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Sunday, August 17, 2025

Medical cannabis (and cannabis oils)


Overview

Medical cannabis refers to regulated preparations of cannabis and cannabinoid-based products intended for therapeutic use. These include plant-derived cannabinoids (such as tetrahydrocannabinol [THC] and cannabidiol [CBD]) as well as synthetic analogues (dronabinol, nabilone). Products vary widely in formulation, cannabinoid content, and route of administration, making it essential to distinguish between standardized pharmaceutical-grade products and cannabis oils or extracts.

While THC is the primary psychoactive component acting at CB1 and CB2 receptors, CBD is non-intoxicating and modulates multiple pathways, including serotonergic and TRP channels. Therapeutically, cannabis products are used in selected indications such as multiple sclerosis spasticity, refractory epilepsy, and chemotherapy-induced nausea and vomiting, though their use in chronic pain remains controversial and inconsistent across guidelines.

Pharmacological Class and Formulations

  • Class: Cannabinoid receptor agonists and modulators

  • ATC Codes: N02BG10 (nabiximols), N03AX24 (cannabidiol), A04AD11 (nabilone)

  • Formulations:

    • Cannabidiol oral solution (100 mg/mL, e.g., Epidiolex/Epidyolex)

    • Nabiximols (THC:CBD 1:1 oromucosal spray)

    • Synthetic cannabinoids: dronabinol (THC), nabilone (THC analogue)

    • Cannabis oils and extracts: variable CBD/THC ratios, non-standardized in many markets

    • Other routes: capsules, oral drops, sprays, vaporized extracts (where regulated)

Mechanism of Action

  • THC: Partial agonist at CB1 receptors (central nervous system → psychoactive effects, analgesia, muscle relaxation, antiemesis) and CB2 receptors (immune modulation).

  • CBD: Low affinity for CB1/CB2; acts as a negative allosteric modulator at CB1, while influencing serotonin 5-HT1A receptors, adenosine, and TRP channels. It may attenuate some adverse effects of THC.

  • Clinical effects: Reduction of spasticity, nausea/vomiting, seizure frequency; modest effects on chronic pain and sleep.

Pharmacokinetics

  • Absorption: Oral bioavailability low (~6–20%); affected by fat intake. Oromucosal sprays provide more consistent absorption. Inhalation provides rapid onset.

  • Distribution: Highly lipophilic, extensive tissue storage, crosses the blood-brain barrier.

  • Metabolism: Hepatic (CYP2C9, CYP2C19, CYP3A4); active metabolites, especially with THC.

  • Elimination: Fecal and urinary routes.

  • Half-life: Highly variable; THC ~25–36 hours, CBD ~18–32 hours. Accumulates with chronic use.

Clinical Indications

Approved Indications (depending on jurisdiction)

  1. Chemotherapy-induced nausea and vomiting (CINV): Nabilone or dronabinol as adjuncts when standard antiemetics fail.

  2. Multiple sclerosis spasticity: Nabiximols oromucosal spray for moderate-to-severe spasticity not relieved by first-line therapy.

  3. Refractory epilepsy: Cannabidiol solution for Lennox–Gastaut syndrome, Dravet syndrome, tuberous sclerosis complex.

  4. Chronic pain: Inconsistent evidence; some guidelines discourage routine use, though non-inhaled cannabis oils may be considered when other options fail.

Investigational / Off-label Uses

  • Palliative care (appetite stimulation, analgesia, symptom relief)

  • Anxiety, PTSD, and sleep disorders

  • Migraine prophylaxis

  • Neuropathic pain beyond MS

Contraindications

  • Hypersensitivity to cannabinoids or excipients

  • Severe psychiatric disorders (e.g., schizophrenia, psychosis)

  • History of substance use disorder (caution or contraindicated)

  • Pregnancy and breastfeeding (potential teratogenic/neurodevelopmental effects)

  • Severe cardiovascular disease (risk of tachycardia, hypotension)

Precautions

  • Neuropsychiatric: THC may cause cognitive impairment, anxiety, paranoia, hallucinations.

  • Driving: THC impairs psychomotor function; avoid operating vehicles/machinery.

  • Pediatric use: Restricted to defined epileptic syndromes under specialist supervision.

  • Hepatic impairment: Dose adjustments required, particularly with CBD.

  • Drug interactions: Cannabinoids are metabolized by CYP enzymes and can alter levels of other drugs.

Adverse Effects

Common

  • Dizziness, drowsiness, fatigue

  • Dry mouth

  • Nausea, diarrhea

  • Impaired concentration, memory disturbance

Less Common

  • Mood changes, anxiety, hallucinations

  • Increased appetite, weight gain

  • Orthostatic hypotension

Serious

  • Psychosis, paranoia (THC-related)

  • Hepatotoxicity (CBD at high doses, particularly with valproate)

  • Dependence and withdrawal symptoms with chronic THC use

Drug Interactions

  • CYP inhibitors (ketoconazole, clarithromycin, fluoxetine): may increase cannabinoid exposure.

  • CYP inducers (rifampin, carbamazepine, phenytoin): reduce cannabinoid levels.

  • CNS depressants (alcohol, benzodiazepines, opioids): additive sedation and respiratory depression.

  • Warfarin and other anticoagulants: CBD may increase INR due to CYP2C9 inhibition.

  • Antiepileptics: CBD may raise clobazam levels; monitor for sedation.

Dosage (General Guidance)

Cannabidiol Oral Solution (Epidiolex/Epidyolex)

  • Starting dose: 2.5 mg/kg twice daily.

  • After 1 week, increase to 5 mg/kg twice daily.

  • Maximum: 10 mg/kg twice daily (20 mg/kg/day).

Nabiximols Oromucosal Spray (THC:CBD 1:1, each spray ~2.7 mg THC + 2.5 mg CBD)

  • Initial: 1 spray daily.

  • Titrate gradually up to maximum of 12 sprays/day, depending on response and tolerability.

Nabilone (Synthetic THC Analogue)

  • 1–2 mg orally twice daily (max 6 mg/day) for chemotherapy-induced nausea and vomiting.

Cannabis Oils / Extracts (Variable formulations)

  • Start low, go slow: often 2.5–5 mg THC or CBD once daily, titrated upward as tolerated.

  • Oils may be THC-dominant, CBD-dominant, or balanced; selection depends on indication.

Monitoring

  • Baseline: psychiatric history, substance use history, liver function (especially with CBD), seizure frequency (if epilepsy).

  • During therapy:

    • Monitor efficacy (pain scores, seizure frequency, spasticity measures).

    • Track adverse effects (cognition, mood, GI tolerance, hepatic function).

    • In long-term THC use: watch for dependence, misuse, and cognitive decline.

Patient Counseling Points

  • Start with the lowest possible dose and titrate slowly.

  • Do not drive or operate machinery after THC-containing products.

  • Avoid alcohol and sedatives while on therapy.

  • Store oils and tablets safely to prevent accidental ingestion, especially in children.

  • Treatment does not cure underlying conditions but may provide symptom control.

  • Report persistent psychiatric symptoms, abdominal pain, or yellowing of skin/eyes.



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