Addiction Biology最新文献

A network meta-analysis (NMA) including randomized controlled trials (RCTs) was conducted to evaluate the effects of different interventions on smoking cessation. Studies were collected from online databases including PubMed, EMBASE, Cochrane Library, and Web of Science based on inclusion and exclusion criteria. Eligible studies were further examined in the NMA to compare the effect of 14 interventions on smoking cessation. Thirty-four studies were examined in the NMA, including a total of 14 interventions and 28 733 participants. The results showed that health education (HE; odds ratio ([OR] = 200.29, 95% CI [1.62, 24 794.61])), other interventions (OI; OR = 29.79, 95% CI [1.07, 882.17]) and multimodal interventions (MUIs; OR = 100.16, 95% CI [2.06, 4867.24]) were better than self-help material (SHM). HE (OR = 243.31, 95% CI [1.39, 42531.33]), MUI (OR = 121.67, 95% CI [1.64, 9004.86]) and financial incentive (FI; OR = 14.09, 95% CI [1.21, 164.31]) had positive effects on smoking cessation rate than smoking cessation or quitting APP (QA). Ranking results showed that HE (83.6%) and motivation interviewing (MI; 69.6%) had better short-term effects on smoking cessation. HE and MUI provided more smoking cessation benefits than SHM and QA. FI was more effective at quitting smoking than QA. Also, HE and MI were more likely to be optimal smoking cessation interventions.

Cocaine use disorder (CUD) is a worldwide public health condition that is suggested to induce pathological changes in macrostructure and microstructure. Repetitive transcranial magnetic stimulation (rTMS) has gained attention as a potential treatment for CUD symptoms. Here, we sought to elucidate whether rTMS induces changes in white matter (WM) microstructure in frontostriatal circuits after 2 weeks of therapy in patients with CUD and to test whether baseline WM microstructure of the same circuits affects clinical improvement. This study consisted of a 2-week, parallel-group, double-blind, randomized controlled clinical trial (acute phase) (sham [n = 23] and active [n = 27]), in which patients received two daily sessions of rTMS on the left dorsolateral prefrontal cortex (lDLPFC) as an add-on treatment. T1-weighted and high angular resolution diffusion-weighted imaging (DWI-HARDI) at baseline and 2 weeks after served to evaluate WM microstructure. After active rTMS, results showed a significant increase in neurite density compared with sham rTMS in WM tracts connecting lDLPFC with left and right ventromedial prefrontal cortex (vmPFC). Similarly, rTMS showed a reduction in orientation dispersion in WM tracts connecting lDLPFC with the left caudate nucleus, left thalamus, and left vmPFC. Results also showed a greater reduction in craving Visual Analogue Scale (VAS) after rTMS when baseline intra-cellular volume fraction (ICVF) was low in WM tracts connecting left caudate nucleus with substantia nigra and left pallidum, as well as left thalamus with substantia nigra and left pallidum. Our results evidence rTMS-induced WM microstructural changes in fronto-striato-thalamic circuits and support its efficacy as a therapeutic tool in treating CUD. Further, individual clinical improvement may rely on the patient's individual structural connectivity integrity.

N-Isopropylbenzylamine (N-ipb), a chain isomer of methamphetamine (METH) with similar physical properties, has been used as a substitute for METH in seized drug samples. However, the abuse potential of N-ipb remains unclear. Therefore, this study aimed to evaluate the abuse potential of N-ipb in comparison to METH, by using conditioned place preference (CPP), locomotor sensitization and intravenous self-administration tests. The results showed that N-ipb at a dose of 3 mg·kg⁻¹ significantly induced CPP in mice, which was comparable to the effect of METH at 1 mg·kg⁻¹. Either acute or repeated N-ipb injections (1 or 3 mg·kg⁻¹) failed to raise the locomotor activity. However, acute treatment with 10 mg·kg⁻¹ N-ipb elevated the locomotor activity compared with saline, while chronic injection of 10 mg·kg⁻¹ N-ipb induced a delayed and attenuated sensitization compared with 1 mg·kg⁻¹ METH. Rats could acquire N-ipb self-administration at a dose of 1 mg·kg⁻¹·infusion⁻¹, and a typical inverted U-shaped dose–response curve was obtained for N-ipb. The mean dose of N-ipb that maintained the maximum response was greater than that of METH, indicating that N-ipb is less potent for reinforcement than METH. In the economic behavioural analysis, comparison of essential values derived from the demand elasticity revealed that N-ipb is less efficacy as a reinforcer than METH. The present data demonstrate that N-ipb functions as a reinforcer and has a potential for abuse. However, the potency of psychomotor stimulation and the reinforcing effectiveness of N-ipb are lower than those of METH.

Alcohol use disorder (AUD) is heritable. Thus, young adults with positive family histories represent an at-risk group relative to those without a family history, and if studied at a time when both groups have similar levels of alcohol use, it provides an opportunity to identify neural processing patterns associated with risk for AUD. Previous studies have shown that diminished response to potential reward is associated with genetic risk for AUD, but it is unclear how threat may modulate this response. We used a modified Monetary Incentive Delay task during fMRI to examine neural correlates of the interaction between threat and reward anticipation in a sample of young adults with (n = 31) and without (n = 44) family histories of harmful alcohol use. We found an interaction (p = 0.048) between cue and group in the right nucleus accumbens where the family history positive group showed less differentiation to the anticipation of gaining $5 and losing $5 relative to gaining $0. The family history-positive group also reported less excitement for trials to gain $5 relative to gaining $0 (p < 0.001). Family history-positive individuals showed less activation in the left insula during both safe and threat blocks compared to family history-negative individuals (p = 0.005), but the groups did not differ as a function of threat (p > 0.70). Young adults with, relative to without, enriched risk for AUD may have diminished reward processing via both neural and behavioural markers to potential rewarding and negative consequences. Neural response to threat may not be a contributing factor to risk at this stage.

Humans demonstrate significant behavioural advantages with particular perceptual dimensions (such as colour or shape) and when the relevant dimension is repeated in consecutive trials. These dimension-related behavioural modulations are significantly altered in neuropsychological and addiction disorders; however, their underlying mechanisms remain unclear. Here, we studied whether these behavioural modulations exist in other trichromatic primate species and whether repeated exposure to opioids influences them. In a target detection task where the target-defining dimension (colour or shape) changed trial by trial, humans exhibited shorter response time (RT) and smaller event-related electrodermal activity with colour dimension; however, macaque monkeys had shorter RT with shape dimension. Although the dimensional biases were in the opposite directions, both species were faster when the relevant dimension was repeated, compared with conditions when it changed, across consecutive trials. These indicate that both species formed dimensional sets and that resulted in a significant ‘switch cost’. Scheduled and repeated exposures to morphine, which is analogous to its clinical and recreational use, significantly augmented the dimensional bias in monkeys and also changed the switch cost depending on the relevant dimension. These cognitive effects occurred when monkeys were in abstinence periods (not under acute morphine effects) but expressing significant morphine-induced conditioned place preference. These findings indicate that significant dimensional biases and set formation are evolutionarily preserved in humans' and monkeys' cognition and that repeated exposure to morphine interacts with their manifestation. Shared neural mechanisms might be involved in the long-lasting effects of morphine and expression of dimensional biases and set formation in anthropoids.

Alcohol use disorder (AUD) is characterized by cycles of abuse, withdrawal, and relapse. Neuroadaptations in the basal ganglia are observed in AUD; specifically in the putamen, globus pallidus (GP), and ventral pallidum (VP). These regions are associated with habit formation, drug-seeking behaviors, and reward processing. While previous studies have shown the crucial role of glial cells in drug seeking, it remains unknown whether glial cells in the basal ganglia are altered in AUD. Glial cells in the putamen, GP, and VP were examined in human post-mortem tissue of AUD and alcohol remission cases. Immunohistochemistry was performed to analyze cell count, staining intensity, and morphology of microglia and astrocytes, using markers Iba-1 and GFAP. Morphological analysis revealed a significant decrease in microglia cell size and process retraction, indicating activation or a dystrophic microglia phenotype in individuals with AUD compared to controls. Microglia staining intensity was also higher in the GP and VP in AUD cases, whereas microglia staining intensity and cell size in remission cases were not different to control cases. In contrast, no astrocyte changes were observed in examined brain regions for both AUD and remission cases compared to controls. These results suggest alcohol exposure alters microglia, potentially contributing to dysfunctions in the basal ganglia that maintain addiction, and abstinence from alcohol may reverse microglia changes and associated dysfunctions. Overall, this study further characterizes AUD neuropathology and implicates microglia in the putamen, GP, and VP as a potential target for therapy.

Online poker gambling (OPG) involves various executive control processes and emotion regulation. In this context, we hypothesized that online poker players, accustomed to handling virtual cards, would show high performance on computerized decision-making tasks such as the Iowa Gambling Task (IGT). Using press advertisements, we recruited a non-gambler group (NG; n = 20) and an OPG group (n = 22). All participants performed the IGT while their cerebral activity was recorded by electroencephalography. Compared with the OPG group, the NG group showed significantly better progression in the IGT in the last trials. Recording of brain activity revealed the appearance of a temporal map between 150 and 175 ms specific to the gain condition in both groups. A second map was observed at 215–295 ms specifically in the NG group, and the generators were identified in the occipital regions. This activity is indicative of a high level of visual awareness; thus, it reflects additional processing of visual information, which can be assumed to be induced by the lower exposure of the NGs to online card games. We hypothesize that the absence of this activity in the OPG group might be due to their online habituation to virtual environments.

Despite synthetic cannabinoids' (SCs) prevalent use among humans, these substances often lack comprehensive pharmacological data, primarily due to their rapid emergence in the market. This study aimed to discern differences and causal factors among four SCs (ADB-BICA, ADB-BINACA, ADB-4en-PINACA and MDMB-4en-PINACA), with respect to locomotor activity, body temperature and nociception threshold. Adult male C57BL/6 mice received intraperitoneal injections of varying doses (0.5, 0.1 and 0.02 mg/kg) of these compounds. Three substances (including ADB-BINACA, ADB-4en-PINACA and MDMB-4en-PINACA) demonstrated dose- and time-dependent hypolocomotive and hypothermic effects. Notably, 0.1 mg/kg MDMB-4en-PINACA exhibited analgesic properties. However, ADB-BICA did not cause any effects. MDMB-4en-PINACA manifested the most potent and sustained effects, followed by ADB-4en-PINACA, ADB-BINACA and ADB-BICA. Additionally, the cannabinoid receptor 1 (CB1R) antagonist AM251 suppressed the effects induced by acute administration of the substances. Analysis of molecular binding configurations revealed that the four SCs adopted a congruent C-shaped geometry, with shared linker binding pockets conducive to robust steric interaction with CB1R. Essential residues PHE²⁶⁸, PHE²⁰⁰ and SER¹⁷³ within CB1R were identified as pivotal contributors to enhancing receptor–ligand associations. During LC-MS/MS analysis, 0.5 mg/kg MDMB-4en-PINACA exhibited the highest plasma concentration and most prolonged detection window post-administration. The study of SCs' pharmacological and pharmacokinetic profiles is crucial for better understanding the main mechanisms of cannabinoid-like effects induced by SCs, interpreting clinical findings related to SC uses and enhancing SCs risk awareness.

Stimulant betel quid (SBQ) containing Piper betle leaf (L), green unripe Areca catechu nut (AN) and the alkalizing agent, slaked lime, is an addictive, carcinogenic stimulant, with no pharmacotherapy, chewed by millions of people in the Asia/Pacific region. We compared the in vivo physiological profile of chewing (1) non-stimulant P. betle leaf+AN (LAN), (2) SBQ utilizing slaked lime and (3) a novel SBQ utilizing Mg(OH)₂, as an alkalizing agent, by measuring physiological parameters of intoxication and these were correlated with in vitro levels of alkaloids measured by UHPLC–MS/MS. Chewing LAN, which contains high levels of arecoline, had no stimulatory physiological effect. Chewing SBQ containing slaked lime or novel SBQ containing Mg(OH)₂, induced equivalent stimulatory physiological responses. In vitro, slaked lime hydrolyzed muscarinic esters in LAN while Mg(OH)₂ did not. The physiological stimulation induced by chewing both SBQ and the lack of physiology to chewing LAN can be explained by changes in lipid solubility of phytochemicals induced by mouth pH during chewing of basic SBQ or acidic LAN. Since antiquity people have added slaked lime to SBQ to enhance absorption of phyto-chemicals across oral membranes to stimulate physiology. The same physiological changes can be induced by substituting slaked lime for less physically and chemically destructive bases. If attitudes regarding SBQ dependence can advance towards the more progressive attitudes already used to help smokers quit tobacco, modern chemistry has the potential to make chewing SBQ safer and quitting programs may become more accessible and efficacious.