Heroin is also widely (and usually illegally) used as a powerful and addictive drug that produces intense euphoria, which often disappears with increasing tolerance. It is thought that heroin's popularity with recreational users, compared to morphine or other opiates, comes from its somewhat different perceived effects. This in turn comes from its high lipid solubility provided by the two acetyl groups, resulting in a very rapid penetration of the blood-brain barrier after use. Heroin can be taken or administered in a number of ways, including snorting and injection. It may also be smoked by inhaling the vapors produced when heated from below (known as "chasing the dragon").

Many users dissolve the drug together with cocaine in a so-called "speedball" or "snowball", which is injected intravenously. This causes an even more intense rush but is more dangerous than heroin alone because the mixture of short-acting stimulant with longer-acting depressant increases the risk of overdosing on one or both drugs. Cocaine is an irritant to all bodily tissues causing eventual necrosis at any site with which it is in frequent contact.[citation needed]

Once in the brain, heroin is rapidly metabolized into morphine by removal of the acetyl groups. It is the morphine molecule that then binds with opioid receptors and produces the subjective effects of the heroin high. Heroin is therefore a prodrug.

The onset of heroin's effects is dependent on the method of administration. Orally, the heroin is totally metabolized in vivo into morphine before crossing the blood-brain barrier, so the effects are the same as morphine when taken by mouth. Snorting heroin results in onset within 10 to 15 minutes. Smoking heroin results in an almost immediate, though mild effect which strengthens the longer it is used in that particular session. Intravenous injection results in rush and euphoria within 7 to 8 seconds, while intramuscular injection takes longer, having an effect within 5 to 8 minutes.

Heroin is a μ-opioid (mu-opioid) agonist. It acts on endogenous μ-opioid receptors that are spread in discrete packets throughout the brain, spinal cord and gut in almost all mammals. Heroin, along with other opioids, are agonists to four endogenous neurotransmitters. They are β-endorphin, dynorphin, leu-enkephalin, and met-enkephalin. The body responds to heroin in the brain by reducing (and sometimes stopping) production of the endogenous opioids when heroin is present. Endorphins are regularly released in the brain and nerves and attenuate pain. Their other functions are still obscure, but are probably related to the effects produced by heroin besides analgesia (antitussin, anti-diarrheal). The reduced endorphin production in heroin users creates a dependence on the heroin, and the cessation of heroin results in extremely uncomfortable symptoms including pain (even in the absence of physical trauma). This set of symptoms is called withdrawal syndrome. It has an onset 6 to 8 hours after the last dose of heroin.

Large doses of heroin can be fatal. The drug can be used for suicide or, as in the case of Sigmund Freud, physician-assisted suicide. Heroin can be used as a murder weapon. The serial killer Dr. Harold Shipman used it on his victims. Dealers can supply unwanted customers with unusually pure heroin, or heroin cut with other dangerous drugs such as fentanyl, resulting in a fatal overdose. It can sometimes be difficult to determine whether a heroin death was an accident, suicide or murder. The death of Joseph Krecker[9] is an example.

In Canada, heroin is a controlled substance under Schedule I of the Controlled Drugs and Substances Act (CDSA). Every person who seeks or obtains the substance without disclosing authorization to obtain such substances 30 days prior to obtaining another prescription from a practitioner is guilty of an indictable offence and liable to imprisonment for a term not exceeding seven years. Possession for purpose of trafficking is guilty of an indictable offence and liable to imprisonment for life.

In Hong Kong, heroin is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purposes. The substance can be be given by pharmacists under a prescription. Anyone who supplies the substance without prescription can be fined $10000(HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a $1,000,000 (HKD) fine and/or 7 years of jail time.

In the United Kingdom, heroin is available on prescription, though it is a restricted Class A drug. According to the British National Formulary (BNF) edition 52, diamorphine hydrochloride may be used in the treatment of acute pain, myocardial infarction, acute pulmonary edema, and chronic pain. The treatment of chronic non-malignant pain must be supervised by a specialist. The BNF notes that all opioid analgesics cause dependence and tolerance but that this is "no deterrent in the control of pain in terminal illness". When used in the palliative care of cancer patients, heroin is often injected using a syringe driver. In comparison to morphine, it may cause less nausea, hypotension, but more sedation and euphoria and can be dissolved in a smaller quantity of liquid.