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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 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.
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 from more general effects on cognition that spread across multiple domains such as arousal and attention.
Aims: The main objective of the study was, therefore, to determine whether drug-induced changes in prospective memory are memory specific or associated with more general drug-induced changes in attention and arousal.
Methods: A placebo-controlled, three-way, cross-over study including 15 regular poly-drug users was set up to test the influence of oral cocaine (300 mg) and vaporised cannabis (300+150 ‘booster’ µg/kg bodyweight) on an event-based prospective memory task. Attentional performance was assessed using a divided attention task and subjective arousal was assessed with the Profile of Mood States questionnaire.
Results: Results showed that cocaine enhanced prospective memory, attention and arousal. Mean performance of prospective memory and attention, as well as levels of arousal were lowest during treatment with cannabis as compared with placebo and cocaine as evinced by a significantly increased trend across treatment conditions. Prospective memory performance was only weakly positively associated to measures of attention and arousal.
Conclusion: Together, these results indicate that cocaine enhancement of prospective memory performance cannot be fully explained by parallel changes in arousal and attention levels, and is likely to represent a direct change in the neural network underlying prospective memory.
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 higher detection rate and a longer detection window in cerumen than in urine. In this study, cerumen from subjects was analyzed after they ingested the designer stimulant 4-fluoroamphetamine (4-FA) in a controlled manner. Methods: Twelve subjects ingested placebo and 100 mg of 4-FA. Five of them were also given 150 mg of 4-FA in 150 mL Royal Club bitter lemon drink at least after 7 days. Cerumen was sampled using cotton swabs at baseline, 1 h after the ingestion of the drug and at the end of the study day (12 h). After extraction with ethyl acetate followed by solid-phase extraction, the extracts were analyzed using liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). Results and discussion: In the cerumen of all 12 subjects, 4-FA was detected 12 h after its ingestion; in most subjects, cerumen was detected after 1 h of ingestion, ranging from 0.06 to 13.90 (median 1.52) ng per swab. The detection of 4-FA in cerumen sampled 7 days or more after the first dose suggested a long detection window of cerumen. Conclusions: Cerumen can be successfully used to detect a single drug ingestion even immediately after the ingestion when a sufficient amount of cerumen is used.
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 and 150 mg 4-fluoroamphetamine (4-FA), a phenethylamine that has been associated with severe cardiovascular and cerebrovascular complications. The study was set-up as a placebo controlled, within subject, phase 1 trial as it was the first to administer 4-FA to humans under controlled conditions. Overall, 4-FA produced a strong elevation in blood pressure up until 4-5 h after administration that was followed by a sustained increase in heart rate. After an interim review of safety data from five participants, a decision was taken to cancel administration of 150 mg. We subsequently obtained complete datasets for placebo and 100 mg 4-FA treatments only. Effects of 4-FA on mood and neurocognitive function were most distinct at 1 h post drug and included significant elevations of vigor, friendliness, elation, arousal, positive mood, as well as improvements in attention and motor performance. Negative affect was also reported as time progressed in the acute phase and even more so during the subacute phase. Overall, the influence of 4-FA on vital signs, mood, and neurocognition was similar to that observed with other stimulants. Present findings confirm clinical observations of acute toxicity among 4-FA users and warrant warnings about potential health risks associated with 4-FA use.
