A comparison between wastewater-based drug data and an illicit drug use survey in a selected community.

BACKGROUND: Estimations of drug use are mostly based on population surveys that can suffer from response biases. The current study evaluates using wastewater-based epidemiology (WBE) for assessing illicit drug use by comparing wastewater data with that from a population survey. METHODS: Introductory letters (29,083) were sent to inhabitants of Lier, Belgium, asking them to participate in an online survey study. Participants were asked to indicate their drug use in the past week for a 12-week period (September-November 2014). Concomitant wastewater samples were collected from the associated wastewater treatment plant in four bi-weekly periods. Samples were analyzed using solid-phase extraction and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). RESULTS: On average, 263 (1%) inhabitants filled out the questionnaire each week. According to the survey results, cannabis was the most used drug, followed by amphetamine, cocaine and methylenedioxymethamphetamine (MDMA). Wastewater data corroborated these results. Cocaine, amphetamine and MDMA showed a significant difference between days of the week. The four sampling periods differed significantly from each other for cocaine, amphetamine and methadone. CONCLUSION: Observed drug consumption patterns from survey and wastewater data match national and international data. Wastewater analyses confirm that WBE can be reliably used to confirm patterns and trends in drug use. Future studies should focus on identifying the most opportune sampling period giving the most reliable estimates of drug use and use smaller, contained communities such as festivals or prisons if methodology allows.

Cannabis and tolerance: acute drug impairment as a function of cannabis use history.

Cannabis use history as predictor of neurocognitive response to cannabis intoxication remains subject to scientific and policy debates. The present study assessed the influence of cannabis on neurocognition in cannabis users whose cannabis use history ranged from infrequent to daily use. Drug users (N = 122) received acute doses of cannabis (300 µg/kg THC), cocaine HCl (300 mg) and placebo. Cocaine served as active control for demonstrating neurocognitive test sensitivity. Executive function, impulse control, attention, psychomotor function and subjective intoxication were significantly worse after cannabis administration relative to placebo. Cocaine improved psychomotor function and attention, impaired impulse control and increased feelings of intoxication. Acute effects of cannabis and cocaine on neurocognitive performance were similar across cannabis users irrespective of their cannabis use history. Absence of tolerance implies that that frequent cannabis use and intoxication can be expected to interfere with neurocognitive performance in many daily environments such as school, work or traffic.

Investigation of agreement between wastewater-based epidemiology and survey data on alcohol and nicotine use in a community.

BACKGROUND/AIMS: Alcohol and nicotine are the two most used substances world-wide and associated with increased burden of disease. Since surveys on substance use may be difficult due to response biases, wastewater-based epidemiology (WBE) was developed as a more objective measure of nicotine and alcohol use. This study compares estimates of nicotine and alcohol use from a wastewater sampling campaign in a medium-sized Belgian city with a concurrently executed population survey. METHODS: 29,083 letters about participation in an online survey study on weekly alcohol and tobacco use were sent to the inhabitants of Lier, Belgium. Wastewater samples were collected from the associated treatment plant in four bi-weekly periods. Samples were analyzed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Ethylsulfate was used as alcohol biomarker and cotinine and trans-3'-hydroxycotinine as nicotine biomarker. RESULTS: 263 (1%) surveys were filled out on average per week. According to survey data, alcohol and nicotine were used less than in the rest of Belgium and this was matched by the wastewater data. Nicotine use, but not alcohol use, showed a significant variation over the sampling periods. Both nicotine and alcohol showed increase use during the weekend while only alcohol showed a different use pattern throughout the week. CONCLUSION: No correlation between WBE and survey data could be demonstrated, possibly due to small sample sizes. However, this study shows that weekly trends in alcohol and nicotine use can be quickly detected from wastewater analysis and the occurrence of major events such as festivals can be identified.

Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes.

The dopamine ß-hydroxylase (DßH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic 'reward' circuit because they experience a drug induced hyperdopaminergic state compared to individuals with high activity DBH genotypes (rs1611115 CC). Regular drug users (N = 122) received acute doses of cannabis (450 µg/kg THC), cocaine HCl 300 mg and placebo. Cognitive impulse control was assessed by means of the Matching Familiar Figures Test (MFFT). Resting state fMRI was measured in a subset of participants to determine functional connectivity between the nucleus accumbens (NAc) and (sub)cortical areas. The influence of cannabis and cocaine on impulsivity and functional connectivity significantly interacted with DBH genotype. Both drugs increased cognitive impulsivity in participants with CT/TT genotypes but not in CC participants. Both drugs also reduced functional connectivity between the NAc and the limbic lobe, prefrontal cortex, striatum and thalamus and primarily in individuals with CT/TT genotypes. Correlational analysis indicated a significant negative association between cognitive impulsivity and functional connectivity in subcortical areas of the brain. It is concluded that interference of cannabis and cocaine with cognitive impulse control and functional corticostriatal connectivity depends on DBH genotype. The present data provide a neural substrate and behavioral mechanism by which drug users can progress to drug seeking and may also offer a rationale for targeted pharmacotherapy in chronic drug users with high risk DBH genotypes.

Psychedelic symptoms of cannabis and cocaine use as a function of trait impulsivity.

Trait impulsivity has been linked to addiction in humans. It has been suggested that drug users with high trait impulsivity levels are more sensitive to subjective drug intoxication. This study assessed whether subjective response to drugs differs between drug users with normal or high levels of trait impulsivity. Regular drug users (N = 122) received doses of cocaine HCl, cannabis, and placebo in a three-way crossover study. Their mood, dissociative state, and psychedelic symptoms were measured with subjective rating scales (CADDS, Bowdle, POMS). Trait impulsivity was assessed with the Barratt Impulsiveness Scale. Cannabis increased dissociation and psychedelic state, as well as fatigue, confusion, depression and anxiety, and decreased arousal, positive mood, vigor, friendliness, and elation. Cocaine increased dissociation, psychedelic state, vigor, friendliness, elation, positive mood, anxiety and arousal, while decreasing fatigue. Only a few subjective items revealed a drug × trait impulsivity interaction, suggesting that psychedelic symptoms were most intense in high impulsivity subjects. Trait impulsiveness ratings were negatively correlated with ratings of vigor (r = -.197) and positively correlated with ratings of loss of thought control (r = .237) during cannabis intoxication. It is concluded that a broad association between trait impulsivity and psychedelic subjective drug experience appears to be absent.

Single doses of THC and cocaine decrease proficiency of impulse control in heavy cannabis users.

BACKGROUND AND PURPOSE: Cannabis is the most popular drug used in the European Union, closely followed by cocaine. Whereas cannabis impairs neurocognitive function in occasional cannabis users, such impairments appear less prominent in heavy users, possibly as a result of tolerance. The present study was designed to assess whether the impairing effects of Δ(9) -tetrahydrocannabinol (THC) in heavy cannabis users would present in a wide range of neuropsychological functions or selectively affect specific performance domains. We also assessed the acute effects of cocaine on neurocognitive functions of heavy cannabis users. EXPERIMENTAL APPROACH: Heavy cannabis users, who had a history of cocaine use (n = 61), participated in a double-blind, placebo-controlled, three-way crossover study. Subjects received single doses of cocaine HCl (300 mg), cannabis (THC µg·kg(-1) ) and placebo, and completed a number of tests measuring impulse control and psychomotor function. KEY RESULTS: Single doses of cannabis impaired psychomotor function and increased response errors during impulsivity tasks. Single doses of cocaine improved psychomotor function and decreased response time in impulsivity tasks, but increased errors. CONCLUSIONS AND IMPLICATIONS: Heavy cannabis users display impairments in a broad range of neuropsychological domains during THC intoxication. Impairments observed in psychomotor tasks, but not in impulsivity tasks, appeared smaller in magnitude as compared with those previously reported in occasional cannabis users. Heavy cannabis users were sensitive to the stimulating and inhibitory effects of cocaine on psychomotor function and impulsivity respectively. The reduction in proficiency in impulse control may put drug users at increased risk of repeated drug use and addiction.

Blockade of 5-HT2 receptor selectively prevents MDMA-induced verbal memory impairment.

3,4-Methylenedioxymethamphetamine (MDMA) or 'ecstasy' has been associated with memory deficits during abstinence and intoxication. The human neuropharmacology of MDMA-induced memory impairment is unknown. This study investigated the role of 5-HT(2A) and 5-HT(1A) receptors in MDMA-induced memory impairment. Ketanserin is a 5-HT(2A) receptor blocker and pindolol a 5-HT(1A) receptor blocker. It was hypothesized that pretreatment with ketanserin and pindolol would protect against MDMA-induced memory impairment. Subjects (N=17) participated in a double-blind, placebo-controlled, within-subject design involving six experimental conditions consisting of pretreatment (T1) and treatment (T2). T1 preceded T2 by 30 min. T1-T2 combinations were: placebo-placebo, pindolol 20 mg-placebo, ketanserin 50 mg-placebo, placebo-MDMA 75 mg, pindolol 20 mg-MDMA 75 mg, and ketanserin 50 mg-MDMA 75 mg. Memory function was assessed at Tmax of MDMA by means of a word-learning task (WLT), a spatial memory task and a prospective memory task. MDMA significantly impaired performance in all memory tasks. Pretreatment with a 5-HT(2A) receptor blocker selectively interacted with subsequent MDMA treatment and prevented MDMA-induced impairment in the WLT, but not in the spatial and prospective memory task. Pretreatment with a 5-HT(1A) blocker did not affect MDMA-induced memory impairment in any of the tasks. Together, the results demonstrate that MDMA-induced impairment of verbal memory as measured in the WLT is mediated by 5-HT(2A) receptor stimulation.