The therapeutic use of heroin: a review of the pharmacological literature

Abstract

Heroin is currently being advocated by some as a superior therapeutic agent for use in terminal illness. However, a review of the literature on heroin presently available does not support this contention. Administered orally, heroin is approximately 1.5 times more potent than morphine in controlling chronic pain in terminal cancer patients. Its effects on mood and the incidence and nature of side effects do not differ from those of morphine except in males where poorer pain control probably accounts for the worse effect on mood. Given parenterally for acute pain, heroin is 2–4 times more potent than morphine and faster in onset of action. When the potency difference is accounted for, the pharmacological effects of heroin do not differ appreciably from those of morphine. Heroin is metabolized to 6-acetylmorphine and morphine. After oral administration of heroin, morphine but not heroin or 6-acetylmorphine is detected in blood. In this case, heroin is a prodrug for the delivery of systemic morphine. Following acute i.v. administration, heroin appears transiently in blood with a half-life of about 3 min. The half-life of heroin exposed to blood or serum in vitro is 9–22 min, indicating that organ metabolism is involved in blood clearance as well. Direct renal clearance of heroin is less than 1% of the administered dose. In animal studies, heroin and 6-acetylmorphine are both more potent and faster acting than morphine as analgesics, effects attributed to their greater lipid solubility and subsequent penetration of the blood-brain barrier. Given centrally, morphine is more potent than heroin and 6-acetylmorphine in producing analgesia. In in vitro receptor binding assays, morphine is slightly more potent than 6-acetylmorphine but considerably more potent than heroin in displacing the radioactive ligand from binding sites. The weak activity of heroin could be accounted for by breakdown to 6-acetylmorphine during the experiment. On the basis of such animal and in vitro data, it has been suggested that heroin could be viewed as a lipid soluble prodrug which determines the distribution of its active metabolites. In addition to its enhanced potency and faster onset of action compared with morphine, heroin is considerably more water soluble than morphine and this property confers a practical advantage when drugs must be injected intramuscularly. There are presently other drugs available which share this property (e.g. hydromorphone, Dilaudid®, about twice as potent and half as soluble as heroin). There is therefore little scientific justification for the support of the legalization of heroin for use in terminal illness. The issue of diversion of heroin into the illicit market is separate from and not relevant to its relative therapeutic effectiveness.