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Director's Report to the National Advisory Council on Drug Abuse - February, 2006

International Research

Research Supported by International Program Supplement Suggests Emancipatory Research Can Promote Recovery

Dr. Alexandre Laudet, National Development and Research Institutes, Inc. (NDRI), and Mr. Gordon Storey, Self-help Addiction Resource Center, Melbourne, presented their research, "Emancipatory Research In The Addiction Field: A Partnership To Promote Empowerment And To Understand The Recovery Process" at the September 2005 Congress of the World Federation for Mental Health in Cairo, Egypt. The authors conclude that emancipatory research can promote recovery by empowering patients, compiling experiential expertise into a credible knowledge base, and improving access to services. Dr. Laudet and Mr. Storey are conducting a pilot study to identify and compare recovery-promoting factors and various paths to resolving harmful drug use in Australia and the United States, supported by an International Program Administrative Supplement, R01-DA014409-03S1.

DISCA-Supported Research Examines Genetic Link to Smoking Cessation

2004 NIDA Distinguished International Scientist Dr. Ivan Berlin, Groupe Haspitalier Universitaire Pitié-Salpêtrière, France, and his DISCA partner, Dr. Liro S. Covey, New York State Psychiatric Institute, have published their joint research in Nicotine & Tobacco Research, 7(5), pp. 725-728, 2005. The authors report on their studies of a polymorphism in the D2 dopamine receptor and its predictive value for the likelihood of successfully quitting smoking.

DISCA-Supported Research Demonstrates Effectiveness of HIV/AIDS Prevention Education in a Chinese Drug Abuse Treatment Setting

2005 NIDA Distinguished International Scientist Dr. Min Zhao, China, and her DISCA partner, Dr. Clyde B. McCoy, University of Miami, have published their joint research in the Journal of Urban Health, Volume 82, Number 3, Supplement 4, iv84-91. The authors found that HIV/AIDS prevention education increased HIV knowledge, improved understanding of HIV prevention methods, and changed attitudes toward HIV/AIDS among a population of injection drug users undergoing treatment in Shanghai.

Research Publications by International Program Alumni Alumni of the NIDA International Program research training and exchange programs authored or coauthored the following recent articles indexed by PubMed:

Former NIDA INVEST Drug Abuse Research Fellows

Clinical Characterization of Use of Acamprosate and Naltrexone: Data from an Addiction Center in India

Basu, D., Jhirwal, O.P., Mattoo, S.K. Am J Addict. 14(4), pp. 381-395, July-September 2005. (INVEST Fellow: Debasish Basu, India, 2001-2002). There are several queries on the effectiveness of acamprosate in pharmacoprophylaxis of alcohol dependence despite studies conducted over the last decade regarding its efficacy. In this retrospective chart review, 62 patients with ICD-10-diagnosed alcohol dependence who received treatment from an addiction center in India were studied to compare those on acamprosate or naltrexone versus those on no prophylactic drugs with regard to their demographic and clinical background and short-term outcome after treatment. Compared to those on naltrexone or no drugs, significantly more patients on acamprosate came from higher socioeconomic strata and had fewer family/marital complications and less comorbid use of opioids and other drugs; however, they also had more liver function impairment and alcoholic liver disease and a higher average duration of relapse in the past (p < 0.05 or less in each case). The group on no drugs had significantly less family/social support (p = 0.006) and poorer motivation rating (p < 0.001) than the other two groups on drugs. Intent-to-treat analysis showed that there was a non-significant trend of a higher proportion of acamprosate patients remaining abstinent (77%) than those on naltrexone (36%) or no drug (50%). At follow-up, acamprosate patients had significantly better functioning in several areas. However, because many of the baseline patient characteristics might themselves have influenced the outcome, no conclusion should be drawn from this data regarding the efficacy of the drug. Logistic regression analysis showed that both family/social support and acamprosate appeared to contribute modestly toward explaining the variance in short-term outcome.

Anti-Allodynic Interactions Between NMDA Receptor Channel Blockers And Morphine Or Clonidine In Neuropathic Rats

Malyshkin, A.A., Medvedev, I.O., Danysz, W., Bespalov, A.Y. Eur J Pharmacol. 519(1-2):80-85, September 5, 2005. (INVEST Fellow: Anton Bespalov, Russia, 1994-1995). Previous studies suggested that combining N-methyl-d-aspartate (NMDA) receptor antagonists with either mu-opioid agonist morphine or alpha2-adrenoreceptor agonist clonidine results in the significant synergistic enhancement of analgesic activity in the animal models of acute and neuropathic pain. When given alone, NMDA receptor antagonists, morphine and clonidine are capable of attenuating tactile allodynia associated with chronic nerve injury. The present study aimed to assess anti-allodynic effects of these compounds and to test additivity of these interactions using isobolographic analysis. Adult male Wistar rats with unilateral loose ligation of sciatic nerve developed significant tactile allodynia (between-paw difference of about 18-20 g). In separate groups of animals, dose-dependent anti-allodynic activity was confirmed for memantine (1.8-17.8 mg/kg), neramexane (1.8-17.8 mg/kg), morphine (1-10 mg/kg) and clonidine (0.01-0.1 mg/kg). In a subsequent series of experiments, memantine (or neramexane) and morphine (or clonidine) were co-administered at the fixed equi-effective dose ratios (six dose levels per drug combination). None of the tested combinations produced supra-additive, synergistic effects. In fact, memantine+clonidine, neramexane+clonidine and morphine+neramexane were producing simple additive effects, while morphine+memantine was characterized as the infra-additive combination. Thus, despite expectations based on previous studies, NMDA receptor channel blockers, memantine and neramexane, produce no synergistic interactions with either morphine or clonidine when administered acutely to rats with nerve injury-induced tactile allodynia.

Multi-level Analysis of Causal Attribution of Injury to Alcohol and Modifying Effects: Data from Two International Emergency Room Projects

Cherpitel ,C.J., Bond, J., Ye,Y., Borges, G., Room, R., Poznyak, V. and Hao, W. Drug Alcohol Depend. October 26, 2005 [Epub ahead of print] (INVEST Fellow: Guilherme Borges, Mexico, 1997-1998). Although alcohol consumption and injury has received a great deal of attention in the literature, less is known about patient's causal attribution of the injury event to their drinking or factors which modify attribution. Hierarchical linear modeling is used to analyze the relationships of the volume of alcohol consumed prior to injury and feeling drunk at the time of the event with causal attribution, as well as the association of aggregate individual-level and socio-cultural variables on these relationships. Data analyzed are from 1955 ER patients who reported drinking prior to injury included in 35 ERs from 24 studies covering 15 countries from the combined Emergency Room Collaborative Alcohol Analysis Project (ERCAAP) and the WHO Collaborative Study on Alcohol and Injuries. Half of those patients drinking prior to injury attributed a causal association of their injury with alcohol consumption, but the rate of causal attribution varied significantly across studies. When controlling for gender and age, the volume of alcohol consumed and feeling drunk (controlling for volume) were both significantly predictive of attribution and this did not vary across studies. Those who drink at least weekly were less likely to attribute causality at a low volume level, but more likely at high volume levels than less frequent drinkers. Attribution of causality was also less likely at low volume levels in those societies with low detrimental drinking patterns, but more likely at high volume levels or when feeling drunk compared to societies with high detrimental drinking patterns. These findings have important implications for brief intervention in the ER if motivation to change drinking behavior is greater among those attributing a causal association of their drinking with injury.

Forensics: Age Written In Teeth By Nuclear Tests

Spalding, K.L., Buchholz, B.A., Bergman, L.E., Druid, H. and Frisen, J. Nature. 437(7057), pp. 333-334, September 15, 2005. (INVEST Fellow: Henrik Druid, Sweden, 2000-2001). Establishing the age at death of individuals is an important step in their identification and can be done with high precision up to adolescence by analysis of dentition, but it is more difficult in adults. Here we show that the amount of radiocarbon present in tooth enamel as a result of nuclear bomb testing during 1955-63 is a remarkably accurate indicator of when a person was born. Age is determined to within 1.6 years, whereas the commonly used morphological evaluation of skeletal remains and tooth wear is sensitive to within 5-10 years in adults.

Toxicological Findings And Manner Of Death In Autopsied Users Of Anabolic Androgenic Steroids

Petersson, A., Garle, M., Holmgren, P., Druid, H., Krantz, P. and Thiblin, I. Drug Alcohol Depend. August 29, 2005 [Epub ahead of print] (INVEST Fellow: Henrik Druid, Sweden, 2000-2001). With the aims of characterizing patterns in toxicological profile and manner of death in deceased users of anabolic androgenic steroids (AAS), a retrospective autopsy protocol study of 52 deceased users of AAS was undertaken. The AAS users were compared to 68 deceased users of amphetamine and/or heroin who were consecutively tested and found to be negative for AAS. Use of AAS was in the majority of cases (79%) associated with concomitant use of psychotropic substances. AAS-related deaths differed in several respects from deaths among users of heroin or amphetamine, most strikingly with regard to: (a) the median age at death, which was significantly lower for AAS users (24.5 years) than for users of heroin and/or amphetamine (34 and 40 years, respectively); (b) the manner of death, with AAS users dying significantly more often from homicide or suicide than users of other drugs; and (c) the body mass index (BMI), with AAS users exhibiting significantly higher BMI than users of other drugs. These results support the earlier reported association between use of AAS and use of other psychoactive substances. In addition, the data suggest that AAS users are more likely to become involved in incidents leading to violent death and have a higher risk of dying at a younger age than users of other drugs.

mu Opioid Receptor Agonist DAMGO-Induced Suppression Of Saccharin Intake In Lewis and Fischer Rats

Liu, C. and Grigson, P. Brain Res. October 27, 2005 [Epub ahead of print] (INVEST Fellow: Chuang Liu, China, 2000-2001). Rats suppress intake of a saccharin cue when paired with a drug of abuse such as morphine or cocaine. Relative to Lewis rats, Fischer rats exhibit greater avoidance of a saccharin cue following saccharin-morphine pairings. Thepresent study used the mu agonist, [d-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin (DAMGO), to test whether strain differences in sensitivity of the mu receptor contribute to this effect. Water-deprived Lewis and Fischer rats were given 5 min access to 0.15% saccharin followed by an icv injection of either DAMGO (0.5 microg/1 microl/rat) or an equal volume of saline. There were six taste-drug pairings occurring at 48 h intervals. The results showed that, relative to the saline treated controls, all rats reduced intake of the saccharin cue following saccharin-DAMGO pairings. No differences occurred between strains. These data suggest that greater morphine-induced suppression of saccharin intake by the Fischer rats is not likely mediated by differences in sensitivity of the mu receptor. Other mechanisms are implicated.

Systemic And Site-Specific Effects Of A-425619, A Selective TRPV1 Receptor Antagonist, On Wide Dynamic Range Neurons In CFA-Treated and Uninjured Rats

McGaraughty, S., Chu, K.L., Faltynek, C.R. and Jarvis, M.F. J Neurophysiol. September 14, 2005 [Epub ahead of print] (INVEST Fellow: Steve McGaraughty, Canada, 1995-1996). Systemic administration of A-425619, a potent and selective TRPV1 receptor antagonist that does not readily enter the CNS, produces antinociception in several rat models of pathological nociception, including complete Freund's adjuvant (CFA)-induced thermal hyperalgesia. In order to further understand the peripheral mechanisms of TRPV1-related antinociception, we examined the effects of systemic and site-specific injections of A-425169 on evoked and spontaneous firing of spinal wide dynamic range (WDR) neurons in uninjured rats and rats with peripheral inflammation (CFA, 48 hrs). In uninjured rats, capsaicin-evoked (1 microg) WDR activity was completely blocked by intraplantar administration of A-425619 (3-100 nmol). Systemic injection of A-425619 (3-30 micromol/kg, i.v.) reduced WDR responses to thermal stimulation in both CFA-inflamed (47 degrees C) and uninjured (52 degrees C) rats. However, the efficacy of A-425619 to attenuate thermal-evoked WDR activity was significantly greater (P < 0.01) in CFA-treated rats. Both intra-dorsal root ganglion (DRG, L5, 20 nmol) and intraplantar (30-300 nmol) injection of A-425619 reduced WDR responses to thermal stimulation. While the effectiveness of A-425619 was similar between CFA-inflamed and uninjured rats following intraplantar injection, the effects of A-425619 after intra-DRG injection were enhanced in the inflamed rats (compared to the uninjured rats). Spontaneous WDR discharges were unaltered by systemic or site-specific injections of A-425619. Thus, noxious thermal stimulation triggers the transmission of TRPV1-related signals to spinal WDR neurons in both inflamed and uninjured animals. The apparent increase in TRPV1 signaling to WDR neurons following injury may be the result of changes to the distribution/sensitization of peripheral TRPV1 receptors.

Substance Use and Multiple Victimization Among Adolescents In South Africa

Morojele, N.K. and Brook, J.S. Addict Behav. October 24, 2005 [Epub ahead of print] (INVEST Fellow: Neo Morojele, South Africa, 1998-1999). The aims of the study were to examine the relationship between multiple victimization and drug use, and the role of drug use and other intra-personal, peer, parental and environmental factors in predicting multiple victimization among adolescents in South Africa. A cross-sectional design was employed. The participants comprised 1474 male and female adolescents aged between 12 and 17 years, from Durban and Cape Town. They completed questionnaire measures assessing demographic characteristics; self, peer and parental drug use; self and peer delinquency; parental child-centeredness and rules; and community drug availability and exposure to violence on television. A measure of multiple victimization assessed whether or not the respondents had experienced two or more different types of violence in their lifetime. There was a significant association between frequency of tobacco, alcohol and marijuana use and multiple victimization. Significant predictors of multiple victimization in multiple logistic regression analyses were variables within intra-personal, peer, parental and environmental domains. Victimization prevention programs in South Africa should be comprehensive and target adolescents' drug use as well as their other psychosocial risk factors.

Predictors Of Cigarette Use Among South African Adolescents

Brook, J.S., Morojele, N.K., Brook, D.W. and Rosen, Z. Into J Behav Med. 12(4), pp. 207-217. (INVEST Fellow: Neo Morojele, South Africa, 1998-1999). This study assessed the interrelation among domains of ethnic factors; the individual's sense of well-being; personality, attitudes, and behaviors; sibling and peer smoking; and adolescent smoking behavior. The sample consisted of 1,468 South African adolescents selected from 4 ethnic groups self-identified as defined by current South African usage: Black (mainly Zulu and Xhosa), Indian, White, and Colored (mixed ancestry). In accordance with family interactional theory, there was a sequence of patterning from ethnic factors and the individual's sense of well-being to adolescent personality, attitudes, and behaviors and models of smoking. All of the 4 domains in the model also had a direct effect on adolescent smoking behavior. The findings suggest 4 possible targets of therapeutic or preventive intervention with regard to adolescent smoking: ethnic factors; the individual's sense of well being; personality, attitudes, and behaviors; and smoking within the peer group.

Interactive Skills Of Infants With Their High-Risk Mothers

Savonlahti, E., Pajulo, M., Ahlqvist, S., Helenius, H., Korvenranta, H., Tamminen, T. and Piha J. Nord J Psychiatry. 59(2), pp. 139-147, 2005. (INVEST Fellow: Marjaterttu Pajulo, Finland, 2003-2004). In this pilot study, the interactive skills of infants with their high-risk, substance-dependent mothers were explored in residential treatment from pregnancy until the infant was 6 months of age. Fourteen mother-infant pairs were videotaped in feeding and free play situations at 6 months after birth. A comparison, low-risk group consisted of 12 ordinary Finnish mother-infant pairs with minimal clinical risks. The findings show significantly higher levels of dyadic interactive deficiencies among the high-risk mother-infant pairs compared to the low-risk pairs, displayed especially in the feeding situation as lack of mutuality and flat, empty, constricted affective tone of interaction. Also, more interactive deficiencies were found among the high-risk infants compared to the low-risk infants, but the differences were not significant. In this study, this finding might reflect the reduced amount of somatic complications and the benefits of treatment, the impacts of which were not explored. The differences between the high- and low-risk infants were displayed as more withdrawal, depressed mood and avoiding behavior and as less alertness and attentional abilities, robustness and focus on parent's emotional state among the high-risk group.

Multidrug Resistance Polypeptide 1 (MDR1, ABCB1) Variant 3435C>T Affects mRNA Stability

Wang, D., Johnson, A.D., Papp, A.C., Kroetz, D.L. and Sadee, W. Pharmacogenet Genomics. 15(10), pp. 693-704, October 2005. (INVEST Fellow: Danxin Wang, China, 1996-1997). ABCB1 (multidrug resistance 1 polypeptide, MDR1, Pgp) is a multispecific efflux transporter of drugs and xenobiotics. Among numerous polymorphisms in human ABCB1, the synonymous SNP 3435C > T has been associated with decreased mRNA and protein levels, via unknown mechanisms. To search for cis-acting polymorphism affecting transcription or mRNA processing, 3435C > T was used as a marker single nucleotide polymorphism (SNP), for measuring differences in allelic mRNA expression. Ratios of allelic abundance in genomic DNA and mRNA (after conversion to cDNA) were measured quantitatively with a primer extension assay, in human liver samples. mRNA expression of the 3435C allele was significantly higher than that of the 3435T allele (3435C/3435T ratios ranging from 1.06-1.61). Cotransfection of equal amounts of ABCB1 expression plasmids containing 3435C or 3435T also revealed higher 3435C mRNA expression. Increasing 3435C/3435T ratios after cessation of transcription indicated that the 3435C > T substitution decreases mRNA stability. 3435C > T is in strong linkage disequilibrium with two other coding SNPs (1236C > T and 2677G > T) forming two abundant haplotypes (ABCB1*1 and ABCB1*13). Transfection of all possible combinations of these three SNPs demonstrated that only 3435T is associated with lower mRNA levels. Calculations of mRNA folding, using Mfold, suggested an effect on mRNA secondary structure. Authors concluded that the abundant 3435C > T SNP appears to be a main factor in allelic variation of ABCB1 mRNA expression in the liver, by changing mRNA stability.

The Novel Dopamine D(3) Receptor Antagonist NGB 2904 Inhibits Cocaine's Rewarding Effects and Cocaine-Induced Reinstatement of Drug-Seeking Behavior in Rats

Xi, Z.X., Newman, A.H., Gilbert, J.G., Pak, A.C., Peng, X.Q., Ashby, C.R., Gitajn, L. and Gardner, E.L. Neuropsychopharmacology. October 5, 2005 [Epub ahead of print](INVEST Fellow: Zhengxiong Xi, China, 1995-1996). Accumulating evidence indicates that dopamine (DA) D(3) receptor antagonists appear highly promising in attenuating cocaine reward and relapse in preclinical models of addiction. In the present study, authors investigated the effects of the novel D(3)-selective antagonist NGB 2904 (N-(4-[4-{2,3-dichlorophenyl}-1-piperazinyl]butyl)-3-fluorenylcarboxamide) on cocaine self-administration, cocaine-enhanced brain stimulation reward (BSR), and cocaine-triggered reinstatement of drug-seeking behavior in male Long-Evans rats. Results showed that: (1) acute intraperitoneal (i.p.) administration of NGB 2904 (0.1-10 mg/kg) failed to alter cocaine self-administration (0.5 mg/kg/infusion) under fixed-ratio 2 (FR2) reinforcement, but 1 or 5 mg/kg NGB 2904 significantly lowered the break-point for cocaine self-administration under progressive-ratio (PR) reinforcement; (2) cocaine (1, 2, and 10 mg/kg) significantly enhanced electrical BSR (decreased brain reward thresholds), while NGB 2904 significantly inhibited the enhancement of BSR elicited by 2 mg/kg, but not 10 mg/kg of cocaine; (3) NGB 2904 alone neither maintained self-administration behavior nor altered brain reward thresholds; and (4) NGB 2904 significantly inhibited cocaine-triggered reinstatement of extinguished drug-seeking behavior, but not sucrose-plus-sucrose-cue-triggered reinstatement of sucrose-seeking behavior. Overall, these data show that the novel D(3)-selective antagonist NGB 2904 attenuates cocaine's rewarding effects as assessed by PR self-administration, BSR, and cocaine-triggered reinstatement of cocaine-seeking behavior. Owing to these properties and to its lack of rewarding effects (as assessed by BSR and by substitution during drug self-administration), NGB 2904 merits further investigation as a potential agent for treatment of cocaine addiction. Neuropsychopharmacology advance online publication, 5 October 2005; doi:10.1038/sj.npp. 1300912.

Simultaneous Intra-Accumbens Remifentanil and Dopamine Kinetics Suggest That Neither Determines Within-Session Operant Responding

Crespo, J.A., Sturm, K., Saria, A. and Zernig, G. Psychopharmacology (Berl). October 12, 2005, 1-9 [Epub ahead of print] (INVEST Fellow: Gerald Zernig, Austria, 1993-1994). The ultra-short-acting mu opioid agonist analgesic/anesthetic remifentanil (RMF) is extremely rapidly eliminated from blood (half-life in rats, 0.3-0.7 min). This extremely fast elimination is thought to be the main reason why RMF maintains such high rates of responding in animal operant-conditioning models of drug addiction. The present study investigated if such a fast elimination of RMF also occurs in the extracellular space of the brain, i.e., in the pharmacokinetic compartment that is thought to be ultimately mediating the reinforcing effect, and hence, the abuse liability of drugs. Nucleus accumbens (NAC) RMF and dopamine (DA) were simultaneously quantified by in vivo microdialysis followed by tandem mass spectrometry both in rats that traversed an alley to receive intravenous injections of 0.032 mg kg(-1) RMF in an operant runway procedure (contingent RMF) and in rats that passively received RMF in the runway (noncontingent RMF). Regardless of the mode of administration (i.e., contingent or noncontingent), intra-accumbens RMF peaked in the first 10-min sample and decreased exponentially with a t(1/2) of 10.0+/-1.2 min (N=31). RMF-stimulated DA peaked in the 10-min sample immediately after the RMF peak and decreased with a time course very similar to that of RMF. Crosscorrelation of the NAC RMF and NAC DA curves showed them to be tightly synchronized. Noncontingent single-dose RMF was eliminated from the whole brain with a half-life of 1.1+/-0.2 min and from blood with a half-life of 0.3 min or less. The comparison of blood-vs.-brain RMF pharmacokinetics with rat RMF self-administration behavior, either in operant runway (present study) or in lever-press-based operant-conditioning procedures, suggests that titration of blood RMF, whole-brain RMF, intra- accumbens RMF, or accumbal DA levels (assessed with the limited temporal resolution of in vivo microdialysis) does not determine a rat's decision to reemit a response during a multiple-injection drug self-administration session.

The AGNP-TDM Expert Group Consensus Guidelines: Focus on Therapeutic Monitoring of Antidepressants

Baumann, P., Ulrich, S., Eckermann, G., Gerlach, M., Kuss, H.J., Laux, G., Muller-Oerlinghausen, B., Rao, M.L., Riederer, P., Zernig, G. and Hiemke, C. Dialogues Clin Neurosci.7(3), pp. 231-247. 2005. (INVEST Fellow: Gerald Zernig, Austria, 1993-1994). Therapeutic drug monitoring (TDM) of psychotropic drugs such as antidepressants has been widely introduced for optimization of pharmacotherapy in psychiatric patients. The interdisciplinary TDM group of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has worked out consensus guidelines with the aim of providing psychiatrists and TDM laboratories with a tool to optimize the use of TDM. Five research-based levels of recommendation were defined with regard to routine monitoring of drug plasma concentrations: (i) strongly recommended; (ii) recommended; (iii) useful; (iv) probably useful; and (v) not recommended. In addition, a list of indications that justify the use of TDM is presented, e.g., control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning drug metabolism, and children, adolescents, and elderly patients. For some drugs, studies on therapeutic ranges are lacking, but target ranges for clinically relevant plasma concentrations are presented for most drugs, based on pharmacokinetic studies reported in the literature. For many antidepressants, a thorough analysis of the literature on studies dealing with the plasma concentration-clinical effectiveness relationship allowed inclusion of therapeutic ranges of plasma concentrations. In addition, recommendations are made with regard to the combination of pharmacogenetic (phenotyping or genotyping) tests with TDM. Finally, practical instructions are given for the laboratory practitioners and the treating physicians how to use TDM: preparation of TDM, drug analysis, reporting and interpretation of results, and adequate use of information for patient treatment TDM is a complex process that needs optimal interdisciplinary coordination of a procedure implicating patients, treating physicians, clinical pharmacologists, and clinical laboratory specialists. These consensus guidelines should be helpful for optimizing TDM of antidepressants.

Former Hubert H. Humphrey Drug Abuse Research Fellows

Opioids and Abnormal Pain Perception: New Evidence From A Study Of Chronic Opioid Addicts and Healthy Subjects

Pud, D., Cohen, D., Lawental, E. and Eisenberg, E. Drug Alcohol Depend. October 13, 2005 [Epub ahead of print] (HHH Fellow: Eli Lawental, Israel, 1993-1994). Recent evidence reported on increased pain sensitivity in animals following parenteral opioid administration and in humans subsequent to intravenous administration of short-acting opioids and possibly in drug addicts. The aims of the present study were to explore the possibilities that (1) pain perception is altered in chronic opioid addicts (OAs); (2) if indeed so, the cessation of opioid consumption resets their altered pain perception. Sixty heroin or methadone OAs who attended a 4-week inpatient detoxification program were exposed to the cold pressor test (CPT) upon entrance to the program, at 7 and 28 days subsequent to the cessation of opioid consumption (verified by repeated urine toxicology tests). Latency of pain onset (s), pain intensity (0-100 VAS), and tolerance (time for hand withdrawal) in response to the CPT were measured. In comparison with 70 healthy controls, the OAs demonstrated prolonged latency (6.6+/-3.5s versus 10.9+/-7.7s; p<0.0001); decreased VAS (74+/-16 versus 55+/-20; p<0.0001); shorter tolerance (56.4+/-51.3s versus 31.7+/-40.7s; p=0.001). No differences between the three time points in any of the three measures were detected in the OAs. The results provide further evidence of opioid-induced hyperalgesia in the OA population, as manifested by their quicker hand withdrawal. In addition, it appears that detoxification from opioids does not reset pain perception for at least 1 month.

Adoption Of The New Antimalarial Drug Policy In Tanzania - A Cross-Sectional Study In the Community

Eriksen, J., Nsimba, S.E., Minzi, O.M., Sanga, A.J., Petzold, M., Gustafsson, L.L., Warsame, M.Y. and Tomson, G. Trop Med Int Health. 10(10), pp. 1038-1046, October 2005. (HHH Fellow: Stephen Nsimba, Tanzania, 2005-2006). The objective of this study was to assess the diffusion of the change of first line antimalarial drug from chloroquine (CQ) to sulphadoxine/pyrimethamine (SP) at household level in a rural district of Tanzania less than a year after the policy implementation. Caretakers in 729 households were interviewed on knowledge of the new policy, home stocking of antimalarials, home-treatment practices of children younger than 5 years with fever, health-seeking behavior and experience of SP. SP and CQ levels in blood were analyzed from 328 children younger than 5 years in the households. Twelve focus group discussions (FGD) were performed with mothers, fathers and health workers. About 51% of the population knew that SP was the first line antimalarial. Only 8% of mothers stocked antimalarials, and only 4% stated self-treatment as the first action. We estimated that 84% of the children who had had fever during the last 4 weeks sought care at public health facilities. SP was detectable in 18% of the total child population and in 32% of those with reported fever, CQ in only 5% and 7%, respectively. The FGDs revealed negative perceptions of SP and fear of severe adverse reactions with mass media reported as key informant. Authors concluded that the policy had diffused to the communities in the sense that CQ had been changed to SP, which was well known as first line treatment. Moreover, there was a reported dramatic change from self-treatment with CQ to seeking care at public health facilities where SP was given under observation.

Comparative Study Of Drug Use Among Undergraduate Students At The University Of Sao Paulo - Sao Paulo Campus In 1996 and 2001

Stempliuk, Vde A., Barroso, L.P., Andrade, A.G., Nicastri, S. and Malbergier, A. Rev Bras Psiquiatr.27(3), pp. 185-193, September 2005. Epub 2005 Oct 4. (HHH Fellows: Vladimir Stempliuk, Brazil, 2003-2004; Sergio Nicastri, Brazil, 1997-1998; and Arthur Guerra de Andrade, Brazil, 1991-1992). The objective of this study was to compare the rate of drug use prevalence and to investigate opinions regarding such use among undergraduate students at the University of Sao Paulo - Sao Paulo campus in 1996 and again in 2001. Both studies followed the same procedures of sampling and data collection. A random sample of undergraduate students, divided into the areas of Humanities, Exact Sciences and Biologic Sciences, responded to an anonymous and self-report survey regarding the use of licit and illicit drugs within the last 30 days, within the last 12 months, and over the lifetime of the subject. The two surveys were compared through the construction of (95%) confidence intervals for the prevalence differences for each substance by area and by total number of students. The Wald test for homogeneity was applied in order to compare the prevalences. High approval of regularly trying and using cocaine, crack, amphetamines, and inhalants was observed. The drugs that showed statistic significant increasing were: lifetime use: alcohol, tobacco, marijuana, inhalants, hallucinogens, amphetamines, anticholines, barbiturics, and any illicit drug; last-12-month use: marijuana, inhalants, amphetamines, hallucinogens, and any illicit drug; last-30-day use: marijuana, inhalants, amphetamines, and any illicit drug. The observed difference in the use of some drugs between the two surveys appears to be a consequence of the higher rates of favorable opinions regarding trying and regularly using some psychoactive substances, a finding that mirrors global trends in drug use.


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