What are the therapeutic benefits and recommended dosing of cannabis (THC/Tetrahydrocannabinol and CBD/Cannabidiol) for adult chronic neuropathic or musculoskeletal pain, chemotherapy‑induced nausea and vomiting, multiple sclerosis spasticity, and refractory epilepsies such as Dravet and Lennox‑Gastaut syndromes?

Therapeutic Benefits of Cannabis and Cannabinoids

Cannabis and cannabinoids have established therapeutic benefits in four specific clinical scenarios: refractory chemotherapy-induced nausea and vomiting, multiple sclerosis spasticity, refractory epilepsies (Dravet and Lennox-Gastaut syndromes), and potentially as adjunctive therapy for chronic pain, though evidence for pain management remains limited and inconsistent. 1, 2

Chemotherapy-Induced Nausea and Vomiting (CINV)

For adults with cancer experiencing refractory nausea or vomiting despite guideline-concordant antiemetic prophylaxis, cannabinoids may be added as salvage therapy. 1

Recommended Agents and Dosing:

• Dronabinol (synthetic THC): Start at 2.5 mg orally three times daily, may titrate up to 10 mg three to four times daily 1
• Nabilone: Initiate at 1 mg orally twice daily, may increase to maximum 2 mg four times daily 1
• 1:1 THC:CBD extract: Quality-controlled oral formulations may be considered, though evidence is weaker than for synthetic cannabinoids 1

Important Context:

• Cannabinoids are one of several options for refractory CINV, not first-line therapy 1
• The 2020 ASCO antiemetics guideline recommends adding olanzapine first (if not already used), then considering other antiemetic classes before cannabinoids 1
• Evidence supporting cannabinoids comes from older trials (1975-1991) that did not compare against current antiemetic regimens 1
• No dose adjustments needed for renal or hepatic impairment 1

Refractory Epilepsy

FDA-approved cannabidiol (Epidiolex) is indicated for three rare, severe forms of epilepsy: Dravet syndrome, Lennox-Gastaut syndrome, and Tuberous Sclerosis Complex. 2

Dosing Protocol:

• Initial dose: 5 mg/kg/day divided into two doses 2
• Titration: Gradually increase to 10-20 mg/kg/day based on tolerance 2
• Maximum dose: 25 mg/kg/day in two divided doses 2

Efficacy Data:

• Median seizure reduction of 41.9% and 37.2% in Lennox-Gastaut syndrome 2
• Significant reduction in seizure frequency in Dravet syndrome 2

Critical Drug Interactions:

• Clobazam: CBD increases N-desmethylclobazam levels via CYP2C19 inhibition, causing enhanced sedation; dose adjustment required 2
• Valproate: Concomitant use significantly increases risk of elevated liver enzymes; monitor closely 2
• Other interactions include rufinamide, zonisamide, topiramate, eslicarbazepine, and warfarin 2

Multiple Sclerosis Spasticity

Cannabis-based medications show modest benefit for MS-related spasticity, though evidence quality is limited. 3, 4

• Nabiximols (THC:CBD spray, not FDA-approved in US) has been studied most extensively 5
• Patients report improvement in muscle spasms and spasticity symptoms 5
• Benefits are typically small to modest in magnitude 4

Chronic Pain

Evidence for cannabis in chronic pain management is inconsistent and generally of low quality, with the most robust data supporting use in neuropathic pain (excluding diabetic neuropathy) rather than musculoskeletal pain. 3, 4

Key Limitations:

• Cancer pain: Evidence remains insufficient to recommend for or against cannabinoids 1
• Chronic pain in cancer survivors: May be considered after weighing benefits and risks, following state regulations, but insufficient evidence for first-line use 1
• Pain is the most common reason patients seek medical cannabis, despite limited supporting evidence 1

Clinical Approach When Considered:

• Reserve for patients who have failed more conservative management 1
• Use as adjunctive therapy, not monotherapy 1
• Start with lowest possible dose and titrate slowly ("start low, go slow") 1

What Cannabis Does NOT Treat

Clinicians should NOT recommend cannabis or cannabinoids as cancer-directed treatment outside clinical trials. 1

• No good-quality evidence supports antineoplastic effects 1
• Using cannabis as cancer treatment may cause significant clinical toxicity (fatigue, confusion, euphoria) and financial burden without benefit 1
• High-dose CBD (≥300 mg/day) should NOT be used for symptom management due to lack of efficacy and risk of reversible liver enzyme abnormalities 1

Pharmacokinetics and Administration Routes

Onset and Duration by Route:

• Inhaled/smoked: Onset in seconds to minutes, duration 2-3 hours; bioavailability 10-35% 1
• Oral/edible: Onset 30 minutes to 2 hours, duration 5-8 hours; bioavailability only 4-12% 1

Critical Safety Point:

Patients must be warned about delayed onset with oral products (≥1 hour) to avoid "stacking doses" that can cause severe adverse effects. 1

• High-fat meals significantly increase oral cannabinoid absorption and may exacerbate side effects 1
• Most cancer specialists prefer oral/edible formulations over inhaled routes 1

Common Adverse Effects

Frequent (Generally Mild to Moderate):

• Dizziness, somnolence, drowsiness 3, 4, 5
• Dry mouth 3, 5
• Decreased appetite, diarrhea (with CBD) 2
• Euphoria, feeling "high" 1, 3
• Confusion, disorientation 1

Serious Concerns:

• Cardiovascular: Tachycardia (beta-adrenergic mediated), orthostatic hypotension, increased myocardial ischemia risk in susceptible individuals 1
• Hepatotoxicity: Reversible liver enzyme elevations, especially with high-dose CBD (≥300 mg/day) or when combined with valproate 1, 2
• Psychiatric: Paranoia, psychosis, hallucinations (particularly with high THC doses) 1, 4
• Cognitive: Impaired memory, learning disruption, reduced educational attainment (especially in adolescents) 4
• Motor vehicle accidents: Avoid driving for 5-8 hours after use, potentially longer in some individuals 1

Special Population Risks:

• Older adults: Higher risk of confusion, falls, and sedation 1, 2
• Adolescents: Increased risk of cannabis use disorder, psychosis/schizophrenia, mood disorders, suicidal behaviors 4, 5
• Pregnancy: FDA and US Surgeon General recommend avoiding all cannabis forms; risks include prematurity and restricted fetal growth 2, 4
• Children: Risk of accidental ingestion; lack of safety packaging for medical cannabis products 5

Clinical Communication and Harm Reduction

Clinicians should routinely and nonjudgmentally inquire about cannabis use in all adults with cancer, given 20-40% report current use. 1

Essential Questions to Ask:

• Goals of cannabis use 1
• THC and CBD content of products 1
• Frequency and amount of use 1
• Route of administration 1
• Subjective effects experienced 1
• Source of products and cost 1

When Patients Use Cannabis Outside Evidence-Based Indications:

• Explore their goals and expectations 1
• Provide unbiased, evidence-based education 1
• Seek to minimize harm rather than simply prohibit use 1
• Remain sensitive to cannabis regulations' disproportionate impacts on marginalized communities 1

Drug Interactions and Perioperative Considerations

Cannabis users may require increased analgesia and anti-emetic prophylaxis perioperatively, though evidence is limited. 1

Anesthetic Concerns:

• Potential difficulty achieving adequate anesthetic depth 1
• Increased cerebral blood flow 1
• Beta-adrenergic mediated tachycardia with acute use 1
• Possible increased myocardial ischemia risk in susceptible patients 1

Immunotherapy Interaction:

Patients on cancer immunotherapy may wish to avoid cannabis, as data suggest some cancer treatments may not work as well when combined with cannabinoids. 1

Evidence Quality and Research Gaps

The certainty of evidence for most cannabis outcomes is low or very low, with access and use having outpaced the science. 1

Major Limitations:

• Most studies are old (1970s-1990s) and don't reflect current chemotherapy or antiemetic regimens 1
• Large variation in cannabis products studied limits direct comparisons 3
• Insufficient federal funding and regulatory barriers hinder research 1
• Schedule I designation creates conflicts between federal and state laws 1
• Limited understanding of pharmacodynamics in humans 2
• Lack of federal oversight for non-pharmaceutical cannabinoid product manufacturing 1

What Remains Unknown:

• Long-term efficacy and safety data 2, 4
• Optimal formulations, doses, and routes of administration 1, 3
• Effectiveness for most cancer-related symptoms beyond refractory CINV 1
• Role in musculoskeletal pain (evidence particularly weak) 3
• Comparative effectiveness between different cannabis strains and preparations 1