Table 3. Top 100 Articles on opioids.
CNS - Central Nervous System
NMDA receptor - N-methyl-D-aspartate receptor
COMT - Catechol-O-methyltransferase
EAPC - European Association for Palliative Care
| Rank | Title | Citation | Citation density | Most Cited (Year) |
| 1 | Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proceedings of the National Academy of Sciences, 1988 | 3149 | 108.59 | 2014 |
| 2 | Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature, 1975 | 2677 | 63.74 | 1977 |
| 3 | The effects of morphine-and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog. Journal of Pharmacology and Experimental Therapeutics, 1976 | 2336 | 56.98 | 1982 |
| 4 | A psychomotor stimulant theory of addiction. Psychological Review, 1987 | 2077 | 69.23 | 1999 |
| 5 | Endogenous opioid peptides: multiple agonists and receptors. Nature, 1977 | 1928 | 48.2 | 1982 |
| 6 | The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain, 1977 | 1843 | 46.08 | 2011 |
| 7 | A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury: results of the Second National Acute Spinal Cord Injury Study. The New England Journal of Medicine, 1990 | 1820 | 67.41 | 2002 |
| 8 | Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends in Pharmacological Sciences, 1992 | 1729 | 69.16 | 1998 |
| 9 | Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature, 1995 | 1636 | 74.36 | 2000 |
| 10 | Cellular and molecular mechanisms of drug dependence. Science, 1988 | 1606 | 55.38 | 2000 |
| 11 | A neuropeptide that activates an opioidlike G protein-coupled receptor. Science, 1995 | 1592 | 72.36 | 2000 |
| 12 | Intrathecal morphine in mice: a new technique. European Journal of Pharmacology, 1980 | 1433 | 38.73 | 2013 |
| 13 | The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. In: The Cocaine Crisis: Springer; 1987 | 1413 | 44.16 | 2011-2012 |
| 14 | Opiate receptor: demonstration in nervous tissue. Science, 1973 | 1367 | 31.07 | 1981 |
| 15 | The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain, 1987 | 1355 | 45.17 | 2011;2014 |
| 16 | Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. Jama, 2000 | 1291 | 75.94 | 2014 |
| 17 | Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. The Journal of Pain, 2009 | 1181 | 147.63 | 2011 |
| 18 | Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene. Nature, 1996 | 1139 | 54.24 | 2001 |
| 19 | beta-Endorphin and adrenocorticotropin are selected concomitantly by the pituitary gland. Science, 1977 | 1101 | 27.53 | 1982 |
| 20 | A potent and selective endogenous agonist for the mu-opiate receptor. Nature, 1997 | 1082 | 54.1 | 1999 |
| 21 | Cloning of a delta opioid receptor by functional expression. Science, 1992 | 1028 | 41.12 | 1994 |
| 22 | P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. Journal of Clinical Investigation, 1996 | 1020 | 48.57 | 2004 |
| 23 | Opioids excite dopamine neurons by hyperpolarization of local interneurons. Journal of Neuroscience, 1992 | 1014 | 40.56 | 2011 |
| 24 | Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Research, 1979 | 1011 | 26.61 | 1986 |
| 25 | Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science, 1991 | 1006 | 37.26 | 1996 |
| 26 | Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology, 1997 | 989 | 49.45 | 2006 |
| 27 | Placebo and opioid analgesia--imaging a shared neuronal network. Science, 2002 | 969 | 64.6 | 2009 |
| 28 | Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science, 1999 | 960 | 53.33 | 2005 |
| 29 | Anatomy of CNS opioid receptors. Trends in Neurosciences, 1988 | 954 | 32.9 | 1994 |
| 30 | Opioid-receptor mRNA expression in the rat CNS: anatomical and functional implications. Trends in Neurosciences, 1995 | 936 | 42.55 | 1999;2000 |
| 31 | Endogenous opioids: biology and function. Annual Review of Neuroscience, 1984 | 916 | 27.76 | 1988 |
| 32 | Common precursor to corticotropins and endorphins. Proceedings of the National Academy of Sciences, 1977 | 913 | 20.83 | 1980 |
| 33 | Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls. Journal of Experimental Psychology: General, 1999 | 911 | 50.61 | 2016 |
| 34 | Dynorphin is a specific endogenous ligand of the kappa opioid receptor. Science, 1982 | 906 | 25.89 | 1983 |
| 35 | Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an 'atypical' opioid analgesic. Journal of Pharmacology and Experimental Therapeutics, 1992 | 898 | 35.92 | 2011 |
| 36 | ORL1, a novel member of the opioid receptor family: cloning, functional expression and localization. FEBS letters, 1994 | 897 | 39 | 2000 |
| 37 | Management of pain in elderly patients with cancer. Jama, 1998 | 896 | 47.16 | 2006 |
| 38 | Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychological Review, 1984 | 895 | 27.12 | 1989 |
| 39 | The delta-opioid receptor: isolation of a cDNA by expression cloning and pharmacological characterization. Proceedings of the National Academy of Sciences, 1992 | 881 | 35.24 | 1994 |
| 40 | Intrathecal and epidural administration of opioids. Anesthesiology, 1984 | 837 | 25.36 | 1989 |
| 41 | Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain, 1988 | 826 | 28.48 | 2003 |
| 42 | COMT val158met genotype affects µ-opioid neurotransmitter responses to a pain stressor. Science, 2003 | 820 | 58.57 | 2009 |
| 43 | Endogenous pain control mechanisms: review and hypothesis. Annals of Neurology, 1978 | 793 | 20.33 | 1984 |
| 44 | Molecular cloning and functional expression of a mu-opioid receptor from rat brain. Molecular Pharmacology, 1993 | 788 | 32.83 | 1996 |
| 45 | Morphine, gabapentin, or their combination for neuropathic pain. The New England Journal of Medicine, 2005 | 787 | 65.56 | 2011 |
| 46 | Single-nucleotide polymorphism in the human mu opioid receptor gene alters β-endorphin binding and activity: possible implications for opiate addiction. Proceedings of the National Academy of Sciences, 1998 | 783 | 41.21 | 2013 |
| 47 | Stereospecific binding of the potent narcotic analgesic [3H] etorphine to rat-brain homogenate. Proceedings of the National Academy of Sciences, 1973 | 770 | 17.5 | 1981 |
| 48 | Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors. Proceedings of the National Academy of Sciences, 1983 | 767 | 22.56 | 1991 |
| 49 | Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common µ1 opioid receptor mechanism. Science, 1997 | 757 | 37.85 | 2007 |
| 50 | Autoradiographic differentiation of mu, delta, and kappa opioid receptors in the rat forebrain and midbrain. Journal of Neuroscience, 1987 | 748 | 24.93 | 1994 |
| 51 | U-50,488: a selective and structurally novel non-Mu (kappa) opioid agonist. Journal of Pharmacology and Experimental Therapeutics, 1983 | 732 | 21.53 | 1991 |
| 52 | Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats. Journal of Pharmacology and Experimental Therapeutics, 1988 | 723 | 24.93 | 1997 |
| 53 | Dynorphin-(1-13), an extraordinarily potent opioid peptide. Proceedings of the National Academy of Sciences, 1979 | 722 | 19 | 1982 |
| 54 | Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms. Neuropsychopharmacology, 1999 | 721 | 40.06 | 2005 |
| 55 | Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain, 2004 | 719 | 55.31 | 2010 |
| 56 | Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proceedings of the National Academy of Sciences, 1992 | 713 | 28.52 | 2012 |
| 57 | Opiate analgesics inhibit substance P release from rat trigeminal nucleus. Nature, 1977 | 702 | 17.55 | 1984 |
| 58 | Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. Model Development. The Journal of the American Society of Anesthesiologists, 1997 | 699 | 34.95 | 2013;2014 |
| 59 | Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. Journal of Neuroscience Methods, 1996 | 698 | 33.24 | 2015 |
| 60 | The Severity of Dependence Scale (SDS): psychometric properties of the SDS in English and Australian samples of heroin, cocaine and amphetamine users. Addiction, 1995 | 696 | 31.64 | 2016 |
| 61 | Mechanisms of hyperalgesian and morphine tolerance: a current view of their possible interactions. Pain, 1995 | 694 | 31.55 | 2005 |
| 62 | The effects of psychosocial services in substance abuse treatment. Addictions Nursing Network, 1993 | 691 | 28.79 | 2004 |
| 63 | Morphine and alternative opioids in cancer pain: the EAPC recommendations. British Journal of Cancer, 2001 | 688 | 43 | 2011 |
| 64 | A medical treatment for diacetylmorphine (heroin) addiction: a clinical trial with methadone hydrochloride. Jama, 1965 | 679 | 13.06 | 1971 |
| 65 | Tolerance of locus coeruleus neurones to morphine and suppression of withdrawal response by clonidine. Nature, 1978 | 675 | 17.31 | 1996 |
| 66 | Immunohistochemical localization of enkephalin in rat brain and spinal cord. Journal of Comparative Neurology, 1978 | 673 | 17.26 | 1983 |
| 67 | Autoradiographic localization of opiate receptors in rat brain. Spinal cord and lower medulla. Brain Research, 1977 | 665 | 16.63 | 1982 |
| 68 | Opioid therapy for chronic pain. The New England Journal of Medicine, 2003 | 659 | 47.07 | 2010 |
| 69 | Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine. Brain Research, 1975 | 657 | 15.64 | 1977 |
| 70 | Opioid-induced hyperalgesia: a qualitative systematic review. The Journal of the American Society of Anesthesiologists, 2006 | 648 | 58.91 | 2012 |
| 71 | The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea‐pig ileum. British Journal of Pharmacology, 1957 | 632 | 10.53 | 1980 |
| 72 | Acute opioid tolerance intraoperative remifentanil increases postoperative pain and morphine requirement. The Journal of the American Society of Anesthesiologists, 2000 | 630 | 37.06 | 2015 |
| 73 | Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the" shell" as compared with the" core" of the rat nucleus accumbens. Proceedings of the National Academy of Sciences, 1995 | 624 | 28.36 | 1999 |
| 74 | A new method for receptor autoradiography: [3 H] opioid receptors in rat brain. Brain Research, 1979 | 620 | 16.32 | 1985 |
| 75 | Organization of endogenous opiate and nonopiate pain control systems. Science, 1982 | 609 | 17.4 | 1986 |
| 76 | Impulsivity as a vulnerability marker for substance-use disorders: review of findings from high-risk research, problem gamblers and genetic association studies. Neuroscience & Biobehavioral Reviews, 2008 | 608 | 67.56 | 2014 |
| 77 | Neurobiology of relapse to heroin and cocaine seeking: a review. Pharmacological Reviews, 2002 | 608 | 40.53 | 2005 |
| 78 | Opioid and nonopioid mechanisms of stress analgesia. Science, 1980 | 606 | 16.38 | 1983 |
| 79 | Cellular and synaptic adaptations mediating opioid dependence. Physiological Reviews, 2001 | 604 | 37.75 | 2006 |
| 80 | Crystal structure of the [micro]-opioid receptor bound to a morphinan antagonist. Nature, 2012 | 594 | 118.8 | 2013 |
| 81 | The enkephalinase inhibitor thiorphan shows antinociceptive activity in mice. Nature, 1980 | 594 | 16.05 | 1989 |
| 82 | Endorphins: profound behavioral effects in rats suggest new etiological factors in mental illness. Science, 1976 | 587 | 14.32 | 1979 |
| 83 | Halothane–morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery. The New England Journal of Medicine, 1992 | 584 | 26.55 | 2001 |
| 84 | Control CfD, Prevention: Vital signs: overdoses of prescription opioid pain relievers - United States, 1999 - 2008. MMWR Morbidity and Mortality Weekly Report, 2011 | 582 | 97 | 2016 |
| 85 | Immunohistochemical studies using antibodies to leucine-enkephalin: initial observations on the nervous system of the rat. Neuroscience, 1976 | 577 | 14.07 | 1980 |
| 86 | The neostriatal mosaic: compartmentalization of corticostriatal input and striatonigral output systems. Nature, 1984 | 571 | 17.3 | 1989 |
| 87 | Cloning and sequence analysis of cDNA for porcine β-neo-endorphin/dynorphin precursor. Nature, 1982 | 571 | 16.31 | 1986 |
| 88 | Classification of opioid receptors. 1983. | 570 | 16.76 | 1986 |
| 89 | Pain relief by intrathecally applied morphine in man. Survey of Anesthesiology, 1979 | 570 | 15 | 1982 |
| 90 | Addictive drugs and brain stimulation reward. Annual Review of Neuroscience, 1996 | 569 | 27.1 | 2005 |
| 91 | Self-administration of psychoactive substances by the monkey. Psychopharmacology, 1969 | 566 | 11.79 | 1976 |
| 92 | Efficacy of oxycodone in neuronathic pain: a randomized trial in postherpetic neuralgia. Neurology, 1998 | 565 | 29.74 | 2003 |
| 93 | Clinical pharmacology of tramadol. Clinical Pharmacokinetics, 2004 | 563 | 43.31 | 2016 |
| 94 | Multiple opiate receptors. Enkephalins and morphine bind to receptors of different specificity. Journal of Biological Chemistry, 1979 | 563 | 14.82 | 1982 |
| 95 | International Union of Pharmacology. XII. Classification of opioid receptors. Pharmacological Reviews, 1996 | 561 | 26.71 | 1999 |
| 96 | Cloning and functional comparison of kappa and delta opioid receptors from mouse brain. Proceedings of the National Academy of Sciences, 1993 | 561 | 23.38 | 1996 |
| 97 | Mu, delta, and kappa opioid receptor mRNA expression in the rat CNS: an in situ hybridization study. Journal of Comparative Neurology, 1994 | 557 | 24.22 | 1999 |
| 98 | Intrathecal morphine inhibits substance P release from mammalian spinal cord in vivo. Nature, 1980 | 551 | 14.89 | 1988 |
| 99 | Opioid complications and side effects. Pain Physician Journal, 2008 | 545 | 60.56 | 2016 |
| 100 | Neurobiological similarities in depression and drug dependence: a self-medication hypothesis. Neuropsychopharmacology, 1998 | 544 | 28.63 | 2002 |