Codeine: The problem with Captain Cody

Saakshi Bangera, DY Patil School of Biotechnology and Bioinformatics

Drug abuse is the addictive overuse of medical drugs for nonmedical purposes and is a global menace today. Cannabis, cocaine, heroin, methamphetamine and opioids are common drugs of abuse. 

Captain Cody – a street name for codeine, is one of the biggest causes of opioid addiction problems in most countries. Obtained from Papaver somniferum, codeine (3-methylmorphine) is a phenanthrene derivative extracted from opium. While codeine is used for therapeutic purposes, its addictive potential must be considered as well. Codeine has the potential to reduce fertility, induce testicular toxicity and low sperm quality through oxidative stress, apoptosis and inflammation. This drug is also capable of inducing cardiovascular and renal damage via caspase 3-dependent apoptosis. Due to the high content of polyunsaturated fatty acids in the brain, it is most susceptible to oxidative damage. This is why oxidative stress is a prime factor in neurodegenerative diseases. Despite the prevalent abuse of codeine, enough research about its neurodegenerative effects is not found. With such a state of research deficiency on the subject, a recent study by a team of researchers from Nigeria, published in the journal Heliyon, helps us understand the oxidative damage on the brain that occurs due to drug abuse by codeine.

Observations from the study

• Effects of codeine on body weight, brain weight, and brain weight index were found

The test subjects for this study were NZ white rabbits. The body weights of the control and test animals were found to be distinctly varied. Test rabbits and the control rabbits had comparable brain OSI.

• High-dose codeine-exposed showed the following observations as compared to the control group:

• The hippocampus displayed a moderate alteration of structural organization.
• The cortex displayed moderately dilated capillaries
• The cerebral cortex showed a mild depletion of Purkinje cells of the Purkinje cells layer.
• Effect on the acetylcholinesterase activity in the brain tissue

Codeine exposure led to a major decrease in acetylcholinesterase activity

• Effect on oxidative stress and pro-inflammatory biomarkers in brain tissue

High-dose codeine-exposed showed the following observations as compared to the control group:

• Showed high concentration of malondialdehyde (MDA)
• A significant increase in the generation was observed. 
• Glutathione (GSH) concentrations were reduced.
• AGE concentration was raised.
• An increase in myeloperoxidase (MPO) activity was seen
• A significant decrease in the activities of antioxidants, superoxide dismutase, catalase, and Glutathione-S-transferase (GST) was observed.

• Effect on genotoxicity and apoptosis in brain tissue

Codeine exposure resulted in an increase in the level of 8-hydroxy-2’-deoxyguanosine (8-OHdG) and a rise in the activity of caspase 3. 

More attention must be given to Codeine abuse

The findings of this study are consistent with the other findings on morphine (a metabolite of codeine). The observations showcasing reduced acetylcholinesterase activity, depletion of Purkinje cells, and caspase 3-mediated apoptosis demonstrate the effect of codeine on the cerebral and cerebellar functions of the brain. The study in discussion has established that codeine use did not affect body weight gain and brain weight index. This proves that codeine suppresses the cellular mechanism but does not alter the fat accumulation of the brain. The reported increase in MDA, H₂O_2, and AGE upon codeine exposure demonstrates that it amplifies the generation of reactive oxygen species and antioxidants consumption. The reported increase in the MPO activity in the brain suggests that codeine triggers neutrophil infiltration in the brain, eventually causing inflammation. Elevated levels of caspase 3 activity were mainly caused by redox dysregulation and inflammatory response induced by codeine. The decrease in the number of Purkinje cells impairs the GABA-ergenic terminals and increases the excitation of the brainstem. 

These findings support the fact that the codeine drug abuse crisis should be given more attention than it presently receives.

Also read: Egg-based influenza virus vaccines – Are they effective?

Reference:

1. A.F. Ajayi, R.E. Akhigbe, Apoptotic inducement of neuronal cells by codeine:possible role of disrupted redox state and caspase 3 signaling, HELIYON,  https://doi.org/10.1016/j.heliyon.2021.e07481

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About the Author: The author is currently pursuing MSc in Biotechnology from DY Patil School of Biotechnology and Bioinformatics. She believes that she doesn’t have a specific area of interest yet. She wishes to explore toxicology and food biotechnology. She’s quite passionate about Biotechnology and aims to grab every opportunity she comes across.