The Role of Adverse Childhood Experiences on People in Opiate Agonist Treatment: The Importance of Feeling Unloved.

INTRODUCTION: Adults in opiate agonist treatment (OAT) often have a background of adverse childhood experiences (ACEs) and are more likely to be exposed to a variety of risks that may trigger post-traumatic stress disorder (PTSD). Summative ACE scores are often used to identify individuals at risk of PTSD and continued substance use. What has not been addressed is whether specific ACE factors are exerting a greater influence on the individual. This study investigated whether specific ACEs predicted PTSD, and current continued substance use among adults in long-term OAT. METHODS: An analysis of data that were collected at the follow-up stage of a study among 131 adults who attended OAT was conducted. Participants attended one of six OAT settings, covering 45% (n = 890) of clients in a defined area of Dublin, Ireland in 2017. Interviews were conducted with 104 participants, 66 males (63%) and 38 females (37%), with an average age of 43 years (SD = 7.4). The Adverse Childhood Questionnaire (ACQ); PTSD checklist (PCL-5); heroin; tranquilliser; cannabis; alcohol; and cocaine used in the previous 28 days were measured using the quantity used score within the Opiate Treatment Index. Socio-demographics and age of first use of these four substances were also collected. The analysis has focussed on relating ACEs to PTSD, age of first drugs use, and current drug use of the participants. RESULTS: Bivariate analysis showed that the summative ACQ score was significantly correlated with age of first opiate use (p = 0.004). Multiple regression analysis showed that the summative ACQ score and tranquilliser use predicted higher levels of PTSD (R2 = 0.50). Four specific ACEs predicted 54% of the variance in PTSD, these were feeling unloved (ß = 0.328) living with a household member who had a problem with alcohol or used illicit street drugs (ß = 0.280); verbal abuse (ß = 0.219); and living with a person who had a mental illness (ß = 0.197). CONCLUSIONS: While a summation of all ten ACEs predicted higher levels of PTSD, the factor "feeling unloved" as a child provided the single strongest predictor and may represent an overarching risk of PTSD and continued substance use in later life among adults in treatment for an opiate use disorder.

New Validated Method for the Determination of Six Opium Alkaloids in Poppy Seed-Containing Bakery Products by High-Performance Liquid Chromatography-Tandem Mass Spectrometry after Magnetic Solid-Phase Extraction.

Bakery products containing poppy seeds are increasingly being commercialized. These seeds may be contaminated with latex from the Papaver somniferum L. plant rich in opium alkaloids (OAs). Therefore, health authorities demand the development of analytical methods to control them. In this study, an efficient and simple method was developed and validated for the first time to analyze six OAs in bakery products by high-performance liquid chromatography-tandem mass spectrometry. For this purpose, a solid-liquid extraction was optimized, and then a magnetic material [magnetite surface-modified with Fe(III) terephthalate, denoted as Fe3O4@TPA-Fe] was used for a fast magnetic solid-phase extraction. The method has been validated with adequate recoveries (70-110%) and relative standard deviations (<20%) and without matrix effects. Nine bakery samples (five breadsticks and four sliced bread) were analyzed; breadsticks showed low amounts of OAs, but two sliced bread showed higher amounts of OAs than the new amount (1.5 mg/kg) set by the Commission Regulation (EU) 2021/2142.

Gabapentinoids and Acetaminophen as Adjuvants for Managing Postoperative Pain.

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.

Lead poisoning among asymptomatic individuals with a long-term history of opiate use in Golestan Cohort Study.

BACKGROUND: Recent reports of lead poisoning suggest that people who use opium may be exposed to high amounts of lead. Here, we investigate the association between opium use and blood lead levels (BLL) in a population-based cohort study. METHODS: In 2017, we studied a random sample of 410 people who currently (both within the past year and the past month) used opium and 104 who did not from participants of the Golestan Cohort Study in northeast Iran. Participants were stratified by sex and tobacco use history, completed a comprehensive opiate and tobacco use questionnaire and provided blood. BLL was measured by Lead Care® II Blood Lead Test Kit, validated by inductively coupled plasma triple quadrupole mass spectrometry. BLL was categorized as "<5 µg/dL", "elevated" (5-10 µg/dL), "high" (10-50 µg/dL), and "very high" (above 50 µg/dL). To assess the association between BLL categories and opiate use, route of consumption and weekly use, we used ordered logistic regression models, and report OR (odds ratio) and 95% CI (confidence interval) adjusted for age, sex, place of residence, education, occupation, household fuel type, and tobacco use. RESULTS: In the cohort, participants used only raw (teriak) or refined (shireh) opium, which were smoked (45%, n = 184), taken orally (46%, n = 189), or both (9%, n = 37), for a mean duration of 24.2 (standard deviation: 11.6) years. The median BLL was significantly higher in people who currently used opium (11.4 µg/dL; IQR: 5.2-23.4) compared with those who did not (2.3 µg/dL; IQR: 2.3-4.2), and the highest median BLL was seen in oral use (21.7 µg/dL; IQR: 12.1-34.1). The BLL was <5 µg/dL among 79.8% of people with no opiate use, compared with only 22.7% in those using opium. BLL was elevated in 21.7%, high in 50.5% and very high in 5.1% of people using opium. About 95% of those with oral (180/189) or dual use (35/37) and 55% (102/184) of those who smoked opium had levels of blood lead above 5 µg/dL. The OR for the association between any opium use and each unit of increase in BLL category was 10.5 (95%CI: 5.8-19.1), and oral use of opium was a very strong predictor of increasing BLL category (OR=74.1; 95%CI: 35.1-156.3). This odds ratio was 38.8 (95%CI: 15.9-95.1) for dual use and 4.9 (95%CI: 2.6-9.1) for opium smoking. There was an independent dose-response association between average weekly dose and BLL among people using opium, overall and when stratified by route of use. CONCLUSION: Our results indicate that regular use of lead-adulterated opium can expose individuals to high levels of lead, which may contribute to mortality and cancer risks associated with long-term opium use.

Elevated serum lead levels in neonates born to mothers suffering from opiate use disorder.

BACKGROUND: This study was performed to investigate lead levels in neonates born to the mothers suffering from opiate use disorder (OUD) and the association of lead levels with the Apgar score. METHODS: The present cross-sectional study included 56 neonates who were referred to the neonatal ward of Amir-Al Momenin Hospital, Zabol. The neonates were divided into two groups: the neonates whose mothers suffered OUD and the control group. Data were collected using a researcher-prepared questionnaire, and blood lead level was determined using the atomic absorption method. Data were statistically analyzed. RESULTS: In all, 56 neonates (28 from OUD mothers and 28 from the control mothers) were included in this study. Among the women with OUD, 16 (57%) used inhaled opium, while 12 (43%) consumed opium orally. There was a significant difference regarding Apgar score (9.76 ± 2.11 versus. 7.11 ± 4.21; p = 0.02) and the neonate's blood lead level (2.33 ± 1.3 µg/dl versus 7.33 ± 5.9 µg/dl) between the control and OUD groups (p < 0.001). The odds ratio of abnormally elevated blood lead level rose with increasing duration of maternal opiate disorder for opiate usage durations of 3 to 5 years (adjusted odds ratio [OR] 42.82, 95% confidence interval [CI] 3.27-561, p = 0.004) and > 5 years (adjusted OR 45.5, 95% CI 2.97-698, p = 0.006). CONCLUSION: The results of this study suggested a significant relationship between maternal opium consumption during pregnancy and neonatal serum lead levels, as well as decreased neonatal Apgar score.

Bupivacaine liposome use reduces length of post-anesthesia care unit stay and postoperative narcotic use following robotic inguinal herniorrhaphy.

In the current opioid crisis, multimodal analgesic protocols should be considered to reduce or eliminate narcotic usage in the postoperative period. We assess the impact of bupivacaine liposome used along with a standard analgesia protocol following robotic inguinal hernia repair. A retrospective review of a prospectively maintained data including robotic inguinal hernia repairs (IHR) by two surgeons in the United States was performed. Within a multimodal analgesic protocol, local anesthetic was administered intraoperatively. One group received a mix of bupivacaine and bupivacaine liposome (BL), and one received standard bupivacaine (SB). Recovery room and home opiate doses were recorded. Primary outcomes included length of stay (LOS) and postoperative medication requirements. Statistical analysis was performed using Chi-square or Fisher's exact test and Mann-Whitney U test as appropriate. 122 robotic IHRs were included; 55 received BL and 67 received SB. Hospital LOS (hours) was reduced in the BL group (2.8 ± 1.1 vs 3.5 ± 1.2; p = 0.0003). There was no significant difference in recovery room parenteral MME requirements between the groups; however, BL group had less oral MME requirements (5.0 ± 6.5 MME vs. 8.1 ± 6.9 MME, p = 0.02). The BL group had a higher rate of zero opiate doses at home (44% vs 5%, p = 0.0005). Of those that did require opiates at home, there was a significant reduction in number of narcotic pills used by the BL compared to the SB group (median 1 vs 5, respectively; p < 0.0001). Intraoperative administration of BL as part of a pain management protocol may decrease length of hospital stay, and reduce or eliminate the need for narcotic analgesic use at home.

Evaluation of Latent Fingerprints for Drug Screening in a Social Care Setting.

Sweat deposited via latent fingerprints (LFPs) was previously used to detect cocaine, opioids, cannabis and amphetamine via a point-of-care test (POCT). This screening method combined non-invasive sampling with a rapid result turnaround to produce a qualitative result outside of the laboratory. We report the novel application of a LFP drug screening test in a social care setting. Clients were tested on either an ad hoc or a routine basis using the POCT DOA114 (Intelligent Fingerprinting Ltd) drug screening cartridge. Screening cutoff values were 45, 35 and 95 pg/fingerprint for benzoylecgonine (BZE), morphine and amphetamine analytes, respectively. Confirmation LFP samples (DOA150, Intelligent Fingerprinting Ltd) and oral fluid (OF) were analyzed using ultra-performance liquid chromatography with tandem mass spectrometry. Thirty-six clients aged 36 ± 11 years participated (53% females). Individuals self-reported alcohol consumption (39%) and smoking (60%). Of 131 screening tests collected over 8 weeks, 14% tested positive for cocaine, 2% tested positive for opioids and 1% tested positive for amphetamine. Polydrug use was indicated in 10% of tests. Of 32 LFP confirmation tests, 63% were positive for cocaine and BZE. Opioids were also detected (31%), with the metabolite 6-monoacetylmorphine (6-MAM) being the most common (16%). In OF, cocaine was the dominant analyte (9%) followed by 6-MAM (5%). On comparing positive LFP screening tests with positive OF samples, we found that 39% and 38% were cocaine and opiate positive, respectively. Of the drugs screened for via the LFP POCT, cocaine was the most prevalent analyte in LFP and OF confirmation samples. The study is a step change in the routine drug screening procedures in a social care setting, especially useful for on-site cocaine detection in clients whose drug use was being monitored. Additionally, testing was easily accepted by clients and social care workers.

Prevalence of general and abdominal obesity and its relationship with opium, total opiate drugs, and chronic smoking: Fasa cohort study.

BACKGROUND AND AIMS: Obesity and drug use are two major global issues today. This study aimed to evaluate the relationship between alcohol and tobacco use with general and central obesity. METHODS: The data of the longitudinal population-based study were collected from the basis of the Fasa Cohort Study (FACS). Participants were 10141 people with 35-70 years old. Data were analyzed by SPSS 20 software. Binary logistic regression (BLR) was used for modelling. A significance level (α) less than 0.05% was considered for hypothesis testing. RESULTS: Of the total participants (N = 10104), 54.8% (n = 5539) were women. The prevalence of central obesity in terms of waist circumference (WC), waist to hip ratio (WHR), and waist to height ratio (WHtR) were calculated 48.20% (N = 4871), 79.50% (N = 8032), and 83.30% (N = 8314). The Odds Ratio (OR) adjusted of Abnormal body mass index (BMI) for Opium and chronic smoking were 0.54 (CI: 0.47-0.63) and 0.47 (CI:0.40-0.56). OR adjusted Abnormal WC for opium and chronic smoking were calculated 0.65 (CI: 0.53-0.80) and 0.57 (CI:0.46-0.72), respectively. Three variables of opium (OR = 0.54, CI: 0.46-0.64), total opiate drugs (OR = 1.46, CI:1.16-1.83) and chronic smoking (OR = 0.58, CI: 0.48-0.70) remained in the modeling for Abnormal WHR. Which were statistically significant. CONCLUSION: Significant and inverse relationships were found between obesity and opium, total opiate drugs, and chronic smoking.

Thalamic Retrieval of Opioid Memories.

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.

Aerodynamic Thermal Breakup Droplet Ionization in Mass Spectrometric Drug Analysis.

Aerodynamic thermal breakup droplet ionization (ATBDI) in mass spectrometric drug analysis is considered. Cocaine, heroin, and the main alkaloids of opium (morphine, codeine, papaverine) were chosen as the test compounds. The principles of ATBDI ionization are discussed. The dependences of the intensities of the peaks of the target compounds on temperature during ATBDI ionization are also considered. In some cases, a comparison of ATBDI ionization with electrospray ionization (ESI) was performed. In addition, a comparison of methods is demonstrated by the analysis of confiscated opium that was provided by the local police department. Five major alkaloids are found in opium: morphine, codeine, thebaine, papaverine, and narcotine.

Matrix-Free Laser Desorption Ionization Mass Spectrometry as an Efficient Tool for the Rapid Detection of Opiates in Crude Extracts of Papaver somniferum.

Having a long history of traditional medicinal applications, Papaver somniferum is also known as a source of various pharmacologically highly active opiates. Consequently, their detection from plant extracts is an important analytical task and generally addressed by methods of GC-MS and LC-MS. However, opiates do also show structural similarities to matrix molecules used in matrix-assisted laser desorption ionization (LDI) and may therefore ionize upon simple laser irradiation. Following this analytical approach, the present work thoroughly evaluated the direct detection of opiates by matrix-free LDI in crude extracts of P. somniferum. The method facilitated the identification of 10 reported opiates by their molecular formulas without any chromatographic prepurification. Moreover, a principal component analysis based on LDI-MS data permitted the correct grouping of all extracts according to their inherent chemistry. Concluding experiments on serial dilutions of thebaine further evaluated potential quantitative applications of the method. Overall results highlight the promising potential of LDI-MS for the swift detection of opiates in complex mixtures.

Older marijuana users in substance abuse treatment: Treatment settings for marijuana-only versus polysubstance use admissions.

OBJECTIVE: Growing numbers of older adult marijuana users make understanding the marijuana-related treatment needs and treatment-related characteristics of this age group increasingly important. In this study, we examined four types of marijuana-involved admissions (marijuana as the only substance; marijuana as the primary substance with other secondary/tertiary substances; marijuana as the secondary substance; and marijuana as the tertiary substance) by treatment setting. METHODS: Data came from the 2012-2017 Treatment Episode Data Set-Admissions (TEDS-A), which includes 851,652 admissions by those aged 55+. Using multinomial logistic regression analysis, we focused on the 120,286 marijuana-involved admissions to test the hypothesis that polysubstance use would be associated with a higher likelihood of using detoxification and rehabilitation settings than ambulatory/outpatient settings. RESULTS: Of all marijuana-involved admissions, 7.5% were marijuana-only, 12.7% were marijuana-primary, 58.4% were marijuana-secondary, and 21.4% were marijuana-tertiary admissions. Compared to marijuana-only admissions, admissions involving other substances were associated with a higher likelihood of detoxification and rehabilitation than ambulatory/outpatient treatment (e.g., RRR = 5.79, 95% CI = 5.08-6.61 for detoxification and RRR = 3.19, 95% CI = 2.89-3.52 for rehabilitation among marijuana-tertiary admissions). Referral source, first age of marijuana use, race/ethnicity, and homelessness were significant covariates. CONCLUSIONS: Given increasing numbers of older-adult marijuana users, healthcare providers should screen older adults for marijuana and other substance use, and substance abuse treatment programs should become more responsive to older adults' needs.

DARK Classics in Chemical Neuroscience: Opium, a Historical Perspective.

Opium is the latex from the opium poppy Papaver somniferum L., which humankind has utilized since ancient Mesopotamia all the way to modern times. Opium used to be surrounded in divine mystery or magic-like abilities and was given to cure a wide variety of diseases until its analgesic, antitussive, and antidiarrheal properties were understood, the resulting alkaloids were isolated, and their structure and properties unmasked. Opium went from being sold in any store front in the form of pills or tinctures with no prescription necessary for purchase or smoked in an opium den down the street, to then bringing about consumer advocacy and the right to know what is in a medication. Legislation was created to limit the prescribing and selling of medications to doctors and pharmacists as well as outlawing opium dens and smoking opium. This review focuses primarily on the uses of opium throughout history, the isolation of the principle alkaloids, and their structure elucidation.

Co-administration of Phycocyanobilin and/or Phase 2-Inducer Nutraceuticals for Prevention of Opiate Tolerance.

Chronic use of opiates for control of chronic pain is complicated by the development of tolerance and hyperalgesia, and hence usually entails dose escalation and diminished efficacy. Our evolving understanding of the mechanisms mediating induction of morphine tolerance may enable discovery of adjunct measures which can prevent this tolerance; this essay proposes that certain nutraceuticals may have utility in this regard. Considerable evidence now points to an obligate role for production of peroxynitrite and other oxidants in the dorsal horn in development of morphine tolerance. Various isoforms of NADPH oxidase are the chief source of the superoxide which gives rise to these oxidants. Since heme oxygenase, via its products bilirubin and carbon monoxide, functions as a physiological inhibitor of various isoforms of NADPH oxidase, phase 2-inducing nutraceuticals with blood brain-barrier permeability such as lipoic acid, an effective inducer of heme oxygenase-1, may have potential for prevention of morphine tolerance; indeed, this has been demonstrated in a mouse study. The phycocyanobilin (PhyCB) chromophore of spirulina, a structural analog of biliverdin, shares bilirubin's ability to inhibit NAPDH oxidase complexes; hence, administration of spirulina or of PhyCB-enriched spirulina extracts merits evaluation in rodent models of morphine tolerance. Uric acid quenches peroxynitrite-derived radicals, and its plasma level can be boosting via supplementation with inosine; indeed, administration of inosine has been shown to counteract development of hyperalgesia in rodents. If practical doses of these agents can be shown to prevent morphine tolerance and hyperalgesia in rodents, their use as adjuvants to clinical opiate therapy should be assessed.

The DARK Side of Total Synthesis: Strategies and Tactics in Psychoactive Drug Production.

Humankind has used and abused psychoactive drugs for millennia. Formally, a psychoactive drug is any agent that alters cognition and mood. The term "psychotropic drug" is neutral and describes the entire class of substrates, licit and illicit, of interest to governmental drug policy. While these drugs are prescribed for issues ranging from pain management to anxiety, they are also used recreationally. In fact, the current opioid epidemic is the deadliest drug crisis in American history. While the topic is highly politicized with racial, gender, and socioeconomic elements, there is no denying the toll drug mis- and overuse is taking on this country. Overdose, fueled by opioids, is the leading cause of death for Americans under 50 years of age, killing ca. 64,000 people in 2016. From a chemistry standpoint, the question is in what ways, if any, did organic chemists contribute to this problem? In this targeted review, we provide brief historical accounts of the main classes of psychoactive drugs and discuss several foundational total syntheses that ultimately provide the groundwork for producing these molecules in academic, industrial, and clandestine settings.

Expertos, juicios y crimen: Pere Mata (1811-1877) y el veneno de María Bonamot / Experts, trials and crimes: Pere Mata (1811-1877) and Maria Bonamot's poison

El siglo XIX fue un periodo en el que se produjo un creciente interés por los venenos y los crímenes por envenenamiento a pesar de no ser formas habituales de homicidio. La nueva toxicología pretendía ofrecer herramientas para combatir este tipo de crímenes. Sin embargo, fueron precisamente los debates surgidos durante los procesos judiciales, los que ayudaron a configurar la toxicología del siglo XIX. Alejados de las pautas ofrecidas en los manuales y ante la necesidad de mostrar a un juez carente de formación en estas materias, la presencia o ausencia del veneno, los toxicólogos del siglo XIX pusieron en juego todas sus estrategias para vencer a otros expertos y convencer a los profanos. A mediados de 1844 se produjo en Madrid un caso de envenenamiento que llamó la atención tanto de la prensa médica como de la prensa periódica española. Dos factores contribuyeron a su popularidad: las fechas en las que se produjo (tan solo un año después de la creación de la cátedra de Medicina Legal en las Facultades de Madrid y Barcelona); y la participación como peritos de algunos de los personajes españoles más influyentes en la medicina legal y toxicología española como es el caso de Pere Mata i Fontanet (1811-1877). Pere Mata desempeñó una labor importante en los tres terrenos que contribuyeron decisivamente a la homogeneidad de la comunidad de toxicólogos: la formación universitaria, la literatura académica y la organización profesional. El análisis de un caso de envenenamiento como el que se desarrolla en este trabajo, permite considerar muchas de las cuestiones relacionadas con la toxicología en el siglo XIX: la constitución de una nueva disciplina académica, la creación de una comunidad de expertos, las controversias públicas y la gestión de las pruebas periciales en los tribunales

The XIXth century saw a growing interest in poisons and crimes by poison although these are not usual ways of murder. New technology aspired to offer tools to combat this type of crimes. However, it was precisely the debates that arose during trials that helped to configure XIXth century toxicology. Far from the guidelines offered in manuals and facing the need to demonstrate to a judge, lacking In training in these subjects the presence or absence of the poison, XIXth century toxicologists used all of their strategies to beat other experts and convince the layperson. In the middle of 1844 there was a case of poisoning in Madrid that caught the attention of both the medical press and the Spanish newspapers. Two factors contributed to its popularity: the date that it happened 8only a year after the creation of the chair of Forensic Medicine at the faculties in Madrid and Barcelona); and the participation as experts of some of the most influential Spaniards in forensic medicine and Spanish toxicology such as Pere Mata I Fontanet (1811-1877). Pere Mata carried out important work in the three fields which decisively contributed to the homogeneity of the community of toxicologists: university training, academic literature and the professional organization. The analysis of a case of poisoning as the one developed in this work permits the consideration of many issues related totoxicology in the XIXth century: the constitution of a new academic subject, the creation of a community of experts, public controversies and the management of expert evidence at trials

Predictive Value of Positive Drug Screening Results in an Urban Outpatient Population.

Urine drug testing (UDT) has become an essential component in the management of patients prescribed opioid analgesics for the treatment of chronic non-malignant pain. Several laboratory methods are available to monitor adherence with the pharmacological regimen and abstinence from illicit or unauthorized medications. Immunochemical screening methods are rapid and economical, but they have limitations, including lack of specificity, and confirmatory methods are often necessary to verify presumptive positive results. We analyzed the results of confirmatory assays in an outpatient setting to determine the predictive value of presumptive positive urine drug screen results using an automated immunoassay for eight common drugs or drug classes. Positive predictive values (PPVs), in descending order, were as follows: cannabinoids (100%), cocaine (100%), opiates (86.8%), benzodiazepines (74.6%), oxycodone (67.6%), methadone (44.1%) and amphetamines (9.3%). The number of positive barbiturate results was too small to be included in the statistical analysis.