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JMIR Public Health and Surveillance Dec 2021Opioid use disorder and its consequences are a persistent public health concern for Australians. Web activity has been used to understand the perception of drug safety...
BACKGROUND
Opioid use disorder and its consequences are a persistent public health concern for Australians. Web activity has been used to understand the perception of drug safety and diversion of drugs in contexts outside of Australia. The anonymity of the internet offers several advantages for surveilling and inquiring about specific covert behaviors, such as diversion or discussion of sensitive subjects where traditional surveillance approaches might be limited.
OBJECTIVE
This study aims to characterize the content of web posts and compare reports of illicit sales of tapentadol and oxycodone from sources originating in Australia. First, post content is evaluated to determine whether internet discussion encourages or discourages proper therapeutic use of the drugs. Second, we hypothesize that tapentadol would have lower street price and fewer illicit sales than oxycodone.
METHODS
Web posts originating in Australia between 2017 and 2019 were collected using the Researched Abuse, Diversion, and Addiction-Related Surveillance System Web Monitoring Program. Using a manual coding process, unstructured post content from social media, blogs, and forums was categorized into topics of discussion related to the harms and behaviors that could lead to harm. Illicit sales data in a structured format were collected through a crowdsourcing website between 2016 and 2019 using the Researched Abuse, Diversion, and Addiction-Related Surveillance System StreetRx Program. In total, 2 multivariable regression models assessed the differences in illicit price and number of sales.
RESULTS
A total of 4.7% (28/600) of tapentadol posts discussed an adverse event, whereas 10.27% (95% CI 9.32-11.21) of oxycodone posts discussed this topic. A total of 10% (60/600) of tapentadol posts discussed unsafe use or side effects, whereas 20.17% (95% CI 18.92-21.41) of oxycodone posts discussed unsafe use or side effects. There were 31 illicit sales reports for tapentadol (geometric mean price per milligram: Aus $0.12 [US $0.09]) and 756 illicit sales reports for oxycodone (Aus $1.28 [US $0.91]). Models detected no differences in the street price or number of sales between the drugs when covariates were included, although the potency of the pill significantly predicted the street price (P<.001) and availability predicted the number of sales (P=.03).
CONCLUSIONS
Australians searching the web for opinions could judge tapentadol as safer than oxycodone because of the web post content. The illicit sales market for tapentadol was smaller than that of oxycodone, and drug potency and licit availability are likely important factors influencing the illicit market.
Topics: Analgesics, Opioid; Australia; Humans; Internet; Oxycodone; Tapentadol
PubMed: 34932012
DOI: 10.2196/29187 -
JAMA Network Open Oct 2021There is a lack of empirical research regarding misuse of buprenorphine hydrochloride.
IMPORTANCE
There is a lack of empirical research regarding misuse of buprenorphine hydrochloride.
OBJECTIVE
To identify prescription opioids that are most frequently misused, assess differences in motivations for misuse between buprenorphine and nonbuprenorphine prescription opioids, and examine trends in and factors associated with buprenorphine misuse among individuals with or without opioid use disorder (OUD).
DESIGN, SETTING, AND PARTICIPANTS
This survey study used nationally representative data on past-year prescription opioid use, misuse, OUD, and motivations for the most recent misuse from the 2015-2019 National Survey on Drug Use and Health (NSDUH). Participants included 214 505 civilian, noninstitutionalized adult NSDUH respondents. Data were collected from January 2015 to December 2019 and analyzed from February 15 to March 15, 2021.
MAIN OUTCOMES AND MEASURES
Buprenorphine use, misuse, and OUD. Misuse was defined as use "in any way that a doctor [physician] did not direct you to use them, including (1) use without a prescription of your own; (2) use in greater amounts, more often, or longer than you were told to take them; or (3) use in any other way a doctor did not direct you to use them."
RESULTS
The 214 505 respondents included in the analysis represented an estimated annual average 246.7 million US adults during 2015-2019 (51.7% [95% CI, 51.4%-52.0%] women; 13.9% [95% CI, 13.7%-14.1%] aged 18-25 y; 40.6% [95% CI, 40.3%-41.0%] aged 26-49 y; 45.5% [95% CI, 45.0-45.9%] aged ≥50 y). In 2019, an estimated 2.4 (95% CI, 2.2-2.7) million US adults used buprenorphine, and an estimated 0.7 (95% CI, 0.5-0.9) million misused buprenorphine compared with an estimated 4.9 (95% CI, 4.4-5.4) million and an estimated 3.0 (95% CI, 2.7-3.2) million who misused hydrocodone and oxycodone, respectively. Prevalence of OUD with buprenorphine misuse trended downward during the period from 2015 to 2019. "Because I am hooked" (27.3% [95% CI, 21.6%-33.8%]) and "to relieve physical pain" (20.5% [95% CI, 14.0%-29.0%]) were the most common motivations for the most recent buprenorphine misuse among adults with OUD. Adults who misused buprenorphine were more likely to report using prescription opioids without having their own prescriptions than those who misused nonbuprenorphine prescription opioids (with OUD: 71.8% [95% CI, 66.4%-76.6%] vs 53.2% [95% CI, 48.5%-57.8%], P < .001; without OUD: 74.7% [95% CI, 68.7%-79.9%] vs 60.0% [58.1%-61.8%], P < .001). Among adults with past-year OUD who used buprenorphine, multivariable multinomial logistic regression results indicated that buprenorphine misuse was associated with being 24 to 34 (adjusted odds ratio [AOR], 2.9 [95% CI, 1.4-5.8]) and 35 to 49 (AOR, 2.3 [95% CI, 1.2-4.5]) years of age, residing in nonmetropolitan areas (AOR, 1.8 [95% CI, 1.0-3.0]), and polysubstance use (eg, past-year prescription stimulant use disorder; AOR, 3.9 [95% CI, 1.3-11.2]) but was negatively associated with receiving treatment for drug use only (AOR, 0.4 [95% CI, 0.3-0.7]).
CONCLUSIONS AND RELEVANCE
These findings suggest that among adults with OUD, prevalence of buprenorphine misuse trended downward from 2015 to 2019. In 2019, nearly three-fourths of US adults reporting past-year buprenorphine use did not misuse their prescribed buprenorphine, and most who misused reported using prescription opioids without having their own prescriptions. These findings underscore the need to pursue actions that expand access to buprenorphine-based OUD treatment, to develop strategies to monitor and reduce buprenorphine misuse, and to address associated conditions (eg, suicide risk, co-occurring mental illness, and polysubstance use).
Topics: Adolescent; Adult; Buprenorphine; Female; Humans; Male; Middle Aged; Opioid-Related Disorders; Surveys and Questionnaires
PubMed: 34652446
DOI: 10.1001/jamanetworkopen.2021.29409 -
Translational Psychiatry Jun 2023Esmethadone (REL-1017) is the opioid-inactive dextro-isomer of methadone and a low-affinity, low-potency uncompetitive NMDA receptor antagonist. In a Phase 2,... (Randomized Controlled Trial)
Randomized Controlled Trial
Esmethadone (REL-1017) is the opioid-inactive dextro-isomer of methadone and a low-affinity, low-potency uncompetitive NMDA receptor antagonist. In a Phase 2, randomized, double-blind, placebo-controlled trial, esmethadone showed rapid, robust, and sustained antidepressant effects. Two studies were conducted to evaluate the abuse potential of esmethadone. Each study utilized a randomized, double-blind, active-, and placebo-controlled crossover design to assess esmethadone compared with oxycodone (Oxycodone Study) or ketamine (Ketamine Study) in healthy recreational drug users. Esmethadone 25 mg (proposed therapeutic daily dose), 75 mg (loading dose), and 150 mg (Maximum Tolerated Dose) were evaluated in each study. Positive controls were oral oxycodone 40 mg and intravenous ketamine 0.5 mg/kg infused over 40 min. The Ketamine study included oral dextromethorphan 300 mg as an exploratory comparator. The primary endpoint was maximum effect (E) for Drug Liking, assessed using a bipolar 100-point visual analog scale (VAS). A total of 47 and 51 participants completed the Oxycodone Study and the Ketamine Study, respectively (Completer Population). In both studies, esmethadone doses ranging from therapeutic (25 mg) to 6 times therapeutic (150 mg) had a meaningful and statistically significantly (p < 0.001) lower Drug Liking VAS E compared with the positive control. Results were consistent for all secondary endpoints in both studies. In both studies, all doses of esmethadone were statistically equivalent to placebo on Drug Liking VAS E (p < 0.05). In the Ketamine Study, Drug Liking VAS E scores for esmethadone at all tested doses were significantly lower vs. dextromethorphan (p < 0.05) (exploratory endpoint). These studies indicate no meaningful abuse potential for esmethadone at all tested doses.
Topics: Humans; Oxycodone; Receptors, N-Methyl-D-Aspartate; Dextromethorphan; Ketamine; Analgesics, Opioid; Cross-Over Studies; Double-Blind Method; Illicit Drugs
PubMed: 37286536
DOI: 10.1038/s41398-023-02473-8 -
Drug and Alcohol Dependence Feb 2020Prescription opioid abuse continues to be a public health concern of epidemic proportions. Notwithstanding the extensive literature regarding opioid action, there has...
BACKGROUND
Prescription opioid abuse continues to be a public health concern of epidemic proportions. Notwithstanding the extensive literature regarding opioid action, there has been little systematic research regarding the effects of opioid dependence and withdrawal on aspects of cognition-related behavior in laboratory animals. The present studies examined the effects of the prescription opioid oxycodone on learning processes in nonhuman primates.
METHODS
The ability of subjects to repeatedly learn novel touchscreen-based visual discriminations was examined during three conditions of opioid exposure. Discrimination learning was examined, first, during oxycodone self-administration (3-hr sessions, 0.1 mg/kg/injection) and, next, during non-contingent chronic treatment with oxycodone (10 mg/kg/day). Finally, discrimination learning was re-examined during antagonist-precipitated opioid withdrawal (0.001-0.1 mg/kg naltrexone) and, subsequently, following abrupt discontinuation of oxycodone treatment.
RESULTS
Although motoric behavior was disrupted by oxycodone, neither the development of discrimination learning nor steady-state performance were impaired following oxycodone self-administration or during non-contingent chronic oxycodone treatment. However, discrimination learning was substantially impaired during oxycodone withdrawal, whether elicited by naltrexone or by abrupt oxycodone discontinuation. Moreover, these learning impairments were concordant with autonomic signs of opioid withdrawal.
CONCLUSIONS
Taken together, the present studies indicate that impairment of learning processes can accompany the unconditioned signs of opioid withdrawal.
Topics: Analgesics, Opioid; Animals; Discrimination Learning; Dose-Response Relationship, Drug; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Oxycodone; Primates; Saimiri; Self Administration; Substance Withdrawal Syndrome
PubMed: 31816487
DOI: 10.1016/j.drugalcdep.2019.107778 -
Biochemical Pharmacology Apr 2022Opioids, and numerous centrally active drugs, are metabolized by cytochrome P450 2D (CYP2D). There are sex and estrous cycle differences in brain oxycodone analgesia....
Opioids, and numerous centrally active drugs, are metabolized by cytochrome P450 2D (CYP2D). There are sex and estrous cycle differences in brain oxycodone analgesia. Here we investigated the mechanism examining the selective role of CYP2D in the brain on sex, estrous cycle, and hormonal regulation. Propranolol, CYP2D-specific mechanism-based inhibitor, or vehicle was delivered into cerebral ventricles 24 h before administering oxycodone (or oxymorphone, negative control) orally to male and female (in estrus and diestrus) rats. Ovariectomized and sham-operated females received no treatment, estradiol, progesterone or vehicle. Analgesia was measured using tail-flick latency, and brain drug and metabolite concentrations were measured by microdialysis. Data were analyzed by two-way or mixed ANOVA. Following propranolol (versus vehicle) inhibition and oral oxycodone, there were greater increases in brain oxycodone concentrations and analgesia, and greater decreases in brain oxymorphone/oxycodone ratios (an in vivo phenotype of CYP2D in brain) in males and females in estrus, compared to females in diestrus; with no impact on plasma drug concentrations. There was no impact of propranolol pre-treatment, sex, or cycle after oral oxymorphone (non-CYP2D substrate) on brain oxymorphone concentrations or analgesia. There was no impact of propranolol pre-treatment following ovariectomy on brain oxycodone concentrations or analgesia, which was restored in ovariectomized females following estradiol, but not progesterone, treatment. Sex, cycle, and estradiol regulation of CYP2D in brain in turn altered brain oxycodone concentration and response, which may contribute to the large inter-individual variation in response to the numerous centrally acting CYP2D substrate drugs, including opioids.
Topics: Analgesia; Analgesics, Opioid; Animals; Brain; Cytochrome P-450 Enzyme System; Estradiol; Estrous Cycle; Female; Male; Oxycodone; Oxymorphone; Pain; Progesterone; Propranolol; Rats; Rats, Wistar
PubMed: 35143755
DOI: 10.1016/j.bcp.2022.114949 -
Cureus Apr 2023Objective Opioid medications are widely recognized for their use in analgesia and their addictive properties that have led to the opioid epidemic. Areas with...
Objective Opioid medications are widely recognized for their use in analgesia and their addictive properties that have led to the opioid epidemic. Areas with historically high prescribing patterns have been shown to suffer more from the crisis. There is also regional variability in these trends. This study is a county level analysis of oxycodone and hydrocodone use in Delaware, Maryland, and Virginia between 2006 and 2014. Materials and methods A retrospective analysis of oxycodone and hydrocodone distributed as collected by the Drug Enforcement Administration's (DEA) Washington Post Automation of Reports and Consolidated Orders System (ARCOS) in Delaware, Maryland, and Virginia. Raw drug weights in each county were adjusted to "daily average dose" (grams/county population/365) using publicly available population estimates for all state counties. Purchasing data collected from ARCOS was used to compare distribution trends during this period. This study was limited in that ARCOS report quantity of drug distribution rather than average dose of script written. Results There was a 57.59% increase in the weight of oxycodone and hydrocodone prescribed between 2006 and 2014. Oxycodone prescriptions increased by 75.50% and hydrocodone by 11.05%. Oxycodone increased across all three states between 2006 and 2010 and declined until 2014. Hydrocodone also increased but to a lesser extent than oxycodone. There was substantial variability in daily average dose of both opioids at the county level in all states. Pharmacies accounted for largest portion of oxycodone (69.17%) and hydrocodone (75.27%) purchased in the region. Hospitals accounted for 26.67% of oxycodone and 22.76% of hydrocodone purchased. Practitioners and mid-level providers, including Nurse Practitioners and Physician Assistants, did not significantly contribute to this increase. Conclusion In the states of Maryland, Delaware, and Virginia, the distribution of the prescription opioids oxycodone and hydrocodone increased by 57.59%. Daily average dose increased between 2006 and 2010 in all three states, followed by a decline until 2014. Variability in daily average dose by county highlights the relationship between geography and likelihood of receiving high-dose opioids. Increased monitoring at regional health centers and improving substance abuse treatment infrastructure at the county level may be a more efficient strategy in combating the opioid epidemic. Future research is needed to understand the socioeconomic trends that may influence prescribing trends of opioid medications.
PubMed: 37252511
DOI: 10.7759/cureus.38211 -
Scandinavian Journal of Pain Apr 2021Opioids are often used in treatment of severe pain, although many patients experience gastrointestinal side-effects like constipation. The aim of the current study was... (Randomized Controlled Trial)
Randomized Controlled Trial
Although tapentadol and oxycodone both increase colonic volume, tapentadol treatment resulted in softer stools and less constipation: a mechanistic study in healthy volunteers.
OBJECTIVES
Opioids are often used in treatment of severe pain, although many patients experience gastrointestinal side-effects like constipation. The aim of the current study was to investigate changes in colonic volume, as the result of both colonic motility and fluid transport, in healthy volunteers during opioid treatment with tapentadol as compared with oxycodone and placebo.
METHODS
In a randomized, double-blind, cross-over study, 21 healthy male volunteers were administered equianalgesic dosages of oral tapentadol (50 mg bid), oxycodone (10 mg bid) or corresponding placebo for 14 days. Segmental colonic volumes were quantified using T2-weighted magnetic resonance images, and gastrointestinal side-effects were assessed with questionnaires.
RESULTS
Total colonic volume increase during treatment was higher during tapentadol and oxycodone treatment (median 48 and 58 mL) compared to placebo (median -14 mL, both p≤0.003). Tapentadol (and placebo) treatment resulted in more bowel movements (both p<0.05) and softer stool consistency as compared with oxycodone (both p<0.01). Only oxycodone treatment was associated with increased constipation, straining during defecation, and tiredness (all p≤0.01). The colonic volume increase during treatment was directly associated with softer stools during tapentadol treatment (p=0.019).
CONCLUSIONS
Tapentadol treatment increased colonic volume without leading to harder stools, likely as the opioid sparing effects result in less water absorption from the gut lumen. Oxycodone treatment also increased colonic volume, but with a simultaneous increase in stool dryness and gastrointestinal and central nervous system side-effects. The results confirm that tapentadol treatment may be advantageous to oxycodone regarding tolerability to pain treatment.
Topics: Colon; Constipation; Cross-Over Studies; Healthy Volunteers; Humans; Male; Oxycodone; Tapentadol
PubMed: 33606931
DOI: 10.1515/sjpain-2020-0151 -
Journal of Analytical Toxicology Jul 2022Peripheral blood (PB) concentrations are generally preferred for postmortem toxicological interpretation, but some autopsy cases may lack blood for sampling due to...
Peripheral blood (PB) concentrations are generally preferred for postmortem toxicological interpretation, but some autopsy cases may lack blood for sampling due to decomposition or large traumas, etc. In such cases, other tissues or bodily fluids must be sampled; however, limited information exists on postmortem concentrations in matrices other than blood. Pericardial fluid (PF), muscle and vitreous humor (VH) have been suggested as alternatives to blood, but only a few studies have investigated the detection of opioids in these matrices. In this study, we aimed to investigate the detection of methadone, buprenorphine, oxycodone, fentanyl and tramadol in postmortem samples of PF, skeletal muscle and VH, in addition to PB and cardiac blood and if drug concentrations in these alternative matrices were comparable to those in PB and thereby useful for interpretation. In most of the 54 included cases, only one opioid was detected. Methadone, oxycodone, fentanyl and tramadol were detected in all of the alternative matrices in almost all cases, while buprenorphine was detected less often. For methadone, the concentrations in the alternative matrices, except in VH, were relatively similar to those in PB. Larger variations in concentrations were found for buprenorphine, oxycodone and tramadol. Quantitative analyses appeared useful for fentanyl, in all of the alternative matrices, but only four cases were included. Toxicological analyses of opioids in these alternative postmortem matrices can be useful for detection, but quantitative results must be interpreted with caution.
Topics: Analgesics, Opioid; Autopsy; Buprenorphine; Fentanyl; Methadone; Oxycodone; Tramadol
PubMed: 34115841
DOI: 10.1093/jat/bkab071 -
Frontiers in Behavioral Neuroscience 2022Rates of relapse to drug use during abstinence are among the highest for opioid use disorder (OUD). In preclinical studies, reinstatement to drug-seeking has been...
INTRODUCTION
Rates of relapse to drug use during abstinence are among the highest for opioid use disorder (OUD). In preclinical studies, reinstatement to drug-seeking has been extensively studied as a model of relapse-but the work has been primarily in males. We asked whether biological sex contributes to behaviors comprising self-administration of the prescription opioid oxycodone in rats, and we calculated the relative contribution of these behavioral measures to reinstatement in male and female rats.
MATERIALS AND METHODS
Rats were trained to self-administer oxycodone (8 days, training phase), after which we examined oxycodone self-administration behaviors for an additional 14 days under three conditions in male and female rats: short access (ShA, 1 h/d), long access (LgA, 6 h/d), and saline self-administration. All rats were then tested for cue-induced reinstatement of drug-seeking after a 14-d forced abstinence period. We quantified the # of infusions, front-loading of drug intake, non-reinforced lever pressing, inter-infusion intervals, escalation of intake, and reinstatement responding on the active lever.
RESULTS
Both male and female rats in LgA and ShA conditions escalated oxycodone intake to a similar extent. However, males had higher levels of non-reinforced responding than females under LgA conditions, and females had greater levels of reinstatement responding than males. We then correlated each addiction-related measure listed above with reinstatement responding in males and females and ranked their respective relative contributions. Although the majority of behavioral measures associated with oxycodone self-administration did not show sex differences on their own, when analyzed together using partial least squares regression, their relative contributions to reinstatement were sex-dependent. Front-loading behavior was calculated to have the highest relative contribution to reinstatement in both sexes, with long and short inter-infusion intervals having the second greatest contribution in females and males, respectively.
DISCUSSION
Our results demonstrate sex differences in some oxycodone self-administration measures. More importantly, we demonstrate that a sex- dependent constellation of self-administration behaviors can predict the magnitude of reinstatement, which holds great promise for relapse prevention in people.
PubMed: 36505730
DOI: 10.3389/fnbeh.2022.1035350 -
Medical Science Monitor : International... Mar 2021BACKGROUND The aim of the present study was to evaluate the effects of different doses of oxycodone during endoscopic injection sclerotherapy (EIS) for esophageal...
BACKGROUND The aim of the present study was to evaluate the effects of different doses of oxycodone during endoscopic injection sclerotherapy (EIS) for esophageal varices with painless sclerosing agents. MATERIAL AND METHODS A total of 119 patients were randomly divided into 3 groups: Group A, midazolam and 0.075 mg/kg oxycodone (n=40); Group B, midazolam and 0.1 mg/kg oxycodone (n=40); and Group C, midazolam and 0.125 mg/kg oxycodone (n=39). The main observation index was the incidence of body movement during the perioperative period. The secondary indices were additional propofol usage; postoperative analgesic usage; other adverse effects, such as hypoxia, myoclonus, and cough; and satisfaction scores for surgeons and patients. RESULTS The incidence rates for body movement during the perioperative period in groups A, B, and C were 33%, 13%, and 0, respectively (P<0.001). The satisfaction scores for surgeons and patients were highest in Group C (0.125 mg/kg oxycodone). The incidence rates for hypoxia before EIS were 15%, 8%, and 33% (P=0.026) and during EIS were 23%, 3%, and 0% (P<0.001), respectively. There were no significant between-group differences with respect to other adverse effects. CONCLUSIONS The ideal dose of oxycodone for perioperative analgesia during EIS for esophageal varices is 0.125 mg/kg.
Topics: Adult; China; Dose-Response Relationship, Drug; Endoscopy; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Incidence; Injections; Liver Cirrhosis; Male; Midazolam; Middle Aged; Oxycodone; Perioperative Period; Prospective Studies; Sclerosing Solutions; Sclerotherapy
PubMed: 33727522
DOI: 10.12659/MSM.929111