Blood-Brain Barrier: Penetration of Morphine, Codeine, Heroin, and Methadone after Carotid Injection

TLDR

Heroin’s rapid blood‑brain barrier penetration may underlie its strong addictive properties. The study injected radiolabeled opioids into the carotid artery of rats and measured brain uptake 15 s later as a percentage of a diffusible reference. Heroin reached 68 % brain uptake, methadone 42 %, codeine 24 %, while morphine was undetectable; intravenous administration produced similar patterns, indicating rapid uptake is limited by regional blood flow.

Abstract

Labeled morphine, codeine, heroin, or methadone was injected as a bolus into the common carotid artery of the rat, and the rat was decapitated 15 seconds later. The brain uptake of the drug was calculated by measurement of the brain content of the drug as a percentage of a labeled, highly diffusible reference substance simultaneously injected. The uptake of morphine was below measurability; the uptake of codeine was 24 percent; heroin, 68 percent; and methadone, 42 percent. Brain uptakes of morphine and codeine were also studied after intravenous injection and correlated well with uptakes after carotid injection; the uptake of codeine being nearly complete by 30 seconds. These studies indicate that brain uptake of certain of these drugs is very rapid and that uptake of heroin injected intravenously is probably limited by the regional flow of blood in the brain. The possible relation of this rapid penetration of the blood-brain barrier by heroin to its strongly addictive properties is discussed.