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Implementation of evidence-based care for heavy drinking and depression remains low in global health systems. We tested the impact of providing community support, training, and clinical packages of varied intensity on depression screening and management for heavy drinking patients in Latin American primary healthcare. Quasi-experimental study involving 58 primary healthcare units in Colombia, Mexico and Peru randomized to receive: (1) usual care (control); (2) training using a brief clinical package; (3) community support plus training using a brief clinical package; (4) community support plus training using a standard clinical package. Outcomes were proportion of: (1) heavy drinking patients screened for depression; (2) screen-positive patients receiving appropriate support; (3) all consulting patients screened for depression, irrespective of drinking status. 550/615 identified heavy drinkers were screened for depression (89.4%). 147/230 patients screening positive for depression received appropriate support (64%). Amongst identified heavy drinkers, adjusting for country, sex, age and provider profession, provision of community support and training had no impact on depression activity rates. Intensity of clinical package also did not affect delivery rates, with comparable performance for brief and standard versions. However, amongst all consulting patients, training providers resulted in significantly higher rates of alcohol measurement and in turn higher depression screening rates; 2.7 times higher compared to those not trained. Training using a brief clinical package increased depression screening rates in Latin American primary healthcare. It is not possible to determine the effectiveness of community support on depression activity rates due to the impact of COVID-19.

Background Opioid-related fatalities are a leading cause of death in Ohio and nationally, with an increasing number of overdoses attributable to fentanyl. Rapid fentanyl test strips can identify fentanyl and some fentanyl analogs in urine samples and are increasingly being used to check illicit drugs for fentanyl before they are used. Fentanyl test strips are a promising harm reduction strategy; however, little is known about the real-world acceptability and impact of fentanyl test strip use. This study investigates fentanyl test strip distribution and education as a harm reduction strategy to prevent overdoses among people who use drugs. Methods The research team will recruit 2400 individuals ≥ 18 years with self-reported use of illicit drugs or drugs purchased on the street within the past 6 months. Recruitment will occur at opioid overdose education and naloxone distribution programs in 16 urban and 12 rural Ohio counties. Participating sites will be randomized at the county level to the intervention or non-intervention study arm. A brief fentanyl test strip educational intervention and fentanyl test strips will be provided to participants recruited from sites in the intervention arm. These participants will be eligible to receive additional fentanyl test strips for 2 years post-enrollment. Participants recruited from sites in the non-intervention arm will not receive fentanyl test strip education or fentanyl test strips. All participants will be followed for 2 years post-enrollment using biweekly, quarterly, and 6-month surveys. Primary outcomes include (1) identification of perceived barriers and facilitating factors associated with incorporating fentanyl test strip education and distribution into opioid overdose education and naloxone distribution programs; (2) differences in knowledge and self-efficacy regarding how to test drugs for fentanyl and strategies for reducing overdose risk between the intervention and non-intervention groups; and (3) differences in non-fatal and fatal overdose rates between the intervention and non-intervention groups. Discussion Findings from this cluster randomized controlled trial will contribute valuable information about the feasibility, acceptability, and impact of integrating fentanyl test strip drug checking in rural and urban communities in Ohio and help guide future overdose prevention interventions. Trial registration ClinicalTrials.gov NCT05463341. Registered on July 19, 2022. https://clinicaltrials.gov/study/NCT05463341

A cross-over controlled administration study of smoked cannabis was carried out on occasional and heavy smokers. The participants smoked a joint (11 % Δ9-tetrahydrocannabinol (THC)) or a matching placebo on two different occasions. Whole blood (WB) and oral fluid (OF) samples were collected before and up to 3.5 h after smoking the joints. Pharmacokinetic analyses were obtained from these data. Questionnaires assessing the subjective effects were administered to the subjects during each session before and after the smoking time period. THC, 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THCCOOH) were analyzed in the blood by gas chromatography or liquid chromatography (LC)-tandem mass spectrometry (MS/MS). The determination of THC, THCCOOH, cannabinol (CBN), and Δ9-tetrahydrocannabinolic acid A (THC-A) was carried out on OF only using LC-MS/MS. In line with the widely accepted assumption that cannabis smoking results in a strong contamination of the oral cavity, we found that THC, and also THC-A, shows a sharp, high concentration peak just after smoking, with a rapid decrease in these levels within 3 h. No obvious differences were found between both groups concerning THC median maximum concentrations measured either in blood or in OF; these levels were equal to 1,338 and 1,041 μg/L in OF and to 82 and 94 μg/L in WB for occasional and heavy smokers, respectively. The initial WB THCCOOH concentration was much higher in regular smokers than in occasional users. Compared with the occasional smokers, the sensation of confusion felt by the regular smokers was much less while the feeling of intoxication remained almost unchanged. Figure Time profiles of THC, 11-OH-THC, and THCCOOH in whole blood for occasional (a) and heavy cannabis smokers (b)

The discovery of erythropoietin (EPO) simplified blood doping in sports, but improved detection methods, for EPO has forced cheating athletes to return to blood transfusion. Autologous blood transfusion with cryopreserved red blood cells (RBCs) is the method of choice, because no valid method exists to accurately detect such event. In endurance sports, it can be estimated that elite athletes improve performance by up to 3% with blood doping, regardless of method. Valid detection methods for autologous blood doping is important to maintain credibility of athletic performances. Recreational male (N = 27) and female (N = 11) athletes served as Transfusion (N = 28) and Control (N = 10) subjects in two different transfusion settings. Hematological variables and physical performance were measured before donation of 450 or 900 mL whole blood, and until four weeks after re-infusion of the cryopreserved RBC fraction. Blood was analyzed for transferrin, iron, Hb, EVF, MCV, MCHC, reticulocytes, leucocytes and EPO. Repeated measures multivariate analysis of variance (MANOVA) and pattern recognition using Principal Component Analysis (PCA) and Orthogonal Projections of Latent Structures (OPLS) discriminant analysis (DA) investigated differences between Control and Transfusion groups over time. Significant increase in performance (15 ± 8%) and VO2max (17 ± 10%) (mean ± SD) could be measured 48 h after RBC re-infusion, and remained increased for up to four weeks in some subjects. In total, 533 blood samples were included in the study (Clean = 220, Transfused = 313). In response to blood transfusion, the largest change in hematological variables occurred 48 h after blood donation, when Control and Transfused groups could be separated with OPLS-DA (R2 = 0.76/Q2 = 0.59). RBC re-infusion resulted in the best model (R2 = 0.40/Q2 = 0.10) at the first sampling point (48 h), predicting one false positive and one false negative. Over all, a 25% and 86% false positives ratio was achieved in two separate trials. In conclusions, autologous re-infusion of RBCs increased VO2max and performance as hypothesized, but hematological profiling by multivariate statistics could not reach the WADA stipulated false positive ratio of <0.001% at any time point investigated. A majority of samples remained within limits of normal individual variation at all times.

Rationale Standardized Field Sobriety Tests (SFST) and oral fluid devices are used to screen for driving impairment and roadside drug detection, respectively. SFST have been validated for alcohol, but their sensitivity to impairment induced by other drugs is relatively unknown. The sensitivity and specificity for Δ 9 -tetrahydrocannabinol (THC) of most oral fluid devices have been low. Objective This study assessed the effects of smoking cannabis with and without alcohol on SFST performance. Presence of THC in oral fluid was examined with two devices (Dräger Drug Test® 5000 and Securetec Drugwipe® 5). Methods Twenty heavy cannabis users (15 males and 5 females; mean age, 24.3 years) participated in a double-blind, placebo-controlled study assessing percentage of impaired individuals on the SFST and the sensitivity of two oral fluid devices. Participants received alcohol doses or alcohol placebo in combination with 400 μg/kg body weight THC. We aimed to reach peak blood alcohol concentration values of 0.5 and 0.7 mg/mL. Results Cannabis was significantly related to performance on the one-leg stand ( p  = 0.037). Alcohol in combination with cannabis was significantly related to impairment on horizontal gaze nystagmus ( p  = 0.029). The Dräger Drug Test® 5000 demonstrated a high sensitivity for THC, whereas the sensitivity of the Securetec Drugwipe® 5 was low. Conclusions SFST were mildly sensitive to impairment from cannabis in heavy users. Lack of sensitivity might be attributed to tolerance and time of testing. SFST were sensitive to both doses of alcohol. The Dräger Drug Test® 5000 appears to be a promising tool for detecting THC in oral fluid as far as correct THC detection is concerned.

Rationale Craving is often assumed to cause ongoing drug use and relapse and is a major focus of addiction research. However, its relationship to drug use has not been adequately documented. Objectives The aim of this study was to investigate the relationship between craving and drug use in real time and in the daily living environments of drug users. Methods In a prospective, longitudinal, cohort design (ecological momentary assessment), 112 cocaine-abusing individuals in methadone maintenance treatment rated their craving and mood at random times (two to five times daily, prompted by electronic diaries) as they went about their everyday activities. They also initiated an electronic diary entry each time they used cocaine. Drug use was monitored by thrice-weekly urine testing. Results During periods of urine-verified cocaine use, ratings of cocaine craving increased across the day and were higher than during periods of urine-verified abstinence. During the 5 h prior to cocaine use, ratings of craving significantly increased. These patterns were not seen in ratings of heroin craving or mood (e.g., feeling happy or bored). Conclusions Cocaine craving is tightly coupled to cocaine use in users’ normal environments. Our findings provide previously unavailable support for a relationship that has been seriously questioned in some theoretical accounts. We discuss what steps will be needed to determine whether craving causes use.

Incorporation rates of the enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA) into hair and nails were investigated after controlled administration. Fifteen subjects without MDMA use received two doses of 125 mg of MDMA. Hair, nail scrapings, and nail clippings were collected 9–77 days after the last administration (median 20 days). Hair samples were analyzed in segments of 1- to 2-cm length. After chiral derivatization with N-(2,4-dinitro-5-fluorophenyl)-L-valinamide, MDMA and MDA diastereomers were analyzed by liquid chromatography-tandem mass spectrometry. Highest concentrations in hair segments corresponded to the time of MDMA intake. They ranged from 101 to 3200 pg/mg and 71 to 860 pg/mg for R- and S-MDMA, and from 3.2 to 116 pg/mg and 4.4 to 108 pg/mg for R- and S-MDA, respectively. MDMA and MDA concentrations in nail scrapings and clippings were significantly lower than in hair samples. There was no significant difference between enantiomeric ratios of R/S-MDMA and R/S-MDA in hair and nail samples (medians 2.2–2.4 for MDMA and 0.85–0.95 for MDA). Metabolite ratios of MDA to MDMA were in the same range in hair and nail samples (medians 0.044–0.055). Our study demonstrates that administration of two representative doses of MDMA was detected in the hair segments corresponding to the time of intake based on average hair growth rates. MDMA was detected in all nail samples regardless of time passed after intake. Comparable R/S ratios in hair and nail samples may indicate that incorporation mechanisms into both matrices are comparable.

The popularity of testosterone among drug users is due to its powerful effects on muscle strength and mass. Important mechanisms behind the myotrophic effects of testosterone were uncovered both in athletes using steroids for several years and in short‐term controlled studies. Both long‐term and short‐term steroid usage accentuates the degree of fibre hypertrophy in human skeletal muscle by enhancing protein synthesis. A mechanism by which testosterone facilitates the hypertrophy of muscle fibres is the activation of satellite cells and the promotion of myonuclear accretion when existing myonuclei become unable to sustain further enhancement of protein synthesis. Interestingly, long‐term steroid usage also enhances the frequency of fibres with centrally located myonuclei, which implies the occurrence of a high regenerative activity. Under the action of testosterone, some daughter cells generated by satellite cell proliferation may escape differentiation and return to quiescence, which help to replenish the satellite cell reserve pool. However, whether long‐term steroid usage induces adverse effects of satellite cells remains unknown. Testosterone might also favour the commitment of pluripotent precursor cells into myotubes and inhibit adipogenic differentiation. The effects of testosterone on skeletal muscle are thought to be mediated via androgen receptors expressed in myonuclei and satellite cells. Some evidence also suggests the existence of an androgen‐receptor‐independent pathway. Clearly, testosterone abuse is associated with an intense recruitment of multiple myogenic pathways. This provides an unfair advantage over non‐drug users. The long‐term consequences on the regenerative capacity of skeletal muscle are unknown. British Journal of Pharmacology (2008) 154, 522–528; doi:fn1; published online 14 April 2008

Enables you to detect, identify, and characterize hundreds of drugs that may be used by athletes Mass spectrometry has become essential to sports drug testing. This book examines both the principles of sports drug testing and the use of mass spectrometry techniques and mass spectral data to detect, identify, and characterize hundreds of known and unknown drugs that athletes may use to enhance their performance. The author provides a detailed overview of the mass spectrometry of numerous classes of therapeutics and agents, various analyzers to detect low- and high-molecular weight drugs, as well as techniques to discriminate between endogenously produced and synthetically derived compounds. Mass Spectrometry in Sports Drug Testing begins with a full chapter dedicated to the history of sports drug testing. Next, the book provides the principles and techniques needed to maximize the specificity and sensitivity of mass spectrometric assays, including: -Detailed, step-by-step assays with sample preparation -Discussion of both chromatographic separation and mass spectrometric analysis -Characterization of analytes in order to unequivocally identify banned substances -Mass spectrometric behavior of low- and high-molecular weight analytes Throughout the book, descriptive examples illustrate the principles, advantages, and limitations of different assays. Mass Spectrometry in Sports Drug Testing not only sets forth the role mass spectrometry plays in detecting drug use among athletes, it also adds new insights into the health and ethical issues of doping in sports.

Conditional cash transfer (CCT) and cognitive-behavioral treatments are evidence-based approaches to reduce stimulant use and sexual risk taking. We describe the adaptation and implementation of sequential behavioral interventions for Cambodian female entertainment and sex workers (FESW) who use amphetamine-type stimulants (ATS): (1) a 12-week CCT intervention; and (2) a 4-week cognitive-behavioral aftercare (AC) group. An ongoing cluster randomized stepped wedge trial in 10 Cambodian provinces is enrolling FESW with confirmed recent ATS use to examine the effectiveness of CCT + AC. In the first six provinces, 138 of the 183 eligible FESW (75 %) enrolled in CCT and completed a median of 25 (interquartile range 9–32) of the 36 urine screening visits. Of the 84 participants who were eligible for AC, 79 completed at least one session (94 %) and 57 completed three or more sessions (68 %). Culturally tailored behavioral interventions to reduce ATS use and optimize HIV prevention are feasible in resource-limited settings.