the 2025 Cochrane review found that abstinence at end of treatment was no more likely with THC preparations compared to placebo (RR 1.04,95% CI 0.71-1.52; moderate-certainty evidence), though these pharmacotherapies should still be considered experimental. 4

The clinical rationale for cannabinoid agonist therapy is that it may help decrease relapse rates by managing withdrawal symptoms occurring within the first few weeks of treatment, even if long-term abstinence rates remain modest. 3

Alternative and Adjunctive Pharmacological Options

N-Acetylcysteine (NAC)

N-acetylcysteine may be considered but evidence shows abstinence is no more likely than placebo (RR 1.17,95% CI 0.73-1.88; moderate-certainty evidence), with probably little to no difference in adverse events. 4

Cannabidiol (CBD)

Cannabidiol evidence is limited and uncertain, with low-certainty evidence showing abstinence may be no more likely than placebo (RR 2.23,95% CI 0.54-9.32). 4

Anticonvulsants and Mood Stabilizers

Gabapentin has weak evidence for reducing cannabis consumption (Cohen's d = 0.26) at evidence level Ib. 5

Anticonvulsants and mood stabilizers carry significant risk, as withdrawal from treatment due to adverse effects was more likely with these medications (RR 2.88,95% CI 1.05-7.86; very low-certainty evidence), which may limit their therapeutic value. 4

Medications to Avoid

Serotonergic antidepressants should be avoided, as evidence suggests they can worsen withdrawal manifestations and increase likelihood of relapse. 5

Symptom-Specific Management

For short-term symptom relief while awaiting cannabinoid agonist therapy: 2

• Anxiety: Consider short-term benzodiazepines at lowest effective dose
• Sleep disturbances: Sleep hygiene counseling plus short-term sleep aids if needed
• Nausea/vomiting: Anti-emetics (note: nausea/vomiting is not in DSM-5 criteria but can occur) 6

Use the Cannabis Withdrawal Scale for standardized assessment and monitoring of symptom severity. 1

Critical Management Algorithm

Step 1: Assessment 1

• Document daily cannabis consumption (amount, THC/CBD content, frequency)
• Screen for DSM-5 CWS criteria (≥3 symptoms)
• Assess for psychiatric comorbidities and polysubstance use

Step 2: Risk Stratification 1

• High risk (>1.5 g/day smoked or >20 mg/day THC oil): Consider cannabinoid agonist therapy
• Low risk (<300 mg/day CBD-dominant or <2-3x/day unknown content): Supportive care only

Step 3: Referral and Treatment Initiation 1

• All suspected CWS cases should be referred to psychiatry or addiction medicine
• Specialists initiate nabilone or nabiximols with appropriate dosing
• Monitor for adverse effects (drowsiness, dizziness, postural hypotension)

Step 4: Supportive Care 2

• Psychoeducation about withdrawal timeline (peaks days 2-6, lasts 1-2 weeks)
• Supportive counseling as first-line non-pharmacological approach
• Consider cognitive-behavioral therapy for ongoing treatment

Special Populations and Complications

Patients with comorbid mental health disorders and polysubstance use may require inpatient admission for medically assisted withdrawal to avoid severe complications. 2

Patients with opioid dependence are less likely to experience CWS, and naltrexone administration has been observed to reduce cannabis self-administration. 1

Perioperative patients require particular vigilance, as CWS could potentially contribute to postoperative morbidity if daily cannabis intake is not replaced or continued. 1

Common Pitfalls to Avoid

Do not prescribe cannabinoid agonists for low-level users, as substitution is not appropriate for patients consuming less than threshold amounts or products with minimal THC content. 1

Do not attempt cannabinoid agonist therapy without specialist consultation, as optimal dosing is not established and requires expertise in cannabinoid prescribing. 1

Do not use serotonergic antidepressants, as they may worsen withdrawal and increase relapse risk. 5

Do not rely solely on pharmacotherapy, as psychotherapeutic techniques remain the foundation of treatment for cannabis dependence, with medications serving as adjuncts. 5