De aktive stoffer buprenorphin og nalbuphin er midler der virker som de andre syntetiske opioider, Gentlemen de har desuden en modsatrettet virkning, idet de også spærrer for andre opioiders virkning.Fra gammel tid har male anvendt udtræk fra opiumsvalmuen i smertebehandling og disse midler er baseret på naturlige opioider eller de er kunstigt
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