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Codeine vs. Hydrocodone: Key Differences, Side Effects & Risks

In the codeine vs. hydrocodone comparison, potency is the defining factor. Although chemically related, since hydrocodone is derived from codeine, the two are not identical; codeine is significantly less potent than its derivative.

Continue reading to discover how these medications compare in terms of effectiveness, side effects, addiction potential, and other key factors.

What Is Codeine, and How Does It Work?

Codeine, prescribed for mild-to-moderate pain

Codeine is an opioid pain medication prescribed for mild-to-moderate pain that is resistant to weaker pain relievers. Although it is also found in cough syrups, recent studies have demonstrated that it offers no greater benefit for suppressing coughs than a placebo.

Available as an oral liquid, injection, or an immediate- or extended-release tablet, codeine is sold as a single-ingredient or combination drug. It is usually combined with acetaminophen (Tylenol® #3 and #4), aspirin (Aspalgin®), or ibuprofen (Solpadeine®, Nurofen Plus®).

This drug works by interacting with the opioid receptors located in the central nervous system (CNS). It binds to these receptors upon consumption, preventing pain signals from reaching the brain. Additionally, it stimulates dopamine release, inducing feelings of euphoria and relaxation.

Like all opioids, codeine can lead to dependence and addiction, especially if abused or used for a prolonged time. Most commonly, this medication is misused in the form of a polysubstance drink called lean, which combines codeine cough syrup with soda, hard candy, alcohol, or other substances.

What Is Hydrocodone, and How Does It Work?

Hydrocodone is an opioid analgesic prescribed for moderate-to-severe pain that cannot be managed with milder painkillers. Like codeine, it also has antitussive properties and can be used to suppress cough.

The single-entity version of this drug is only available as an extended-release tablet or capsule and marketed as Zohydro® ER and Hysingla® ER.

However, this medication is most commonly prescribed as a combination drug containing acetaminophen in oral liquid, tablet, or capsule form. Hydrocodone/acetaminophen used to be sold under Norco®, Lortab®, Vicodin®, and Lorcet® brands, but it is now available only as a generic drug.

Hydrocodone also works by attaching to opioid receptors, thereby disrupting the transmission of pain signals between the body and the brain. Besides pain relief, it also induces feelings of euphoria and relaxation by triggering a sudden dopamine rush.

Although it’s an effective analgesic, it has a high potential for abuse, dependence, and addiction. Hydros, Fluff, and Vikes are some of its street names.

Now that you’re more familiar with both opioids, it’s time for a detailed comparison of codeine vs. hydrocodone.

Codeine vs. Hydrocodone: Understanding the Key Differences

Codeine vs. Hydrocodone: Understanding the Key Differences

The key difference between codeine and hydrocodone is strength; the latter is around six times more potent.

With this in mind, let’s compare codeine vs. hydrocodone effectiveness, chemical compositions, cost, and potential for opioid addiction and overdose.

Codeine vs. Hydrocodone: Effectiveness

Despite the difference in codeine vs. hydrocodone potency, both medications are highly effective in relieving pain.

A study done by University of Pittsburgh researchers found that hydrocodone and codeine provide comparable pain relief for patients with acute musculoskeletal pain. However, researchers conclude that hydrocodone may be more effective since it is associated with fewer reports of inadequate pain relief.

Similarly, Montefiore Medical Center researchers suggest that both codeine/acetaminophen and hydrocodone/acetaminophen decrease acute extremity pain scores by 50%.

When it comes to codeine vs. hydrocodone cough syrup, there’s also little, if any, difference in their effectiveness in suppressing cough.

Codeine vs. Hydrocodone: Chemical Composition

The primary distinction in codeine vs. hydrocodone chemical composition is that codeine is a naturally occurring opioid, while hydrocodone is semi-synthetic.

Codeine is an opiate derived directly from the opium poppy plant. Meanwhile, hydrocodone is produced by synthesizing codeine, but it can also be derived from thebaine, another opium alkaloid.

However, this doesn’t mean that hydrocodone has codeine in it; although related, these drugs have different chemical structures.

Codeine vs. Hydrocodone: Addictiveness

Codeine and hydrocodone are highly addictive. Nonetheless, hydrocodone has a higher potential for addiction, as evident from the fact that it is treated as a Schedule II controlled substance. Meanwhile, codeine products fall under Schedule III or Schedule V, depending on their strength.

Still, both can lead to opioid abuse, dependence, and addiction. In 2023, hydrocodone was the most frequently misused prescription painkiller in the United States, whereas codeine was the third. A staggering 66.4% of Americans abusing prescription pain relievers misused either of these drugs.

Codeine vs. Hydrocodone: Cost

The cost of codeine and hydrocodone largely depends on the drug’s formulation, prescription strength, and other factors. For example, a single 15 mg codeine tablet costs around $0.70, whereas one containing 325 mg/2.5 mg acetaminophen/hydrocodone costs about $0.52. However, you might have to pay upwards of $7 for an oral capsule with 10 mg extended-release hydrocodone. 

Generic versions of both drugs are more affordable and often covered by insurance.

Codeine vs. Hydrocodone: Overdose

Both codeine and hydrocodone can cause a potentially fatal opioid overdose if taken in higher doses than prescribed. However, hydrocodone can cause an overdose in lower doses than codeine because it is more potent.

To reduce the risk of a codeine or hydrocodone overdose, take these drugs strictly as prescribed and track your medication intake to ensure you don’t take an extra dose by accident. If you or someone you know is displaying signs of an overdose (slowed breathing, pinpoint pupils, profound confusion, etc.), call 911 immediately.

Next, let’s discuss potential codeine and hydrocodone side effects.

Codeine vs. Hydrocodone Side Effects

Codeine and hydrocodone cause similar side effects, including:

  • Nausea
  • Vomiting
  • Sedation
  • Confusion
  • Headache
  • Dry mouth
  • Constipation
  • Lightheadedness

The earlier-mentioned study by University of Pittsburgh researchers found that hydrocodone is less likely to cause CNS side effects, such as sedation and lightheadedness. Talk to your doctor if you experience any unwanted effects after taking either of these medications; allergic reactions and other severe adverse events may require immediate medical care.

Importantly, prolonged use of codeine or hydrocodone can lead to tolerance, abuse, dependence, and addiction. It also increases the risk of other adverse effects, such as fertility problems, chronic constipation, hormonal imbalances, and organ damage.

Mixing opioids with other substances without the doctor’s approval significantly increases the risk of side effects.

On this note, let’s explore hydrocodone vs. codeine drug interactions.

Hydrocodone and Codeine Drug Interactions

Interaction with various drugs

Hydrocodone and codeine can interact with various drugs, including but not limited to:

  • Alcohol
  • Other opioids
  • Muscle relaxers
  • Antidepressants
  • Benzodiazepines
  • Seizure medication
  • Antifungal medications
  • Antipsychotic medication
  • Clarithomycin, among other antibiotics

Taking hydrocodone or codeine with other substances can have potentially life-threatening consequences, amplifying the risk of respiratory depression, overdose, and other adverse effects. Inform your doctor about any other medications and supplements you’re taking to ensure they won’t interact with these opioids.

Other Risk Factors of Codeine and Hydrocodone

Some other risk factors that increase the likelihood of adverse effects associated with codeine and hydrocodone include:

  • Head injury
  • Respiratory issues
  • Cardiovascular disease
  • Liver or kidney problems
  • Codeine or hydrocodone allergy
  • Substance use disorders (SUDs)

Before initiating opioid therapy, discuss your medical history with your doctor.

Furthermore, codeine and hydrocodone may not be suitable for patients expecting or planning to have a baby. Besides preterm birth, stillbirth, and other devastating outcomes, opioid use during pregnancy can lead to neonatal abstinence syndrome (NAS).

If the mother uses either of these drugs while pregnant, her newborn may suffer from codeine or hydrocodone withdrawal symptoms upon birth. This condition is also associated with long-term complications, such as developmental delays, motor problems, and behavioral issues.

Physical Dependence and Addiction to Opioids

Physical dependence and addiction to opioids are different conditions, even though they often co-occur.

Codeine or hydrocodone dependence is mainly physical; it stems from the chemical changes that happen in the CNS with prolonged opioid use. Therefore, anyone taking these drugs can become dependent, including those who follow their doctor’s instructions.

Treating physical dependence is of utmost importance, as this condition can develop into an addiction, which is largely psychological. People with hydrocodone or codeine addiction cannot resist taking these drugs, even when they wreak havoc on their lives.

Signs and Symptoms of Opioid Dependence

To reduce the likelihood of developing codeine or hydrocodone addiction, seek professional help as soon as you notice the following signs of opioid dependence in yourself or a loved one:

  • Tolerance. Repeated opioid exposure stimulates the production of opioid receptors. As a result, you’ll eventually need to increase your codeine or hydrocodone dosage to achieve the same effects as before. If your initial dose is losing effectiveness, consult with your doctor; don’t take more medication than prescribed, as this increases the risk of addiction and overdose.
  • Withdrawal symptoms. If you become dependent on codeine or hydrocodone, you’ll inevitably experience uncomfortable opioid withdrawal symptoms upon drug discontinuation. Since vomiting, fever, muscle aches, depression, cravings, and other withdrawal symptoms can be virtually unbearable, lots of people continue to take opioids not to feel sick, even when their initial pain has subsided.

ANR Treatment for Codeine or Hydrocodone Dependence

ANR performed under sedation

Accelerated Neuro-Regulation (ANR) is an innovative opioid dependence treatment developed by Dr. Andre Waismann. It differs from traditional approaches in that it addresses the root of the issue instead of merely managing its symptoms.

ANR treatment re-regulates the endorphin-receptor system imbalance, returning the brain to its pre-dependence state. More specifically, this procedure modulates the nervous system to decrease the production of opioid receptors while allowing the body to remove opioids and resume proper endorphin production.

Because ANR is performed under sedation, patients don’t experience the discomfort of going through opioid withdrawals.

Benefits of Undergoing ANR Treatment

The key benefits of undergoing ANR treatment include:

  • Patient safety. To ensure utmost patient safety, ANR is performed strictly in an ICU setting of fully accredited hospitals with advanced medical equipment. Our team comprises highly experienced and compassionate board-certified healthcare professionals, including anesthesiologists and critical care physicians. 
  • Lasting results. Because ANR resolves the root of opioid dependence, it negates cravings and other withdrawal symptoms, allowing patients to leave the fear of relapse behind.
  • Personalized approach. At ANR Clinic, each patient receives a treatment plan tailored to their unique medical history and needs. As such, ANR is suitable for almost everyone, including those with co-occurring health conditions.

As of today, ANR has helped close to 25,000 people worldwide break free from opioid dependence. Here’s one of our many success stories:

YouTube video

Ready to reclaim your life? Contact us today for a free consultation with no obligation; we ensure 100% confidentiality.

Key Takeaways

Despite their differences, hydrocodone and codeine carry similar risks, including opioid dependence, addiction, and overdose. For your own safety, you should only take them if non-opioid pain medications fail to provide adequate pain relief. Most importantly, carefully follow your doctor’s instructions while using them.

Before you go, let’s summarize the key points we covered today:

  • Codeine and hydrocodone are prescription opioids with antitussive properties.
  • Although hydrocodone is more potent than codeine, they produce comparable analgesic effects.
  • Compared to codeine, hydrocodone is less likely to cause CNS side effects, such as lightheadedness.
  • Anyone taking hydrocodone or codeine can become dependent because these medications gradually alter brain chemistry.
  • ANR is an ultra-modern treatment that supports long-lasting recovery by modulating the endorphin-receptor system.

Hydrocodone vs. Codeine FAQ

#1. Is codeine the same as hydrocodone?

Codeine is not the same as hydrocodone. Although both belong to the class of opioids, codeine is an opiate, whereas hydrocodone is a semi-synthetic opioid. Hydrocodone, which is stronger than codeine, is used for moderate-to-severe pain. Meanwhile, codeine is prescribed for milder pain that requires opioid treatment.

#2. Can you mix codeine and hydrocodone?

You should never mix codeine and hydrocodone. Mixing opioid analgesics considerably increases the risk of respiratory depression and opioid overdose, which can be fatal if not treated promptly.

#3. Can you take hydrocodone if you’re allergic to codeine?

Consult with your doctor to find out whether you can take hydrocodone if you’re allergic to codeine. Most people allergic to this opioid don’t tolerate hydrocodone, but some tolerate it better due to their structural differences. Your doctor can help you determine which medications are right for you.

Reclaim your life with the revolutionary ANR treatment.

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Dr. Andre Waismann

Dr. Waismann identified the biological roots of opioid dependency, Since then he has successfully treated more than 25,000 patients worldwide that are struggling with opioid addiction.


Throughout his career, he has lectured and educated health professionals in dozens of countries around the world to this day.

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