What is the recommended approach for prescribing Cannabidiol (CBD) to patients, considering factors such as age, weight, medical history, and current health status?

How to Prescribe CBD

CBD should only be prescribed as FDA-approved Epidiolex for rare epilepsy syndromes (Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex), and clinicians should not recommend CBD for other conditions outside of clinical trials due to lack of proven efficacy and significant safety concerns. 1, 2

FDA-Approved CBD: Epidiolex Only

• Epidiolex is the sole FDA-approved CBD medication as of 2024, indicated exclusively for three rare epilepsy conditions. 1, 2
• Dosing for Epidiolex: 5-25 mg/kg/day administered twice daily, with slow titration over approximately 2 weeks. 2, 3
• All other CBD products (oils, edibles, topicals) remain federally unapproved despite state-level medical marijuana programs. 4, 5

Critical Safety Monitoring Requirements

Hepatotoxicity Surveillance

• Monitor liver enzymes before initiating CBD and regularly during treatment, as approximately 13% of patients develop dose-related, reversible transaminase elevations, typically within the first 2 months. 1, 2
• No cases of liver enzyme elevation occurred with CBD doses below 300 mg/day in pooled analyses. 1
• Meta-analysis demonstrated a 6-fold increase in liver enzyme elevation with CBD use, with drug-induced liver injury occurring in 3% of patients. 1
• One-third of transaminase elevations resolve spontaneously; remaining cases improve with dose reduction or discontinuation. 1

Drug-Drug Interactions

• CBD inhibits CYP3A4, CYP2C19, and P-glycoprotein, creating high potential for clinically significant drug interactions. 1, 6
• Very high-risk interactions: warfarin (requires close INR monitoring and dose adjustment). 1, 6
• High-risk interactions: buprenorphine and tacrolimus (require dose adjustments and enhanced monitoring). 1
• For epilepsy patients, CBD significantly interacts with clobazam and valproate, necessitating dose reductions of these antiepileptic drugs. 2
• Consider reducing substrate medication doses by 50% when initiating CBD, then titrate based on therapeutic drug monitoring. 6

Conditions Where CBD Should NOT Be Prescribed

Cancer-Related Symptoms

• Do not recommend CBD ≥300 mg/day for cancer symptom management outside clinical trials due to lack of proven efficacy and hepatotoxicity risk. 1
• For refractory chemotherapy-induced nausea/vomiting, use FDA-approved synthetic cannabinoids (dronabinol or nabilone) instead, or quality-controlled 1:1 THC:CBD extracts where legally available. 1
• Evidence remains insufficient for CBD in managing cancer pain, sleep disturbances, anxiety, or quality of life. 1

Psychiatric Conditions

• Cannabis and CBD can paradoxically worsen anxiety disorders rather than improve them, particularly in vulnerable populations. 4, 5
• No FDA approval exists for PTSD, generalized anxiety disorder, depression, or any psychiatric condition. 4, 5
• Older adults using cannabis face higher risk for behavioral health issues including anxiety, depression, sedation, and myocardial ischemia. 4, 5

Chronic Pain

• While chronic pain is the most common qualifying condition in state medical marijuana programs, evidence for CBD efficacy in pain management remains insufficient to support prescribing. 1
• A 2022 meta-analysis found only very small improvements in cancer pain with cannabinoids (weighted mean difference -0.19 on 10-cm VAS), with moderate certainty of evidence. 1

Absolute Contraindications

High-Risk Populations Requiring Complete Avoidance

• Pregnant and breastfeeding individuals: CBD may negatively affect fetal brain development and increase premature birth risk. 1, 2, 5
• Adolescents: Face elevated risks including neurodevelopmental decline, psychotic disorders, depression, and suicidal ideation. 4, 2, 5
• Elderly patients (≥65 years): Higher risk for sedation, obtundation, myocardial ischemia/infarction, and behavioral health deterioration. 1, 5

Dosing Algorithm for Epidiolex (FDA-Approved Indication Only)

Initiation and Titration

• Start low and go slow: Begin at modest doses and titrate over 2 weeks to minimize adverse effects. 1, 3
• For epilepsy syndromes: Initial dose 2.5 mg/kg twice daily, increase to maintenance dose of 5 mg/kg twice daily after 1 week. 2
• Maximum dose: 10 mg/kg twice daily (total 20 mg/kg/day) if needed for seizure control. 2
• Obtain baseline liver function tests before initiation and monitor at 1 month, 3 months, then periodically. 2

Common Adverse Effects

• Most frequent: Dizziness, confusion, dry mouth, fatigue, sedation (dose-dependent). 1, 3
• Serious but rare: Tachycardia, orthostatic hypotension, severe confusion, paranoia. 1
• Unlike opioids, CBD overdose does not cause respiratory depression, but can cause distressing symptoms and increase fall risk. 1

Critical Clinical Pitfalls to Avoid

• Do not extrapolate Epidiolex data to over-the-counter CBD products: These lack quality control, standardization, and proven efficacy. 2
• Do not assume state medical marijuana program approval equals FDA approval: Cannabis remains Schedule I federally with "no currently accepted medical use." 1, 4, 5
• Do not prescribe CBD as cancer-directed treatment: May cause significant clinical toxicities (fatigue, confusion) and financial burden without evidence of benefit. 1
• Do not ignore potential for cannabinoid hyperemesis syndrome: Can develop after long-standing use (>4 times/week for >1 year), characterized by cyclical vomiting relieved by hot showers. 1

Patient Counseling Requirements

Nonjudgmental Inquiry

• Routinely ask all patients about cannabis/CBD use in a nonjudgmental manner, regardless of legal status. 1
• Remain sensitive to cannabis regulations' disproportionate impacts on marginalized communities and avoid racial, ethnic, or socioeconomic biases. 1

Harm Reduction When Patients Use CBD Outside Recommendations

• When patients use CBD outside evidence-based indications, explore their goals, provide education, and seek to minimize harm. 1
• Discuss lack of quality control in non-pharmaceutical CBD products, potential drug interactions, and absence of efficacy data. 1, 2
• Direct patients to appropriate resources rather than dismissing their concerns. 1

Documentation and Monitoring

• Document baseline and ongoing liver function tests with specific attention to transaminases. 1, 2
• Record all concomitant medications and assess for CYP450-mediated interactions before prescribing. 1, 6
• Monitor for emergence of psychiatric symptoms, particularly anxiety and depression. 4, 5
• Assess driving ability and counsel about impaired reaction time and coordination. 1
• Screen for development of cannabis use disorder symptoms: irritability, insomnia, headaches. 1