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ACS Chemical Neuroscience Sep 2017Opioids are among the most effective pain relievers; however, their abuse has been on the rise worldwide evident from an alarming increase in accidental opioid... (Review)
Review
Opioids are among the most effective pain relievers; however, their abuse has been on the rise worldwide evident from an alarming increase in accidental opioid overdoses. This demands for an urgent increase in scientific endeavors for better understanding of main cellular mechanisms and circuits involved in opiate addiction. Preclinical studies strongly suggest that memories associated with positive and negative opioid experiences are critical in promoting compulsive opiate-seeking and opiate-taking behaviors, and relapse. Particular focus on synaptic plasticity as the cellular correlate of learning and memory has rapidly evolved in drug addiction field over the past two decades. Several critical addiction-related brain areas are identified, one of which is the ventral tegmental area (VTA), an area intensively studied as the initial locus for drug reward. Here, we provide an update to our previous review on "Opiates and Plasticity" highlighting the most recent discoveries of synaptic plasticity associated with opiates in the VTA. Electrophysiological studies of plasticity of addiction to date have been invaluable in addressing learning processes and mechanisms that underlie motivated and addictive behaviors, and now with the availability of powerful technologies of transgenic approaches and optogenetics, circuit-based studies hold high promise in fostering synaptic studies of opiate addiction.
Topics: Analgesics, Opioid; Animals; Epigenesis, Genetic; Humans; Neuronal Plasticity; Opiate Alkaloids; Opioid-Related Disorders; Synapses; Ventral Tegmental Area
PubMed: 28768409
DOI: 10.1021/acschemneuro.7b00281 -
International Journal of Environmental... Jan 2023The aim of the current study was to examine the effects of length of abstinence on decision making (impulsive choice) and response inhibition (impulsive action) in...
The aim of the current study was to examine the effects of length of abstinence on decision making (impulsive choice) and response inhibition (impulsive action) in former opiate users (OU). Participants included 45 OU in early remission [0−12 months of abstinence], 68 OU in sustained remission [>12 months of abstinence], and 68 control participants. Decision making was assessed with the Iowa Gambling Task (IGT), the Cambridge Gambling Task (CGT), and the Monetary Choice Questionnaire (MCQ). Response inhibition was examined with the Stop Signal Task (SST), and the Go/No-Go Task (GNG). Results revealed group differences in decision making under risk (CGT) and ambiguity (IGT), where control participants displayed better decision making compared to OU in early remission. Both groups of former OU were also characterized by higher discounting of delayed rewards (MCQ). Regression analyses revealed minimal effects of length of abstinence on performance on decision-making tasks and no effects on delay discounting. In addition, both OU groups showed reduced action inhibition (GNG) relative to controls and there were no group differences in action cancellation (SST). Length of abstinence had no effect on response inhibition. Overall, our findings suggest that neurocognitive function may not fully recover even with protracted abstinence, which should be addressed by relapse prevention and cognitive remediation programs for OU.
Topics: Humans; Decision Making; Opiate Alkaloids; Impulsive Behavior; Gambling; Reward
PubMed: 36674000
DOI: 10.3390/ijerph20021236 -
Behavioural Brain Research Feb 2023Gender differences have been observed in the vulnerability to drug abuse and in the different stages of the addictive process. In opiate dependence, differences between...
Gender differences have been observed in the vulnerability to drug abuse and in the different stages of the addictive process. In opiate dependence, differences between sexes have been shown in humans and laboratory animals in various phases of opiate addiction, especially in withdrawal-associated negative affective states. Using a Y-maze conditioned place aversion paradigm, we investigated potential sex differences in the expression and extinction of the aversive memory of precipitated opiate withdrawal state in morphine-dependent rats. No significant difference between sexes was observed in the occurrence of withdrawal signs following naloxone injection during conditioning. Moreover, opiate withdrawal memory expression and extinction following repeated testing was demonstrated in both male and female rats, with no significant differences between sexes. Finally, we report spontaneous recovery following extinction of opiate withdrawal memory. Altogether these data provide further evidence that persistent withdrawal-related memories may be strong drivers of opiate dependence, and demonstrate that both males and females can be used in experimental rodent cohorts to better understand opiate-related effects, reward, aversive state of withdrawal, abstinence and relapse.
Topics: Humans; Rats; Animals; Female; Male; Opiate Alkaloids; Substance Withdrawal Syndrome; Avoidance Learning; Naloxone; Analgesics, Opioid; Morphine Dependence; Opioid-Related Disorders; Morphine; Narcotic Antagonists
PubMed: 36174840
DOI: 10.1016/j.bbr.2022.114122 -
Journal of Psychopharmacology (Oxford,... Sep 2022The benzodiazepine drug alprazolam, a fast-acting tranquiliser, cannot be prescribed on the National Health Service in the United Kingdom. Illicit alprazolam supply and...
BACKGROUND
The benzodiazepine drug alprazolam, a fast-acting tranquiliser, cannot be prescribed on the National Health Service in the United Kingdom. Illicit alprazolam supply and consumption have increased. Concern about increasing numbers of alprazolam-related fatalities started circulating in 2018. However, statistics on this issue are very limited. This study examined patterns in such mortality in Scotland.
METHODS
Statistics on deaths where alprazolam was mentioned in the 'cause of death' were obtained from official mortality registers. Anonymised Scottish case-level data were obtained. Data were examined in respect of the characteristics of decedents and deaths using descriptive statistics.
RESULTS
Scotland registered 370 deaths in 2004-2020; 366 of these occurred in 2015-2020: most involved males (77.1%); mean age 39.0 (SD 12.6) years. The principal underlying cause of death was accidental poisoning: opiates/opioids (77.9%); sedatives/hypnotics (15.0%). Two deaths involved alprazolam alone. Main drug groups implicated: opiates/opioids (94.8%), 'other benzodiazepines' (67.2%), gabapentinoids (42.9%), stimulants (30.1%), antidepressants (15.0%). Two-thirds (64.2%) involved combinations of central nervous system (CNS) depressants.
DISCUSSION
Alprazolam-related deaths are likely due to an increasing illicit supply. The fall in deaths in 2019-2020 is partially due to increased use of designer benzodiazepines. Treatment for alprazolam dependence is growing. Clinicians need to be aware of continuing recreational alprazolam use. When such consumption occurs with CNS depressants, overdose and death risks increase.
CONCLUSIONS
More awareness of alprazolam contributing to deaths, especially in conjunction with other CNS depressants, is needed by consumers and clinicians. Improved monitoring of illicit supplies could identify emerging issues of medicines' abuse.
Topics: Adult; Alprazolam; Analgesics, Opioid; Benzodiazepines; Central Nervous System Depressants; Humans; Hypnotics and Sedatives; Male; Opiate Alkaloids; Scotland; State Medicine
PubMed: 35912873
DOI: 10.1177/02698811221104065 -
Journal of Addictive Diseases Oct 2010Urine toxicology screening testing is an important standard of care in the addiction and pain treatment setting, offering a reproducible, unbiased, and accurate... (Review)
Review
Urine toxicology screening testing is an important standard of care in the addiction and pain treatment setting, offering a reproducible, unbiased, and accurate laboratory test to monitor patients and provide objective support for clinical observations. It has been shown that physicians do not have proficiency in the ordering or interpretation of these tests. This article is an attempt to respond to that need. Current antibody-based enzymatic immunoassays (EIAs) used for urine toxicology screening are useful to detect classes of drugs (ex., opiate) but cannot determine which specific drug (ex., morphine) is present. Gas chromatography and mass spectroscopy can determine exactly which drugs are present, allowing prescribed (or illicit) opiates and benzodiazepines to be identified. This article will discuss principles and details of opiate and benzodiazepine EIA and gas chromatography and mass spectroscopy urine toxicology testing. The approach to detecting patients attributing positive opiate EIAs to prescription opiates who are using heroin or other opioids will be reviewed. Cases of controlled prescription drugs that do not produce the expected positive urine tests (ex., oxycodone producing negative opiate screening tests) will be discussed. How to differentiate codeine from heroin and the role of poppy seeds in toxicology will be examined. The case of an anti-depressant drug that produces false-positive benzodiazepine results and antibiotics that cause positive opiate urine toxicology results will be reviewed. Common benzodiazepines (ex., clonazepam and lorazepam) that do not reliably produce positive benzodiazepine EIAs will be discussed. The approach to detection and management of all these types of toxicology cases will be reviewed, and it is hoped that the analyses presented will impart an adequate information base to medical providers and staff members of drug treatment and pain centers, enabling them to order and interpret these tests in the clinic more effectively as an integrated part of whole patient care.
Topics: Benzodiazepines; False Positive Reactions; Gas Chromatography-Mass Spectrometry; Humans; Immunoenzyme Techniques; Opiate Alkaloids; Substance Abuse Detection
PubMed: 20924879
DOI: 10.1080/10550887.2010.509277 -
European Journal of Preventive... Mar 2021Tens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of...
AIMS
Tens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors.
METHODS AND RESULTS
In the population-based Golestan Cohort Study-50 045 Iranian participants, 40-75 years, 58% women-we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders-i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4-20) years. During 548 940 person-years-median of 11.3 years, >99% success follow-up-3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49-1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors.
CONCLUSION
Long-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended.
Topics: Cardiovascular Diseases; Cohort Studies; Female; Humans; Iran; Male; Mortality; Opiate Alkaloids; Risk Factors
PubMed: 33624066
DOI: 10.1093/eurjpc/zwaa006 -
BMJ Case Reports Mar 2021
Topics: Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Opiate Alkaloids
PubMed: 33737284
DOI: 10.1136/bcr-2021-242762 -
The Urologic Clinics of North America Feb 2014A large number of environmental and lifestyle factors may negatively affect spermatogenesis and male fertility. This article enumerates the current state of knowledge... (Review)
Review
A large number of environmental and lifestyle factors may negatively affect spermatogenesis and male fertility. This article enumerates the current state of knowledge regarding those that have been identified, and extrapolates the predicted magnitude of these effects over the next 20 years based on current societal trends. However, it is likely that additional factors have yet to be recognized. Additional research is needed to further define and clarify environmental factors that affect male fertility in order to mitigate their effects.
Topics: Alcoholism; Anabolic Agents; Cell Phone; Conservation of Natural Resources; Diet; Environment; Exercise; Fertility; Hot Temperature; Humans; Life Style; Male; Marijuana Smoking; Obesity; Opiate Alkaloids; Risk Factors; Smoking; Stress, Psychological
PubMed: 24286767
DOI: 10.1016/j.ucl.2013.08.017 -
Brain Injury Jun 2020To assess the validity of the Westmead PTA scale in school-aged children treated with opiate analgesics.
OBJECTIVE
To assess the validity of the Westmead PTA scale in school-aged children treated with opiate analgesics.
METHOD
Twenty-eight hospitalized children without brain injury, aged between 8 and 16 years treated with opiate analgesics for pain relief following surgery were tested on the Westmead PTA scale. Pain and stress levels were also self-reported each day.
RESULTS
Only 29% (n = 7) of children assessed over four days obtained a maximum score of 12/12 on three consecutive days, thus 71% would have been deemed to have been in PTA when they were not. The percentage of children who obtained a maximum score significantly decreased over consecutive days of assessment, due to an increase in error rate on picture memory items. Self-reported pain and stress ratings were not correlated with PTA scores.
CONCLUSIONS
Opiate analgesia can disrupt performance on the Westmead PTA scale in school-aged children resulting in a high false-positive error rate. It is therefore important to record pain medication schedules and interpret results cautiously when opiate analgesia is used following a TBI. Alteration of the method of administration of the memory items should be researched as this may increase the validity of the scale for children with TBI treated with opiate analgesics.
Topics: Adolescent; Amnesia; Amnesia, Retrograde; Analgesics, Opioid; Child; Humans; Opiate Alkaloids; Schools
PubMed: 32497441
DOI: 10.1080/02699052.2020.1763460 -
Neuron Sep 2020Opioids are commonly used as analgesics for severe pain, but their addictive potential has sparked a misuse epidemic. In this issue of Neuron, Keyes et al. (2020)...
Opioids are commonly used as analgesics for severe pain, but their addictive potential has sparked a misuse epidemic. In this issue of Neuron, Keyes et al. (2020) examine the contributions of distinct paraventricular thalamus (PVT) outputs to contextual opioid memories. They identify a PVT→NAc→LH circuit essential for recall of opioid experiences.
Topics: Analgesics, Opioid; Neural Pathways; Neurons; Opiate Alkaloids; Thalamus
PubMed: 32971000
DOI: 10.1016/j.neuron.2020.09.006