The Parma integrated model for intervention on pathological addictions in an Italian prison: process description and preliminary findings.

Background - Interventions for inmates with Pathological Addiction (PA) still remain a problematic issue in Italian prisons, despite a 1999 major government reform transferring PA care in prison to the National Health Service. Aim of this research was to describe the integrated intervention model implemented for prisoners with PA in the Parma Penitentiary Institutes from January 2020 to June 2020. This specific approach is based on "person-tailored" therapeutic-rehabilitation programs in line with local community PA services. Methods - All the procedures were first carefully illustrated, especially the service for newly admitted inmates and the specialized rehabilitation treatments provided. A process analysis on the first six months of clinical activity was then performed. Results - Since January 2020, 178 subjects entered the service for newly admitted inmates: 55 (30.9%) were taken in charge for a PA. Conclusions - Our results support the feasibility of an integrated intervention model for PA in Italian prisons, based on specialized psychiatric treatments planned and provided in collaboration with inmates and their community health and social services.

Mental health interventions in an Italian prison: the Parma integrated approach.

PURPOSE: Mental health interventions for Italian prisoners with mental disorders remain a problematic issue, despite radical changes in general psychiatric care and a 2008 major government reform transferring mental health care in prison to the National Health Service. The aim of this study is to describe the mental health intervention model implemented since January 2020 for prisoners allocated in the Parma Penitentiary Institutes (PPI). This approach is specifically based on specialized, "person-centered" and "person-tailored" therapeutic-rehabilitation plans in line with psychiatric treatments usually provided in community mental health-care centers of the Parma Department of Mental Health. DESIGN/METHODOLOGY/APPROACH: All the processes and procedures included in the PPI intervention model were first carefully illustrated, paying special attention to the service for newly admitted prisoners and each typology of specialized therapeutic-rehabilitation treatment potentially provided. Additionally, a preliminary descriptive process analysis of the first six months of clinical activity was also performed. FINDINGS: Since January 2020, 178 individuals entered the PPI service for newly admitted prisoners. In total, 83 (46.7%) of them were engaged in the services of the PPI mental health-care team (35 with pathological addiction and 48 with mental disorders): 56 prisoners were offered an integrated mental health intervention and 27 exclusively an individual psychological or psychiatric treatment. ORIGINALITY/VALUE: The results support the potential applicability of an integrated mental health intervention in prison, planning a person-tailored rehabilitation in close collaboration with the prisoners, their families and the local mental health/social services.

Psychobiological responses to unpleasant emotions in cannabis users.

Aim of this paper is to investigate the psychobiological reactions to experimentally induced negative emotional states in active marijuana-dependent smokers and whether changes in emotional reactivity were reversed by prolonged abstinence. Twenty-eight patients were randomly included into group A (fourteen active marijuana-dependent smokers) or group B (fourteen abstinent marijuana-dependent subjects). Emotional response evaluation of group B subjects was assessed after 6 months of abstinence. Fourteen healthy volunteers, matched for age and sex, were used as controls. Psychometric and emotional response evaluations were performed by administering Symptoms Check List-90 and State-Trait Anxiety Inventory Y-1 (STAI). Neutral and unpleasant set of pictures selected from the international affective picture system and the Self-Assesment Manikin procedure (SAM) have been used to determine ratings of pleasure and arousal. Before and after the experimental session, blood samples were collected to determine ACTH and cortisol plasma levels. Active cannabis users displayed significantly higher levels of pleasantness SAM scores and lower levels of arousal SAM scores compared to abstinent cannabis users and controls in response to emotional task. In a close parallel with psychological data, hormonal findings indicate a persistent hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis in cannabis users, particularly among active marijuana smokers, and an impaired hormonal reaction to negative emotions, in comparison with healthy subjects. The capacity of the HPA axis to respond to stressful stimuli/negative emotions seems to be only partially recovered after 6 months of abstinence. Ours findings, although obtained in a small number of subjects, suggest an association between active cannabis use, subjective reduced sensitivity to negative emotions and threat and HPA axis dysfunction.

Pharmacology and toxicology of Cannabis derivatives and endocannabinoid agonists.

For centuries Cannabis sativa and cannabis extracts have been used in natural medicine. Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis. In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma. On the other hand the severe side effects and the high abuse liability of these agents represent a serious limitation in their medical use. In addition, diversion in the use of these active ingredients for recreational purpose is a concern. Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications. Likely, in the near future few of these new molecules will be available for clinical use. The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists.

Adrenocorticotropic hormone and cortisol plasma levels directly correlate with childhood neglect and depression measures in addicted patients.

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been reported to be involved in vulnerability to alcohol and drug dependence in humans, possibly underlying both addictive behaviour and depression susceptibility. The aim of the present study was to investigate the possible interactions between childhood adverse experiences, depressive symptoms and HPA axis function in addicted patients, in comparison with healthy control. Eighty-two abstinent heroin or cocaine dependent patients and 44 normal controls, matched for age and sex, completed the symptoms Check List-90 (SCL-90), measuring depressive symptoms, and the Childhood Experience of Care and Abuse Questionnaire. Blood samples were collected to determine adrenocorticotropic hormone (ACTH) and cortisol basal plasma levels at 8:00 and 8:30 a.m. Addicted individuals showed significantly higher neglect and depression scores and ACTH-cortisol plasma levels respect to control subjects. Depression scores at SCL-90 in addicted patients positively correlated with plasma ACTH and cortisol values. In turn, plasma ACTH levels were directly associated with childhood neglect measures, reaching statistical significance with 'mother-neglect' scores. Plasma cortisol levels were related to 'father antipathy' among cocaine addicts. These findings suggest the possibility that childhood experience of neglect and poor parent-child attachment may have a persistent effect on HPA axis function as an adult, partially contributing, together with genetic factors and other environmental conditions, to both depressive traits and substance abuse neurobiological vulnerability.

Combination of olanzapine with opioid-agonists in the treatment of heroin-addicted patients affected by comorbid schizophrenia spectrum disorders.

The objective of this study was to evaluate the efficacy of olanzapine (OLA) in heroin-dependent patients affected by comorbid schizophrenia spectrum disorders (SSD). Sixty-one patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for heroin dependence and the criteria for SSD (schizophrenia and schizotypal and schizoaffective-bipolar disorders) were treated in a 12-week prospective observational trial of substitution treatment in combination with OLA or typical antipsychotic haloperidol. Patients were included into 2 subgroups, in relationship with treatment, for the evaluation of the end points at week 12: group 1, SSD treated with OLA (35 patients); group 2, SSD treated with haloperidol (26 patients). Efficacy measures were retention in treatment, Symptoms Checklist-90 score changes, negative urinalyses results, and craving reduction. The rate of patients who remained in treatment at week 12 in group 1 SSD, treated with OLA, was significantly higher (32[91.4%]) than that of group 2 SSD (13 [50%]), treated with the typical antipsychotic (P < 0.001). The decrease in Symptoms Checklist-90 total scores from baseline, as expression of an improvement in comorbid psychopathology in the patients who completed the treatment, was significantly more consistent in group 1 than in group 2 patients (P < 0.01). Among the patients who remained in treatment, 64.4% achieved early full substance abuse remission, whereas 35.6% achieved partial substance abuse remission, with a significant difference between 1 (78.13%) and 2 (46.1%) treatment subgroups (P = 0.04). Although obtained by an observational-open clinical study with multiple limitations, our findings suggest that OLA may be able to increase retention and negative urinalyses rates during opioid agonist maintenance treatment in the patients with SSD and to improve psychopathology symptoms and tolerability in these dually diagnosed heroin addicts. Preliminary accurate diagnostic assessment and appropriate psychoactive medication in addicted patients affected by schizophrenia and schizotypal and schizoaffective-bipolar disorders seem to obtain less adverse effects and a more successful outcome of drug dependence treatment.

Experimentally induced aggressiveness in heroin-dependent patients treated with buprenorphine: comparison of patients receiving methadone and healthy subjects.

Objective measures of experimentally induced aggressiveness were evaluated in heroin-dependent patients (HDP), 15 receiving buprenorphine (BUP) and 15 receiving methadone (METH) treatment. HDP were randomly assigned to BUP and METH groups. Fifteen healthy subjects (CONT) were included in the study as controls. During a laboratory task, the Point Subtraction Aggression Paradigm, subjects earned monetary reinforcement and could respond by ostensibly subtracting money from a fictitious subject (the aggressive response). Money-earning (points maintained) responses did not differ in BUP patients and in controls. In contrast, point-maintained responses were significantly lower in the group of HDP treated with METH than in both the BUP and CONT groups. Aggressive responses were significantly higher in the HDP group than in the CONT group. No significant differences in aggressive responses were found between the BUP and METH groups. Baseline concentrations of plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) were higher in HDP than in CONT. During the experimental task, ACTH and CORT increased significantly less in METH patients than in BUP patients and CONT. Norepinephrine (NE) and epinephrine (EPI) levels increased significantly more in HDP than in CONT, without any difference between the METH and BUP patients. PSAP aggressive responses positively correlated with NE and EPI changes, as well as with Buss-Durkee Hostility Inventory (BDHI) scores in both METH and BUP patients and also in CONT subjects. No correlation was found between the extent of heroin exposure, drug doses and aggressiveness levels. BUP, similarly to METH, does not seem to affect outward-directed aggressiveness, as aggressive responses related more to monoamine levels and personality traits than to the action of opioid agonists. Money-earning responses seemed to be unimpaired in BUP patients.

Buprenorphine treatment outcome in dually diagnosed heroin dependent patients: A retrospective study.

The present study compared retrospectively in a clinical non-experimental setting the efficacy of buprenorphine (BUP) in different subgroups of dually diagnosed and non-dually diagnosed opioid-dependent patients: all the subjects included in the study showed severe long-lasting heroin addiction and 68.4% were affected by psychiatric comorbidity. Participants (206) (mean age 32.2+/-8.9, 177 males-29 females) were applicants to a long-term buprenorphine treatment program (mean doses 7.9+/-0.42 mg). Aim of the study was to evaluate dual diagnosis variables possibly influencing retention rate and abstinence from illicit drugs. The patients were divided into 5 subgroups on the basis of dual diagnosis: group 1: major depression (MD) 29.61%; group 2: generalized anxiety (GAD) (11.2%); group 3: personality disorders (PD), antisocial-borderline (21.84%); group 4: schizophrenia (SC)(6.3%); group 5: substance use disorder without overt psychiatric comorbidity (SUD) (31.1%). Group 1 patients affected by MD showed the highest retention rate at 12 months (72.1%) in comparison with the other groups of patients: group 2 GAD (39.1%), group 3 PD (17.8%), group 4 SC (7.7%) and group 5 SUD, without comorbidity (45.3%) (p=0.006, p<0.001, p<0.001, p=0.002). Similarly, at 12 months, the patients affected by MD showed less risk of illicit opioid use (16.4%) than those affected by GAD (34.8%), PD (42.2%), SC (53.8%) and SUD without comorbidity (34.4%) (p=0.06, p=0.003, p=0.008, p=0.017). When evaluated on the whole sample, retention rate was not influenced by dose. In contrast, the higher BUP doses were associated with less risk of illicit opioid use, than lower doses (p<0.001). Multivariate analysis and factor analysis showed a greater association of outcome measures (retention rate and negative urines rate) with comorbid diagnosis (depression) (respectively 0.64) than with buprenorphine doses (respectively 0.54). Our data need to be interpreted with caution because of the retrospective methodology applied to a clinical non-experimental setting. BUP seems to be more effective in opioid-dependent patients affected by depression, probably due to the kappa opioid-receptors antagonist action, counteracting dysphoria, negativism and anxiety. High doses of BUP appear to predict a better outcome, in terms of negative urines, but not in terms of retention.

Allelic association of a dopamine transporter gene polymorphism with antisocial behaviour in heroin-dependent patients.

Polymorphism of a variable number of tandem repeats (VNTR) in the 3' untranslated region of exon 15 of the SLC6A3 gene, coding for the dopamine transporter (DAT), was analysed to test whether length variation contributes to differences in the individual susceptibility to aggressive - criminal behaviour and liability to heroin dependence. The repeat number of the DAT polymorphism was assessed in 125 healthy subjects and 104 heroin-dependent subjects (including 52 addicted individuals with violent behaviour and criminal records). There was no significant difference in the frequencies of genotypes and alleles between heroin-dependent subjects and control subjects. On the contrary, there was a significant difference between offenders and non-offenders, p = 0.004 and p = 0.002, respectively, among heroin-dependent subjects. No association was found between DAT polymorphism and history of suicide. Buss - Durkee Hostility Inventory (BDHI) mean total scores were significantly higher in heroin addicts than in controls (p < 0.001) and in antisocial - violent heroin addicts in comparison with addicted individuals without antisocial behaviour (p < 0.005). The regression analysis of BDHI subscales, performed to provide an estimate of the magnitude of any potential effect on the risk of aggressiveness associated with the variants in DAT VNTR, showed that the presence of the 9 - 9 genotype significantly increases the risk of irritability and direct aggressiveness more than six and 10 times with respect to the 9 - 10 genotype. Our findings suggest that the 9-repeat allele of the DAT polymorphism confers increased susceptibility to antisocial - violent behaviour and aggressiveness, rather than drug dependence per se in heroin-dependent males.

Aggressive responding in abstinent heroin addicts: neuroendocrine and personality correlates.

Objective measures of experimentally induced aggressiveness were evaluated in 20 abstinent heroin-dependent subjects, in comparison with 20 normal healthy male subjects. All the subjects were preliminarily submitted to DSM-IV interviews, Buss-Durkee Hostility Inventory (BDHI) and Minnesota Multiphasic Personality Inventory (MMPI II). During a laboratory task, the Point Subtraction Aggression Paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses and were provoked by the subtraction of money, which was attributed to a fictitious other participant. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response). Money-earning responses were not different in drug-free heroin addicts and controls during the first two sessions and significantly lower during the third session in heroin-dependent subjects (t=2.99, P<.01). Aggressive responses were significantly higher (F=4.9, P<.01) in heroin addicted individuals, in comparison with controls. During the experimentally induced aggressiveness, plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) concentrations increased less significantly, and norepinephrine (NE) and epinephrine (EPI) levels, together with heart rate (HR), increased more significantly in abstinent heroin-dependent subjects than in healthy subjects. PSAP aggressive responses positively correlated with catecholamine changes, BDHI "direct" and "irritability" scores, MMPI "psychopathic deviate" scores in heroin-dependent subjects and controls, and with CORT responses only in healthy subjects. No correlation was found between heroin-exposure extent (substance abuse history duration) and aggressiveness levels. The present findings suggest that heroin-dependent patients have higher outward-directed aggressiveness than healthy subjects, in relation with monoamine hyperreactivity, after long-term opiate discontinuation. Aggressiveness in heroin addicts seems to be related more to the personality traits than to drug effects. The impairment of hypothalamus-pituitary-adrenal (HPA) axis in abstinent addicted individuals could be due to a long-lasting action exerted by opiates on proopiomelanocortin (POMC) or to a premorbid psychobiological condition, in association with increased sympathetic arousal.

Long-term immune-endocrine effects of bereavement: relationships with anxiety levels and mood.

Psychological, endocrine and immune parameters were measured over a 6-month period in 14 healthy subjects who underwent an unpredictable acute emotional stress (e.g. sudden death of a loved one) compared with 14 controls who did not. Probands were profoundly stressed as assessed 10 days after bereavement by their scores on the Hamilton Rating Scales of Anxiety and Depression, adrenocorticotropin and cortisol plasma concentrations, and non-suppression in response to dexamethasone. Functional alterations of immune parameters, such as responsiveness of peripheral blood lymphocytes to mitogens, were found 40 days after bereavement. Despite a normal number of circulating lymphocyte subsets, the functional activity of natural killer (NK) cells was markedly reduced at day 40. Changes in the intracellular concentration of beta-endorphin in peripheral blood mononuclear cells correlated with anxiety and depression scores. Controls showed no changes in psychometric, endocrine and immune measures during the 6-month study. Cluster analysis revealed two groups of bereaved subjects with different patterns of immune and endocrine changes: (1) Five subjects, characterized by harm-avoidant temperament and long-lasting dysphoric mood, showed reduced responsiveness of peripheral blood lymphocytes to mitogens, decreased NK cell activity and non-suppression in response to dexamethasone that persisted for 6 months. (2) Nine subjects showed significant changes only during the early phase after bereavement. Our data suggest that the immunological consequences of stress do not simply overlap with psychological and endocrine alterations, and are particularly severe and long-lasting in a subgroup of subjects, indicating the importance of individual variability in the capacity to cope with stress.

Hypothalamic-pituitary-adrenal axis responses to stress in subjects with 3,4-methylenedioxy-methamphetamine ('ecstasy') use history: correlation with dopamine receptor sensitivity.

Fifteen 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') users who did not have other drug dependencies or prolonged alcohol abuse and 15 control subjects were studied. All the subjects were exposed to the same psychosocial stressor (Stroop Color-Word Interference Task, public speaking and mental arithmetic in front of an audience) 3 weeks after MDMA discontinuation. Plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol were measured immediately before the tests began and at their end, 30 min later. Growth hormone (GH) responses to the dopaminergic agonist bromocriptine and psychometric measures (Tridimensional Personality Questionnaire, Minnesota Multiphasic Personality Inventory, Buss-Durkee Hostility Inventory) were also obtained 4 weeks after MDMA discontinuation for the same subjects. ACTH and cortisol basal levels were significantly higher in ecstasy users than in control subjects. In contrast, ACTH and cortisol responses to stress were significantly blunted in MDMA users. The sensitivity of dopamine D2 receptors, reflected by GH responses to bromocriptine challenge, was reduced in MDMA users compared with controls. The responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis (ACTH and cortisol delta peaks) correlated directly with GH areas under curves in response to bromocriptine, and inversely with psychometric measures of aggressiveness and novelty seeking. No correlation was found between hormonal measures and the extent of MDMA exposure. Reduced D2 receptor sensitivity, HPA basal hyperactivation and reduced responsiveness to stress may represent a complex neuroendocrine dysfunction associated with MDMA use. The present findings do not exclude the possibility that dopamine dysfunction partly predated MDMA exposure.

Long-term methadone maintenance effectiveness: psychosocial and pharmacological variables.

Data were collected from 265 heroin-dependent patients in long-term methadone maintenance treatment for methadone dosage, administration method, illicit drug and problematic alcohol use, psychiatric diagnoses, quality of interpersonal relationships, employment, legal problems, health, and cravings. Patients receiving higher methadone doses (more than 80 mg) were more likely to respond to methadone treatment than patients receiving lower doses. Superior outcome was also related to good quality of interpersonal relationships, stable employment, and lower craving scores. Comorbid psychiatric disorders did not appear to influence methadone effectiveness, but psychopharmacological treatment associated with methadone was associated with a lower rate of urine samples positive for drug use. Administration of methadone weekly or twice weekly ("home methadone") was less effective than daily administration. Although our results were obtained through a descriptive study, which does not permit a prospective evaluation, they suggest the need for higher methadone doses. Job and family relationships appear to be associated, together with psychopharmacological treatment, with a more effective outcome.

Neuroendocrine and behavioural responses to opioid receptor-antagonist during heroin detoxification: relationship with personality traits.

The present study investigated clinical, cardiovascular and neuroendocrine consequences of rapid opioid detoxification (ROD) in heroin-dependent individuals, affected, or not, by comorbid antisocial personality disorder (ASPD). Thirty-two patients underwent ROD and subsequent treatment with daily naltrexone: 3 days detoxification procedures were performed utilizing clonidine, baclofen, oxazepam and ketoprofene, without anaesthesia. Withdrawal symptoms, mood changes, cardiovascular indexes (heart rate, blood pressure), norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH) and cortisol (CORT) were evaluated during naloxone-naltrexone administration on the second day of detoxification treatment. The patients were divided into two groups following DSM-IV criteria for ASPD. Group A comprised 14 ASPD patients and group B comprised 18 patients without ASPD. Slight and transient withdrawal symptoms and mood changes were demonstrated on the second day in the whole sample of patients, in association with a significant, but moderate, elevation of heart rate, blood pressure, NE (two-fold), EPI (five-fold), ACTH (two-fold) and CORT (two-fold) plasma levels, in response to opioid receptor-antagonist administration. When evaluated separately in ASPD (group A) and non-ASPD patients (group B), significantly higher withdrawal symptoms and mood changes, heart rate, blood pressure, NE, ACTH and cortisol levels were observed in ASPD subjects. By contrast, no differences were found in EPI responses to naloxone-naltrexone administration between group A and B patients. The significant differences demonstrated in clinical and neuroendocrine responses to opioid receptor-antagonist administration, in relation to personality traits, could be due to reduced alpha-adrenergic receptor sensitivity, which was previously reported in ASPD, with a possible impairment of clonidine action. Our study suggests that a detailed diagnostic assessment before detoxification procedure may help to predict treatment outcome.

Emotional perception and neuroendocrine changes.

The present study was designed to investigate the neuroendocrine modifications during affective states. In particular, we investigate if the pleasantness of the stimuli has a different effect on neuroendocrine responses. To address this issue, we compared the effects of pleasant, neutral, and unpleasant pictures on catecholamine, adrenocorticotrophic hormone (ACTH), cortisol, and prolactin plasma levels. Ten male participants were submitted to three experimental sessions, each on one of the three experimental days, a week apart in a counterbalanced order. Although in the subjective arousal rating, pleasant (erotic pictures) and unpleasant stimuli (pictures of mutilated bodies) receive the same high score, a different neuroendocrine pattern was obtained: unpleasant stimuli elicited a decrease in prolactin concentration and increases in noradrenaline, cortisol, and ACTH levels, whereas pleasant slide set viewing induced an increase in prolactin levels. The results suggest that the neuroendocrine system responds selectively to affective motivationally relevant pictures.

Effects of (+/-) 3,4-methylene-dioxymethamphetamine (ecstasy) on dopamine system function in humans.

Twelve (+/-) 3,4-methylenedioxymethamphetamine (MDMA) users, who did not show other drug dependencies or prolonged alcohol abuse (group A), and 12 control subjects (group B) were included in the study. Prolactin (PRL) and growth hormone (GH) responses to the dopaminergic agonist bromocriptine (BROM) and psychometric measures were evaluated 3 weeks after MDMA discontinuation. PRL decreased both in A and B subjects after BROM suppression, without any significant difference between the two groups. PRL responses to BROM in MDMA users were in the normal range. In contrast, GH responses to BROM stimulation were found significantly reduced in ecstasy users, in comparison with control subjects (P < 0.001; F = 6.26). MDMA users showed higher scores on the Novelty Seeking (NS) scale at the Three dimensional Personality Questionnaire (TPQ), on direct aggressiveness subscale at Buss Durkee Hostility Inventory (BDHI), on subscale D (depression) at Minnesota Multiphasic Personality Inventory (MMPI 2) and on Hamilton Depression Rating Scale (HDRS) than control subjects. PRL areas under the curves (AUCs) showed a significant inverse correlation with NS scores both in A and B subjects. GH AUCs directly correlated with NS scores in healthy subjects, but not in MDMA users. No other psychometric measure correlated with hormonal responses. GH AUCs were inversely correlated with the measures of MDMA exposure (r = -0.48; P < 0.01). Lower GH response to BROM in A subjects (MDMA users) could reflect reduced D2 receptor sensitivity in the hypothalamus, possibly due to increased intrasynaptic dopamine concentration. Although the hypothesis of dopaminergic changes associated with a premorbid condition cannot be completely excluded, the inverse correlation between DA receptors sensitivity and the extent of ecstasy exposure may suggest a direct pharmacological action of MDMA on brain dopamine function in humans.

[MDMA (ecstasy): neuroendocrine and behavioral features]. / MDMA (ecstasy): aspetti neuroendocrini e comportamentali.

Long lasting 5HT system impairment has been demonstrated in experimental animals exposed to ecstasy use; MDMA seems to be able to induce behavioral conditioning and reiterated use because of its dopaminergic action. Among behavioral aspects of ecstasy users mood disorders, irritability and difficult in relationships, interpersonal difficulties, high levels of impulsiveness and hostility, high sensation seeking, cognitive and attentive deficit have been reported. A derangement of serotonin system function was reported also in humans exposed to ecstasy, as confirmed by neuroendocrine challenges and brain imaging techniques. Recent researches suggest functional changes in dopaminergic system too. The persistence of behavioral and neuroendocrine changes many months after MDMA's discontinuation, indicate a lack of reversibility in the dysfunction induced by ecstasy, or the persistence of psychobiological traits that could preexist to MDMA exposure, possibly involved in substance abuse vulnerability.