Is Dihydrocodeine Stronger Than Codeine?

Is Dihydrocodeine Stronger Than Codeine?

What types of medications are they?

Dihydrocodeine – indicated for moderate to severe pain - and codeine – indicated for moderate pain - are both opioid medications. While they are chemically similar, in that they are both derived from opium, and both belong to a class of compounds called morphinans which share similar molecular structures, there are differences in how effectively they reduce pain. You can read about how long dihyrocodeine remains in your system here.

What evidence do we have about their strength?

Studies directly comparing the two medication’s strength are rare, and the ones that are available are generally of a poor evidential quality. However, some studies shed light on the differences in strength. For example, Leppert (2010) conducted a review that found that dihydrocodeine was twice as potent as codeine in reducing pain. A Cochrane review in 2000 reviewed the efficacy of dihydrocodeine for acute postoperative pain and found that dihydrocodeine was effective in reducing pain post-surgery, but the quality of studies was poor.

Why the difference in strengths?

Dihydrocodeine and codeine are both opioids derived from the opium poppy. They work by binding to opioid receptors in the brain to reduce the sensation of pain. As mentioned above, there are studies that have shown that Dihydrocodeine is typically considered to be more potent than codeine. Sobczak, Ł., & Goryński (2020) found that it is approximately 1.2 times as potent as morphine. This means it can provide effective pain relief at lower doses. One thing to consider is that the strength of a medication can be dose dependent, in other words, if you take more of a medication this could lead to a stronger pain-relieving effect.

One possible reason why dihydrocodeine may be more effective than codeine is related to the compounds the two medications are metabolised into. They are both known as prodrugs, which means that they are metabolised in the liver into their active metabolites. Dihydrocodeine is metabolised into dihydromorphine which has a higher affinity – a term that denotes the strength and stability of the interaction between a medication and its target receptors, in this case opioid receptors in the brain and spinal cord. In other words the stronger and more stable a bond is, the more prolonged the pain relieving effect. Contrastingly, codeine is metabolised into morphine, which has been shown to have a lower affinity for opioid receptors, and therefore lower potency in reducing pain. This is not to say that codeine cannot reduce pain, but from a purely physiological standpoint its metabolites represent less affinity to opioid receptors in comparison to dihydromorphine and therefore may mean it reduces pain less effectively than dihydrocodeine.

Another likely reason why dihydrocodeine maybe more potent that codeine is to do with first-pass metabolism. This is metabolism of a medication that occurs in the liver by specific enzymes – namely the cytochrome P450 (CYP) enzymes. Depending on the extent of the first pass metabolism, this can significantly reduce the amount of active drug that can enter your blood stream and interact with opioid receptors. Is is thought that dihydrocodeine undergoes less first pass metabolism compared to codeine. This means that more of dihydrocodeine’s active drug enters the blood and interacts with opioid receptors in the brain and spinal cord. Ultimately reducing your pain more effectively than codeine.

There may also be differences in relation to underlying genetics of the person taking the medications. For those people whose CYP2D6 enzyme activity, in particular for those who are poor metabolisers of this enzyme, which is required to metabolise codeine into morphine, may which metabolise these drugs less effectively. This variability can lead to inadequate pain relief.

Conclusion

Based on the latest clinical evidence, dihydrocodeine is generally considered stronger than codeine in terms of potency and pain relief effectiveness. However, the choice between the two should be guided by individual your needs, specific pain conditions, and tolerance to opioids. If you are in pain, and want to consult with me about suitable treatments, you can do so here.

References

1. Leppert, W. (2010). Dihydrocodeine as an Opioid Analgesic for the Treatment of Moderate to Severe Chronic Pain. Current Drug Metabolism, 11(6), 494–506. https://doi.org/10.2174/138920010791636211

2. Drewes, A. M., Jensen, R. D., Nielsen, L. M., Droney, J., Christrup, L. L., Arendt-Nielsen, L., Riley, J., & Dahan, A. (2012). Differences between opioids: pharmacological, experimental, clinical and economical perspectives. British Journal of Clinical Pharmacology, 75(1), 60–78. https://doi.org/10.1111/j.1365-2125.2012.04317.x

3. Sobczak, Ł., & Goryński, K. (2020). Pharmacological Aspects of Over-the-Counter Opioid Drugs Misuse. Molecules, 25(17), 3905. https://doi.org/10.3390/molecules25173905

4. Moore, R. A., Edwards, J., Derry, S., & McQuay, H. J. (2000). Single dose oral dihydrocodeine for acute postoperative pain. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.cd002760

5. “Weak” opioid analgesics. Codeine, dihydrocodeine and tramadol: no less risky than morphine. (2016). Prescrire International, 25(168), 45–50. https://pubmed.ncbi.nlm.nih.gov/27042732/