Which of the following is the primary active metabolite of cannabis that contributes to its psychoactive effects?

Explanation

## Primary Active Component of Cannabis Responsible for Psychoactive Effects **Key Point:** Tetrahydrocannabinol (THC) is the primary psychoactive compound in cannabis. It is the parent compound — not a metabolite — that is chiefly responsible for the acute intoxicating effects of cannabis by acting as a partial agonist at CB1 receptors in the CNS. ### Pharmacology of THC **High-Yield:** THC (Δ9-THC) is absorbed via inhalation or oral ingestion and acts directly on cannabinoid CB1 receptors in the brain, producing euphoria, altered perception, and psychomotor impairment. It undergoes hepatic oxidation via CYP3A4 and CYP2C9 to form: 1. **11-hydroxy-THC** — an active metabolite with high CNS penetration; contributes to psychoactive effects (especially after oral ingestion) but is NOT the primary contributor overall. 2. **11-nor-9-carboxy-THC (11-COOH-THC)** — an inactive metabolite; the principal urinary marker used in drug screening. ### Comparison of Cannabis Compounds | Compound | Psychoactive | CNS Penetration | Clinical Significance | | --- | --- | --- | --- | | THC (parent) | **Yes (primary)** | High | **Primary psychoactive compound** | | 11-hydroxy-THC | Yes (active metabolite) | Very High | Active metabolite; more prominent after oral use | | 11-nor-9-carboxy-THC | No | Low | Inactive; urine drug screen marker | | Cannabidiol (CBD) | No | Moderate | Non-intoxicating; anxiolytic, anticonvulsant | **Clinical Pearl:** While 11-hydroxy-THC has greater CNS penetration and potency per molecule, THC remains the primary driver of psychoactive effects because it is present in far greater quantities and is the direct pharmacologically active compound. 11-hydroxy-THC plays a more significant role after oral (edible) cannabis use due to first-pass hepatic metabolism (per Goodman & Gilman's Pharmacology, 13th ed.). **Mnemonic:** **THC = The High Compound** — THC is the primary psychoactive agent; 11-OH-THC is its active metabolite; 11-COOH-THC is the inactive urinary marker. *(Reference: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th ed.; KD Tripathi Essentials of Medical Pharmacology, 8th ed.)*