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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 -
Pain Management May 2018To provide an update on prescription of naloxone as a harm-reduction strategy, PubMed was searched to identify publications relevant to naloxone prescribing for reversal... (Review)
Review
To provide an update on prescription of naloxone as a harm-reduction strategy, PubMed was searched to identify publications relevant to naloxone prescribing for reversal of opioid overdose. Opportunities now exist to expand naloxone use, although evidence suggests these are often missed or underexploited. The US FDA has approved an intranasal naloxone spray and an autoinjector naloxone formulation for community use. Effective use of naloxone in community settings requires screening to identify patients at risk of opioid overdose, discussing naloxone use with patients and their relatives, and providing appropriate training. The tools exist to expand the use of naloxone more widely into the community, thereby creating an opportunity to reduce opioid overdose fatalities.
Topics: Administration, Intranasal; Analgesics, Opioid; Drug Overdose; Drug Prescriptions; Humans; Naloxone; Opiate Alkaloids
PubMed: 29667859
DOI: 10.2217/pmt-2017-0065 -
AANA Journal Jun 2022With the current opiate epidemic in the United States, there is renewed interest in evaluating non-opiate adjuvant medications as effective alternatives for the...
With the current opiate epidemic in the United States, there is renewed interest in evaluating non-opiate adjuvant medications as effective alternatives for the prevention and treatment of postoperative pain. A systematic review of randomized, controlled trials on Pub Med, Medline, and Embase was conducted looking on postoperative pain management from 2008 to 2018. Studies were included if they used a gabapentenoid with or without acetaminophen and evaluated supplemental opiate use. All adult (18 years or older) surgical populations were considered for inclusion, and fourteen clinical trials met inclusion criteria. Gabapentenoid dosing varied among studies. In nine of fourteen studies, there was a finding of superiority as compared to placebo in managing postoperative pain and decreasing supplemental opiate use. Pregabalin was used in twelve of the fourteen studies and gabapentin was used in two of the fourteen studies. Of the nine studies that found a benefit from using a gabapentoid, all included pregabalin. While the rate of adverse effects was low in all studies, it was found to increase as dosages increased. Results support that pregabalin has a role in decreasing postoperative pain intensity and supplemental opiate use; however, the optimal dose or dosing regimen is not yet well understood.
Topics: Acetaminophen; Adult; Analgesics; Analgesics, Opioid; Cyclohexanecarboxylic Acids; Humans; Opiate Alkaloids; Pain, Postoperative; Pregabalin; gamma-Aminobutyric Acid
PubMed: 35604860
DOI: No ID Found -
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 -
Neuroscience and Biobehavioral Reviews Dec 2016Opiate use is associated with deficits in decision-making. However, the impact of abstinence and co-morbid factors, like head injury and poly-substance abuse, on this... (Meta-Analysis)
Meta-Analysis Review
Opiate use is associated with deficits in decision-making. However, the impact of abstinence and co-morbid factors, like head injury and poly-substance abuse, on this ability, is currently unclear. This meta-analysis aimed to assess 1) the magnitude of decision-making deficits in opiate users; 2) whether co-morbid factors moderate the severity of these deficits; 3) whether ex-opiate users demonstrate smaller decision-making deficits than current users; and 4) whether the length of abstinence is related to the magnitude of decision-making deficits. We analysed 22 studies that compared the performance of current and ex-opiate users to healthy controls on decision-making measures such as the Iowa Gambling Task. Current users demonstrated a moderately strong impairment in decision-making relative to controls, which was not significantly moderated by co-morbid factors. The magnitude of the impairment did not significantly differ between studies assessing current or ex-users, and this impairment was not related to length of abstinence. Thus, it appears that opiate users have relatively severe decision-making deficits that persist at least 1.5 years after cessation of use.
Topics: Decision Making; Gambling; Humans; Neuropsychological Tests; Opiate Alkaloids; Substance-Related Disorders
PubMed: 27649645
DOI: 10.1016/j.neubiorev.2016.09.011 -
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 -
Sleep Sep 2023Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found...
Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found that chronic opiate usage in humans and long-term opiate administration to mice significantly increased the number of detected hypocretin/orexin (Hcrt) neurons, decreased their size, and increased Hcrt level in the hypothalamus. We also found that opiates significantly decreased cataplexy in human narcoleptics as well as in narcoleptic mice and that cessation of locus coeruleus neuronal activity preceded and was tightly linked to cataplectic attacks in narcoleptic dogs. We tested the hypothesis that SXB produces changes similar to opiates and now report that chronic SXB administration significantly increased the size of Hcrt neurons, the reverse of what we had seen with opiates in humans and mice. Levels of Hcrt in the hypothalamus were nonsignificantly lower, in contrast to the significant increase in hypothalamic Hcrt level after opiates. SXB decreased tyrosine hydroxylase levels in the locus coeruleus, the major descending projection of the hypocretin system, also the reverse of what we saw with opioids. Therefore despite some similar effects on narcoleptic symptomatology, SXB does not produce anatomical changes similar to those elicited by opiates. Analysis of changes in other links in the cataplexy pathway might further illuminate SXB's mechanism of action on narcolepsy.
Topics: Humans; Mice; Animals; Dogs; Orexins; Sodium Oxybate; Cataplexy; Locus Coeruleus; Narcolepsy; Neurons; Opiate Alkaloids
PubMed: 37155728
DOI: 10.1093/sleep/zsad135 -
Accident; Analysis and Prevention Feb 2021Pharmacological differences among different drug classes influence human cognition, visual, and motor behavior in different ways. These differences impact driving...
BACKGROUND AND AIMS
Pharmacological differences among different drug classes influence human cognition, visual, and motor behavior in different ways. These differences impact driving safety, and therefore individuals who use stimulant and opioid drugs might experience different patterns in driving safety and impairment in driving performance. This study examined the effect of long-term use of stimulant drugs and of opiate drugs on driving performance, hazard perception, visual search skills and psychomotor skills related to driving.
METHODS
A total of 75 individuals, including 28 predominantly stimulant users, 22 predominantly opiate users and 25 healthy non-drug users, participated. Driving performance and psychomotor skills were assessed via a 15-minute drive in a simulator; hazard perception was assessed via a computerized task; and visual search skill was assessed by eye tracking.
RESULTS
ANOVA analyses indicate both stimulant and opiate users drove at higher speeds and experienced more crashes than the healthy non-drug users. Stimulant but not opiate users violated red light regulations more often than the healthy non-drug users. In the hazard perception task, stimulant drug users performed more poorly than both opioid drug users and healthy non-drug users. Specifically, they had lower saccade movement scores and higher average fixation times.
CONCLUSIONS
Results confirm that both stimulant drug users and opiate drug users show impaired driving performance compared to healthy non-drug users. Stimulant drug users possessed poorer hazard perception skills compared to the opiate users and the control group, perhaps as a result of cognitive deficits created by the drug use.
Topics: Accidents, Traffic; Analgesics, Opioid; Automobile Driving; Cognition; Humans; Opiate Alkaloids; Pharmaceutical Preparations; Psychomotor Performance
PubMed: 33271373
DOI: 10.1016/j.aap.2020.105885 -
Journal of Veterinary Pharmacology and... Jul 2022Opiates have a long history of medical use as effective analgesics associated with well-described side effects, including euphoria, respiratory depression, constipation,... (Review)
Review
Opiates have a long history of medical use as effective analgesics associated with well-described side effects, including euphoria, respiratory depression, constipation, bradycardia, and histamine release, among others. The search for opiate analogs that retain effective analgesic qualities without detrimental side effects has yielded numerous compounds, including buprenorphine. Early studies of buprenorphine demonstrated analgesic effectiveness with a favorable safety profile, leading to the approval of formulations for use in humans. Since then, advances in receptor theory and molecular cloning of opioid receptors have led to a deeper understanding of buprenorphine pharmacology. More recent studies of receptor affinity and intrinsic activity have shown that buprenorphine is a μ- and κ-opioid receptor agonist, a nociceptin orphanin peptide agonist, and a δ-opioid receptor antagonist. Buprenorphine appears to have a primary spinal analgesic mechanism with complex supraspinal actions. It is considered a full agonist for pain but a partial agonist for other clinical endpoints such as respiratory depression. In feline medicine, buprenorphine is approved as low- and high-concentration injectable solutions, in addition to the most recently introduced long-acting transdermal formulation. Several investigational and compounded formulations have also been evaluated. There are contrasting differentiable features that include pharmacokinetics, onsets- and durations-of-action, routes of administration, and formulation constituents. Available buprenorphine formulations allow clinicians to select a formulation based on the anticipated duration of pain associated with various surgical procedures, and to provide interventions as needed. In light of the newly approved transdermal buprenorphine solution in cats and progress in buprenorphine pharmacology, the objective of this review is to examine the history and pharmacology of buprenorphine relative to full opioid agonists, where appropriate, integrating these insights into advances within feline medicine.
Topics: Analgesics; Analgesics, Opioid; Animals; Buprenorphine; Cat Diseases; Cats; Pain; Respiratory Insufficiency
PubMed: 35790013
DOI: 10.1111/jvp.13073