Morphine is the Major Metabolite of Heroin
Heroin is hydrolyzed to both morphine and 6-monoacetylmorphine, with morphine being the major metabolite of heroin. 1
Metabolism of Heroin
Heroin (diacetylmorphine) undergoes a sequential metabolic process in the body:
- Initial Metabolism: After administration, heroin is rapidly deacetylated to 6-monoacetylmorphine (6-MAM)
- Secondary Metabolism: 6-MAM is then further deacetylated to morphine
- Tertiary Metabolism: Morphine is subsequently metabolized to morphine-3-glucuronide and morphine-6-glucuronide
This metabolic pathway is well-established in the scientific literature, with morphine being the predominant end metabolite that persists in the body 2, 3.
Pharmacological Activity of Heroin and Its Metabolites
- Heroin itself: Acts primarily as a prodrug with minimal direct receptor activity
- 6-MAM: Intermediate metabolite with rapid but short-lived activity
- Morphine: Major active metabolite responsible for prolonged opioid effects
- Morphine-6-glucuronide: Active metabolite that contributes to analgesia and may worsen adverse effects in patients with renal insufficiency 1
Research indicates that while 6-MAM may be responsible for the initial rapid neural effects of intravenous heroin administration 4, morphine is the predominant metabolite that accounts for the majority of heroin's duration of action and clinical effects.
Clinical Implications
Understanding heroin's metabolism to morphine has important implications:
- Drug Testing: Detection of morphine in biological samples is used as evidence of heroin use
- Treatment Approaches: Medications like naloxone that antagonize morphine's effects are effective in treating heroin overdose
- Pharmacokinetics: The terminal half-life of heroin is approximately 7.6 minutes, while morphine has a much longer duration in the body 5
Comparison with Other Substances
Unlike heroin:
- Marijuana's major metabolites include 11-hydroxy-THC and THC-COOH, not morphine
- Phencyclidine (PCP) is primarily metabolized to 4-phenyl-4-piperidinocyclohexanol
- Quinine is metabolized to 3-hydroxyquinine and other metabolites, not morphine
Important Considerations
When evaluating patients with suspected heroin use:
- Morphine may be detected in urine for 2-3 days after heroin use
- The presence of 6-MAM in biological samples provides definitive evidence of heroin use (rather than prescribed morphine)
- Codeine is also metabolized to morphine, which can complicate interpretation of drug testing results 1
In conclusion, the answer to the question "Morphine is the major metabolite of:" is heroin (option D).