Thursday, 27th November 2014

Ecstasy

Ecstasy & Aggression/Violence

Introduction

The use of ecstasy is commonly associated with reduction of aggression and increase in empathy between individuals under the influence. Gilman attributed the decline in football hooliganism to increased use of ecstasy amongst young working class males. One might expect drugs of the ecstasy-type which increase central nervous system stimulant neurotransimtters such as noradrenaline, dopamine and serotonin to increase aggressive behaviour. Ecstasy-type drugs such as MDMA increase serotonin secretion, both physical and mental effects can be blocked by drugs preventing serotonin release. Over the longer term however, MDMA depresses serotonin function via its neurotoxic effect on serotonergic neurones, reducing the capacity of the nervous system to produce the neurotransmitter.

 

Studies involving Ecstasy & Violence or Psychosis

Buchanan reported symptoms of intoxication to include "tachycardia, hypertension, hyperthermia, diaphoresis, mydriasis, agitation, muscle rigidity, and hyper-reflexia" In Spain, Bone Pina et al reported a case history of "recurrent paranoid psychotic episodes in a patient with a history of abuse of ecstasy, that persisted after a long withdrawal time... The characteristics of this case are... paranoid psychosis after abuse of MDMA, in which the sudden appearance, and the symptomatolgy of an intense feeling of threat and physical violence outstands, accompanied by abnormal corporal perceptions." In Croatia, Miras reported a case of "acute paranoid psychosis in a patient who took MDMA (Ecstasy), became violent and was prosecuted by law", and in Germany, Weinmann et al reported the case of a 19-year old man having taken 10 ecstasy tablets, reporting the symptoms as "strong sweating, sudden aggressiveness followed by hallucinations, subsequent failure of motoric coordination, severe spasms of arms and back, complete depression of the respiratory system, unconsciousness, and collapse."

 

In France, Vaiva at al reported an individual suffering long-term psychotic symptoms following "accidental" intoxication with ecstasy and alcohol and noted "Twelve cases of acute psychotic episodes after taking ecstasy have been reported in the literature ... The present subject had not displayed any previous psychotic behavior when tested with a proven standardized interview technique; this was confirmed by his peers and his family."

 

In an Italian study of 150 drug treatment patients, Schifano et al reported "Fifty-three percent of the total sample were found to be affected by one or more psychopathological problems; the most frequent were depression, psychotic disorders, cognitive disturbances, bulimic episodes, impulse control disorders, panic disorders, social phobia. Those who were free from any psychopathological problem, compared to the others, had taken a smaller number of MDMA tablets in their lifetime, for a shorter duration and with a lower frequency." Also in Italy, Pallanti et al described three case histories of patients who developed panic disorders following recreational ecstasy use, followed by persistent agoraphobia.

 

In a study of UK clubbers who had either taken ecstasy on more than 10 occasions, fewer than 10 occasions, or not at all, Parrott & Lasky found "All three groups reported positive moods at the dance club (on-drug), although there were borderline trends (P < 0.10) for less sadness/depression in the MDMA subgroups. However 2 days afterwards, the ecstasy users felt significantly more depressed, abnormal, unsociable, unpleasant, and less good tempered, than the controls. Cognitive performance on both tasks (verbal recall, visual scanning) was significantly reduced on-MDMA. Memory recall was also significantly impaired in drug-free MDMA users, with regular ecstasy users displaying the worst memory scores at every test session." Similar results were found by Curran et al, who reported "MDMA users rated elevated mood on day 1 but significantly low mood on day 5, at which point some participants scored within the range for clinical depression."

 

Long-term ecstasy use is associated with serotonin depletion. Gerra et al found ecstasy users showed increased "Dysphoria and mood changes... tiredness ... sensation-seeking behaviour.. at the clinical evaluation. Significantly higher scores were found in MDMA individuals than in controls... for depression... hostility... guilt... Depression... and for novelty-seeking"

 

Navarro found mice treated with MDMA exhibited "a behavioral profile characterized by a reduction of aggression (threat and attack) without a concomitant increase of immobility, accompanied by a decrease of social investigation and a increment of exploration from a distance, avoidance/flee and defense/submission behaviors." Similarly Miczek et al reported "MDMA dose-dependently decreased aggressive behavior" in mice. In rats, Morley found "MDMA decreased aggressive behaviours at all doses tested, while the highest dose (5 mg/kg) also significantly increased the duration of social interaction." whereas Miller at al noted rats treated with a metabolite of ecstasy "became hyperactive and aggressive... consistent with... some of the behavioral alterations seen after administration of MDA and MDMA"

 

Morgan found no differences between ecstasy users and controls, but noted "ecstasy users... were more psychologically disturbed and impulsive than nondrug controls. The ... studies indicated that ecstasy users exhibited elevated impulsivity on both self-report and behavioral measures and that those who had taken the most ecstasy had the most elevated trait impulsiveness scores." McCann et al found "MDMA users had lower scores on personality measures of impulsivity (p = .004) and indirect hostility (p = .009)... Further, differences in personality support the view that 5-HT systems are involved in modulating impulsive and aggressive personality traits."

 

Ecstasy use is associated with reckless behaviour and a reduced concern for personal safety. The case of a young man fatally injured as a result of car-surfing under the influence of ecstasy and excess alcohol was considered by Hooft et al to be "another example of the bizarre and reckless behaviour which may result from the euphorogenic activity of ecstasy and the circumstances in which it is commonly used." In a study of young gay men in San Francisco, ecstasy and alcohol were associated with a greater tendency to engage in unprotected anal sex and risk of contracting the HIV virus. Similar results were found in New York, where "MDMA use was strongly and significantly associated with a history of recent unprotected anal intercourse."


Shapiro reports moderate doses to give a mild euphoric rush, followed by feelings of serenity and calmness, and the dissipation of anger and hostility. There is heightened perception of surroundings without the distortions of LSD, states that flashbacks can occur some time after using the drug. High doses caused problems including anxiety, panic, confusion, insomnia, psychosis and visual and auditory hallucinations, leaving the user in a weakened physical and mental condition.

 

Serotonin (5-hydroxy-tryptamine or 5-HT) and Violence/Aggression

Disorders of serotonin metabolism are also associated with agitation, violent and/or aggressive behaviour in mood disorders, suicide attempts and suicide completion. Serum cholesterol levels affect serotonin binding to influence mood states, including criminal levels of violence. Serotonin reuptake inhibitors (SSRIs) such as Prozac, have been implicated in violent acts, but some clinical studies of SSRIs have shown "the frequency of aggressive incidents was significantly lower" and suggested efficacy in treating "impulse control disorders; eating disorders; addictive disorders; and aggressive, violent, self-destructive, and suicidal behaviors.".

 

In 1992, Linnoila & Virkkunen proposed the existence of what they termed the "low serontonin syndrome" characterised by "impulsive, externally directed aggressive behavior", and in a contemporaneous forensic review, Volavka et al noted "Recent studies implicate disturbances of central serotonergic functions in impulsive homicide and arson." In 1990, Virkkunen et al reported "Low (serotonin metabolite) concentration has been found to be associated with a history of paternal alcoholism... in subjects who are prone to exhibit impulsive, aggressive behaviour under the influence of alcohol." Apter et al reported "Serotonin abnormalities appear to be related to a variety of psychopathological dimensions such as anxiety, depressed mood, impulsivity, and aggression dysregulation." Brown & Linnoila concluded "The original studies, which reported an association between low (serotonin metabolite) concentration and impulsive, destructive behaviors, particularly where aggression and violence are involved, have now been replicated rather consistently in a number of countries and cultures." Roy & Linnoila had reported "A defect in central serotonin metabolism may manifest itself in poor impulse control leading to attempts at suicide, violence towards others, and Type II alcohol abuse." and postulated in 1988 "serotonergic deficits may predispose individuals to poor impulse control, disturbance of glucose metabolism, alcohol abuse, violent behavior and suicide."

 

Courtet et al reported "There is compelling evidence that serotonin system dysfunction is associated with certain behavioral disorders, such as suicidal behavior and impulsive aggression." Similarly, Balaban et al commented "Recent genetic work has suggested that abnormalities in serotonin biochemistry are directly causally linked to aggressive behavior, and there appears to be a consensus in the psychiatric literature that low levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid are specifically associated with impulsive violent behavior."

 

In a 1988 review, Burrowes et al concluded "Violent behavior is reviewed in regard to its relationship with genetic, hormonal, neurochemical, electrical, substance abuse, and psychiatric factors. The most significant relationships were found between violent behavior and the neurotransmitter serotonin.". In 1987 Mann reported "indices of serotonergic function appear to correlate with violent and impulsive suicidal behavior". Van Praag et al noted in 1986 "decreased central 5-HT metabolism is related to (auto)aggression, rather than to depression"

 

In 1985, Lidberg et al found "men who had killed a sexual partner, and those who had attempted suicide, had lower levels of the serotonin metabolite, 5-HIAA in spinal fluid than the controls." In a 1976 study, Asberg et al first noted a relationship between violent suicide and low serotonin metabolite levels in the cerebrospinal fluid.

 

Hillbrand et al studying psychiatric patients, reported findings "consistent with the... substantive literature linking both aggression and depression to depressed central serotonergic activity." Terao et al reported "serum cholesterol levels may be positively associated with serotonergic receptor function. The existence of such an association may provide an explanation for reported increases in depression, suicide and violence in individuals with low or lowered cholesterol." Buydens-Branchey et al concluded "Evidence exists... for a causal link between low brain serotonin (5-HT) activity and.. poor impulse, aggression and mood control"

 

Askenazy et al, studying hospitalised and control adolescents, found "Mean platelet serotonin concentration was significantly higher in the impulsive group than in the control group. Platelet serotonin concentration was positively correlated with the intensity of impulsivity in the patient group."
Goodman & New summarised "The underlying biologic basis for impulsive aggression is centered on the serotonin hypothesis; that central 5-HT function is inversely related to aggression and suicidality. More recent research refines the theory to include associated brain regions, receptor types and neuromodulators potentially involved in the etiology of aggressivity."

 

It is also suggested that disorders of serotonin metabolism can increase the risk of "early onset alcoholism associated with antisocial personality disorder and impulsive, habitually violent behavior.", and low serotonin-metabolite levels to be strongly associated with "Impulsive violence, suicide, and depression". Unis et al reported "Our findings are consistent with a relationship between 5-HT dysregulation and aggressive behavior in incarcerated adolescent boys with conduct disorder, particularly of childhood onset." Cleare et al found "an inverse relationship between central serotonin function and aggression/hostility in healthy males, similar to that seen in previous studies using violent or highly aggressive populations." In mice, destruction of serotonin receptors was found by Scearce Levie et al to produce "increased aggression and impulsivity, behavioral patterns that are also associated with reduced 5-HT function"

Payet reported "low (serotonin) concentration in the brain causes more violent suicides or suicidal behaviors, as well as more aggressiveness and impulsiveness." Tiihonen et al found "habitual impulsive aggressive behaviour in man is associated with a decrease in the 5-HT transporter density."


Myers and Vondruska, in a paper examining the American legal response to cases of violent crime allegedly due to involuntary intoxication of SSRI drugs (Prozac), concluded "Currently there is a lack of convincing scientific evidence that clearly confirms or negates the postulated relationship between antidepressant agents and violent behavior.". In a similar vein, Berman et al concluded "A rich literature exists to support the notion that monoamine (i.e., serotonin, dopamine, and norepinephrine) neurotransmitter functioning is related to human aggressive behaviour. Results from these studies provide, at best, indirect evidence that neurotransmitter abnormalities are involved in violent criminal behavior."

 

Moffitt et al studied blood serotonin levels in a large population, finding in violent men that whole blood serotonin levels were significantly higher than either the general population, or a control group of nonviolent men. Lavine reported "Abnormal functioning of these (serotonergic) systems may also be complicated or caused by abuse of various psychoactive substances, particularly alcohol and stimulants."

 

Higley et al studying alcoholism in monkeys, noted "Behaviorally, subjects with low (serotonin metabolite levels) demonstrated impaired impulse control, which resulted in excessive and inappropriate aggression, infrequent and inept social behaviors, low social status, social isolation and expulsion from social groups at an early age, and high rates of early mortality. ... these findings were consistent with predictions from Cloninger's type II model of excessive alcohol consumption among men who exhibit impaired impulse control and violent and antisocial behaviors.", having earlier found "(serotonin metabolite) concentrations were negatively correlated with impulsive behavior, and severe, unrestrained aggression" Virkkunen et al reported "...alcoholic, impulsive, habitually violent offenders have been found to have low brain serotonin (5-hydroxytryptamine; 5-HT) turnover which is associated with impaired impulse control, a history of suicide attempts" and that "Low (serotonin metabolite levels) combined with hyoglycemic tendency also predicts future violence under the influence of alcohol."

 

Fuller, reporting from Eli Lilly research labs (manufacturers of Prozac), stated "The evidence shows that diminished serotonergic function can be linked to aggressive behavior and that treatments that increase serotonergic function reduce aggression. Embedded in this large body of data are studies done specifically with fluoxetine (Prozac), a serotonin uptake-inhibiting antidepressant drug suggested by some individuals charged with criminal aggression and by their attorneys to cause aggressive violence. Contrary to those charges, extensive studies of fluoxetine in animals have shown that fluoxetine decreases aggressive behavior in various species and models of aggression. Clinical studies of fluoxetine in aggressive behavior have been more limited, but findings in those studies seem consistent with the anti-aggressive effects of fluoxetine found in animal studies."

 

In substance abusers treated with serotonin-stimulating drug (fenfluramine), Fishbein et al found "...the more impulsive subjects reported a decrease in subjective states of depression, hostility and anxiety after drug treatment. These data further support the hypothesis of altered serotonergic activity in aggressive and impulsive behaviors." Research on platelet serotonin uptake by Brown et al supported "the hypothesis of disturbed serotonergic function in aggression and suggest that the primary relationship is in the "control" of aggression."

 

Ecstasy and Alcohol

Meehan et al found ecstasy altered preferences, substituting as a discriminative stimulus for alcohol in rats bred to drink heavily, but not in light-drinking rats, concluding that there was a "growing body of evidence suggesting serotonergic mediation of some of the behavioral effects of ethanol.". A similar effect was noted by Resvani et al, who found "MDMA significantly decreased ethanol intake... and increased water intake" and added "(MDMA) failed to exert any significant effect on the pharmacokinetics of alcohol, indicating a central effect."

 

In Humans, MDMA and alcohol causes "a time-dependent immune dysfunction in association with serum concentrations of the drug". Ramcharan et al described one patient who recovered from an overdose after taking 50 tablets with alcohol and oxazepam.

 

Miczek et al reported "Many violent crimes have been associated with alcohol intoxication, but experimental research in laboratory animals has been largely inconclusive on alcohol effects on aggression." and concluded "The role of serotonin (5-HT) will have to be newly defined in light of the findings that ethanol increases 5-HT release in several forebrain areas, in a dose range that can stimulate aggressive behavior in a subgroup of individuals."

 

Higley et al found serotonin levels in monkeys to correlate with excessive alcohol consumption, and lead to "deficits in impulse control... such as entering food baited traps, jumping from dangerous heights to get from one tree to another, and consuming large amounts of alcohol,... impaired social competence, social alienation, and unrestrained, violent aggression."

 

Pihl et al reported "The consumption of an intoxicating dose of alcohol increases the likelihood of violent behaviour (via) potentiation, inhibition, and disorganization of behaviour... mediated by serotonergic activity", and also that "subjects with low brain serotonin levels may be particularly susceptible to alcohol-induced violence."

 

Linnoila et al found serotonin deficits to be common in patients with early-onset antisocial and violent male alcoholics. Virkkunen et al reported "Alcoholic, impulsive offenders with intermittent explosive disorder had a low mean (serotonin metabolite) concentration", and "There is ample evidence that low (serotonin metabolite) concentration is associated with a tendency to exhibit impulsive violent behavior under the influence of alcohol."


Naranjo reported "Adverse social consequences related to alcohol intoxication include impaired driving, acts of aggression and violence towards self and others, and various types of accidents."

 

In a 1988 review Goodwin concluded "Mounting evidence from spinal fluid studies has rekindled interest in a key role for serotonin in the early onset form of alcoholism. One hypothesis now being explored is that genetically low brain serotonin function may be part of the predisposition to this form of alcoholism. It is known that acute alcohol intake transiently increases brain serotonin turnover. Thus, drinking might be viewed as an attempt to correct a deficit, only to produce further serotonin depletion as the drug's effect wears off, setting up a vicious cycle of repeated attempts to self-medicate. Impulsive, violent, and suicidal behavior as well as alcohol abuse are associated with the low brain serotonin activity." Roy et al noted "Relatively high percentages of alcoholics attempt and commit suicide and have impulsive antisocial personality disorder" and suggested "there may be a sizable subgroup of alcoholics who have a reduced central serotonin turnover."

 

Summary - Ecstasy & Violence

Ecstasy produces a short-term increase in serotonin secretion, and raised levels of serotonin in the brain. There is compelling evidence for a role played by serotonin metabolism in violent and aggressive criminal behaviour, attributed by most authors to a low level of serotonin in the brain and cerebrospinal fluid (CSF).

 

On the face of it, the widespread anecdotal reports of the calming and anti-aggressive properties of ecstasy are supported by the scientific literature. However, the long-term depletion of serotonin levels following prolonged or heavy use of ecstasy could well contribute to an increased propensity for violent behaviour or suicidal tendencies. There is increasing evidence of psychological disturbance among heavy or long-term ecstasy users.


There have been a number of reports linking serotonin reuptake inhibitor drugs (SSRIs such as Prozac or Seroxat) to violent assaults or suicides. These would appear to represent paradoxical effects, and were dismissed by a researcher working for the drug"s manufacturers, but the number of such reports lends credence to the suggestion that paradoxical effects (increased serotonin increasing rather than reducing the tendency to violence) cannot be ruled out, at least in susceptible individuals.

 

Due primarily the legal position, and the relatively recent advent of widespread use of ecstasy in the western world, no consistent clinical research projects have adequately investigated the relationship between ecstasy use and violence at the present time. There does appear to be a relationship between use of ecstasy and reckless behaviour, such as unprotected anal sex among young gay men at risk of HIV.

 

Similarly, there have been few studies investigating the behavioural effects of ecstasy combined with alcohol, including violent or aggressive behaviour. It is well-known that most ecstasy users avoid alcohol - this may be due in part to the dehydrating properties of both drugs. There is substantial scientific evidence linking a tendency for early-onset alcoholism, combined with violent or aggressive behaviour, with disorders of serotonin metabolism.