Cardiovascular and pulmonary complications of recreational drugs: A pictorial review.

Recreational drug abuse constitutes a serious health problem worldwide. Consumption of cocaine, amphetamine-type stimulants, opioids and cannabis can lead to multiple acute and chronic cardiopulmonary complications, resulting in high morbidity and mortality. These complications may be first detected at imaging, since clinical presentation is usually non-specific. Cardiovascular complications include myocardial infarction, endocarditis, aortic dissection, infectious pseudoaneurysm, retained needle fragments, cardiomyopathy and pulmonary arterial hypertension. Pulmonary complications encompass pulmonary oedema, crack lung, pneumonia, septic emboli, barotrauma, airway disease, emphysema and excipient lung disease. Knowledge of the cardiopulmonary imaging manifestations of illicit drug use in conjunction with clinical history and a high grade of suspicion enable an accurate diagnosis and appropriate management plan. In this article we aim to provide a pictorial review of the most frequent cardiopulmonary manifestations of recreational drugs, emphasizing the underlying pathophysiologic mechanisms and the various imaging appearances.

Identifying the role of (dis)inhibition in the vicious cycle of substance use through ecological momentary assessment and resting-state fMRI.

Functional inhibition is known to improve treatment outcomes in substance use disorder (SUD), potentially through craving management enabled by underlying cerebral integrity. Whereas treatment is challenged by a multitude of substances that patients often use, no study has yet unraveled if inhibition and related cerebral integrity could prevent relapse from multiples substances, that is, one's primary drug of choice and secondary ones. Individuals with primary alcohol, cannabis, or tobacco use disorders completed intensive Ecological Momentary Assessment (EMA) coupled with resting-state functional MRI (rs-fMRI) to characterize the extent to which inhibition and cerebral substrates interact with craving and use of primary and any substances. Participants were 64 patients with SUD and 35 healthy controls who completed one week EMA using Smartphones to report 5 times daily their craving intensity and substance use and to complete Stroop inhibition testing twice daily. Subsamples of 40 patients with SUD and 34 control individuals underwent rs-fMRI. Mixed Model Analysis revealed that reported use of any substance by SUD individuals predicted later use of any and primary substance, whereas use of the primary substance only predicted higher use of that same substances. Craving and inhibition level independently predicted later use but did not significantly interact. Preserved inhibition performance additionally influenced use indirectly by mediating the link between subsequent uses and by being linked to rs-fMRI connectivity strength in fronto-frontal and cerebello-occipital connections. As hypothesized, preserved inhibition performance, reinforced by the integrity of inhibitory neurofunctional substrates, may partake in breaking an unhealthy substance use pattern for a primary substance but may not generalize to non-target substances or to craving management.

Imaging neuroinflammation in individuals with substance use disorders.

Increasing evidence suggests a role of neuroinflammation in substance use disorders (SUDs). This Review presents findings from neuroimaging studies assessing brain markers of inflammation in vivo in individuals with SUDs. Most studies investigated the translocator protein 18 kDa (TSPO) using PET; neuroimmune markers myo-inositol, choline-containing compounds, and N-acetyl aspartate using magnetic resonance spectroscopy; and fractional anisotropy using MRI. Study findings have contributed to a greater understanding of neuroimmune function in the pathophysiology of SUDs, including its temporal dynamics (i.e., acute versus chronic substance use) and new targets for SUD treatment.

Multi-level prediction of substance use: Interaction of white matter integrity, resting-state connectivity and inhibitory control measured repeatedly in every-day life.

Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone-based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict use. Thus, we aimed to assess white matter integrity interaction with everyday inhibition deficits and related resting-state network connectivity to identify multi-dimensional predictors of substance use. Thirty-eight patients treated for alcohol, cannabis or tobacco use disorder completed 1 week of EMA to report substance use five times and complete Stroop inhibition testing twice daily. Before EMA tracking, participants underwent resting state functional MRI and diffusion tensor imaging (DTI) scanning. Regression analyses were conducted between mean Stroop performances and whole-brain fractional anisotropy (FA) in white matter. Moderation testing was conducted between mean FA within significant clusters as moderator and the link between momentary Stroop performance and use as outcome. Predictions between FA and resting-state connectivity strength in known inhibition-related networks were assessed using mixed modelling. Higher FA values in the anterior corpus callosum and bilateral anterior corona radiata predicted higher mean Stroop performance during the EMA week and stronger functional connectivity in occipital-frontal-cerebellar regions. Integrity in these regions moderated the link between inhibitory control and substance use, whereby stronger inhibition was predictive of the lowest probability of use for the highest FA values. In conclusion, compromised white matter structural integrity in anterior brain systems appears to underlie impairment in inhibitory control functional networks and compromised ability to refrain from substance use.

Widespread reductions in cortical thickness following ketamine abuse.

BACKGROUND: Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine. METHODS: We acquired structural brain images for patients with ketamine use disorder and drug-free healthy controls. We used FreeSurfer software to measure cortical thickness for 68 brain regions. We compared cortical thickness between the 2 groups using analysis of covariance with covariates of age, gender, educational level, smoking, drinking, and whole-brain mean cortical thickness. RESULTS: We included images from 95 patients with ketamine use disorder and 169 controls. Compared with healthy controls, patients with ketamine use disorder had widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed among ketamine users relative to comparison participants. Estimated total lifetime ketamine consumption was correlated with reductions in the right inferior parietal and the right rostral middle frontal cortical thickness. LIMITATIONS: We conducted a retrospective cross-sectional study, but longitudinal studies are needed to further validate decreased cortical thickness after nonmedical use of ketamine. CONCLUSION: This study provided evidence that, compared with healthy controls, chronic ketamine users have widespread reductions in cortical thickness. Our study underscores the importance of the long-term effects of ketamine on brain structure and serves as a reference for the antidepressant use of ketamine.

Substance use disorders are characterised by increased voxel-wise intrinsic measures in sensorimotor cortices: An ALE meta-analysis.

Substance use disorders (SUDs) are severe psychiatric illnesses. Seed region and independent component analyses are currently the dominant connectivity measures but carry the risk of false negatives due to selection. They can be complemented by a data-driven and whole-brain usage of voxel-wise intrinsic measures (VIMs). We meta-analytically integrated VIMs, namely regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), voxel-mirrored homotopy connectivity (VMHC) and degree centrality (DC) across different SUDs using the Activation Likelihood Estimation (ALE) algorithm, functionally decoded emerging clusters, and analysed their connectivity profiles. Our systematic search identified 51 studies including 1439 SUD participants. Although no overall convergent pattern of alterations across VIMs in SUDs was found, sensitivity analyses demonstrated two ALE-derived clusters of increased ReHo and ALFF in SUDs, which peaked in the left pre- and postcentral cortices. Subsequent analyses showed their involvement in action execution, somesthesis, finger tapping and vibrotactile monitoring/discrimination. Their numerous clinical correlates across included studies highlight the under-discussed role of sensorimotor cortices in SUD, urging a more attentive exploration of their clinical significance.

Corticostriatal responses to social reward are linked to trait reward sensitivity and subclinical substance use in young adults.

Aberrant levels of reward sensitivity have been linked to substance use disorder and are characterized by alterations in reward processing in the ventral striatum (VS). Less is known about how reward sensitivity and subclinical substance use relate to striatal function during social rewards (e.g. positive peer feedback). Testing this relation is critical for predicting risk for development of substance use disorder. In this pre-registered study, participants (N = 44) underwent fMRI while completing well-matched tasks that assess neural response to reward in social and monetary domains. Contrary to our hypotheses, aberrant reward sensitivity blunted the relationship between substance use and striatal activation during receipt of rewards, regardless of domain. Moreover, exploratory whole-brain analyses showed unique relations between substance use and social rewards in temporoparietal junction. Psychophysiological interactions demonstrated that aberrant reward sensitivity is associated with increased connectivity between the VS and ventromedial prefrontal cortex during social rewards. Finally, we found that substance use was associated with decreased connectivity between the VS and dorsomedial prefrontal cortex for social rewards, independent of reward sensitivity. These findings demonstrate nuanced relations between reward sensitivity and substance use, even among those without substance use disorder, and suggest altered reward-related engagement of cortico-VS responses as potential predictors of developing disordered behavior.

Neuromelanin levels in individuals with substance use disorders: A systematic review and meta-analysis.

Dopamine's role in addiction has been extensively studied, revealing disruptions in its functioning throughout all addiction stages. Neuromelanin in the substantia nigra (SN) may reflect dopamine auto-oxidation, and can be quantified using neuromelaninsensitive magnetic resonance imaging (neuromelanin-MRI) in a non-invasive manner.In this pre-registered systematic review, we assess the current body of evidence related to neuromelanin levels in substance use disorders, using both post-mortem and MRI examinations. The systematic search identified 10 relevant articles, primarily focusing on the substantia nigra. An early-stage meta-analysis (n = 6) revealed varied observations ranging from standardized mean differences of -3.55 to +0.62, with a pooled estimate of -0.44 (95 % CI = -1.52, 0.65), but there was insufficient power to detect differences in neuromelanin content among individuals with substance use disorders. Our gap analysis highlights the lack of sufficient replication studies, with existing studies lacking the power to detect a true difference, and a complete lack of neuromelanin studies on certain substances of clinical interest. We provide recommendations for future studies of dopaminergic neurobiology in addictions and related psychiatric comorbidities.

Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity: A Systematic Review.

Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Spectrum of Thoracic Imaging Findings in the Setting of Substance Abuse.

ABSTRACT: Substance abuse continues to be prevalent nationwide and can lead to a myriad of chest pathologies. Imaging findings are vast and can include nodules, masses, ground-glass opacities, airspace disease, and cysts. Radiologists with awareness of these manifestations can assist in early identification of disease in situations where information is unable to be obtained from the patient. This review focuses on thoracic imaging findings associated with various forms of substance abuse, which are organized by portal of entry into the thorax: inhalation, ingestion, and injection.

Neural underpinnings of response inhibition in substance use disorders: weak meta-analytic evidence for a widely used construct.

RATIONALE: Substance use disorders (SUDs) rank among the most severely debilitating psychiatric conditions. Among others, decreased response inhibition capacities could make it more difficult for patients to abstain from drug use and maintain abstinence. However, meta-analyses on the neural basis of response inhibition in SUDs yielded conflicting results. OBJECTIVE: In this study, we revisited the neuroimaging research field and summarized the existing fMRI literature on overt response inhibition (Go/NoGo and stop-signal paradigms) across different SUDs. METHODS: We performed a systematic literature review and an activation likelihood estimation (ALE) meta-analysis to investigate the actual convergence of functional deviations observed in SUD samples. Results were further supplied by consecutive robustness measures and a post-hoc random-effects meta-analysis of behavioural data. RESULTS: We identified k = 21 eligible studies for our analysis. The ALE analysis indicated a significant cluster of convergence with its statistical peak in the right anterior insula. Consecutive analyses, however, indicated this result was not robust and susceptible towards publication bias. Additionally, a post-hoc random effects meta-analysis of the behavioural parameters of Go/NoGo and stop-signal paradigms reported by the included studies revealed no significant differences in task performance comparing SUD samples and controls. CONCLUSION: We discuss that the role of task-based response inhibition may require some refinement as an overarching marker for SUD pathology. Finally, we give a few prospects for future research that should be further explored in this context.

Similarity and difference in large-scale functional network alternations between behavioral addictions and substance use disorder: a comparative meta-analysis.

Behavioral addiction (BA) and substance use disorder (SUD) share similarities and differences in clinical symptoms, cognitive functions, and behavioral attributes. However, little is known about whether and how functional networks in the human brain manifest commonalities and differences between BA and SUD. Voxel-wise meta-analyses of resting-state functional connectivity (rs-FC) were conducted in BA and SUD separately, followed by quantitative conjunction analyses to identify the common and distinct alterations across both the BA and SUD groups. A total of 92 datasets with 2444 addicted patients and 2712 healthy controls (HCs) were eligible for the meta-analysis. Our findings demonstrated that BA and SUD exhibited common alterations in rs-FC between frontoparietal network (FPN) and other high-level neurocognitive networks (i.e. default mode network (DMN), affective network (AN), and salience network (SN)) as well as hyperconnectivity between SN seeds and the Rolandic operculum in SSN. In addition, compared with BA, SUD exhibited several distinct within- and between-network rs-FC alterations mainly involved in the DMN and FPN. Further, altered within- and between-network rs-FC showed significant association with clinical characteristics such as the severity of addiction in BA and duration of substance usage in SUD. The common rs-FC alterations in BA and SUD exhibited the relationship with consistent aberrant behaviors in both addiction groups, such as impaired inhibition control and salience attribution. By contrast, the distinct rs-FC alterations might suggest specific substance effects on the brain neural transmitter systems in SUD.

Neuroimaging in Adolescents: Post-Traumatic Stress Disorder and Risk for Substance Use Disorders.

Trauma in childhood and adolescence has long-term negative consequences in brain development and behavior and increases the risk for psychiatric disorders. Among them, post-traumatic stress disorder (PTSD) during adolescence illustrates the connection between trauma and substance misuse, as adolescents may utilize substances to cope with PTSD. Drug misuse may in turn lead to neuroadaptations in learning processes that facilitate the consolidation of traumatic memories that perpetuate PTSD. This reflects, apart from common genetic and epigenetic modifications, overlapping neurocircuitry engagement triggered by stress and drug misuse that includes structural and functional changes in limbic brain regions and the salience, default-mode, and frontoparietal networks. Effective strategies to prevent PTSD are needed to limit the negative consequences associated with the later development of a substance use disorder (SUD). In this review, we will examine the link between PTSD and SUDs, along with the resulting effects on memory, focusing on the connection between the development of an SUD in individuals who struggled with PTSD in adolescence. Neuroimaging has emerged as a powerful tool to provide insight into the brain mechanisms underlying the connection of PTSD in adolescence and the development of SUDs.

Effects of Substance Use and Antisocial Personality on Neuroimaging-Based Machine Learning Prediction of Schizophrenia.

BACKGROUND AND HYPOTHESIS: Neuroimaging-based machine learning (ML) algorithms have the potential to aid the clinical diagnosis of schizophrenia. However, literature on the effect of prevalent comorbidities such as substance use disorder (SUD) and antisocial personality (ASPD) on these models' performance has remained unexplored. We investigated whether the presence of SUD or ASPD affects the performance of neuroimaging-based ML models trained to discern patients with schizophrenia (SCH) from controls. STUDY DESIGN: We trained an ML model on structural MRI data from public datasets to distinguish between SCH and controls (SCH = 347, controls = 341). We then investigated the model's performance in two independent samples of individuals undergoing forensic psychiatric examination: sample 1 was used for sensitivity analysis to discern ASPD (N = 52) from SCH (N = 66), and sample 2 was used for specificity analysis to discern ASPD (N = 26) from controls (N = 25). Both samples included individuals with SUD. STUDY RESULTS: In sample 1, 94.4% of SCH with comorbid ASPD and SUD were classified as SCH, followed by patients with SCH + SUD (78.8% classified as SCH) and patients with SCH (60.0% classified as SCH). The model failed to discern SCH without comorbidities from ASPD + SUD (AUC = 0.562, 95%CI = 0.400-0.723). In sample 2, the model's specificity to predict controls was 84.0%. In both samples, about half of the ASPD + SUD were misclassified as SCH. Data-driven functional characterization revealed associations between the classification as SCH and cognition-related brain regions. CONCLUSION: Altogether, ASPD and SUD appear to have effects on ML prediction performance, which potentially results from converging cognition-related brain abnormalities between SCH, ASPD, and SUD.

Do mindfulness-based interventions change brain function in people with substance dependence? A systematic review of the fMRI evidence.

BACKGROUND: Substance use disorders (SUDs) affect ~ 35 million people globally and are associated with strong cravings, stress, and brain alterations. Mindfulness-based interventions (MBIs) can mitigate the adverse psychosocial outcomes of SUDs, but the underlying neurobiology is unclear. Emerging findings were systematically synthesised from fMRI studies about MBI-associated changes in brain function in SUDs and their associations with mindfulness, drug quantity, and craving. METHODS: PsycINFO, Medline, CINAHL, PubMed, Scopus, and Web of Science were searched. Seven studies met inclusion criteria. RESULTS: Group by time effects indicated that MBIs in SUDs (6 tobacco and 1 opioid) were associated with changes in the function of brain pathways implicated in mindfulness and addiction (e.g., anterior cingulate cortex and striatum), which correlated with greater mindfulness, lower craving and drug quantity. CONCLUSIONS: The evidence for fMRI-related changes with MBI in SUD is currently limited. More fMRI studies are required to identify how MBIs mitigate and facilitate recovery from aberrant brain functioning in SUDs.

Sex differences in emotion- and reward-related neural responses predicting increases in substance use in adolescence.

Adolescent substance use is a significant public health problem and there is a need for effective substance use preventions. To develop effective preventions, it is important to identify neurobiological risk factors that predict increases in substance use in adolescence and to understand potential sex differences in risk mechanisms. The present study used functional magnetic resonance imaging and hierarchical linear modeling to examine negative emotion- and reward-related neural responses in early adolescence predicting growth in substance use to middle adolescence in 81 youth, by sex. Adolescent neural responses to negative emotional stimuli and monetary reward receipt were assessed at age 12-14. Adolescents reported on substance use at age 12-14 and at 6 month, and 1, 2, and 3 year follow-ups. Adolescent neural responses did not predict initiation of substance use (yes/no), but, among users, neural responses predicted growth in substance use frequency. For girls, heightened right amygdala responses to negative emotional stimuli in early adolescence predicted growth in substance use frequency through middle adolescence. For boys, blunted left nucleus accumbens and bilateral ventromedial prefrontal cortex responses to monetary reward predicted growth in substance use frequency. Findings suggest different emotion and reward-related predictors of the development of substance use for adolescent girls versus boys.

Latent profiles of substance use, early life stress, and attention/externalizing problems and their association with neural correlates of reinforcement learning in adolescents.

BACKGROUND: Adolescent substance use, externalizing and attention problems, and early life stress (ELS) commonly co-occur. These psychopathologies show overlapping neural dysfunction in the form of reduced recruitment of reward processing neuro-circuitries. However, it is unclear to what extent these psychopathologies show common v. different neural dysfunctions as a function of symptom profiles, as no studies have directly compared neural dysfunctions associated with each of these psychopathologies to each other. METHODS: In study 1, a latent profile analysis (LPA) was conducted in a sample of 266 adolescents (aged 13-18, 41.7% female, 58.3% male) from a residential youth care facility and the surrounding community to investigate substance use, externalizing and attention problems, and ELS psychopathologies and their co-presentation. In study 2, we examined a subsample of 174 participants who completed the Passive Avoidance learning task during functional magnetic resonance imaging to examine differential and/or common reward processing neuro-circuitry dysfunctions associated with symptom profiles based on these co-presentations. RESULTS: In study 1, LPA identified profiles of substance use plus rule-breaking behaviors, attention-deficit hyperactivity disorder, and ELS. In study 2, the substance use/rule-breaking profile was associated with reduced recruitment of reward processing and attentional neuro-circuitries during the Passive Avoidance task (p < 0.05, corrected for multiple comparisons). CONCLUSIONS: Findings indicate that there is reduced responsivity of striato-cortical regions when receiving outcomes on an instrumental learning task within a profile of adolescents with substance use and rule-breaking behaviors. Mitigating reward processing dysfunction specifically may represent a potential intervention target for substance-use psychopathologies accompanied by rule-breaking behaviors.

Striatal hypoactivation during monetary loss anticipation in individuals with substance use disorders in a heterogenous urban American Indian sample.

Research suggests that disproportionate exposure to risk factors places American Indian (AI) peoples at higher risk for substance use disorders (SUD). Although SUD is linked to striatal prioritization of drug rewards over other appetitive stimuli, there are gaps in the literature related to the investigation of aversive valuation processing, and inclusion of AI samples. To address these gaps, this study compared striatal anticipatory gain and loss processing between AI-identified with SUD (SUD+; n = 52) and without SUD (SUD-; n = 35) groups from the Tulsa 1000 study who completed a monetary incentive delay (MID) task during functional magnetic resonance imaging. Results indicated that striatal activations in the nucleus accumbens (NAcc), caudate, and putamen were greatest for anticipating gains (ps < 0.001) but showed no group differences. In contrast to gains, the SUD+ exhibited lower NAcc (p = .01, d =0.53) and putamen (p = .04, d =0.40) activation to anticipating large losses than the comparison group. Within SUD+ , lower striatal responses during loss anticipations were associated with slower MID reaction times (NAcc: r = -0.43; putamen: r = -0.35) during loss trials. This is among the first imaging studies to examine underlying neural mechanisms associated with SUD within AIs. Attenuated loss processing provides initial evidence of a potential mechanism wherein blunted prediction of aversive consequences may be a defining feature of SUD that can inform future prevention and intervention targets.

Selective α3ß4 Nicotinic Acetylcholine Receptor Ligand as a Potential Tracer for Drug Addiction.

α3ß4 Nicotinic acetylcholine receptor (nAChR) has been recognized as an emerging biomarker for the early detection of drug addiction. Herein, α3ß4 nAChR ligands were designed and synthesized to improve the binding affinity and selectivity of two lead compounds, (S)-QND8 and (S)-T2, for the development of an α3ß4 nAChR tracer. The structural modification was achieved by retaining the key features and expanding the molecular structure with a benzyloxy group to increase the lipophilicity for blood-brain barrier penetration and to extend the ligand-receptor interaction. The preserved key features are a fluorine atom for radiotracer development and a p-hydroxyl motif for ligand-receptor binding affinity. Four (R)- and (S)-quinuclidine-triazole (AK1-AK4) were synthesized and the binding affinity, together with selectivity to α3ß4 nAChR subtype, were determined by competitive radioligand binding assay using [3H]epibatidine as a radioligand. Among all modified compounds, AK3 showed the highest binding affinity and selectivity to α3ß4 nAChR with a Ki value of 3.18 nM, comparable to (S)-QND8 and (S)-T2 and 3069-fold higher affinity to α3ß4 nAChR in comparison to α7 nAChR. The α3ß4 nAChR selectivity of AK3 was considerably higher than those of (S)-QND8 (11.8-fold) and (S)-T2 (294-fold). AK3 was shown to be a promising α3ß4 nAChR tracer for further development as a radiotracer for drug addiction.