Named Bioactive Compounds · Compound
Tetrahydrocannabinol (Tetrahydrocannabinol)
Strong Evidencecompound
Hermetica Superfood Encyclopedia
Tetrahydrocannabinol (THC) is the primary psychoactive cannabinoid in cannabis that binds to CB1 and CB2 receptors in the endocannabinoid system. Clinical studies demonstrate its efficacy in treating advanced cancer pain, neuropathic pain, and chemotherapy-induced nausea through cannabinoid receptor activation.
Tetrahydrocannabinol (THC), specifically Δ9-tetrahydrocannabinol, is the primary psychoactive compound in Cannabis sativa or Cannabis indica, originating from the trichomes of female flowers and leaves. It is typically extracted via solvent methods (e.g., ethanol) or CO2 supercritical extraction to produce oils or isolates, and belongs to the cannabinoid class featuring a dibenzopyran structure with a pentyl side chain.
Key clinical evidence includes a multicenter RCT (n=177) showing THC:CBD extract superiority for cancer pain (PMID: 19896326), and a phase III trial (n=100) demonstrating transdermal THC:CBD efficacy for neuropathic pain (PMID: 39720705). Additional smaller trials explored THC for MS spasticity, trichotillomania, and esophageal pain, though meta-analyses note limitations including small sample sizes and short durations.
Clinically studied doses include: oral THC 20 mg in standardized extracts (with or without 640 mg CBD), dronabinol 2.5-15 mg/day for trichotillomania, dronabinol 5 mg twice daily for esophageal pain, and transdermal THC:CBD patches (specific doses undisclosed). Consult a healthcare provider before starting any new supplement.
Tetrahydrocannabinol (THC, Δ9-THC) is a lipophilic terpenophenolic compound (C₂₁H₃₀O₂, MW 314.47 g/mol) and is not a nutritional substance in the conventional sense — it contains no meaningful macronutrients, vitamins, minerals, fiber, or protein. Its relevance is entirely pharmacological/bioactive. Key details: • Primary bioactive: Δ9-tetrahydrocannabinol, a partial agonist at cannabinoid receptors CB1 (Ki ~5–40 nM) and CB2 (Ki ~35–80 nM). • Typical concentrations in Cannabis sativa flower range from 1–30% w/w THC depending on cultivar; pharmaceutical-grade preparations (e.g., dronabinol) are purified to ≥95–99% THC. • Oral bioavailability is low and highly variable: approximately 6–20% due to extensive first-pass hepatic metabolism via CYP2C9 and CYP3A4, producing the active metabolite 11-hydroxy-THC (11-OH-THC, which is itself psychoactive and has higher BBB penetration) and inactive 11-nor-9-carboxy-THC (THC-COOH). • Inhaled bioavailability is substantially higher: approximately 10–35%, with rapid onset (minutes) vs. oral (30–90 min). • THC is highly lipophilic (log P ~7.0), resulting in large volume of distribution (~10 L/kg), extensive tissue accumulation in adipose tissue, and prolonged terminal elimination half-life (1–3 days acutely, up to 12+ days with chronic use due to redistribution from fat stores). • Protein binding: ~95–99%, primarily to lipoproteins and albumin. • Oromucosal/transdermal delivery (e.g., nabiximols spray, transdermal patches) offers intermediate bioavailability, partially bypassing first-pass metabolism. • Co-administration with lipid-rich foods increases oral bioavailability by 2–3 fold due to enhanced lymphatic absorption. • Contains no calories, vitamins, minerals, or dietary fiber in purified form. When consumed as whole-plant cannabis (edibles, oils), any nutritional content is attributable to the carrier matrix (e.g., oils, butter, food ingredients), not THC itself. • Other co-occurring bioactive compounds in whole-plant cannabis include cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), >100 other phytocannabinoids, terpenes (myrcene, limonene, β-caryophyllene, linalool, α-pinene at 0.1–3% w/w), and flavonoids (cannflavins A, B, C) — these may modulate THC pharmacology via the proposed 'entourage effect.'
THC acts as a partial agonist at CB1 receptors in the brain and CB2 receptors in immune tissues, modulating neurotransmitter release and pain signaling pathways. It inhibits adenylyl cyclase, reduces cAMP levels, and affects calcium and potassium ion channels. THC also interacts with the vanilloid receptor TRPV1 and can influence serotonin and dopamine pathways.
A multicenter RCT (n=177) showed THC:CBD extract significantly reduced cancer pain scores in patients with inadequate opioid response. Phase III trials (n=100) demonstrated significant improvements in neuropathic pain scores using transdermal THC:CBD over 12 weeks. Multiple controlled studies support THC's antiemetic effects for chemotherapy-induced nausea. Evidence quality ranges from moderate to high for pain management applications.
Common side effects include dizziness, drowsiness, dry mouth, and cognitive impairment. THC can interact with CYP2C9 and CYP3A4 substrates, potentially affecting warfarin and other medications. Contraindicated in patients with severe cardiovascular disease, psychotic disorders, or substance abuse history. Pregnancy safety is not established and use should be avoided during pregnancy and breastfeeding.
