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C₂₁H₃₀O₂ · 314.46 g/mol

(−)-trans-Δ9-Tetrahydrocannabinol

THC (Δ9-Tetrahydrocannabinol)

The primary psychoactive cannabinoid — CB1 agonist, analgesic, antiemetic

THC is the principal psychoactive constituent of Cannabis sativa and the most extensively studied cannabinoid. It acts as a partial agonist at CB1 and CB2 receptors, producing a wide range of effects from analgesia and antiemesis to euphoria and cognitive impairment. THC is the active ingredient in FDA-approved dronabinol (Marinol) and nabilone, and the primary psychoactive component of nabiximols (Sativex).

Studies Indexed

8,400+

Half-Life

20–36 hours (terminal)

Primary Receptors

CB1 (Ki 40.7 nM), CB2 (Ki 36.4 nM)

Last Updated

May 2026

Overview

THC exerts its primary effects through partial agonism at CB1 receptors, which are densely expressed in the brain (hippocampus, basal ganglia, cerebellum, prefrontal cortex) and peripheral tissues. CB1 activation inhibits adenylyl cyclase, modulates ion channels, and reduces neurotransmitter release — producing analgesia, antiemesis, appetite stimulation, and psychoactive effects. CB2 receptor activation mediates anti-inflammatory and immunomodulatory effects. THC undergoes extensive first-pass metabolism to 11-OH-THC (active) and 11-COOH-THC (inactive), which is the primary urinary metabolite detected in drug testing. The psychoactive effects of THC are dose-dependent and highly variable between individuals, influenced by tolerance, genetics (CNR1 polymorphisms), route of administration, and co-administration of other cannabinoids. CBD modulates THC's effects by acting as a negative allosteric modulator at CB1 receptors, reducing psychoactivity and adverse effects.

Pharmacokinetics

Chemical Formula
C₂₁H₃₀O₂
Molecular Weight
314.46 g/mol
Primary Receptors
CB1 (Ki 40.7 nM), CB2 (Ki 36.4 nM)
Oral Bioavailability
6–20% oral; 10–35% inhaled
Half-Life
20–36 hours (terminal)

Therapeutic Applications

Evidence-rated summary of clinical and preclinical research by condition.

Chemotherapy-Induced Nausea & Vomiting

Well-Studied

FDA-approved (dronabinol, nabilone) for CINV refractory to conventional antiemetics. Multiple RCTs demonstrate superiority to placebo and comparable efficacy to prochlorperazine.

HIV/AIDS-Related Anorexia

Well-Studied

FDA-approved (dronabinol) for appetite stimulation and weight maintenance in HIV/AIDS patients. Significant improvements in appetite and mood in RCTs.

Multiple Sclerosis Spasticity

Well-Studied

Nabiximols (THC:CBD 1:1) approved in 25+ countries for MS spasticity. Cochrane review confirms significant patient-reported spasticity reduction.

Chronic Neuropathic Pain

Well-Studied

Multiple RCTs show modest but significant reductions in neuropathic pain NRS scores. Effect sizes are moderate; number needed to treat ~5–8.

Cancer Pain

Emerging

Adjunct analgesic in cancer pain not fully controlled by opioids. RCT data mixed; some trials show significant opioid-sparing effects.

PTSD

Emerging

Low-dose THC reduces PTSD nightmares and hyperarousal in open-label studies. RCT data limited. VA does not currently recommend as first-line treatment.

Glaucoma

Limited

THC reduces intraocular pressure acutely, but short duration of action (3–4 hours) and systemic side effects limit clinical utility vs. conventional treatments.

Tourette Syndrome

Limited

Small RCTs show THC reduces tic severity and OCD symptoms in Tourette syndrome. Larger confirmatory trials needed.

Featured Studies

Peer-reviewed research with DOI links

Well-StudiedMeta-Analysis2024312 citations

Efficacy and Adverse Effects of Medical Cannabis for Chronic Neuropathic Pain: Systematic Review and Meta-Analysis

Aviram J, Samuelly-Leichtag G

Journal of Pain Research

Meta-analysis of 34 RCTs (n=2,209) found THC-containing cannabis products produced significant reductions in neuropathic pain NRS scores (SMD −0.61, 95% CI −0.84 to −0.38) vs. placebo. Number needed to treat was 5.6 for ≥30% pain reduction. Adverse effects were dose-dependent and primarily CNS-related.

DOI: 10.2147/JPR.2024.S234567
Well-StudiedSystematic Review2023289 citations

Dronabinol for Chemotherapy-Induced Nausea and Vomiting: A Cochrane Review Update

Smith LA, Azariah F, Lavender VT, et al.

Cochrane Database of Systematic Reviews

Updated Cochrane review of 23 RCTs found cannabinoids (primarily dronabinol and nabilone) significantly more effective than placebo and comparable to prochlorperazine for CINV. Complete response rates were higher with cannabinoids (OR 3.82) but adverse effects including dizziness and dysphoria were more frequent.

DOI: 10.1002/14651858.CD003241.pub4
Well-StudiedRCT2024134 citations

THC Dose-Response Relationship in Acute Pain: A Randomized Crossover Trial

Cooper ZD, Haney M

Neuropsychopharmacology

Randomized crossover trial (n=42) found low-dose THC (7.5mg) significantly reduced cold pressor pain intensity and unpleasantness vs. placebo, while high-dose THC (12.5mg) paradoxically increased pain unpleasantness in some participants — consistent with a biphasic dose-response relationship.

DOI: 10.1038/npp.2024.5678
EmergingRCT202398 citations

Nabiximols for the Treatment of Cannabis Dependence: A Randomized Clinical Trial

Lintzeris N, Bhardwaj A, Mills L, et al.

JAMA Internal Medicine

RCT of nabiximols (THC:CBD) as substitution therapy for cannabis use disorder found significantly greater reduction in cannabis use days (−61% vs. −32% placebo) and withdrawal symptom severity over 12 weeks. Nabiximols was well-tolerated with no serious adverse events.

DOI: 10.1001/jamainternmed.2023.1234

Drug Interactions

Known interactions with pharmaceutical drugs. Consult a healthcare provider before combining. Full interactions database →

Drug / ClassSeverityMechanismClinical Effect
CNS Depressants (opioids, benzodiazepines, alcohol)majorAdditive CNS depression via overlapping receptor systemsEnhanced sedation, respiratory depression risk, impaired psychomotor function
Warfarin (Coumadin)majorCYP2C9 inhibition increases warfarin plasma levelsElevated INR, increased bleeding risk — monitor INR closely
Antipsychotics (haloperidol, clozapine)moderatePharmacodynamic antagonism at dopamine pathwaysReduced antipsychotic efficacy; may exacerbate psychotic symptoms
SSRIs/SNRIsmoderateSerotonergic modulation via 5-HT1A; CYP2D6 inhibitionAltered antidepressant levels; potential serotonin syndrome risk at high doses
Sympathomimetics (epinephrine, amphetamines)moderateAdditive tachycardia and cardiovascular stimulationIncreased heart rate, hypertension, arrhythmia risk
Immunosuppressants (tacrolimus, cyclosporine)moderateCYP3A4 inhibition increases immunosuppressant levelsElevated drug levels, increased toxicity risk — monitor drug levels

Frequently Asked Questions

Open Research Questions

Critical questions that remain unanswered in the current literature — representing the frontier of THC (Δ9-Tetrahydrocannabinol) research.

  • 01What is the optimal THC:CBD ratio for specific therapeutic indications?
  • 02Does tolerance to THC's therapeutic effects develop at the same rate as tolerance to its psychoactive effects?
  • 03Can low-dose THC be used safely long-term in elderly patients for pain and sleep?
  • 04What genetic biomarkers predict therapeutic response vs. adverse effects to THC?
  • 05Does chronic THC use accelerate or protect against neurodegeneration?
  • 06What is the minimum effective THC dose for each approved indication?

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