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Medical Science Monitor : International... Jun 2017Over the course of human history, it has been common to use plants for medicinal purposes, such as for providing relief from particular maladies and self-medication.... (Review)
Review
Over the course of human history, it has been common to use plants for medicinal purposes, such as for providing relief from particular maladies and self-medication. Opium represents one longstanding remedy that has been used to address a range of medical conditions, alleviating discomfort often in ways that have proven pleasurable. Opium is a combination of compounds obtained from the mature fruit of opium poppy, papaver somniferum. Morphine and its biosynthetic precursors thebaine and codeine constitute the main bioactive opiate alkaloids contained in opium. Opium usage in ancient cultures is well documented, as is its major extract morphine. The presence of endogenous opiate alkaloids and opioid peptides in animals owe their discovery to their consistent actions at particular concentrations via stereo select receptors. In vitro expression of morphine within a microbiological industrial setting underscores the role it plays as a multi-purpose pharmacological agent, as well as reinforcing why it can also lead to long-term social dependence. Furthermore, it clearly establishes a reciprocal effect of human intelligence on modifying evolutionary processes in papaver somniferum and related plant species.
Topics: Administration, Oral; Analgesics; Analgesics, Opioid; Anesthetics; Culture; Humans; Infant
PubMed: 28609429
DOI: 10.12659/msm.905167 -
Neurologia (Barcelona, Spain) Apr 2015Morphine shares with other opiates and drugs of abuse the ability to modify the plasticity of brain areas that regulate the morphology of dendrites and spines, which are... (Review)
Review
INTRODUCTION
Morphine shares with other opiates and drugs of abuse the ability to modify the plasticity of brain areas that regulate the morphology of dendrites and spines, which are the primary sites of excitatory synapses in regions of the brain involved in incentive motivation, rewards, and learning.
OBJECTIVE
In this review we discuss the impact of morphine use during the prenatal period of brain development and its long-term consequences in murines, and then link those consequences to similar effects occurring in human neonates and adults.
DEVELOPMENT
Repeated exposure to morphine as treatment for pain in terminally ill patients produces long-term changes in the density of postsynaptic sites (dendrites and spines) in sensitive areas of the brain, such as the prefrontal cortex, the limbic system (hippocampus, amygdala), and caudate nuclei and nucleus accumbens. This article reviews the cellular mechanisms and receptors involved, primarily dopaminergic and glutamatergic receptors, as well as synaptic plasticity brought about by changes in dendritic spines in these areas.
CONCLUSIONS
The actions of morphine on both developing and adult brains produce alterations in the plasticity of excitatory postsynaptic sites of the brain areas involved in limbic system functions (reward and learning). Doctors need further studies on plasticity in dendrites and spines and on signaling molecules, such as calcium, in order to improve treatments for addiction.
Topics: Amygdala; Animals; Brain; Dendritic Spines; Hippocampus; Humans; Morphine; Neuronal Plasticity; Receptors, Opioid
PubMed: 25444409
DOI: 10.1016/j.nrl.2014.08.004 -
International Journal of Epidemiology Mar 2021Many diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and...
BACKGROUND
Many diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and cause-specific mortality.
METHODS
Golestan Cohort study is a prospective population-based study in Iran. A total of 50 045 people-aged 40-75, 28 811 women, 8487 opiate users, 3548 diabetic patients-were followed during a median of 11.1 years, with over 99% success follow-up. Hazard ratio and 95% confidence intervals (HRs, 95% CIs), and preventable death attributable to each risk factor, were calculated.
RESULTS
After 533 309 person-years, 7060 deaths occurred: 4178 (10.8%) of non-diabetic non-opiate users, 757 (25.3%) diabetic non-users, 1906 (24.0%) non-diabetic opiate users and 219 (39.8%) diabetic opiate users. Compared with non-diabetic non-users, HRs (95% CIs) for all-cause mortality were 2.17 (2.00-2.35) in diabetic non-opiate users, 1.63 (1.53-1.74) in non-diabetic opiate users and 2.76 (2.40-3.17) in diabetic opiate users. Among those who both had diabetes and used opiates, 63.8% (95% CI: 58.3%-68.5%) of all deaths were attributable to these risk factors, compared with 53.9% (95% CI: 50%-57.4%) in people who only had diabetes and 38.7% (95% CI: 34.6%-42.5%) in non-diabetic opiate users. Diabetes was more strongly associated with cardiovascular than cancer mortality. The risk of early mortality in known cases of diabetes did not depend on whether they started opiate use before or after their diagnosis.
CONCLUSIONS
Using opiates is detrimental to the health of diabetic patients. Public awareness about the health effects of opiates, and improvement of diabetes care especially among individuals with or at risk of opiate use, are necessary.
Topics: Analgesics, Opioid; Cause of Death; Cohort Studies; Diabetes Mellitus; Female; Humans; Iran; Opiate Alkaloids; Prospective Studies; Risk Factors
PubMed: 32810213
DOI: 10.1093/ije/dyaa126 -
Journal of the American College of... Jan 2020
Topics: Acute Coronary Syndrome; Clopidogrel; Coronary Angiography; Humans; Morphine; Opiate Alkaloids; Prasugrel Hydrochloride
PubMed: 31976868
DOI: 10.1016/j.jacc.2019.11.023 -
Progress in Neuro-psychopharmacology &... Dec 2021The deleterious effects of the drug addiction epidemic are compounded by treatment strategies that are only marginally efficacious. Memantine is a unique glutamatergic... (Review)
Review
The deleterious effects of the drug addiction epidemic are compounded by treatment strategies that are only marginally efficacious. Memantine is a unique glutamatergic medication with proven ability to attenuate drug addiction in preclinical models. However, clinical translational studies are inconsistent. In this review, we summarize preclinical evidences and clinical trials that investigated the efficacy of memantine in treating patients with alcohol, opiate, cocaine, and nicotine use disorders and discuss the results from a mechanistic point of view. Memantine has shown efficacy in reducing alcohol and opiate craving, consumption, and withdrawal severity. However, in cocaine and nicotine use disorders, memantine did not have significant effect on cravings or consumption. Additionally, memantine was associated with increased subjective effects of alcohol, cocaine, and nicotine. We discuss possible mechanisms behind this variability. Since memantine transiently blocks NMDA receptors and protects neurons from overstimulation by excessive synaptic glutamate, its efficacy should be observed in drug phases that cause hyperglutamatergic states, while hypoglutamatergic drug use states would not resolve with blocking NMDA receptors. Second, memantine pharmacokinetic studies have been done in rodents and healthy volunteers, but not in patients with substance use disorder. Memantine, opiates, cocaine, and nicotine share the same transporter family at the blood brain barrier. This shared transport mechanism could impact brain concentrations of memantine and its effects. In conclusion, memantine remains an intriguing compound in our pharmacopeia with controversial results in treating certain aspects of drug addiction. Further studies are needed to understand the clinical and biological correlates of its efficacy.
Topics: Animals; Brain; Cocaine; Ethanol; Excitatory Amino Acid Antagonists; Glutamic Acid; Humans; Memantine; Neurons; Opiate Alkaloids; Receptors, N-Methyl-D-Aspartate; Substance-Related Disorders
PubMed: 34324921
DOI: 10.1016/j.pnpbp.2021.110409 -
American Journal of Nephrology 2016More than 50% of American adolescents and adults report having used illicit drugs in their lifetime. We examined the association of lifetime opiate and cocaine use with...
BACKGROUND
More than 50% of American adolescents and adults report having used illicit drugs in their lifetime. We examined the association of lifetime opiate and cocaine use with reduced kidney function, albuminuria and rapid kidney function decline among urban-dwelling adults.
METHODS
Our prospective cohort included 2,286 Healthy Aging in Neighborhoods of Diversity across the Life Span study participants who were community-dwelling adults residing in Baltimore, MD. The predictive variables were lifetime opiate and cocaine use, defined as use of opiates or crack/cocaine ≥5 times. Outcomes included prevalent reduced estimated glomerular filtration rate (eGFR; <60 ml/min/1.73 m2 by Chronic Kidney Disease (CKD)-Epidemiology Collaboration), albuminuria (albumin-to-creatinine ratio >30 mg/g, n = 1,652) and rapid kidney function decline (>3 ml/min/1.73 m2 per year over a median of 4.7 years, n = 1,660).
RESULTS
Participants' mean age was 48 years, 15% reported opiate use, and 22% reported cocaine use. A total of 115 (5.0%) participants had reduced eGFR, 190 (11.5%) had albuminuria and 230 (13.8%) experienced rapid decline in kidney function. In adjusted logistic regression analyses, both substances were associated with greater odds of reduced eGFR (OR 2.71, 95% CI 1.50-4.89 for opiates; OR 1.40, 95% CI 0.87-2.24 for cocaine). Both substances were associated with greater odds of albuminuria (OR 1.20, 95% CI 0.83-1.73 for opiates; OR 1.80, 95% CI 1.29-2.51 for cocaine). Neither substance was associated with the rapid decline of kidney function.
CONCLUSIONS
Lifetime opiate and cocaine use was associated with prevalent reduced eGFR and albuminuria, yet not with rapid kidney function decline. The use of opiate and cocaine may be an important risk factor for CKD in urban populations.
Topics: Adult; Albuminuria; Cocaine; Cohort Studies; Female; Glomerular Filtration Rate; Humans; Illicit Drugs; Kidney; Male; Middle Aged; Opiate Alkaloids; Renal Insufficiency, Chronic; Risk Factors
PubMed: 27788520
DOI: 10.1159/000452348 -
The Cochrane Database of Systematic... Jun 2015The review represents one in a family of four reviews focusing on a range of different interventions for drug-using offenders. This specific review considers... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The review represents one in a family of four reviews focusing on a range of different interventions for drug-using offenders. This specific review considers pharmacological interventions aimed at reducing drug use or criminal activity, or both, for illicit drug-using offenders.
OBJECTIVES
To assess the effectiveness of pharmacological interventions for drug-using offenders in reducing criminal activity or drug use, or both.
SEARCH METHODS
We searched Fourteen electronic bibliographic databases up to May 2014 and five additional Web resources (between 2004 and November 2011). We contacted experts in the field for further information.
SELECTION CRITERIA
We included randomised controlled trials assessing the efficacy of any pharmacological intervention a component of which is designed to reduce, eliminate or prevent relapse of drug use or criminal activity, or both, in drug-using offenders. We also report data on the cost and cost-effectiveness of interventions.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by Cochrane.
MAIN RESULTS
Fourteen trials with 2647 participants met the inclusion criteria. The interventions included in this review report on agonistic pharmacological interventions (buprenorphine, methadone and naltrexone) compared to no intervention, other non-pharmacological treatments (e.g. counselling) and other pharmacological drugs. The methodological trial quality was poorly described, and most studies were rated as 'unclear' by the reviewers. The biggest threats to risk of bias were generated through blinding (performance and detection bias) and incomplete outcome data (attrition bias). Studies could not be combined all together because the comparisons were too different. Only subgroup analysis for type of pharmacological treatment were done. When compared to non-pharmacological, we found low quality evidence that agonist treatments are not effective in reducing drug use or criminal activity, objective results (biological) (two studies, 237 participants (RR 0.72 (95% CI 0.51 to 1.00); subjective (self-report), (three studies, 317 participants (RR 0.61 95% CI 0.31 to 1.18); self-report drug use (three studies, 510 participants (SMD: -0.62 (95% CI -0.85 to -0.39). We found low quality of evidence that antagonist treatment was not effective in reducing drug use (one study, 63 participants (RR 0.69, 95% CI 0.28 to 1.70) but we found moderate quality of evidence that they significantly reduced criminal activity (two studies, 114 participants, (RR 0.40, 95% CI 0.21 to 0.74).Findings on the effects of individual pharmacological interventions on drug use and criminal activity showed mixed results. In the comparison of methadone to buprenorphine, diamorphine and naltrexone, no significant differences were displayed for either treatment for self report dichotomous drug use (two studies, 370 participants (RR 1.04, 95% CI 0.69 to 1.55), continuous measures of drug use (one study, 81 participants, (mean difference (MD) 0.70, 95% CI -5.33 to 6.73); or criminal activity (one study, 116 participants, (RR 1.25, 95% CI 0.83 to 1.88) between methadone and buprenorphine. Similar results were found for comparisons with diamorphine with no significant differences between the drugs for self report dichotomous drug use for arrest (one study, 825 participants, (RR 1.25, 95% CI 1.03 to 1.51) or naltrexone for dichotomous measures of reincarceration (one study, 44 participants, (RR 1.10, 95% CI 0.37 to 3.26), and continuous outcome measure of crime, (MD -0.50, 95% CI -8.04 to 7.04) or self report drug use (MD 4.60, 95% CI -3.54 to 12.74).
AUTHORS' CONCLUSIONS
When compared to non-pharmacological treatment, agonist treatments did not seem effective in reducing drug use or criminal activity. Antagonist treatments were not effective in reducing drug use but significantly reduced criminal activity. When comparing the drugs to one another we found no significant differences between the drug comparisons (methadone versus buprenorphine, diamorphine and naltrexone) on any of the outcome measures. Caution should be taken when interpreting these findings, as the conclusions are based on a small number of trials, and generalisation of these study findings should be limited mainly to male adult offenders. Additionally, many studies were rated at high risk of bias.
Topics: Adult; Buprenorphine; Crime; Criminals; Female; Heroin; Humans; Male; Methadone; Naltrexone; Narcotics; Opiate Substitution Treatment; Randomized Controlled Trials as Topic; Substance-Related Disorders
PubMed: 26035084
DOI: 10.1002/14651858.CD010862.pub2 -
Neuroscience and Biobehavioral Reviews Feb 2021Since the discovery of pain relieving and rewarding properties of opiates such as morphine or heroin, the human mu-opioid system has been a target for medical research... (Review)
Review
Since the discovery of pain relieving and rewarding properties of opiates such as morphine or heroin, the human mu-opioid system has been a target for medical research on pain processing and addiction. Indeed, pain and pleasure act mutually inhibitory on each other and the mu-opioid system has been suggested as an underlying common neurobiological mechanism. Recently, research interest extended the role of the endogenous mu-opioid system beyond the hedonic value of pain and pleasure towards human social-emotional behavior. Here we propose a mu-opioid feedback model of social behavior. This model is based upon recent findings of opioid modulation of human social learning, bonding and empathy in relation to affiliative and protective tendencies. Fundamental to the model is that the mu-opioid system reinforces socially affiliative or protective behavior in response to positive and negative social experiences with long-term consequences for social behavior and health. The functional implications for stress, anxiety, depression and attachment behaviors are discussed.
Topics: Analgesics, Opioid; Feedback; Humans; Morphine; Receptors, Opioid, mu; Social Behavior
PubMed: 33359094
DOI: 10.1016/j.neubiorev.2020.12.013 -
Molecules and Cells Sep 2016Morphine is the most potent analgesic for chronic pain, but its clinical use has been limited by the opiate's innate tendency to produce tolerance, severe withdrawal... (Review)
Review
Morphine is the most potent analgesic for chronic pain, but its clinical use has been limited by the opiate's innate tendency to produce tolerance, severe withdrawal symptoms and rewarding properties with a high risk of relapse. To understand the addictive properties of morphine, past studies have focused on relevant molecular and cellular changes in the brain, highlighting the functional roles of reward-related brain regions. Given the accumulated findings, a recent, emerging trend in morphine research is that of examining the dynamics of neuronal interactions in brain reward circuits under the influence of morphine action. In this review, we highlight recent findings on the roles of several reward circuits involved in morphine addiction based on pharmacological, molecular and physiological evidences.
Topics: Animals; Brain; Humans; Morphine; Morphine Dependence; Neural Pathways; Substance Withdrawal Syndrome
PubMed: 27506251
DOI: 10.14348/molcells.2016.0137 -
The British Journal of General Practice... Apr 2017More than 200 opiate overdose deaths occur annually in Ireland. Overdose prevention and management, including naloxone prescription, should be a priority for healthcare...
BACKGROUND
More than 200 opiate overdose deaths occur annually in Ireland. Overdose prevention and management, including naloxone prescription, should be a priority for healthcare services. Naloxone is an effective overdose treatment and is now being considered for wider lay use.
AIM
To establish GPs' views and experiences of opiate addiction, overdose care, and naloxone provision.
DESIGN AND SETTING
An anonymous postal survey to GPs affiliated with the Department of Academic General Practice, University College Dublin, Ireland.
METHOD
A total of 714 GPs were invited to complete an anonymous postal survey. Results were compared with a parallel GP trainee survey.
RESULTS
A total of 448/714 (62.7%) GPs responded. Approximately one-third of GPs were based in urban, rural, and mixed areas. Over 75% of GPs who responded had patients who used illicit opiates, and 25% prescribed methadone. Two-thirds of GPs were in favour of increased naloxone availability in the community; almost one-third would take part in such a scheme. A higher proportion of GP trainees had used naloxone to treat opiate overdose than qualified GPs. In addition, a higher proportion of GP trainees were willing to be involved in naloxone distribution than qualified GPs. Intranasal naloxone was much preferred to single (<0.001) or multiple dose (<0.001) intramuscular naloxone. Few GPs objected to wider naloxone availability, with 66.1% ( = 292) being in favour.
CONCLUSION
GPs report extensive contact with people who have opiate use disorders but provide limited opiate agonist treatment. They support wider availability of naloxone and would participate in its expansion. Development and evaluation of an implementation strategy to support GP-based distribution is urgently needed.
Topics: Drug Overdose; Education, Medical, Graduate; General Practice; Health Knowledge, Attitudes, Practice; Humans; Ireland; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Practice Patterns, Physicians'; Preventive Health Services; Program Development; Program Evaluation
PubMed: 28246098
DOI: 10.3399/bjgp17X689857