ArticleThe Journal of pharmacology and experimental therapeutics2015
Curcumin attenuates opioid tolerance and dependence by inhibiting Ca2+/calmodulin-dependent protein kinase II α activity.
Article in The Journal of pharmacology and experimental therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Dopamine D2 Receptors, D1/D2 Receptor Heteromers and CaMKII Signaling in the Neurobiology of Drug Addiction.Molecular neurobiology · 2026Review
- Curcumin as theranostics: imaging-guided therapeutics in oncology and neurodegenerative diseases.Frontiers in nutrition · 2026Review
- Review
- Nanotherapeutics for Alleviating Anesthesia-Associated Complications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- The endogenous opioid system in the medial prefrontal cortex mediates ketamine's antidepressant-like actions.Research square · 2023Article
- Teneligliptin Co-Infusion Alleviates Morphine Tolerance by Inhibition of Spinal Microglial Cell Activation in Streptozotocin-Induced Diabetic Rats.Antioxidants (Basel, Switzerland) · 2023Article
- Calcium/calmodulin-dependent protein kinase II is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rat nucleus accumbens.The Korean journal of pain · 2023Article
- The role of the gut microbiome and microbial metabolism in mediating opioid-induced changes in the epigenome.Frontiers in microbiology · 2023Review
- Case Report: Developmental Delay and Acute Neuropsychiatric Episodes Associated With aFrontiers in pharmacology · 2022Article
- The Role of CaMKII and ERK Signaling in Addiction.International journal of molecular sciences · 2021Review
- Curcumin Delivery Mediated by Bio-Based Nanoparticles: A Review.Molecules (Basel, Switzerland) · 2020Review
- Morphine Addiction and Oxidative Stress: The Potential Effects of Thioredoxin-1.Frontiers in pharmacology · 2020Review
- Formulations of Curcumin Nanoparticles for Brain Diseases.Biomolecules · 2019Review
- The Attenuating Effect of Curcumin on Morphine Dependence in Rats: The Involvement of Spinal Microglial Cells and Inflammatory Cytokines.Iranian journal of pharmaceutical research : IJPR · 2019Article
- AMPA receptor positive allosteric modulators attenuate morphine tolerance and dependence.Neuropharmacology · 2018Article
- Current Treatment Options for Peripheral Nerve Hyperexcitability Syndromes.Current treatment options in neurology · 2018Review
- CaMKIIα Mediates the Effect of IL-17 To Promote Ongoing Spontaneous and Evoked Pain in Multiple Sclerosis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Protective effects of curcumin against rotenone-induced rat model of Parkinson's disease: in vivo electrophysiological and behavioral study.Metabolic brain disease · 2017Article
- siRNA capsulated brain-targeted nanoparticles specifically knock down OATP2B1 in mice: a mechanism for acute morphine tolerance suppression.Scientific reports · 2016Article
- Combining pain therapy with lifestyle: the role of personalized nutrition and nutritional supplements according to the SIMPAR Feed Your Destiny approach.Journal of pain research · 2016Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca(2+)/calmodulin-dependent protein kinase II α (CaMKIIα), a protein kinase that has been previously proposed to be critical for opioid tolerance and dependence. In this study, we used state-of-the-art polymeric formulation technology to produce poly(lactic-co-glycolic acid) (PLGA)-curcumin nanoparticles (nanocurcumin) to overcome the drug's poor solubility and bioavailability, which has made it extremely difficult for studying in vivo pharmacological actions of curcumin. We found that PLGA-curcumin nanoparticles reduced the dose requirement by 11- to 33-fold. Pretreatment with PLGA-curcumin (by mouth) prevented the development of opioid tolerance and dependence in a dose-dependent manner, with ED50 values of 3.9 and 3.2 mg/kg, respectively. PLGA-curcumin dose-dependently attenuated already-established opioid tolerance (ED50 = 12.6 mg/kg p.o.) and dependence (ED50 = 3.1 mg/kg p.o.). Curcumin or PLGA-curcumin did not produce antinociception by itself or affect morphine (1-10 mg/kg) antinociception. Moreover, we found that the behavioral effects of curcumin on opioid tolerance and dependence correlated with its inhibition of morphine-induced CaMKIIα activation in the brain. These results suggest that curcumin may attenuate opioid tolerance and dependence by suppressing CaMKIIα activity.
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