Dihydrocodeine: Difference between revisions

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==Pharmacology==
==Pharmacology==


Normally, we take dihydrocodeine in orally. As it is an opioid, it has a opioid effects, and most of dihydrocodeine’s opioid receptor effect is on to µ-receptor. <ref>Sobczak, Ł., & Goryński, K. (2020). Pharmacological Aspects of Over-the-Counter Opioid Drugs Misuse. *Table 2.1*. [https://pmc.ncbi.nlm.nih.gov/articles/PMC7504308/ PMC7504308]</ref> It is twice stronger than codeine, and 1/6 times of morphine orally. <ref>Leppert, W. (2010). Dihydrocodeine as an opioid analgesic for the treatment of moderate to severe chronic pain. *Current Drug Metabolism*, 11(6), pp. 515-520. [https://pubmed.ncbi.nlm.nih.gov/20540693/ PMID: 20540693]</ref> Dihydrocodeine is a famous prodrug that metabolizes in the liver, especially through the CYP2D6 enzyme. But also, it activates in CYP3A4. Through CYP2D6, dihydrocodeine became dihydromorphine, which is 1.3 times stronger than the original morphine. But less than 10% of the dihydrocodeine convert to dihydromorphine <ref>Webb, J. A., Rostami-Hodjegan, A., Abdul-Manap, R., Hofmann, U., Mikus, G., & Kamali, F. (2001). Contribution of dihydrocodeine and dihydromorphine to analgesia following dihydrocodeine administration in man: a PK–PD modelling analysis. *British Journal of Clinical Pharmacology*, 52(6), pp. 619–628. [https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1046/j.0306-5251.2001.01414.x DOI: 10.1046/j.0306-5251.2001.01414.x]</ref>, and other metabolism such as nordihydrocodeine is known as meaningless opioid receptor. Even dihydrocodeine itself is an opioid receptor, but is so weak which the article says “It has been suggested that dihydrocodeine have little analgesic effect their own, but rather function as prodrugs” <ref>Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. *British Journal of Clinical Pharmacology*, 45(6), 575–581. [https://pmc.ncbi.nlm.nih.gov/articles/PMC1873649/ PMC1873649]</ref>  Substances metabolised by CYP3A4 is nordihydrocodeine, which is also not a good receptor in opioid.  
Normally, we take dihydrocodeine in orally. As it is an opioid, it has a opioid effects, and most of dihydrocodeine’s opioid receptor effect is on to µ-opioid receptor. <ref>Sobczak, Ł., & Goryński, K. (2020). Pharmacological Aspects of Over-the-Counter Opioid Drugs Misuse. *Table 2.1*. [https://pmc.ncbi.nlm.nih.gov/articles/PMC7504308/ PMC7504308]</ref> It is twice stronger than codeine, and 1/6 times of morphine orally. <ref>Leppert, W. (2010). Dihydrocodeine as an opioid analgesic for the treatment of moderate to severe chronic pain. *Current Drug Metabolism*, 11(6), pp. 515-520. [https://pubmed.ncbi.nlm.nih.gov/20540693/ PMID: 20540693]</ref> Dihydrocodeine is a famous prodrug that metabolizes in the liver, especially through the CYP2D6 enzyme. But also, it activates in CYP3A4. Through CYP2D6, dihydrocodeine is O-methylated into dihydromorphine, which is 1.3 times stronger than the original morphine. But less than 10% of the dihydrocodeine convert to dihydromorphine <ref>Webb, J. A., Rostami-Hodjegan, A., Abdul-Manap, R., Hofmann, U., Mikus, G., & Kamali, F. (2001). Contribution of dihydrocodeine and dihydromorphine to analgesia following dihydrocodeine administration in man: a PK–PD modelling analysis. *British Journal of Clinical Pharmacology*, 52(6), pp. 619–628. [https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1046/j.0306-5251.2001.01414.x DOI: 10.1046/j.0306-5251.2001.01414.x]</ref>, and other metabolism is known as meaningless opioid receptor. Even dihydrocodeine itself is an opioid receptor, but is so weak which the article says “It has been suggested that dihydrocodeine have little analgesic effect their own, but rather function as prodrugs” <ref>Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. *British Journal of Clinical Pharmacology*, 45(6), 575–581. [https://pmc.ncbi.nlm.nih.gov/articles/PMC1873649/ PMC1873649]</ref>  Substances metabolised by CYP3A4 is nordihydrocodeine, demethylated dehydrocodeine, which is also not a good receptor in opioid. Also through UGT in the liver, Dihydrocodeine metabolises form 3- and 6-glucuronides. This is the most metabolation, which can be 85% of the whole metabolation. UGT 2B7 is known as the most responsible for DHC-6-Glucuronide formation. <ref>Armstrong, S. C., & Cozza, K. L. (2003). Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part II. *Psychosomatics*, 44(6), 518–525. [https://doi.org/10.1176/appi.psy.44.6.518 DOI: 10.1176/appi.psy.44.6.518]</ref>


So most of the effects are from dihydromorphine, and some people say because dihydrocodeine itself has an opioid effect, it has no ceiling effect, but no. If you are a person who can feel euphoria with dihydrocodeine itself, you can even have euphoria with 5 tablets of DXM, which is not an opioid, but has some opioid effects. <ref>Goldstein, A., & Naidu, A. (1990). Dextrorphan binds to opioid receptors in guinea-pig brain membranes and is an antagonist at opioid receptors in myenteric plexus. *Proceedings of the National Academy of Sciences*, 87(5), 1629-1632. [https://pmc.ncbi.nlm.nih.gov/articles/PMC53526/ PMC53526]</ref>
The effect of the dihydrocodeine has differed by person because of genetic polymorphism. 5-10% of white people and some more percentage of Asian people has low metabolism in CYP2D6, which is a very big variable of dihydrocodeine as a drug. <ref>Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. ''British Journal of Clinical Pharmacology'', 45(6), pp. 575–581 [https://pmc.ncbi.nlm.nih.gov/articles/PMC1873649/ PMC1873649]</ref> Because CYP2D6 metabolism is almost all of this drug’s effect, CYP2D6 inhibitors such as Fluoxetin, Paroxetine, Bupropion, Quinidine makes dihydrocodeine’s effect weaker. <ref>Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. ''British Journal of Clinical Pharmacology'', 45(6), 575–581. [https://pmc.ncbi.nlm.nih.gov/articles/PMC1873649/ PMC1873649]</ref>


The effect of the dihydrocodeine has differed by person because of genetic polymorphism. 5-10% of white people and some more percentage of Asian people has low metabolism in CYP2D6, which is a very big variable of dihydrocodeine as a drug. <ref>Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. ''British Journal of Clinical Pharmacology'', 45(6), pp. 575–581 [https://pmc.ncbi.nlm.nih.gov/articles/PMC1873649/ PMC1873649]</ref> Because CYP2D6 metabolism is almost all of this drug’s effect, CYP2D6 inhibitors such as Fluoxetin, Paroxetine, Bupropion, Quinidine makes dihydrocodeine’s effect weaker. <ref>Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. ''British Journal of Clinical Pharmacology'', 45(6), 575–581. [https://pmc.ncbi.nlm.nih.gov/articles/PMC1873649/ PMC1873649]</ref>
Because of these lots of variables, many souces says different streangth about dihydrocodeine and dihydromorphine. But the interest part of the dihydrocodeine is, there could be more potent of DHC-6-Glucuronide formation in opioid receptors. There are recent research using Quinidine and inject dihydrocodeine, and see how they feels. <ref>Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine: a cross-over study with extensive and quinidine-induced poor metabolizers. ''British Journal of Clinical Pharmacology'', 45(6), 575–581. [https://pmc.ncbi.nlm.nih.gov/articles/PMC1873649/ PMC1873649]</ref> <ref>Webb, J. A., Rostami-Hodjegan, A., Abdul-Manap, R., Hofmann, U., Mikus, G., & Kamali, F. (2001). Contribution of dihydrocodeine and dihydromorphine to analgesia following dihydrocodeine administration in man: a PK–PD modelling analysis. ''British Journal of Clinical Pharmacology'', 52(4), 35–43. [https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1046/j.0306-5251.2001.01414.x DOI: 10.1046/j.0306-5251.2001.01414.x]</ref> In this two research, still they are saying that dihydromorphine convertion is the most important metabolition. But <ref>Armstrong, S. C., & Cozza, K. L. (2003). Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part II. *Psychosomatics*, 44(6), 518–525. [https://doi.org/10.1176/appi.psy.44.6.518 DOI: 10.1176/appi.psy.44.6.518]</ref> in this research, they says the theoretical medical action could not really act in the real case. In this research, they says DHC-6-Glucuronide formation could have more portential than we think. I look foward to further research.




Revision as of 10:00, 8 March 2026

Dihydrocodeine is a semi-synthetic opioid developed in 1908 in Germany based on codeine and morphine. It was first marketed in 1911.[1] It is 2 times stronger than the original codeine,[2] and 1/6 times than the oral morphine.[3] Usually prescribed for pain relief or antitussive. If it is prescribed for pain relief, usually they use XR which lasts for 12 hours, giving them 60mg per dose, and 60-120mg per day. [4] If it is for cough, they usually use 10mg per dose, and 3 doses per day. [5] But they use tablets combined with things like Paracetamol, Methylephedrine, Guaifenesin, Chlorpheniramine, or Caffeine.

[6]

semi-synthetic opioid
Chemical name: Morphinan-6-ol,

4,5-epoxy-3-metoxy-17-metyl-, (5α,6α)-

Chemical Formula: C18-H23-N-O3
Molecule weight: 301
Routes of administration: oral has to be the most good way to take Dihydrocodeine. About the prodrug oral vs other route, please go to the hyperlinked document
Oral bioactivity: 21% (range 12-34;rathers between person’s activity of CYP2D6). [7] It can be more active when it takes together with grapefruit
Oral Dose of recreational use
Dosage Levels
20-50mg Minimal
50-100mg Light
100-150mg Common
150-200mg Strong
200-400mg+ Heavy
Pharmacological Profile
Onset 45-55 minutes
Comeup 40-50 minutes
Peak 2-2.5 hours
Offset 3-4 hours
Total Duration 7-8 hours
Half-life 3.3-4.5 hours

[8]

Chemical

Pharmacology

Normally, we take dihydrocodeine in orally. As it is an opioid, it has a opioid effects, and most of dihydrocodeine’s opioid receptor effect is on to µ-opioid receptor. [9] It is twice stronger than codeine, and 1/6 times of morphine orally. [10] Dihydrocodeine is a famous prodrug that metabolizes in the liver, especially through the CYP2D6 enzyme. But also, it activates in CYP3A4. Through CYP2D6, dihydrocodeine is O-methylated into dihydromorphine, which is 1.3 times stronger than the original morphine. But less than 10% of the dihydrocodeine convert to dihydromorphine [11], and other metabolism is known as meaningless opioid receptor. Even dihydrocodeine itself is an opioid receptor, but is so weak which the article says “It has been suggested that dihydrocodeine have little analgesic effect their own, but rather function as prodrugs” [12] Substances metabolised by CYP3A4 is nordihydrocodeine, demethylated dehydrocodeine, which is also not a good receptor in opioid. Also through UGT in the liver, Dihydrocodeine metabolises form 3- and 6-glucuronides. This is the most metabolation, which can be 85% of the whole metabolation. UGT 2B7 is known as the most responsible for DHC-6-Glucuronide formation. [13]

The effect of the dihydrocodeine has differed by person because of genetic polymorphism. 5-10% of white people and some more percentage of Asian people has low metabolism in CYP2D6, which is a very big variable of dihydrocodeine as a drug. [14] Because CYP2D6 metabolism is almost all of this drug’s effect, CYP2D6 inhibitors such as Fluoxetin, Paroxetine, Bupropion, Quinidine makes dihydrocodeine’s effect weaker. [15]

Because of these lots of variables, many souces says different streangth about dihydrocodeine and dihydromorphine. But the interest part of the dihydrocodeine is, there could be more potent of DHC-6-Glucuronide formation in opioid receptors. There are recent research using Quinidine and inject dihydrocodeine, and see how they feels. [16] [17] In this two research, still they are saying that dihydromorphine convertion is the most important metabolition. But [18] in this research, they says the theoretical medical action could not really act in the real case. In this research, they says DHC-6-Glucuronide formation could have more portential than we think. I look foward to further research.


Different routes of taking dihydrocodeine

Medical Use

Substance Effects

Desired Effects

Side Effects

Harm, Tocity, social problem of Dihydrocodeine

Combinations with other substances

Good Combinations

Bad Combinations

History

References

  1. ↑ Stolerman, I. P. (Ed.). (2010). *Encyclopedia of Psychopharmacology*. Springer-Verlag Berlin Heidelberg.
  2. ↑ Sobczak, Ł., & Goryński, K. (2020). Pharmacological Aspects of Over-the-Counter Opioid Drugs Misuse. *Table 2.3*. PMC7504308
  3. ↑ Leppert, W. (2010). Dihydrocodeine as an opioid analgesic for the treatment of moderate to severe chronic pain. *Current Drug Metabolism*, 11(6), pp. 515-520. PMID: 20540693
  4. ↑ 약학정보원. (n.d.). drug_cd=A11A0410A0051 디코데서방정 의약품 정보. 약학정보원 의약품상세정보.
  5. ↑ 약학정보원. (n.d.). 코푸정 의약품 정보. 약학정보원 의약품상세정보, Medication information of SS Bron from Japan.
  6. ↑ photo of the chemical structure is from wikipedia, [1]
  7. ↑ Rowell, F. J., Seymour, R. A., & Rawlins, M. D. (1983). Pharmacokinetics of intravenous and oral dihydrocodeine and its acid metabolites. *European Journal of Clinical Pharmacology*, 25(3), pp. 419–424.
  8. ↑ Rowell, F. J., Seymour, R. A., & Rawlins, M. D. (1983). Pharmacokinetics of intravenous and oral dihydrocodeine and its acid metabolites. *European Journal of Clinical Pharmacology*, 25(3), 419–424.
  9. ↑ Sobczak, Ł., & Goryński, K. (2020). Pharmacological Aspects of Over-the-Counter Opioid Drugs Misuse. *Table 2.1*. PMC7504308
  10. ↑ Leppert, W. (2010). Dihydrocodeine as an opioid analgesic for the treatment of moderate to severe chronic pain. *Current Drug Metabolism*, 11(6), pp. 515-520. PMID: 20540693
  11. ↑ Webb, J. A., Rostami-Hodjegan, A., Abdul-Manap, R., Hofmann, U., Mikus, G., & Kamali, F. (2001). Contribution of dihydrocodeine and dihydromorphine to analgesia following dihydrocodeine administration in man: a PK–PD modelling analysis. *British Journal of Clinical Pharmacology*, 52(6), pp. 619–628. DOI: 10.1046/j.0306-5251.2001.01414.x
  12. ↑ Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. *British Journal of Clinical Pharmacology*, 45(6), 575–581. PMC1873649
  13. ↑ Armstrong, S. C., & Cozza, K. L. (2003). Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part II. *Psychosomatics*, 44(6), 518–525. DOI: 10.1176/appi.psy.44.6.518
  14. ↑ Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. British Journal of Clinical Pharmacology, 45(6), pp. 575–581 PMC1873649
  15. ↑ Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. British Journal of Clinical Pharmacology, 45(6), 575–581. PMC1873649
  16. ↑ Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine: a cross-over study with extensive and quinidine-induced poor metabolizers. British Journal of Clinical Pharmacology, 45(6), 575–581. PMC1873649
  17. ↑ Webb, J. A., Rostami-Hodjegan, A., Abdul-Manap, R., Hofmann, U., Mikus, G., & Kamali, F. (2001). Contribution of dihydrocodeine and dihydromorphine to analgesia following dihydrocodeine administration in man: a PK–PD modelling analysis. British Journal of Clinical Pharmacology, 52(4), 35–43. DOI: 10.1046/j.0306-5251.2001.01414.x
  18. ↑ Armstrong, S. C., & Cozza, K. L. (2003). Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part II. *Psychosomatics*, 44(6), 518–525. DOI: 10.1176/appi.psy.44.6.518
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