The effect of acute tryptophan depletion on mood and impulsivity in polydrug ecstasy users (original) (raw)
Related papers
Psychopharmacology, 2004
Rationale: Neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") on the serotonin (5-HT) system have been described in animals and humans, but little is known about long-term effects of ecstasy use on mood. Objectives: To investigate shortterm and long-term effects of ecstasy use on mood and its association with 5-HT neurotoxicity, dose, and gender in humans. Methods: Fifteen moderate ecstasy users, 23 heavy ecstasy users, 16 former heavy ecstasy users and 15 drug-using, but ecstasy-naive controls were included. Mood was assessed using the Composite International Diagnostic Interview (CIDI) and the Beck Depression Inventory (BDI). Outcomes were correlated with 5-HT transporter (SERT) density, assessed with [ 123 I]b-CIT single photon emission computed tomography (SPECT). Results: The prevalence of mood disorders assessed by CIDI did not differ between all groups. The overall test for differences in BDI scores between groups was near significance (P=0.056), with BDI scores higher in former heavy ecstasy users than in ecstasy-naive controls (P=0.045). BDI scores were correlated with the total number of ecstasy tablets used (r=0.310; P=0.021). No associations between CIDI or BDI outcomes and SERT density or gender were observed. Conclusions: These results suggest that ecstasy use is not associated with clinical depression (CIDI). However, the number of ecstasy tablets taken lifetime was associated with higher BDI scores for depressive mood, and this relationship seemed to persist after ecstasy use had stopped. We did not find that depressed mood in ecstasy users was associated with decrease in SERT density. Prospective studies are needed to establish the causal relationship between ecstasy use and depressed mood.
Psychobiological problems in heavy 'ecstasy' (MDMA) polydrug users
Drug and Alcohol Dependence, 2000
Twelve heavy recreational ecstasy drug users (30-1000 occasions), 16 light ecstasy users (1 -20 occasions) and 22 non ecstasy user controls, with group mean ages around 21 years, were compared. Three self-rating questionnaires were completed when drug-free: the SCL-90 (an outpatient psychiatric symptom checklist), the impulsiveness venturesomeness and empathy (IVE) scale; and the uplifts, hassles, stresses and cognitive failures questionnaire. Heavy Ecstasy users reported significantly higher scores than controls on the following SCL-90 factors: paranoid ideation, psychoticism, somatisation, obsessionality, anxiety, hostility, phobic anxiety, altered appetite and restless sleep, together with greater IVE impulsiveness. Light ecstasy users generally produced intermediate scores, with significantly higher scores than controls on two factors and significantly lower scores than heavy ecstasy users on another two. Previous reports have described various psychiatric and psychobiological disorders in recreational ecstasy users, but it is not known how typical they are, being mainly based on individual case studies. This is the first study to describe psychological problems in a non clinical sample of young recreational ecstasy users. However, our ecstasy users were polydrug users, with both groups showing significantly greater usage of amphetamine, LSD and cocaine, than the controls. These other illicit drugs probably contributed to their adverse psychobiological profiles, while there is also the possibility of pre-existing differences between ecstasy users and non users. However, since repeated MDMA can cause serotonergic neurotoxicity in laboratory animals and man, these problems may reflect reduced serotonin activity induced by regular ecstasy use.
Biological Psychiatry, 2000
Background: Fifteen (Ϯ)3,4-Methylenedioxymethamphetamine (MDMA) users, who did not show other drug dependencies or prolonged alcohol abuse, and 15 control subjects were included in the study. Methods: Prolactin (PRL) and cortisol (CORT) responses to the serotonergic agonist d-fenfluramine (D-fen), clinical psychobehavioral changes, and psychometric measures were evaluated 3 weeks and then 12 months after MDMA discontinuation. Results: MDMA users showed significantly reduced PRL and CORT responses in comparison with control subjects at 3 weeks (respectively, p Ͻ .001; p Ͻ .005). The responses of PRL to D-fen were unmodified at 12 months after prolonged abstinence and were significantly reduced in comparison with controls (p Ͻ .001). In contrast, CORT responses in MDMA users were restored after 12 months of abstinence, with significantly higher responses to D-fen, in comparison with 3-week responses (p Ͻ .05). MDMA users' high scores on the Novelty Seeking (NS) scale on the Tridimensional Personality Questionnaire (TPQ) appeared unchanged by long-term abstinence. In contrast, Buss Durkee Hostility Inventory (BDHI) (Buss and Durkee 1957) direct and guilt scores decreased significantly after 12 months of abstinence. PRL AUCs at 12 months were inversely correlated with the measures of MDMA exposure (r ϭ Ϫ.538).
The effects of tryptophan depletion on impulsivity and mood in healthy men and women
Reduced serotonergic neurotransmission contributes to the pathophysiology of mood disorders, and the majority of modern antidepressants block the serotonin reuptake in the brain. It is also known that people with major depressive disorder are frequently found to have impaired impulse control, and that impulsivity is associated with serotonin. In two separate studies with healthy participants using different designs and a technique called acute tryptophan depletion, which decreases serotonin levels in the brain, men adopted an impulsive response style, but did not experience any mood changes. The second and largest study included both men and women, and the findings regarding men were replicated. However, women reported a worsening of their mood, and they adopted a more cautious response style commonly associated with depression. The lowered mood reported by women in response to tryptophan depletion was also influenced by variation in the promoter region of the triallelic serotonin t...
Effects of (±) 3,4-methylene–dioxymethamphetamine (ecstasy) on dopamine system function in humans
Behavioural Brain Research, 2002
Twelve (9/) 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 B/0.001; F0/6.26). 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/(/0.48; P B/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.
Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users
…, 2003
Rationale: Chronic recreational ecstasy (MDMA) use has often been reported to be associated with psychopathology, memory impairments and serotonergic alterations. However, the findings have not been consistent. Objectives: To attempt to replicate these findings, to investigate whether such alterations would be reversible and whether they could be predicted by parameters of previous drug use. Methods: In a cross-sectional design, 30 current and 31 ex-ecstasy users with ecstasy abstinence of at least 5 months, and 29 polydrug and 30 drug-naive controls were compared on measures of psychopathology, cognitive performance and serotonin transporter availability. Results: The groups did not differ significantly in age, gender distribution, education level and premorbid intelligence. The ecstasy groups did not differ significantly from polydrug controls on most of the relevant parameters of concomitant illegal drug use. Reported drug use was confirmed by hair and urine analyses. All three groups of drug users exhibited significantly elevated psychopathology compared with drug-naive controls. Only ex-ecstasy users were significantly impaired on verbal recall. Current ecstasy users showed significantly reduced distribution volume ratios of serotonin transporter availability in the mesencephalon and caudate nucleus. Regression analyses indicated that psychopa-thology and serotonergic alterations were best predicted by the number of ecstasy tablets taken on a typical event.
Cognitive performance and serotonergic function in users of ecstasy
…, 2001
Rationale: (±) 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") has been shown to cause long term damage to serotonergic cerebral neurons in animals. The neurotoxic effects in humans are less clear and little is known about the functional consequences, although some studies suggest memory impairment. Given the widespread use of MDMA, our lack of knowledge raises concerns. Objective: We investigated, in humans, the relation between past use of ecstasy and cognitive performance as well as serotonergic function. Methods: Two groups of 21 males with moderate and heavy recreational use of MDMA, respectively, and a control group of 20 males without use of MDMA were compared. All were from the same subculture. Reaction time, direct recall, and recognition were assessed. Serotonergic function was measured by the neuro-endocrine response to a placebo-controlled, crossover challenge with dexfenfluramine. Results: Ecstasy users showed a broad pattern of statistically significant, but clinically small, impairment of memory and prolonged reaction times. Heavy users were affected stronger than moderate users. Release of cortisol but not of prolactin after dexfenfluramine administration was significantly reduced in both groups of ecstasy users compared with the controls. Analyses of covariance showed that likely confounding variables including recent exposure to ecstasy, psychosocial profiles and use of other drugs did not explain the differences found between the groups. Conclusions: These results provide further evidence that use of ecstasy may be associated with impairment of memory and of serotonergic function. These findings are compatible with neurotoxicity of ecstasy as shown in animals.
Antidepressant‐like effects of ecstasy in subjects with a predisposition to depression
Addictive Behaviors, 2012
Positive effects of ecstasy on mood and self-esteem due to increased synaptic serotonin levels may indicate a potential antidepressant-like action. This effect may be more prominent in subjects with a pre-existing mood disturbance who may use ecstasy more frequently as a 'self-medication'. This study compared depressive symptoms and the immediate effects of ecstasy on mood in subjects with (WP) and without (NP) a predisposition to depression. Methods: Current ecstasy users were assessed using the Profile of Mood States (POMS) and Beck Depression Inventory (BDI) when drug-free, and during social gathering, when 20 subjects voluntarily consumed ecstasy (ecstasy group) and 20 abstained from ecstasy (control group). Predisposition to depression was determined using the Brief Symptom Inventory. During social gathering, POMS and BDI were administered 60 min after ecstasy consumption, or at matched time for controls. 3,4-Methylenedioxymethamphetamine (MDMA) exposure was confirmed using saliva samples collected 60 min after pill ingestion. Results: There was no difference in ecstasy use patterns between the groups. When drug-free, the WP subjects had greater mood disturbance and depressive symptoms than the NP group (POMS: NP 5.85 ± 1.63, WP 14.5± 2.81, p b 0.05, BDI: NP 4.9± 0.86, WP 11.2± 1.65, p b 0.01). During social gathering, WP subjects who consumed ecstasy reported a significant decrease in depressive symptoms (F(1,35)= 5.47, p b 0.05). Conclusions: A decrease in depressive symptoms was observed in subjects predisposed to depression. This antidepressant-like action of MDMA may contribute to its use, particularly among people with an existing or latent depressive disorder.
Striatal serotonin is depleted in brain of a human MDMA (Ecstasy) user
Neurology, 2000
Article abstract The authors found that striatal levels of serotonin and those of its metabolite 5-hydroxyindoleacetic acid were severely depleted by 50 to 80% in brain of a chronic user of methylenedioxymethamphetamine (MDMA) whereas concentrations of dopamine were within the normal control range. Our data suggest that MDMA exposure in the human can cause decreased tissue stores of serotonin and therefore some of the behavioral effects of this drug of abuse could be caused by massive release and depletion of brain serotonin.