[About the use of ketamine in emergency psychiatric settings]. / À propos de l'utilisation du traitement de la kétamine aux urgences psychiatriques.

Ketamine and its S-enantiomer, esketamine, have shown to be promising molecules for use in psychiatry. Widely investigated for the treatment of drug-resistant depression, they could be used in emergency conditions, due to their rapid onset of action, in two main conditions : 1) psychomotor agitation, and 2) acute suicidal ideation and behavior (suicidal crisis). In particular, intranasal administration offers a non-invasive, safe and very easy to administer option. An effect begins a few hours to a day after intake and lasts for about a week. These molecules present an innovative option for the future and their specific use in psychiatric emergencies.

La kétamine et son énantiomère S, l'eskétamine, se sont révélés être des molécules prometteuses pour leur utilisation en psychiatrie. Largement étudiées pour le traitement de la dépression pharmacorésistante, elles pourraient être utilisées dans des conditions d'urgence et, grâce à leur rapidité d'action, dans deux situations : 1) l'agitation psychomotrice, et 2) l'idéation et le comportement suicidaire aigus (crise suicidaire). En particulier, l'administration par voie intranasale offre une option non invasive, sûre et facile à utiliser. On observe un effet quelques heures à un jour après la prise, qui perdure pendant environ une semaine. Ces molécules représentent une option innovatrice pour le futur et pour une utilisation spécifique aux urgences psychiatriques.

Effect of Ketamine on Rumination in Treatment-Resistant Depressive Patients.

BACKGROUND: A rapid antidepressant effect of ketamine has repeatedly been documented in the literature, and identifying clinical features associated with a better response to this treatment is currently an essential question. Considering the relationship between rumination and depression and the need to identify potential predictors of response to ketamine, we analyzed the effect of a single injection of ketamine 0.5 mg/kg on rumination in treatment-resistant depressive (TRD) patients and explored whether baseline ruminative style and early improvements of rumination would predict a greater antidepressant effect of ketamine. METHODS: Ten TRD outpatients who participated in a 4-week open study on the antidepressant effect of ketamine also completed the Ruminative Response Scale the day before, the day after, and a week after ketamine administration. RESULTS: We found that in our patients, a single rapid 1-minute intravenous injection of ketamine 0.5 mg/kg was efficacious in reducing rumination, but neither severity of rumination at baseline nor early improvements of rumination after ketamine injection predicted antidepressant response. CONCLUSIONS: Our preliminary data suggest that a single injection of ketamine 0.5 mg/kg can be efficacious in reducing rumination in TRD patients but rumination does not seem to be a useful clinical predictor of response to ketamine. Larger studies are necessary to confirm these results.

[Facilitating access to somatic care for adults suffering from severe mental disabilities]. / Pour un accès facilité aux soins somatiques des adultes en situation de handicap mental sévère.

For the purpose of improving the management of somatic disorders among patients suffering from severe intellectual development and autism spectrum disorders, a specific admissions mechanism has been implemented at Geneva University Hospitals (HUG). The Adult Psychiatric Hospital Unit (UPHA), a complex intervention unit, collaborates with HUG's Disability Program. From May 2018 to May 2019, 29 requests for hospitalizations were accepted. These requests primarily originated from private practice physicians (42 %). In some cases, immediate admissions were urgently organized, and in others a 13-day waiting period was imposed. Hospitalizations were adapted to the patient: more often than not, these were short (48 %), with 6 hospitalizations extended for an average 103-day period. A clinical case illustrates the healthcare management provided.

Afin d'améliorer la prise en charge somatique des patients avec troubles sévères du développement intellectuel et du spectre de l'autisme, un dispositif d'accueil a été mis en place aux Hôpitaux universitaires de Genève (HUG). Dans ce dispositif, l'Unité de psychiatrie hospitalière adulte (UPHA), une unité d'intervention complexe (UIC), collabore avec le Programme Handicap des HUG. De mai 2018 à mai 2019, 29 demandes d'hospitalisation pour soins ou bilans somatiques, évaluées en amont, ont été acceptées. Ces demandes venaient prioritairement des médecins de ville (42 %). Un accueil rapide a été organisé en urgence ou avec un délai moyen de 13 jours. Les séjours étaient adaptés : le plus souvent courts (48 %), 6 séjours ont été prolongés, avec une durée moyenne de séjour de 103 jours. Un cas clinique illustre le type de prise en charge.

[Drug management of behavioral disorders in people with developmental and intellectual disability]. / Gestion médicamenteuse des troubles du comportement de la personne en situation de handicap mental.

Behavioral disorders in people with developmental and intellectual disability are frequent but their management is rarely taught. This article is to help primary physicians prescribe drug treatment. We will also discuss the key elements of two of the most commonly used classes of drugs, taking into account the patient's co-morbidities, contraindications and the main side effects.

Les troubles du comportement chez la personne en situation de handicap mental sont fréquents, mais leur prise en charge est peu enseignée aux médecins de premier recours. Cet article a pour objectif d'aider à la prescription d'un traitement médicamenteux. Nous discutons des éléments clés des deux classes de médicaments les plus utilisés, en tenant compte des comorbidités du patient, des contre-indications et des principaux effets secondaires.

Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: The antidepressant effect of ketamine is associated with increased activity in the reward circuitry of the brain and a suppression of circuitry that mediates perceptual processing of negative emotions. The duration of ketamine effect on these brain structures remains to be defined. WHAT THIS ARTICLE TELLS US THAT IS NEW: As expected, ketamine administration led to an improvement in mood and global vigilance. The improvement in mood was accompanied by an increased recruitment of the orbitofrontal cortex, ventral striatum, medial substantial nigra and ventral tegmental area, structures that are part of the reward circuitry.Responses in the mesolimbic structures (amygdala, medial substantial nigra and ventral tegmental area, orbitofrontal cortex) to negative stimuli were decreased after ketamine administration.The data are consistent with the premise that ketamine induces sustained changes in the mesolimbic neural circuits to reset pathological reward and emotional processing. BACKGROUND: Ketamine rapidly improves maladaptive mood states in major depressive disorder, and some of the neural substrates underlying this therapeutic effect have been identified. This study aimed to identify functional changes within neural networks that may underlie the impact of ketamine on both reward and emotional processing in patients with treatment-resistant major depression. METHODS: Ten adult patients with a Montgomery-Åsberg Depression Rating Scale score above 25 were enrolled to receive a single intravenous administration of ketamine (0.5 mg/kg). Patients' performance along with related neural network activations were analyzed in a game-like reward task and in an emotional judgment task using functional magnetic resonance imaging 1 day before and 1 and 7 days after ketamine administration. RESULTS: A significant correlation (R = 0.46, P = 0.03) between the improvement of depression scores and the enhanced reaction time for positive items was found in the game-like reward task 1 day after ketamine administration. This enhanced sensitivity for rewarded items was accompanied by increased activity of reward-related brain regions, including the orbitofrontal cortex, ventral striatum, and the ventral tegmental area, an effect that persisted up to 1 week after ketamine injection. In the emotional judgment task, it was found that ketamine rapidly modified local brain activities in response to emotionally negative, positive, or neutral stimuli in the amygdala, insula, anterior cingulate cortex, and in the ventral tegmental area. CONCLUSIONS: Single bolus ketamine administration rapidly triggers lasting changes in mesolimbic neural networks to improve pathologic reward and emotional processing in patients with major depressive disorder.

Novel NEXMIF pathogenic variant in a boy with severe autistic features, intellectual disability, and epilepsy, and his mildly affected mother.

Intellectual disability (ID) and autism spectrum disorders are complex neurodevelopmental disorders occurring among all ethnic and socioeconomic groups. Pathogenic variants in the neurite extension and migration factor (NEXMIF) gene (formerly named KIAA2022) on the X chromosome are responsible for ID, autistic behavior, epilepsy, or dysmorphic features in males. Most affected females described had a milder phenotype or were asymptomatic obligate carriers. We report here for the first time mother-to-son transmission of a novel NEXMIF truncating variant without X-inactivation skewing in the blood. Truncating gene variant leads to symptomatic mother to severely affected son transmission. Our findings emphasize that NEXMIF sequencing should be strongly considered in patients with unexplained autism spectrum disorder, ID, and epilepsy, irrespective of gender. Such testing could increase our knowledge of the pathogenicity of NEXMIF variants and improve genetic counseling.

Efficacy and Safety of a Rapid Intravenous Injection of Ketamine 0.5 mg/kg in Treatment-Resistant Major Depression: An Open 4-Week Longitudinal Study.

BACKGROUND: Ketamine has been documented for its rapid antidepressant effects. However, optimal dose and delivery route have not yet been thoroughly investigated. The objectives of this study were to document the safety and test the antidepressant and antisuicidal effects of a single rapid 1-minute injection of ketamine 0.5 mg/kg in treatment-resistant depression (TRD). METHODS: Ten patients with TRD were included in an open, noncontrolled 4-week study and received a rapid intravenous dose of ketamine 0.5 mg/kg. Main outcome measure was the Montgomery-Åsberg Depression Rating Scale and suicidality was assessed using the Scale for Suicide Ideation. RESULTS: Rapid injection of ketamine elicited transient increase of blood pressure and altered states of consciousness in all patients and mild psychotomimetic effects in 4 patients, which all resolved without any intervention. Decrease of depression severity was observed from 40-minute postinjection until day 15. Eight patients became responders within 1 day and all were nonresponders after 4 weeks. The decrease of suicidal ideation was significant until day 7. Analysis indicated that higher severity of depression and anxiety at baseline predicted a larger Montgomery-Åsberg Depression Rating Scale decrease after 4 weeks. CONCLUSIONS: This study suggests that in well-controlled medical settings with adequate monitoring, a single rapid 1-minute injection of ketamine 0.5 mg/kg can be well tolerated and is efficacious in rapidly reducing depression symptoms and suicidal thoughts in outpatients with TRD. These findings are relevant to the practice of general clinical psychiatry and emergency departments were ketamine can have a place in acute management of TRD. Larger studies are necessary to confirm these results.

[Intellectual disability: contribution of genetic studies to the etiological diagnosis]. / Handicap intellectuel : apport de la génétique pour le diagnostic étiologique.

The multidiscipinary care of patients with intellectual disability requires a structured and systematic etiological process. Today, advances in technology make it possible to perform diagnostic genetic analyzes that are highly contributive in this process. The CGH-array (Comparative Genomic Hybridization array) makes it possible to search for chromosomal anomalies with a very high level of resolution; high throughput sequencing can detect gene abnormalities on the whole exome or on a panel of genes. For the patient the detection of genetic anomalies aims to improve the quality of care; for related parties, genetic counseling is systematically offered.

La prise en charge multidisciplinaire des patients présentant un handicap intellectuel impose la mise en œuvre d'une démarche étiologique structurée et systématique. Les avancées technologiques permettent aujourd'hui la réalisation d'analyses génétiques diagnostiques très contributives. Le CGH-array (puce d'hybridation génomique comparative) permet de rechercher des anomalies chromosomiques avec un très haut niveau de résolution; le séquençage à haut débit permet de détecter des anomalies géniques sur l'exome entier ou sur un panel de gènes. Pour le patient, la détection d'anomalies génétiques a pour objectif d'améliorer la qualité de la prise en charge; pour les apparentés, un conseil génétique est systématiquement proposé.

[Adults with intellectual disability : actual concepts and clinical challenges]. / Le handicap intellectuel chez l'adulte : concepts actuels et défis dans l'approche clinique.

The condition of the adult with intellectual disability (AWID) includes the largely autonomous, integrated person but also the one in need of constant support, with grossly altered communication abilities, frequently affected by somatic and mental comorbidities and non-adapted behaviors. Their prevalence is about 1 % of the adult population. They should benefit from particular attention of health care professionals, including in mental health. However, their access to health care is often limited and their quality of life and life expectancy are diminished. Recent advances in the field of ID include modified diagnostic criteria, as well as individualized care in a multidisciplinary approach in partnership with relatives and professionals from the community/service providers. These approaches allow to better address special needs of AWID.

La condition de l'adulte porteur d'un diagnostic de handicap intellectuel (ADHI) va de la personne largement autonome et intégrée dans la communauté à celle nécessitant une surveillance constante, avec des difficultés de communication, des comorbidités somatiques et mentales et des comportements non adaptés. Leur prévalence est d'environ 1 % de la population adulte. Elles devraient bénéficier d'une attention particulière de la part des professionnels de la santé, y compris mentale. Cependant, l'accès aux soins et leur qualité sont souvent limités. L'espérance et la qualité de vie des ADHI sont diminuées. Des évolutions dans le domaine du handicap intellectuel concernent le diagnostic et les approches de soins individualisés et intégrés en partenariat avec les proches et le réseau. Elles permettent de mieux répondre aux spécificités de l'ADHI.

[Treatment resistant depression: therapy and novel neuromodulatory treatments]. / Dépression résistant au traitement: enjeux, thérapie et place des nouvelles approches de neurostimulation.

Unipolar depression is among the leading cause of invalidity and disability-adjusted life-years. Many depressed patients do not respond to several antidepressant treatments. Several treatments have been investigated in resistant depression using electrical or magnetic stimulation of the brain. In this field, electroconvulsivotherapy remains to date the only treatment validated for efficacy and security. Novel neuromodulatory treatments used in neurological conditions are currently under investigation. Vagus nerve stimulation and deep brain stimulation may offer long-term efficacy and therefore justify expensive and highly specialized treatment programs.

[Treating depression: decision analysis for the general practitioner]. / Dépression: analyse décisionnelle pour la prise en charge par le médecin de premier recours.

Unipolar depression is among the leading causes of invalidity and disability-adjusted life-years. General practitioners frequently encounter patients suffering from depressive syndromes and very often, it's they, who make the initial diagnosis, take care of these patients, eventually prescribe an antidepressant treatment, identify difficult cases and address them to the specialists of mental health. In this article, we present concepts of diagnosis and differential diagnoses of depression, its therapy and the collaboration between the general practitioner and the psychiatrist/psychotherapist.

Neurodevelopmental Disorders: From Pathophysiology to Novel Therapeutic Approaches.

This special issue of Biomedicines on Neurodevelopmental Disorders (NDD): "From Pathophysiology to Novel Therapeutic Approaches", is a precursor of what we hope will develop into a thriving and inspiring transdisciplinary field, including genetics, psychiatry, neurology, as well as basic and applied neurosciences and molecular biology in the research area [...].

The utility of the autism-spectrum quotient to screen for autism spectrum disorder in adults with attention deficit/hyperactivity disorder.

The co-occurrence of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) has been reported to be highly prevalent in adults. However, very few studies have assessed the usefulness of screening instruments to detect this co-occurrence, particularly when screening for ASD in the context of ADHD. Our study aimed at assessing the utility of the autism-spectrum quotient (AQ) as a screening tool of ASD in a sample of 153 adults referred for ADHD assessment. Our results showed that the AQ is of limited use in this context as its positive predictive value was low (47%). Particularly, the more severe the attentional deficits the more likely individuals with ADHD were to be misclassified as having a co-occurring ASD based on the AQ. However, the "imagination" subscale of the AQ was able to discriminate those who met ASD criteria from those who did not, suggesting that targeting imagination impairments might be useful when assessing for the ADHD+ASD co-occurrence in clinical settings.

Chronic vagus nerve stimulation for treatment-resistant depression increases regional cerebral blood flow in the dorsolateral prefrontal cortex.

The purpose of the present study was to assess the effects of vagus nerve stimulation (VNS) therapy on regional cerebral blood flow (rCBF) in depressed patients. Regional cerebral blood flow (rCBF) was assessed by [(99m)Tc]-HMPAO-single photon emission computed tomography (SPECT) before and after 10weeks of VNS in patients participating in an open, uncontrolled European multi-center study investigating efficacy and safety of VNS. Patients suffered from major depression, with a baseline score of≥20 on the 24-item Hamilton Depression Rating Scale (HDRS) and had been unsuccessfully treated with at least two adequately prescribed antidepressant drugs. Data of 15 patients could be analyzed using SPM 2. After 10weeks of VNS (20Hz, 500µs pulse width, stimulation during 30s every 5min at the maximal comfortable level) rCBF was increased in the left dorsolateral/ventrolateral prefrontal cortex (Brodmann areas 46 and 47) and decreased in the right posterior cingulate area, the lingual gyrus and the left insula. Our findings are in line with earlier results which showed that VNS increases rCBF in the left dorsolateral prefrontal cortex. The modulation of the activity in this region could be associated with the antidepressant efficacy of VNS.

Pegylated human interferon alpha 2a does not induce depression-associated changes in mice.

Interferon (IFN) alpha proteins are proinflammatory cytokines having immunomodulating and antiviral properties. States during which cytokine systems are activated (e.g., during viral infection or during treatment of chronic hepatitis C and various malignancies with IFN alpha, etc.) can be associated with depression-like syndromes or even full-blown depressive episodes. Therefore, the role of IFN alpha and other cytokines in the pathogenesis of depressive disorder ("cytokine hypothesis of depression") has been assessed for many years with contradictory results. We have investigated whether intraperitoneal administration of high doses (up to 600 µg/kg body weight) of pegylated, recombinant human IFN alpha 2a in mice induces changes known to be associated with depression using three different readouts: behavior in a model of despair (Porsolt swim test), presence of anhedonia (sucrose preference test), and sensitivity of the hypothalamic-pituitary-adrenal system (dexamethasone suppression test). We also assessed potential IFN-induced changes in gene expression in the liver. In none of the performed experiments, depression-associated effects could be found despite very high serum levels of IFN-induced antiviral activity compared to levels measured in hepatitis C virus (HCV) patients treated routinely with pegylated recombinant human IFN alpha 2a. The lack of such expected effects is probably due to the fact that pegylated human recombinant IFN alpha 2a does not activate the murine class I IFN receptor. Our results do not support the hypothesis that administration of recombinant pegylated human IFN alpha to mice produces a robust model of depression.

Prevalence of Polypharmacy and Inappropriate Medication in Adults With Intellectual Disabilities in a Hospital Setting in Switzerland.

Background: Polypharmacy and inappropriate prescription are frequent in vulnerable and multi-morbid populations. Adults with intellectual disability (ID) are at risk of being polymedicated because they often present with multiple comorbidities and challenging behaviors. Aim: The objective of this study was thus to evaluate the prevalence of potentially inappropriate medications (PIM) and polypharmacy in a hospital unit dedicated to adults with ID. Methods: A 10-month prospective observational study took place at a hospital unit specializing in the care of adults with ID in Geneva, Switzerland. Once a week, health and prescription data were collected and screened for PIM according to preset definitions. Results: Fourteen patients consented to participate, leading to 20 hospitalization events assessed during the study. Hospitalizations lasted 12.8 weeks on average. ID severities ranged from mild to profound, all degrees of severity being equally represented. One hundred percent of the patients were polymedicated (defined as five drugs or more prescribed simultaneously). A mean number of 9.4 drugs were prescribed per week, including 5.3 psychotropic drugs. The number of prescribed drugs remained stable throughout the hospitalizations. Antipsychotics were the most prescribed drug class (19% of all prescribed drugs), followed by benzodiazepines (13%) and laxatives (12%). A total of 114 PIM were recorded with an average of 5.7 PIM per hospitalization. Conclusions: This study showed that polypharmacy and inappropriate prescription are very common in adults with ID, even though the literature and expert positions advocate for deprescription in these patients. Specific prescribing and deprescribing guidelines are needed for that specific population.

TOP-ID: a Delphi technique-guided development of a prescription and deprescription tool for adults with intellectual disabilities.

OBJECTIVES: Adults with an intellectual disability (AWID) are often polymedicated because of somatic and psychiatric health problems. Besides, they may display challenging behaviours, leading to off-label prescription of psychotropic drugs, without efficacy and with numerous adverse effects. In this context, a prescription/deprescription tool (Tool for Optimising Prescription in Intellectual Disability/TOP-ID) was developed to improve the care of AWID. This paper describes how TOP-ID was designed. DESIGN: Four-step consensus-based process involving a review of the literature, eight semistructured interviews and a two-round Delphi process. SETTING: Seventeen general practices and university and general hospitals from Belgium, France and Switzerland. PARTICIPANTS: Eighteen French-speaking physicians from different domains of expertise participated in the Delphi process. PRIMARY AND SECONDARY OUTCOME MEASURES: For the Delphi iteration process, consensus was defined as at least a 65% agreement between the experts. RESULTS: Two rounds were needed for the Delphi process. Eighty-one items of the tool were submitted to 18 out of 35 recruited French-speaking experts during the first round. Sixty-nine per cent of the items reached a rate of agreement of 65% or more in that round. Thirteen questions were reformulated and resubmitted for the second Delphi iteration round. All of the statements reached a rate of agreement of 65% or more in the second round. CONCLUSION: TOP-ID is the first prescription-deprescription tool developed specifically for AWIDs in French. It is intended to help prescribers document patient care in order to reduce prescription errors and to improve safety. The next steps of the project include the development of an electronic version of TOP-ID and a utility study.

Pain interventions in adults with intellectual disability: A scoping review and pharmacological considerations.

BACKGROUND AND OBJECTIVE: Having to deal on a daily routine with prescriptions in adults with intellectual disability (ID), we systematically reviewed the literature on the specificities of pain interventions in that population, focusing on medication and trying to gather practical information on appropriate pain treatments. Given the scarcity of the literature on the topic, we also discussed the pharmacological considerations to be taken into account when prescribing analgesic drugs in that vulnerable population. DATABASES AND DATA TREATMENT: Articles on pain and ID were searched in the Medline and Google scholar electronic databases using the key words "Intellectual Disability," "Developmental Disability" and specific keywords for pharmacological and non-pharmacological pain interventions. Preset outcomes about pharmacological treatment specificity, efficacy and safety were then collected. RESULTS: One hundred and fifty-two articles were found and 16 were retained based on our inclusion and exclusion criteria. Of the 16 articles, five were topical reviews. Among the 11 remaining articles, five discussed pharmacological interventions, four considered non-pharmacological interventions and two discussed both. As anticipated, the literature matching our specific outcomes about the pharmacological treatment of pain was scarce and for the most part not designed to answer the questions of specificity, efficacy and safety of pain treatment in adults with ID. CONCLUSION: The specificity of analgesic treatments in adults with ID is a totally unexplored domain. In the absence of clinical guidelines, pharmacological facts-such as inter-individual variability in drug response, pharmacokinetic and pharmacodynamic interactions, frequent co-morbidities and ease of administration-must be systematically integrated, when prescribing in the population of adults with ID. SIGNIFICANCE: This review synthesizes the state of research on pain interventions in adults with ID and is one of the rare articles addressing the specificities of analgesic prescriptions in this population.

Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression.

Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto-striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system--in which the nucleus accumbens is a key structure--are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression.

Cerebral blood flow effects of acute intravenous heroin administration.

We examined acute effects of intravenous diacetylmorphine (heroin) administration - which induces a characteristic biphasic response: A short rush-sensation associated with intense pleasurable feelings followed by a subjectively different period of euphoria on cerebral blood flow. This was assessed in nine male heroin dependent patients participating in a heroin maintenance program in a setting resembling everyday pattern of heroin abuse. 99mTc-HMPAO was administered 45 s (rush) and 15 min (euphoria) after administration of i.v. heroin and 45 s after administration of saline (placebo). Plasma concentration of diacetylmorphine and its metabolites were measured with high-pressure liquid chromatography (HPLC). Compared to the euphoria condition, rush was associated with blood flow increase in the left posterior cerebellar lobe, left anterior cingulate gyrus and right precuneus. Our results are in line with recent reports indicating that the cerebellum is an important component in functional brain systems subserving sensory and motor integration, learning, modulation of affect, motivation and social behaviour, which all play important roles in reinforcing properties of opioids.