Heroin Research Articles

Lactose-free infant formula does not change outcomes of neonatal abstinence syndrome (NAS): a randomized clinical trial.

To determine if lactose-free formula, compared to lactose-containing formula, decreases the cumulative morphine dose required to treat neonatal abstinence syndrome (NAS). In a double-blind clinical trial, we randomized 74 infants (36-42 weeks gestation) at risk for developing NAS due to in-utero exposure to opioids to receive either lactose-free (Similac Sensitive®) or lactose-containing (Similac Advance®) infant formula. The primary outcome measure was the cumulative dose of morphine used for the treatment of NAS during the first 14 days of life. Data on 69 (4 withdrew consent and 1 ineligible)/74 randomized infants were analyzed. Patient characteristics between the infant groups fed lactose-free (n = 34) vs. lactose-containing (n = 35) infant formula were similar except more common maternal heroin abuse in the latter group (p = 0.013). Cumulative morphine dose (20.7 ± 19.8 vs. 23 ± 23.5 mg, p = 0.61) between the two groups were similar. Lactose-free vs. lactose-containing infant formula did not change the outcomes of infants with NAS.

Identification and characterization of tweets related to the 2015 Indiana HIV outbreak: A retrospective infoveillance study.

From late 2014 through 2015, Scott County, Indiana faced an HIV outbreak triggered by opioid abuse and transition to injection drug use. Investigating the origins, risk factors, and responses related to this outbreak is critical to inform future surveillance, interventions, and policymaking. In response, this retrospective infoveillance study identifies and characterizes user-generated messages related to opioid abuse, heroin injection drug use, and HIV status using natural language processing (NLP) among Twitter users in Indiana during the period of this HIV outbreak. Our study consisted of two phases: data collection and processing, and data analysis. We collected Indiana geolocated tweets from the public Twitter API using Amazon Web Services EC2 instances filtered for geocoded messages in the immediate pre and post period of the outbreak. In the data analysis phase we applied an unsupervised machine learning approach using NLP called the Biterm Topic Model (BTM) to identify tweets related to opioid, heroin/injection, and HIV behavior and then examined these messages for HIV risk-related topics that could be associated with the outbreak. More than 10 million geocoded tweets occurring in Indiana during the immediate pre and post period of the outbreak were collected for analysis. Using BTM, we identified 1350 tweets thought to be relevant to the outbreak and then confirmed 358 tweets using human annotation. The most prevalent themes identified were tweets related to self-reported abuse of illicit and prescription drugs, opioid use disorder, self-reported HIV status, and public sentiment regarding the outbreak. Geospatial analysis found that these messages clustered in population dense areas outside of the outbreak, including Indianapolis and neighboring Clark County. This infoveillance study characterized the social media conversations of communities in Indiana in the pre and post period of the 2015 HIV outbreak. Behavioral themes detected reflect discussion about risk factors related to HIV transmission stemming from opioid and heroin abuse for priority populations, and also help identify community attitudes that could have motivated or detracted the use of HIV prevention methods, along with helping identify factors that can impede access to prevention services. Infoveillance approaches, such as the analysis conducted in this study, represent a possibly strategy to detect "signal" of the emergence of risk factors associated with an outbreak though may be limited in their scope and generalizability. Our results, in conjunction with other forms of public health surveillance, can leverage the growing ubiquity of social media platforms to better detect opioid-related HIV risk knowledge, attitudes and behavior, as well as inform future prevention efforts.

Neurotransmitter system aberrations in patients with drug addiction.

Drug dependence may affect the neurotransmitter system levels in the human body. This study recruited 113 healthy control subjects, 118 heroin-dependent patients and 118 methamphetamine-dependent patients and examined the serum 5-HT, dopamine, glutamate and norepinephrine levels in the 349 volunteers. ELISA assays demonstrated that the serum 5-HT levels were significantly reduced in the drug-dependent patients, whereas the serum dopamine and glutamate levels were both significantly increased in the drug-dependent patients when compared with control subjects. In contrast, the norepinephrine levels did not exhibit a significant difference between the drug-dependent and control subjects. We also used qRT-PCR to analyze the transcriptional expression levels of 5-HT1A, 5-HT1B, dopmaine-D1 and dopamine-D2 receptors in the blood of drug-dependent patients and controls, and the results show that only 5-HT1B receptor levels were dysfunctional in the heroin abusers. In addition, our results suggest that serum 5-HT, dopamine, and glutamate levels had the potential to differ between drug abusers and controls, and combining those three potential biomarkers provided an accurate means to differentiate between the drug-dependent and control subjects. Taken together, our study reveals a differential profile of neurotransmitters in the heroin-dependent patients and methamphetamine-dependent patients, and this revelation may contribute to understanding the pathophysiology of drug addiction.

Increased expression of plasma hsa-miR-181a in male patients with heroin addiction use disorder.

BackgroundDrug addiction is an uncontrolled, chronic, and recurrent encephalopathy that presently lacks specific and characteristic biomarkers for diagnosis and treatment. As regulators of gene expression, microRNAs (miRNAs) are increasingly used for diagnostic and prognostic purposes in various disease states. Previous studies indicated that miRNAs play important roles in the development and progression of drug addictions, including addiction to methamphetamine, cocaine, alcohol, and heroin.MethodsWe identified significant miRNAs using the microarray method and then validated the hsa‐miR‐181a expression levels in 53 heroin addiction patients and 49 normal controls using quantitative real‐time reverse transcription‐polymerase chain reaction (qRT‐PCR). Finally, the potential associations between transcriptional levels in heroin addiction patients and their clinicopathological features were analyzed.ResultsA total of 2006 miRNAs were differentially expressed between heroin addiction patients and normal controls. The top 10 up‐regulated miRNAs in patients were hsa‐miR‐21a, hsa‐miR‐181a, hsa‐miR‐4459, hsa‐miR‐4430, hsa‐miR‐4306, hsa‐miR‐22‐3P, hsa‐miR‐486‐5P, hsa‐miR‐371b‐5P, hsa‐miR‐92a‐3P, and hsa‐miR‐5001‐5P. The top 10 down‐regulated miRNAs in patients were hsa‐miR‐3195, hsa‐miR‐4767, hsa‐miR‐3135b, hsa‐miR‐6087, hsa‐miR‐1181, hsa‐miR‐4785, hsa‐miR‐718, hsa‐miR‐3141, hsa‐miR‐652‐5P, and hsa‐miR‐6126. The expression level of hsa‐miR‐181a in heroin addiction patients was significantly increased compared with that in normal controls (P < .001). The area under the receiver operating characteristic curve of hsa‐miR‐181a was 0.783, the sensitivity was 0.867, and the specificity was 0.551.ConclusionsThe increased expression of hsa‐miR‐181a in the plasma of heroin patients may be a consequence of the pathological process of heroin abuse. This study highlights the potential of hsa‐miR‐181a as a novel biomarker for the diagnosis of heroin addiction.

The Effectiveness of Cognitive Rehabilitation on Improving Response Inhibition in Men with Heroin Abuse

The Effectiveness of Cognitive Rehabilitation on Improving Response Inhibition in Men with Heroin Abuse

Correlation Between Protamine-2 and miRNA-122 in Sperm from Heroin-addicted Men: A Case-Control Study.

Recreational use of illicit drugs is one of the main factors affecting male fertility. However, the mechanisms of heroin smoke-associated damage to mature spermatozoa are still completely unknown. The aim of this study was to concomitantly examine the levels of protamine-2 gene and protein concentrations, the amount of miRNA-122 in seminal plasma and semen analysis findings in heroin-addicted men. In a case control study, twenty-four fertile men that lacked any recreational drug abuse were considered as the healthy group, and 24 addicted men who used only heroin for at least four months were selected as the addicted group. Semen samples were gathered by masturbation after 2 - 5 days of sexual abstinence. Following the preparation of a semen analysis by computer-assisted sperm analysis according to WHO (2010), the level of protamine-2 gene expression in sperm and miRNA-122 in seminal plasma was measured using real-time sqPCR. Also, protamine-2 protein concentrations were quantified by nuclear protein extraction, SDS-Page and western blotting. Among the studied variables, body mass index (27.75±0.88 vs. 22.30±0.36, p=0.001), seminal pH (7.79±0.06 vs. 7.58±0.06, p=0.003), white blood cell count in semen (1.69±0.41 vs. 8.61±1.73, p=0.001), motility (65.51±2.57 vs. 41.96±3.58, p=0.001) and survival rate (87.41±1.00 vs. 71.50±4.59, p=0.002) of sperm cells was significantly different between the healthy and addicted groups. In addition, the levels of protamine-2 gene and protein expression in the addicted group (0.05±0.02 and 0.10±0.02, respectively) were significantly lower than the healthy group (3.59±0.94 and 0.27±0.06, respectively) (p=0.002 and p=0.017, respectively). Seminal miRNA-122 levels in addicted men (3.51±0.73) were statistically higher than in healthy men (1.52±0.54) (p=0.034). However, there were some significant relationship between the studied parameters and addiction (p<0.05). This is one study on human infertility that evaluates the effects of heroin on protamine deficiency and seminal small RNAs expression levels. Heroin abuse may lead to male infertility by causing leukocytospermia, asthenozoospermia, protamine deficiency, and seminal plasma miRNA profile alteration.

Differences in the amplitude of low-frequency fluctuation between methamphetamine and heroin use disorder individuals: A resting-state fMRI study.

IntroductionMethamphetamine has surpassed heroin as the most popular abused drug in China. Although the use of both heroin and methamphetamine leads to use disorders through dysfunction of the dopamine pathway, the incidence of psychiatric disorder caused by methamphetamine abuse is higher than the incidence of psychiatric disorder caused by heroin abuse. The difference in resting‐state function between heroin use disorder (HUD) and methamphetamine use disorder (MAUD) and the relationship between resting‐state function and psychiatric disorder related to MAUD are unknown.MethodsIn the present study, 21 male individuals with MAUD, 21 demographically matched individuals with HUD, and 21 normal controls (NC) were recruited. The amplitude of low‐frequency fluctuation (ALFF) during resting‐state brain function was measured by magnetic resonance imaging. Psychiatric status was evaluated by the Symptom Checklist‐90 (SCL90).ResultsIndividuals with MAUD had increased SCL90 scores compared to those of the NC for anxiety, paranoia, and additional items, and the hostility score was significantly increased compared to that of individuals with HUD. There is no significant difference between HUD and NC individuals. Individuals with MAUD had increased ALFF compared to those of the NC for thalamus, right postcentral, and right inferior temporal gyri, but a decreased ALFF in the cerebellum. Individuals with HUD had significantly increased ALFF compared to those of the NC for left middle frontal gyrus but a decreased ALFF in the left postcentral gyrus. Individuals with MAUD had significantly increased ALFF compared to those of the HUD for thalamus, the right inferior temporal, and bilateral postcentral gyri, and the ALFF of cerebellum and left middle frontal was significantly increased.ConclusionsMethamphetamine can induce more serious psychiatric disorders than heroin. The resting‐state function involved in mood adjustment, the auditory, and memory‐related brain regions may affect psychotic symptoms related to MAUD.

Identification of characteristic heroin metabolites in urine based on data-mining technology and multivariate statistics analysis combined with a targeted verification approach for distinguishing heroin abusers

A common phenomenon shows that ingestion of opium poppy shell-containing drugs can result in a “false-positive” urinalysis test result for mandatory or workplace heroin abuse screening. Owing to the short detection window (8 h in urine) of the characteristic heroin metabolite 6-monoacetylmorphine (6-MAM) confirmation or exclusion of heroin abusers still presents major challenges for toxicologists. In this work, we developed an ultra-performance liquid chromatography-time-of-flight mass spectrometry method (UPLC-TOF-MS) with online data acquisition and multiple post-data-mining technologies combined with a multivariate statistical and batch validation analysis workflow to assess the characteristic urine metabolites of heroin abusers. Based on the proposed methods, 28 characteristic metabolites were structurally identified, and their fragmentation patterns and metabolite pathways were also summarized. Correlation analysis was used to investigate the internal relationship and similarities among the identified metabolites, and seven representative metabolites were selected as “Target-metabolites”. Multi-batch urine of samples of heroin abusers were certified based on the UPLC-MS/MS method for further validation of the practicability of using this method for routine analysis. Overall, the target-metabolites can be utilized as assistant “biomarkers” in workplace or mandatory drug screenings. This approach encourages further studies on the development of the “false-positive” identification system.

Dysregulated expression of the alternatively spliced variant mRNAs of the mu opioid receptor gene, OPRM1, in the medial prefrontal cortex of male human heroin abusers and heroin self-administering male rats.

Heroin, a mu agonist, acts through the mu opioid receptor. The mu opioid receptor gene, OPRM1, undergoes extensive alternative splicing, creating an array of splice variants that are conserved from rodent to humans. Increasing evidence suggests that these OPRM1 splice variants are pharmacologically important in mediating various actions of mu opioids, including analgesia, tolerance, physical dependence, rewarding behavior, as well as addiction. In the present study, we examine expression of the OPRM1 splice variant mRNAs in the medial prefrontal cortex (mPFC), one of the major brain regions involved in decision-making and drug-seeking behaviors, of male human heroin abusers and male rats that developed stable heroin-seeking behavior using an intravenous heroin self-administration (SA) model. The results show similar expression profiles among multiple OPRM1 splice variants in both human control subjects and saline control rats, illustrating conservation of OPRM1 alternative splicing from rodent to humans. Moreover, the expressions of several OPRM1 splice variant mRNAs were dysregulated in the postmortem mPFCs from heroin abusers compared to the control subjects. Similar patterns were observed in the rat heroin SA model. These findings suggest potential roles of the OPRM1 splice variants in heroin addiction that could be mechanistically explored using the rat heroin SA model.

SAT-372 A Case of Hypercalcemia Secondary to Rhabdomyolysis Induced by Heroin Use

Background: Rhabdomyolysis is a potential life threatening condition defined as injury of the skeletal muscle, which results in the release of intracellular contents into the circulation. This muscle injury is often associated with the development of myoglobinuria, electrolyte abnormalities, and often ARF; it can be caused by diverse mechanisms including drugs and toxins. We present a case of rhabdomyolysis complicated by hypercalcemia and ARF in a patient with a history of polysubstance abuse after using intravenous heroin. Case: A 28 y/o male with h/o polysubstance comes to the ED with c/o fatigue, nausea, vomiting and decreased urine output for about 5 days; patient acknowledged using heroin and afterwards he developed weakness and tenderness in upper and lower extremities. Additionally he admitted cocaine and marijuana abuse. On physical exam vital signs were unremarkable and he had some mild tenderness to palpation mostly of the quadriceps bilaterally. Laboratory data was significant for acute kidney injury (cr 11.33 mg/dl, n: 0.7–1.5 mg/dl) and CPK 171920 u/l (n: 22–269 u/l). He received 2 L of NS in the ED and was started on NS at 100cc/hour.He underwent hemodialysis on day 2; initially he was treated for hypocalcemia with calcium and vitamin D supplementation until day 11 were hypercalcemia (calcium 12.7 mg/dl, n: 8.7–10.3 mg/dl; ionized calcium 1.7 mmol/l, n: 1.12–1.32) was noted; this was associated with concomitant suppression of PTH (5 pg/ml, n: 10–65 pg/ml). He remained asymptomatic from calcium abnormalities during his hospitalization, his urine output recovered progressively, hemodialysis was discontinued on day 13. Upon discharge was recommended to f/u with nephrology. Discussion: Various neurological and neuromuscular complications of heroin abuse have been described; one of these is rhabdomyolysis; its pathophysiology in heroin abuse is thought to be multifactorial; including acidosis, hypoxia, muscle compression and adulterants found in heroin. Narcotics may also have direct cell toxicity and alter membrane transport. Usually upon initial presentation hypocalcemia is one of the most common electrolyte imbalances seen with rhabdomyolysis. The proposed mechanism is precipitation of serum calcium salts in necrotic muscle. This may be followed by hypercalcemia during the diuretic phase of ARF which appears to be a relatively unusual complication associated with the presence of severe muscle damage due to metastatic calcium salts that are liberated from the necrotic muscle and the return to the serum. Conclusion: This case report highlights the importance of recognizing potential electrolyte imbalances in patients with rhabdomyolysis; it appears, that concomitant rhabdomyolysis and ARF are needed for a patient to develop hypercalcemia.Serum calcium should always be routinely measured and the appropriate treatment should be implemented to improve outcomes.

Determining the Concentration of Morphine and Codeine in Poppy Seeds for Drug Test Defense

TRAVIS HARDING, MARK FLOOD, ANDREAS BAUR, and KRISTY HENSON. Department of Natural Sciences, Fairmont State University, Fairmont, WV, 26554. Determining the Concentration of Morphine and Codeine in Poppy Seeds for Drug Test Defense.The purpose of this research was to determine the concentration of opiates, morphine and codeine, in poppy seeds in effort to combat the “poppy seed defense”. Morphine and codeine are naturally occurring substances belonging to a class of drugs labeled opioid analgesics, commonly known as narcotics. There has been an increase in concerns involving false-positive opiate drug test. Distinguishing between legitimate dietary poppy seed ingestion versus non-prescribed opiate or heroin abuse is important for individuals subject to routine drug testing. Poppy seeds were purchased from supermarkets and were mechanically ground up by either 1) a blender or 2) a mortar and pestle, which best simulates human mastication. The ground up seed products were placed in a solution matrix to simulate a human oral cavity (target concentration of 30 ng/mL). Morphine and codeine concentrations from the samples will be tested using Thin Layer Chromatography, immunoassay (Opiate ELISA), and a validated Gas Chromatography-Mass Spectroscopy (GC-MS) Selected Ion Monitoring (SIM) system. The screening cutoff concentration ranges from 0 ng/mL to 40 ng/mL. Preliminary results from previous constructed experiments showed a positive color change for the opiate assay from blue to yellow within one hour (National Institute on Drug Abuse Research). The average absorbance at a dual wavelength of 450 nm and 650 nm was 1.238 correlating to a morphine concentration of about 5.1 ng/mL. Initial GC-MS results showed morphine and internal standard morphine-D3 had mass to charge ratios of 432 m/z and 429 m/z with an average concentration of 7.5 ng/mL respectively. This research was made possible by NASA West Virginia Space Grant Consortium, Training Grant #NNX15AI01H.

Cross-Generational THC Exposure Alters Heroin Reinforcement in Adult Male Offspring

BackgroundAn emerging area of preclinical research has investigated whether drug use in parents prior to conception influences drug responsivity in their offspring. The present work sought to further characterize such effects with cannabis by examining whether a parental THC history modified locomotor sensitization to morphine and self-administration of heroin in adult progeny. MethodsMale and female Sprague Dawley rats were exposed to eight injections of 0 or 1.5 mg/kg THC during adolescence and bred with subjects from the same dose group. In Experiment 1, adult male and female offspring (F1-THC and F1-Veh) underwent locomotor sensitization procedures with morphine over five trials followed by a 5-day abstinence period and a final morphine challenge. In Experiment 2, subjects were trained to self-administer heroin and tested under a number of conditions (FR1, FR5, FR10, PR, dose response assessment, extinction, cue- + stress-induced reinstatement). ResultsGermline THC exposure had no effect on morphine locomotor sensitization. However, F1-THC males displayed a reduced motivation to self-administer heroin relative to F1-Veh males. ConclusionsThe present data indicate that parental THC exposure alters the reinforcing properties of heroin in a sex-specific manner. As such, mild to moderate cannabis use during adolescence may alter heroin abuse liability for males in the subsequent generation, but have limited effects on females.

Vascular Injuries in Intravenous Drug Addicts—A Single-Center Experience

Infected false aneurysms (IFA) caused by intravenous drug abuse are uncommon but challenging lesions. The best approach for the surgical management of this condition is still unknown. The aim is to present a single-center 14-year experience in the IFA treatment in intravenous drug abusers, thus providing additional data regarding the treatment options and outcome in these patients. A retrospective analysis of 32 consecutive patients with vascular injuries secondary to intravenous drug abuse, during the period from January 2004 to April 2018, was performed. Data of interest were extracted from patients' medical history records, anesthesia charts, and database implemented in daily practice, or were obtained by personal contact. The diagnosis was set based on history, physical examination and/or color Doppler sonography, multidetector computed tomographic angiography, and digital subtraction angiography. The outcome included graft patency, limb amputation, and mortality. During study period, 32 heroin abusers, predominantly males (81%), were surgically treated due to vascular injuries, with mean age of 35.2 years. The vast majority of patients have had an injury of the lower extremity blood vessels (84.3%) and the common femoral artery was the most common site of injury (59.4%). Three-quarters of patients underwent resection of the false aneurysm and ligation of the artery without reconstruction of the blood vessel. In 7 cases (21.9%), arterial reconstruction was performed with overall failure rate of 42.86%. The overall mortality rate was 6.25% and the rate of extremity salvage was 96.7%. The best treatment option is yet to be found, but based on the results of the present study, ligation of affected artery without revascularization seems to be an efficient, safe, and optimal treatment method, with minor risk of the extremity loss.

Heroin Abuse among IDU and Local PO Dispensing Levels in Ontario Cities

Background: Amid Ontario’s growing opioid crisis, heroin abuse remains widespread in select urban areas and contributes to a large proportion of opioid overdoses provincially. Compared to prescription opioids (POs), heroin is especially hazardous to abuse since it is illicitly manufactured and frequently consumed by injection. PO abuse can also transition to heroin if access to preferred POs is impacted via diversion, dispensing or prescribing. However, the dynamics between preferences for heroin and local PO saturation (in this case, dispensing) are not well understood.&#x0D; Methods: Heroin abuse data were gathered from PHAC’s I-Track surveillance system while PO dispensing data were from the Ontario Drug Benefit (ODB) claims database. Using an unmatched repeated cross-sectional design, datasets spanning 2003 to 2011 were merged. The hierarchical structure consisted of individual-level I-Track responses nested within year and again within five city-level (Kingston, London, Sudbury, Thunder Bay and Toronto) dispensing rates. Mixed-effects multilevel logistic regressions were used to examine relationships.&#x0D; Results: Almost one third (30.5%) of I-Track respondents abused heroin in the previous six months with marked variation by city, from roughly half of Toronto participants (51.0%) to about one in twenty (5.2%) in Thunder Bay. The final multivariate model for heroin abuse contained morphine dispensing (OR=1.04, p=0.011), present age (OR=0.99, p=0.045) and age of first injection (OR=0.97, p≤0.001). That is, considering age and age of first injection, heroin abuse was 4.4% more likely among IDU with each increase in annual morphine dispensing rates in their respective cities.&#x0D; Implications: The connection between heroin abuse and dispensing rates of chemically similar morphine, but not other POs, reflects a substitution effect for specific opioid types regardless of whether illicit or prescription. Precautions should be taken to prevent heroin abuse and establish harm reduction strategies before expected interference to local dispensing levels of any chemically analogous POs (particularly morphine).

Altered serum microRNA expression profile in subjects with heroin and methamphetamine use disorder

ObjectivesDrug abuse is one of the most severe global social and public health problems, especially in China. However, objective blood biomarkers that are easy to detect are still in great need. This study was aim to explore the expression pattern of circulating microRNAs (miRNAs) in subjects with drug addiction and test the potential of altered serum miRNAs as noninvasive diagnostic tools for drug abuse. MethodsSerum samples were obtained from 42 heroin abusers, 42 methamphetamine (MA) abusers and 42 controls. Microarray-based miRNA analysis was first applied to screen unique serum miRNA profiles in drug abusers on a training set of serum samples from 12 heroin abusers, 12 MA abusers and 12 control subjects. The expression levels of selected candidate miRNAs were subsequently verified in individual samples of the training set and further confirmed independently in a validation set of samples from 30 heroin abusers, 30 MA abusers and 30 controls using real-time quantitative polymerase chain reaction (RT-qPCR). ResultsMicroarray analysis identified 116 and 109 significantly altered miRNAs in heroin abusers and MA abusers, respectively. Three miRNAs, including let-7b-5p, miR-206 and miR-486-5p, were verified to be significantly and steadily increased in heroin abusers, and miR-9-3p was significantly increased in MA abusers compared with normal controls. The areas under the curve (AUCs) of the ROC curve of these miRNAs ranged from 0.718 to 0.867. ConclusionsOur study raises the possibility that the altered serum miRNAs could potentially be used as an auxiliary tool to identify individuals in drug abuse and addiction.

Determination of Morphine, Fentanyl and Their Metabolites in Small Sample Volumes Using Liquid Chromatography Tandem Mass Spectrometry.

The USA and numerous other countries worldwide are currently experiencing a public health crisis due to the abuse of heroin and illicitly manufactured fentanyl. We have developed a liquid chromatography tandem mass spectrometry (LC-MS-MS)-based method for the detection of morphine, fentanyl and their metabolites, including morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), normorphine, norfentanyl and deuterated internal standards in limited sample volumes with the limit of detection of 5.0/0.5ng/mL (morphine, M3G, M6G, normorphine/fentanyl, norfentanyl). The inter-assay precision (%CV) was less than 12% for all assays, and the inter-assay bias (%) was less than 5%. The ruggedness of the method, dilution effect and carryover were also investigated as part of the study. The simultaneous quantification of morphine, fentanyl and its metabolites via this simple and time- and cost-efficient method could be successfully applied to samples taken for pharmacokinetic evaluation (antemortem and postmortem) after a single dose of morphine or co-administration of morphine with other drugs (e.g., fentanyl) in rats.

Adolescent cannabis exposure increases heroin reinforcement in rats genetically vulnerable to addiction

On the basis of epidemiological studies it has been proposed that cannabis use plays a causal role in the abuse of highly addictive drugs (Gateway Hypothesis). However, epidemiological studies are intrinsically unable to provide evidence of causality. Experimental studies can provide this evidence but they are feasible only in animal models and to date such evidence is lacking. In view of the importance of genetic factors in drug abuse, we investigated the influence of adolescent cannabis exposure on adult heroin reinforcement in two inbred rat strains differentially vulnerable to drugs of abuse, addiction prone Lewis (LEW) and addiction resistant Fischer 344 (F344) strains.Male LEW and F344 rats aged six weeks were exposed to increasing Δ9-tetrahydrocannabinol (THC) doses, twice a day for 3 days (2, 4, 8 mg/kg, i.p.). At adulthood they were allowed to self-administer heroin (0.025 mg/kg) under both Fixed- (FR) and Progressive- (PR) ratio schedules of responding. Following extinction, responding was reinstated by drug-cues and/or by heroin priming.THC pre-exposure increased responding for heroin and heroin intake under FR-3 and FR-5 as well as PR protocols and increased breaking point in PR schedules in LEW but not F344 rats. Drug cues and heroin priming reinstated responding in LEW and F344, but THC pre-exposure increased reinstatement by priming in LEW rats and by cues in F344 rats.These observations show that in genetically predisposed individuals, adolescent cannabis exposure increases heroin reinforcing properties, thus providing a mechanism for a causal role of adolescent cannabis use in heroin abuse.

Induction of Noninflammatory Pain in an Experimental Foot Lameness Model in Horses

The mechanism by which nonsteroidal anti-inflammatory drugs mitigate pain caused by a heart bar shoe (HBS) model of lameness is unknown. The purpose of this study was to determine if this HBS model of lameness induces inflammation in horses. Five healthy adult horses from a university teaching herd were enrolled. A custom HBS was applied to the left front foot of each horse, followed by induction of the American Association of Equine Practitioners Lameness Score of 4. Inflammatory markers including serum amyloid A (SAA) concentration, local venous tumor necrosis factor alpha and prostaglandin E2 (PGE2) concentrations, and foot temperature were measured before lameness induction and 1, 3, and 13 hours after lameness induction. Lameness induction using the HBS model did not significantly increase production of plasma SAA, tumor necrosis factor alpha, or PGE2 concentrations at measured time points. Immediately and 1 hour after lameness induction, dorsal coronary band temperatures were higher in the left front foot compared with the right front foot, but there was no difference at 3 or 13 hours. In conclusion, the HBS model did not induce inflammation as assessed by select inflammatory markers, suggesting that the HBS model induces mechanical rather than inflammatory pain. This should be considered when using the HBS model to assess analgesic drugs in horses.

Prevalence, Clinical Features and Comorbidities of Alcohol and Substance Use Disorders Among Patients Admitted to Psychiatry Outpatient Clinic

Objective: Comorbidity of substance use disorders and other psychiatric disorders is common. However, data on the prevalence of substance use disorders in general psychiatric outpatient population is rather scarce. Method: In order to investigate the prevalence of substance use disorders among the patients who admitted to the general psychiatric outpatient unit and followed with any psychiatric diagnosis, 734 consecutive adult patients were included in this study. Michigan Alcoholism Screening Test–AD was administered to these patients. Substance screening form and SCID-I dependence module were administered to 47 patients (6.4%) who had a MAST-AD score above 4. Later, SCID-II and the rest of SCID-I were administered to 33 patients (4.5%) who met any diagnostic criteria on this module. Results: From these 734 patients, 33 (4.5%) had alcohol or substance use disorder: Five patients (0.7%) had alcohol dependence, 26 patients (3.5%) had alcohol abuse and 3 patients (0.4%) had multiple substance dependence. There were 9 patients (1.2%) with cannabis abuse, 4 patients (0.5%) with ecstasy abuse, 1 patient (0.1%) with heroin abuse, 1 patient with (0.1%) biperiden abuse and 9 patients (1.2%) with benzodiazepin abuse. From this 33 patients, 7 (1.0%) patients were diagnosed with borderline personality disorder, 2 (0.3%) with antisocial personality disorder, 1 patient (0.1%) with paranoid personality disorder, 1 patient (0.1%) with narcissistic personality disorder, 2 patients (0.3%) with avoidant personality disorder, 1 patient (0.1%) with schizoid personality disorder and 1 patient (0.1%) with dependent personality disorder. With SCID-I, we found 5 (0.7%) major depressive disorder, 3 (0.4%) bipolar I, 1 (0.1%) distimic disorder, 2 (0.3%) paranoid schizophrenia, 1 (0.1%) delusional disorder, 3 (0.4%) generalized anxiety disorder, 3 (0.4%) panic disorder, 1 (0.1%) panic disorder with agoraphobia, 1 (0.1%) anxiety disorder not otherwise specified, 1 (0.1%) social phobia and 1 (0.1%) post traumatic stress disorder. Conclusion: These results suggest that substance use disorders are prevalent among general psychiatric outpatients. Substance use disorders should be carefully assessed in the patients with diagnoses of mood disorders, anxiety disorders or personality disorders.

La literatura contra el virus del poder : un estudio sobre "Naked lunch" de William Burroughs

This work is an inmersion inside the first part of the works of the american writer William Burroughs. The center of it is Naked Lunch, his most famous novel. Through the lenght of this work we discuss how the the literature of this author faces the dominant ideology of the late capitalism as to its domination on the individuais subjects to its system, begining with junkies (people addicted to heroin) up to all the beings which compose it, In dialogue with some the strongest critics of this system, such as the philosophers Theodore W. Adorno and Max Horkheimer, the role of literatura is iluminated, especially in it most radical forms, inside the struggle to find freedom inside the political, social, economical, cultural, and bodily submission to the capitalist hegemony, its instititutions and forms of goverment.