Effects of hydrocodone: A Synthesis of Findings from 18 Studies

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Original Abstract of the Article

Main Research Findings

Hydrocodone is an opioid medication widely used for the treatment of moderate to severe chronic pain. 、 12 Hydrocodone is metabolized in the liver and undergoes metabolism by cytochrome P450 enzymes (CYP). 、 12 、 Hydrocodone is metabolized by both CYP3A4 and CYP2D6. 、 12 CYP3A4 yields norhydrocodone, a major inactive metabolite, whereas CYP2D6 yields hydromorphone, a minor active metabolite. 12 Paroxetine is a strong selective inhibitor of CYP2D6. 12 Co-administration of paroxetine with hydrocodone may increase the concentration of hydromorphone in plasma and alter the effects of hydrocodone. 12 However, some behavioral effects of hydrocodone are not modified by marked inhibition of CYP2D6, suggesting that these effects of HC are not due to its conversion to HM but, rather, that both HC and HM act directly on mu receptors. 5 Chronic exposure to hydrocodone can reduce the expression of astrocytic glutamate transporters in the reward system, but ceftriaxone can normalize the expression of these glutamate transporters and improve behavioral effects associated with hydrocodone. 18 Hydrocodone affects dopamine D2 receptors, which can lead to behavioral changes such as hyperactivity and drug dependence. 7 、 11 Compared to oxycodone and morphine, hydrocodone has a weaker effect on D2 receptors, suggesting a lower risk of drug dependence. 7 Ethanol can delay the development of tolerance to oxycodone and hydrocodone and reverse tolerance to these drugs. 14 Hydrocodone is used for the treatment of non-cancer pain, but it has side effects and the risk of dependence. 9 Hydrocodone and morphine possess similar rewarding effects and reduce ERK and CREB phosphorylation in the nucleus accumbens. 10 The rescheduling of hydrocodone (from Schedule III to II) has encouraged healthcare professionals to be more cautious when prescribing hydrocodone. 15 Hydrocodone may have higher plasma concentrations in patients with impaired renal or hepatic function. 17 Ceftriaxone has been shown to attenuate hydrocodone-seeking behavior and regulate glial glutamate transporters. 6

Benefits and Risks

Benefit Summary

Hydrocodone is effective in the treatment of moderate to severe chronic pain. 、 12 Ceftriaxone may improve the hydrocodone-induced decline in glutamate transporters and reduce the risk of dependence on hydrocodone. 18 Ethanol may delay the development of tolerance to hydrocodone. 14

Risk Summary

Hydrocodone has side effects and the risk of dependence and abuse. 9 、 10 The effects of hydrocodone may be enhanced when combined with CYP2D6 inhibitors, such as paroxetine. 12 Hydrocodone may have higher plasma concentrations in patients with impaired renal or hepatic function. 17

Comparison Between Studies

Similarities Between Studies

Many studies show that hydrocodone is effective in the treatment of pain. 、 12 、 1 、 2 、 3 、 7 、 14 、 9 、 10 However, studies also indicate that hydrocodone has side effects and the risk of dependence. 9 、 10 It is also established that hydrocodone is metabolized by enzymes such as CYP2D6. 、 12 、

Differences Between Studies

Some studies focus on comparing hydrocodone to other opioid medications, especially oxycodone and morphine. 7 、 14 、 8 These studies suggest that hydrocodone may have a weaker effect on D2 receptors, potentially leading to a lower risk of drug dependence compared to other opioid drugs. 7 Studies also indicate that the effects of hydrocodone may be altered when combined with CYP2D6 inhibitors. 12 Some research focuses on the behavioral effects of hydrocodone, particularly the rewarding effects and potential for dependence. 10 、 6 These studies suggest that hydrocodone may affect the reward system similarly to other opioid drugs and has a risk of dependence. 10 、 6 Research also indicates that hydrocodone may impact the regulation of the neurotransmitter glutamate, an effect that may be improved by ceftriaxone. 18 、 6

Consistency and Contradictions in the Results

Multiple studies demonstrate that hydrocodone is effective in treating pain. 、 12 、 1 、 2 、 3 、 7 、 14 、 9 、 10 However, it is also indicated that hydrocodone poses risks of side effects and dependence. 9 、 10 When comparing hydrocodone to other opioid medications, conflicting results exist. 7 、 14 While some studies suggest that hydrocodone has a lower risk of drug dependence compared to other opioids, others suggest that hydrocodone also carries a risk of dependence. 7 、 10 Future research should aim to resolve these contradictions and establish clearer guidelines for the safe use and effective management of hydrocodone.

Points to Note When Applying the Results to Real Life

Hydrocodone is an effective medication for the treatment of moderate to severe chronic pain, but it carries risks of side effects and dependence. 、 12 、 9 、 10 It is crucial to follow your doctor's instructions when taking hydrocodone, and avoid stopping or altering the dosage without consulting them. 9 、 10 If you are taking CYP2D6 inhibitors, consult your doctor. 12 If you have impaired renal or hepatic function, consult your doctor. 17 Hydrocodone has a risk of abuse, so it's important to be mindful of its storage location. 15

Limitations of Current Research

Many studies on hydrocodone have been conducted with small sample sizes, limiting the generalizability of their findings. 12 、 10 Also, many studies are limited to specific populations, such as those of a particular age group or those with certain medical conditions, further limiting the generalizability of the findings. 1 、 2 、 3 Future research should involve larger sample sizes, encompass diverse populations, and include longer-term follow-up. 12 、 10 Additionally, research on specific aspects, such as the regulation of glutamate by hydrocodone, the effects of ceftriaxone, and the interaction with ethanol, is limited. 18 、 14 Further research is needed in these areas.

Future Research Directions

While hydrocodone is widely used for pain management, further research is required to ensure its safe use and effective management. 、 12 Future research should prioritize exploring the following aspects:

  • Comparative studies of hydrocodone with other opioid medications
  • Evaluation of the risks of side effects and dependence associated with hydrocodone
  • Research on the combination of hydrocodone and CYP2D6 inhibitors
  • Studies on the impact of renal and hepatic function on the effects of hydrocodone
  • Research on the regulation of the neurotransmitter glutamate by hydrocodone
  • Research on the efficacy of glutamate transporter modulators, such as ceftriaxone
  • Research on the interaction of ethanol with hydrocodone

Conclusion

Hydrocodone is an effective medication for the treatment of moderate to severe chronic pain, but it carries risks of side effects and dependence. 、 12 、 9 、 10 It is crucial to follow your doctor's instructions when taking hydrocodone and avoid stopping or altering the dosage without consulting them. 9 、 10 Further research is needed on hydrocodone, and the findings should inform the establishment of guidelines for its safe use and effective management. 12 、 10 Research is also needed on specific aspects such as the regulation of glutamate by hydrocodone, the effects of ceftriaxone, and the interaction with ethanol. 18 、 14

Literature analysis of 18 papers
Positive Content
10
Neutral Content
2
Negative Content
6
Article Type
7
0
0
0
18
1.

Hydrocodone versus codeine in acute musculoskeletal pain.

Author: TurturroM A, ParisP M, YealyD M, MenegazziJ J

Treats acute pain

Hydrocodone and codeine were compared for efficacy and side effects in treating acute musculoskeletal pain. A larger study is needed to determine the optimal use of these drugs for pain management.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

Characterizing the subjective, psychomotor, and physiological effects of a hydrocodone combination product (Hycodan) in non-drug-abusing volunteers.

Author: ZacnyJames P

Pain relief
Cognitive impairment

Hycodan, a hydrocodone combination product, produces effects similar to morphine, a prototypic mu agonist, at the highest dose tested. Both drugs induce both pleasant and unpleasant subjective effects, but do not significantly influence post-session liking or desire to re-administer the drug.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

3.

Profiling the subjective, psychomotor, and physiological effects of a hydrocodone/acetaminophen product in recreational drug users.

Author: ZacnyJames P, GutierrezSandra, BolbolanShahla A

Abuse potential

This study profiled the subjective, psychomotor, and physiological effects of hydrocodone/acetaminophen (HYD/ACET) in a population of recreational drug users. HYD/ACET had abuse liability-related subjective effects, suggesting that it has potential for abuse and dependence.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

4.

Characterizing the subjective, psychomotor, and physiological effects of a hydrocodone combination product (Hycodan) in non-drug-abusing volunteers.

Author: ZacnyJames P

Pain relief
Cognitive impairment

Hycodan, a hydrocodone combination product, produces effects similar to morphine, a prototypic mu agonist, at the highest dose tested. Both drugs induce both pleasant and unpleasant subjective effects, but do not significantly influence post-session liking or desire to re-administer the drug.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

6.

Effects of ceftriaxone on hydrocodone seeking behavior and glial glutamate transporters in P rats.

Author: AlshehriFahad S, HakamiAlqassem Y, AlthobaitiYusuf S, SariYoussef

Opioid relapse prevention

Ceftriaxone, a drug that increases the levels of glutamate transporters, may help reduce relapse in hydrocodone addiction. In a study with alcohol-preferring rats, ceftriaxone treatment reduced hydrocodone reinstatement and normalized the expression of the cystine/glutamate transporter, which is decreased by hydrocodone exposure.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Differential effects of oxycodone, hydrocodone, and morphine on the responses of D2/D3 dopamine receptors.

Author: EmeryMichael A, BatesM L Shawn, WellmanPaul J, EitanShoshana

Pain management
Addiction
Mental illness

This study found that different opioids differentially modulate the responses of D2-like dopamine receptors, suggesting varying risks to the dopamine reward system.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Subjective, psychomotor, and physiological effects profile of hydrocodone/acetaminophen and oxycodone/acetaminophen combination products.

Author: ZacnyJames P, GutierrezSandra

Miosis
Psychomotor impairment
Subjective effects

In a study of 16 healthy volunteers, oxycodone/acetaminophen produced a wider spectrum of subjective effects than hydrocodone/acetaminophen at the 10 mg opioid dose. Both drug combinations impaired psychomotor performance at the 10 mg opioid dose.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

10.

Hydrocodone and morphine possess similar rewarding effects and reduce ERK and CREB phosphorylation in the nucleus accumbens.

Author: TenayucaJohn M, NazarianArbi

Hydrocodone euphoria
Hydrocodone reward

This study investigated the rewarding properties of hydrocodone and morphine in rats using the conditioned place preference paradigm (CPP). Both drugs produced a CPP at the 5 mg/kg dose, suggesting that hydrocodone possesses similar rewarding properties as morphine. Both drugs also reduced phosphorylation levels of ERK and CREB proteins in the nucleus accumbens, indicating that both drugs exert their effects through similar signal transduction pathways involved in drug reward.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

Effects of paroxetine, a CYP2D6 inhibitor, on the pharmacokinetic properties of hydrocodone after coadministration with a single-entity, once-daily, extended-release hydrocodone tablet.

Author: KapilRam P, FriedmanKristen, CiprianoAlessandra, MichelsGregory, ShetManjunath, MondalSabiha A, HarrisStephen C

Treats chronic pain

This study examines the influence of paroxetine, a CYP2D6 inhibitor, on the pharmacokinetic properties of hydrocodone in healthy adults. The coadministration of paroxetine significantly altered the pharmacokinetic parameters of hydrocodone.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Effects of Rescheduling Hydrocodone on Opioid Prescribing in Ohio.

Author: LiuYingna, BakerOlesya, SchuurJeremiah D, WeinerScott G

Decreased hydrocodone prescriptions

The 2014 rescheduling of hydrocodone from schedule III to II was associated with declines in hydrocodone prescriptions in Ohio. The effect was more pronounced in internists and anesthesiologists compared to emergency physicians.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

Ethanol Reversal of Tolerance to the Antinociceptive Effects of Oxycodone and Hydrocodone.

Author: JacobJoanna C, PoklisJustin L, AkbaraliHamid I, HendersonGraeme, DeweyWilliam L

Opioid tolerance reversal

This study compared the development of tolerance to oxycodone and hydrocodone with that of morphine and the reversal of tolerance by ethanol. Ethanol reversed tolerance to all three opioids, but oxycodone tolerance was more resistant to oral ethanol reversal. This suggests a metabolic component of oxycodone tolerance.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

16.

Profiling the subjective, psychomotor, and physiological effects of a hydrocodone/acetaminophen product in recreational drug users.

Author: ZacnyJames P, GutierrezSandra, BolbolanShahla A

Abuse potential

This study profiled the subjective, psychomotor, and physiological effects of hydrocodone/acetaminophen (HYD/ACET) in a population of recreational drug users. HYD/ACET had abuse liability-related subjective effects, suggesting that it has potential for abuse and dependence.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

17.

Effects of Renal Impairment and Hepatic Impairment on the Pharmacokinetics of Hydrocodone After Administration of a Hydrocodone Extended-Release Tablet Formulated With Abuse-Deterrence Technology.

Author: DarwishMona, YangRonghua, TracewellWilliam, RobertsonPhilmore, BondMary

Altered systemic exposure

This study evaluated the effects of renal and hepatic impairment on the pharmacokinetics of a hydrocodone extended-release (ER) formulation. Systemic exposure to hydrocodone ER was altered in both renally and hepatically impaired populations, suggesting the need for careful dose titration.

Controlled Clinical TrialA clinical trial that evaluates the effectiveness of a treatment by comparing a group that receives the intervention with a group that receives a placebo or standard treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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