Eef Theunissen

Eef Theunissen
Maastricht University | UM · Department of Neuropsychology and Psychopharmacology

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111
Publications
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Publications

Publications (111)
Article
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Currently, the assessment of the neurobehavioral consequences of repeated cannabis use is restricted to studies in which brain function of chronic cannabis users is compared to that of non-cannabis using controls. The assumption of such studies is that changes in brain function of chronic users are caused by repeated and prolonged exposure to acute...
Article
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Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of c...
Article
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Some evidence suggests that males and females may differ in their responses to acute cannabis effects, including subjective drug effects and behavioural effects, and cannabinoid pharmacokinetics. This is significant given current changes to cannabis-related policies and, in consequence, increased cannabis accessibility. The present study combines d...
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Introduction Kratom (Mitragyna speciosa) is a tropical plant traditionally used as an ethnomedicinal remedy for several conditions in South East Asia. Despite the increased interest in its therapeutical benefits in Western countries, little scientific evidence is available to support such claims, and existing data remain limited to kratom's chronic...
Chapter
Phase 1 trials are an important step in drug development and are usually the first that involve human participants. Their main objective is most often to determine a safe and effective dose range for further clinical development of the drug. Specific guidelines and regulations apply to these type of trials and have been laid down by health authorit...
Article
Acute cannabis intoxication may induce neurocognitive impairment and is a possible cause of human error, injury and psychological distress. One of the major concerns raised about increasing cannabis legalization and the therapeutic use of cannabis is that it will increase cannabis‐related harm. However, the impairing effect of cannabis during intox...
Preprint
Full-text available
Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of c...
Article
Full-text available
Background Synthetic cannabinoids (SCs) are the largest class of novel psychoactive substances (NPS) and are associated with an increased risk of overdosing and adverse events such as psychosis. JWH-018 is one of the earliest SCs and still widely available in large parts of the world. Controlled studies to assess the safety and behavioural profiles...
Article
Background Smoking mixtures containing synthetic cannabinoids (SCs) have become very popular over the last years but pose a serious risk for public health. Limited knowledge is, however, available regarding the acute effects of SCs on cognition and psychomotor performance. Earlier we demonstrated signs of impairment in healthy volunteers after admi...
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Importance Cannabis use has been associated with increased crash risk, but the effect of cannabidiol (CBD) on driving is unclear. Objective To determine the driving impairment caused by vaporized cannabis containing Δ⁹-tetrahydrocannabinol (THC) and CBD. Design, Setting, and Participants A double-blind, within-participants, randomized clinical tr...
Article
The assessment of cannabinoid concentrations in blood with regard to psychoactive effects is particularly important in traffic offences. A direct correlation is not established, but Huestis et al. have established calculation models for estimating the time of consumption (J Anal Toxicol 16, 283 ff). However, in view of recent studies on abstinence...
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There is a popular interest in microdosing with psychedelics such as LSD. This practice of using one-tenth of a full psychedelic dose according to a specific dosing schedule, anecdotally enhances mood and performance. Nonetheless, controlled research on the efficacy of microdosing is scarce. The main objective of the present dose-finding study was...
Article
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"Microdoses" of lysergic acid diethylamide (LSD) are used recreationally to enhance mood and cognition. Increasing interest has also been seen in developing LSD into a medication. Therefore, we performed a pharmacokinetic-pharmacodynamic study using very low doses of LSD. Single doses of LSD base (5, 10, and 20 µg) and placebo were administered in...
Article
Despite preclinical evidence for psychedelic-induced neuroplasticity, confirmation in humans is grossly lacking. Given the increased interest in using low doses of psychedelics for psychiatric indications, and the importance of neuroplasticity in the therapeutic response, this placebo-controlled within-subject study investigated the effect of singl...
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Background Lysergic acid diethylamide (LSD) is an ergot alkaloid derivative with psychedelic properties that has been implicated in the management of persistent pain. Clinical studies in the 1960s and 1970s have demonstrated profound analgesic effects of full doses of LSD in terminally ill patients, but this line of research evaporated after LSD wa...
Article
Introduction Cerumen was found to be a promising alternative specimen for the detection of drugs. In a pilot study, drugs of abuse were identified at a high detection rate and a longer detection window for abused drugs than in urine. In the present study, cerumen from subjects was analyzed after controlled oral ingestion of the designer stimulant 4...
Article
The rapid proliferation of new synthetic cannabinoid receptor agonists (SCRAs) has initiated considerable interest in the development of so-called “untargeted” screening strategies. One of these new screening technologies involves the activity-based detection of SCRAs. In this study, we evaluated whether (synthetic) cannabinoid activity can be dete...
Article
Acute exposure to cannabis comes with neurocognitive impairment, leading to increased risk of human error and injury. Evidence however indicates that such acute effects are less prominent in chronic users, suggesting cannabis tolerance. Models of cannabis tolerance stress the importance of neurobiological or behavioral adaptations following repeate...
Article
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Mephedrone (4-MMC, mephedrone) is a synthetic cathinone derivative included in the class of new psychoactive substances. It is commonly used simultaneously with alcohol (ethanol). The aim of the present study was to evaluate the interactions on subjective, cardiovascular and hormone effects and pharmacokinetics between mephedrone and alcohol in hum...
Article
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Cannabis is the most commonly used illicit drug in the world. However, because of a changing legal landscape and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly cannabis impairment. Importantly, a growing body of evidence suggests that regular cannabis users develop tolerance to the impairing, as...
Article
Each year, synthetic drugs are occurring in high numbers in the illicit drug market. But data on their pharmacology and toxicology are scarcely available. Therefore, a pilot study was performed to evaluate excretion of 4-fluoroamphetamine (4FA) in humans and identify metabolites in urine. Twelve subjects ingested 100 mg and five 150 mg 4-FA in a bi...
Preprint
Full-text available
Cannabis is the most commonly used illicit drug in the world. However due to a changing legal landscape, and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly, cannabis impairment. Importantly, a growing body of evidence suggests regular cannabis users develop tolerance to the impairing, as well as...
Article
Anecdotal evidence suggests that cocaine use will help overcome creative 'blocks' by enhancing flexible thinking. Given that cocaine is likely to enhance dopamine (DA) levels, which in turn are positively associated with divergent thinking (DT); is a possibility that is tested in the present study. Furthermore, the impact of cocaine is tested on co...
Article
Introduction Each year, synthetic drugs are occurring in high numbers in the illicit drug market. But data on their pharmacology and toxicology are scarcely available. Therefore, a controlled study was performed to evaluate pharmacokinetic parameters of 4‐fluoroamphetamine (4FA) in humans and to compare it with its effects. Methods Twelve subjects...
Article
Introduction: Synthetic cannabinoid mixtures have been easily accessible for years, leading to the belief that these products were natural and harmless, which contributed to their popularity. Nevertheless, there are many reports of users ending up in hospital due to severe side effects such as tachycardia, aggression, and psychosis. Controlled stud...
Article
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The phenethylamine 4-fluoroamphetamine (4-FA) is a so-called novel psychoactive substance with a chemical structure resembling that of amphetamine and MDMA. Since 4-FA users report their subjective experience ranges between the effects induced by amphetamine and MDMA, and it is known that both substances can produce an altered state of consciousnes...
Article
Cannabis is the most commonly used illicit drug and is known to alter state of consciousness and impair neurocognitive function. However, the mechanisms underlying these effects have yet to be fully elucidated. Rodent studies suggest that Δ9-tetrahydrocannabinol (THC) activates dopaminergic neurons in the limbic system, subsequently enhancing dopam...
Article
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Background: New psychoactive substances (NPS) are chemical analogues designed to mimic the effects of various classic recreational drugs of abuse including MDMA, LSD, and cannabis. NPS use is associated with concern about the acute and longer-term effects particular substances might have, with abuse and addiction as potential consequences. Impulsi...
Article
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Availability of novel psychoactive substances (NPS) exponentially increased over the last years. Risk evaluations of NPS are hampered by the lack of pharmacological studies in humans on health parameters. The aim of the present study was to evaluate safety and neurocognitive function of healthy volunteers (N = 12) who received single doses of 100 a...
Article
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Background: Prospective memory is the ability to recall intended actions or events at the right time or in the right context. While cannabis is known to impair prospective memory, the acute effect of cocaine is unknown. In addition, it is not clear whether changes in prospective memory represent specific alterations in memory processing or result...
Article
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MDMA exerts its main effects via the serotonergic system and the serotonin transporter. The gene coding for this transporter determines the expression rate of the transporter. Previously it was shown that healthy individuals with the short allelic variant ('s-group') of the 5-HTTLPR-polymorphism displayed more anxiety and negative mood, and had a l...
Article
Each year, synthetic cannabinoids are occurring in high numbers on the illicit drug market but data obtained after controlled application are rare. The present study on pharmacokinetics in urine is part of a pilot study on adverse effects of JWH-018, which is one of the oldest and best known synthetic cannabinoids. Six subjects inhaled smoke from 2...
Article
Background and purpose: Synthetic cannabinoids (often sold as Spice or K2) have become a very popular alternative to cannabis due to the easy access and portrayed safety. Controlled studies on the behavioral effects of synthetic cannabinoids are currently lacking, which hampers risk assessments of these compounds. Experimental approach: This is...
Article
Background: Each year, synthetic cannabinoids are occurring in high numbers on the illicit drug market, but data on their detectability are rarely available. Therefore, a pilot study was performed to assess adverse effects of JWH-018, which is one of the oldest and best known synthetic cannabinoids. Oral fluid has been evaluated as a specimen for...
Article
Background Each year, synthetic cannabinoids are occurring in high numbers in the illicit drug market. But data on their pharmacology and toxicology are scarcely available. Therefore, a pilot study was performed to assess adverse effects of JWH-018, which is one of the oldest and best known synthetic cannabinoids. Methods Six subjects inhaled smoke...
Article
Full-text available
Introduction: The on-the-road highway driving test is generally regarded as a gold standard for assessing drug-induced driving impairment. The primary outcome measure is the standard deviation of lateral position (SDLP), a measure of road tracking error or "weaving". The test has been calibrated for incremental doses of alcohol almost 30 years ago...
Article
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The dopamine β-hydroxylase (DβH) 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...
Article
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Scientific Reports 6 : Article number: 26843 10.1038/srep26843 ; published online: 26 May 2016 ; updated: 02 September 2016 This Article contains an error in the Author Contributions statement. “J.G.R. and R.J.V. designed the study and operated as PIs. J.H.v.
Article
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Rationale: Alcohol and cannabis use have been implicated in aggression. Alcohol consumption is known to facilitate aggression, whereas a causal link between cannabis and aggression has not been clearly demonstrated. Objectives: This study investigated the acute effects of alcohol and cannabis on subjective aggression in alcohol and cannabis user...
Article
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Introduction: Ayahuasca is a South American psychotropic plant tea traditionally used in Amazonian shamanism. The tea contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT), plus β-carboline alkaloids with monoamine oxidase-inhibiting properties. Increasing evidence from anecdotal reports and open-label studies indicates tha...
Article
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Objective: Previous studies demonstrated that mequitazine produces mild sedation after single doses. Its enantiomer, l-mequitazine, has a stronger potency for the H1 receptor. The aim of the current study was to assess the effects of l-mequitazine and mequitazine, alone and with alcohol, on driving. Methods: Twenty-five healthy volunteers were t...
Article
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Recreational use of mephedrone, alone and in combination with alcohol, has increased over the past years. Pharmacological properties of mephedrone share similarities with methylenedioxymethamphetamine (MDMA), but its effect on neurocognitive function has not been well established in humans. The present study assessed the effect of mephedrone alone...
Article
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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...
Article
Introduction Mephedrone is a synthetic cathinone derivative included in the class of “New-Novel Psychoactive Substances”. Synthetic cathinones are marketed as “bath salts” or “plant food” and gained notable popularity for similar effects to 4-methylenedioxymethamphetamine (MDMA, ecstasy), or amphetamines. Mephedrone is commonly consumed simultaneou...
Article
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Background Ecstasy use has been associated with short-term and long-term memory deficits on a standard Word Learning Task (WLT). The clinical relevance of this has been debated and is currently unknown. The present study aimed at evaluating the clinical relevance of verbal memory impairment in Ecstasy users. To that end, clinical memory impairment...
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Drugs of abuse stimulate striatal dopamine release and activate reward pathways. This study examined the impact of alcohol and cannabis marketing on the reward circuit in alcohol and cannabis users while sober and intoxicated. It was predicted that alcohol and cannabis marketing would increase striatal activation when sober and that reward sensitiv...
Article
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Chronic or repeated cocaine use has been linked to impairments in social skills. It is not clear whether cocaine is responsible for this impairment or whether other factors, like polydrug use, distort the observed relation. We aimed to investigate this relation by means of a placebo-controlled experimental study. Additionally, associations between...
Article
Some drugs of abuse may produce dissociative symptoms, but this aspect has been understudied. We explored the dissociative potential of three recreational drugs (3,4-methylenedioxymethamphetamine (MDMA), cannabis, and cocaine) during intoxication and compared their effects to literature reports of dissociative states in various samples. Two placebo...
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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) recei...
Article
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Rationale: One of the most often reported cognitive deficits of acute cannabis administration is an impaired recall of previously learned information. Objective: The aim of the present study was to determine whether cannabis-induced memory impairment in humans is mediated via glutamatergic or cholinergic pathways. Methods: Fifteen occasional c...
Article
This chapter concentrates on the effect of psychoactive prescription drugs on driving performance using the on-the-road driving test. It provides an overview of medicinal drugs that could impair driving performance as tested with the on-the-road driving test. Hypnotics are meant to induce sleep in patients who suffer from insomnia. However, hypnoti...
Article
Cannabis is the most popular drug used in the European Union, closely followed by cocaine. Whereas cannabis has been shown to impair 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...
Article
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Release of dopamine in the nucleus accumbens (NAcc) is essential for acute drug reward. The present study was designed to trace the reinforcing effect of dopamine release by measuring the functional connectivity (FC) between the NAcc and brain regions involved in a limbic cortical-subcortical circuit during a dopaminergic challenge. Twenty healthy...
Article
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Rationale: P-glycoprotein (P-gp) is a drug efflux pump expressed, amongst others, on the luminal surface of the cerebral endothelial cells forming the blood-brain barrier. Studies in rodents have demonstrated that antihistamines that are substrates of the P-gp transporter display no or minor central nervous system (CNS) effects as compared to anti...
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Oral fluid (OF) tests aid in identifying drivers under the influence of drugs. In this study, 17 heavy cannabis users consumed alcohol to achieve steady blood alcohol concentrations of 0 to 0.7 g/L and smoked cannabis 3 h afterward. OF samples were obtained before and up to 4 h after smoking and on-site tests were performed (Dräger DrugTest 5000 an...