The structures of heroin and morphine are quite similar, with heroin being formed by acetylation of morphine:

structures of heroin and morphine

Why is heroin so much more potent than morphine, when their structures are so similar? What biochemical effects lead to heroin's prevalence as a recreational drug, and consequently, the much higher number of fatalities from overdosing on heroin as compared to morphine.

This Source has an attached reference1, which claims the following:

It has been reported that Diamorphine is twice as potent as morphine .


We found no significant differences between the groups over a 24-hour period in the degree of euphoria, nausea and vomiting or sedation, as assessed by subjective visual analogue scores, or in pain relief, nausea and euphoria as assessed by verbal rating. There was, in addition, no significant difference in the requirements for antiemetics between the two groups. Both groups demonstrated relatively low nausea scores. The mean amount of morphine demanded was approximately twice that of diamorphine.


The scientific basis for the alleged superiority of diamorphine over morphine is dubious and since diamorphine is metabolised to monacetyl morphine, and morphine itself, it would be surprising if there were a marked difference. Very few studies authenticate this claim of superiority and the present study is no exception.

This does not explain the prevalence of heroin compared to morphine. Over 15,000 people died in the US from heroin overdose2, whereas the number for morphine is quite less. Are the reasons behind this purely sociological (easier access to heroin compared to morphine), or is there some chemistry that I am missing out on here?


  1. Robinson, S. L., et al. “Morphine Compared with Diamorphine.: A Comparison of Dose Requirements and Side-Effects after Hip Surgery.” Anaesthesia, vol. 46, no. 7, July 1991, pp. 538–40. doi:10.1111/j.1365-2044.1991.tb09650.x.
  2. CDC Heroin Overdose data. Link.

The answer to this question lies in the pharmacokinetics of these two drugs: the acetyl groups cause Heroin to be 200 times more lipid soluble than Morphine1. Another example of a common drug would be Fentanyl, which is 580 times more lipid soluble than morphine, with a structure very similar to that of Morphine.

Increased lipid solubility allows these drugs to pass more rapidly across the blood-brain barrier into the Central Nervous System, giving them more analgesic potency and a more rapid onset of action than morphine (the peak blood level of heroin when used intravenously is around 5 minutes2, whereas that of fentanyl is 1.7 minutes3).

As for the sociological aspects, the high potency of these drugs acts as a positive feedback loop. The heroin/fentanyl dose is smaller than morphine, which is preferable for drug smugglers, as they have to smuggle less of the drug, reducing their risk. This explains the high potency and usage of heroin as a recreational drug as compared to morphine.


  1. Mahesh Trivedi, Shafee Shaikh, Carl Gwinnut: "Pharmacology of Opioids", Updates in Anaesthesia, 2007, pp. 118-124. Link.
  2. Oelhaf RC, Azadfard M. Heroin Toxicity. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; Jan 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430736/
  3. Fentanyl Citrate Injection, USP. FDA Label.
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    $\begingroup$ A nice compilation of information, but there is a simple fact missing. Heroin is a prodrug. It has psychoactive properties itself, and is metabolized to morphine. Thus in equimolar amounts it gives the same as morphine plus its potency before breaking down. $\endgroup$ – Andrew Kovács Aug 29 '20 at 15:15
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    $\begingroup$ @AndrewKovács While true, this is irrelevant because the active ingredient can't have an effect if it can't get to where it acts. Potency is about speed of action and the amount reaching the site of action. $\endgroup$ – matt_black Aug 29 '20 at 17:03
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    $\begingroup$ The only other thing worth mentioning is that the WHO Pain Pyramid of analgesia explicitly has diamorphine as an end point. It is very rarely prescribed; almost always for palliative (end-of-life) care and when literally everything else hasn't worked. Morphine, on the other hand, is incredibly commonly prescribed, not just IV but orally (gel oromorph; liquid solutions) and similar. The vast majority of heroin users are addicts, not after analgesia: their doses, routes, and lack of medical training often leaves them found dead in the community – the difference is more than acetyl groups alone. $\endgroup$ – Landak Aug 30 '20 at 10:14
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    $\begingroup$ @NilayGhosh Codeine is actually the monomethyl form of morphine, not the monoacetyl. $\endgroup$ – Aniruddha Deb Aug 30 '20 at 14:09
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    $\begingroup$ Yes, extra monomethyl group. Need to brush up my biochem :( . Nevertheless, the three structures are more or less same; having no carbon, 1 extra carbon and 4 extra carbons in the three structures respectively. $\endgroup$ – Nilay Ghosh Aug 30 '20 at 14:57

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