Subarachnoid haemorrhage associated with MDMA abuse.

Gledhill, Jane; Moore, Dan; Bell, Derek; Henry, John A.

doi:10.1136/jnnp.56.9.1036

Cited by 69 publications

(20 citation statements)

References 13 publications

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“…MDMA has also been reported to cause hypertensia and arrhythmias (Bedford-Russel, 1992;Henry et al, 1992;Screaton et al, 1992). These vascular problems, together with forced cerebrovascular dilatation and coagulopathy are probably responsible for cases of cerebral hemorrhage in some subjects (Harries and DeSilva, 1992;Gledhill et al, 1993). The hyperthermic effect may be a causal factor in a number of deaths in human recreational MDMA users who have presented for emergency treatment with symptoms including convulsions, disseminated intravenous coagulation, rhabdomyelosis, and acute renal failure (Brown and Osterloh, 1987;Chadwick et al, 1991;Fahal et al, 1992;Henry et al, 1992;Screaton et al, 1992; see also Table 1).…”

Section: Acute Effectsmentioning

confidence: 95%

Causes and consequences of the loss of serotonergic presynapses elicited by the consumption of 3,4-methylenedioxymethamphetamine (MDMA, ?ecstasy?) and its congeners

Huether

Zhou

Rüther

1997

J. Neural Transmission

125

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The massive and prolonged stimulation of serotonin (5-HT)-release and the increased dopaminergic activity are responsible for the acute psychomimetic and psychostimulatory effects of 3,4-methylenedioxy-methamphetamine (MDMA, "ecstasy") and its congeners. In vulnerable subjects, at high doses or repeated use, and under certain unfavorable conditions (crowding, high ambient temperature), severe, in some cases fatal, averse systemic reactions (hyperthermia, serotonin-syndrome) may occur during the first few hours. Animal experiments revealed the existence of similar differences in vulnerability and similar dose- and context-related influences on a similar sequence of acute responses. The severity of these acute systemic responses is closely related to the severity of the long-term damage to 5-HT axon terminals caused by the administration of substituted amphetamines. Attempts to identify the mechanisms involved in this selective degeneration of 5-HT presynapses brought to light a multitude of different factors and conditions which either attenuate or potentiate the loss of 5-HT terminals caused by MDMA and related amphetamine derivatives. These puzzling observations suggest that the degeneration of 5-HT presynapses represents only the final step in a sequence of events which compromise the ability of 5-HT terminals to maintain their functional and structural integrity. Substituted amphetamines selectively tax energy metabolism in 5-HT presynapses through their ability to exchange with 5-HT and to dissipate transmembrane ion gradients. The active carrier systems in the vesicular and presynaptic membrane operate at a permanently activated state. The resulting energy deficit can no longer adequately restored by the 5-HT presynapses when their availability of substrates for ATP production is additionally reduced by the hyperthermic and other energy consuming reactions which are elicited by the systemic administration of substituted amphetamines. The exhaustion of energy in 5-HT nerve terminals compromised all energy-requiring endogenous mechanisms involved in the regulation of transmembrane-ion exchange, internal Ca(++)-homeostasis, prevention of oxidative stress, detoxification, and repair. Above a critical threshold the failure of these self-protective mechanisms will lead to the degeneration of the 5-HT axon terminals. Based on the role of 5-HT as a global modulatory transmitter-system involved in the stabilization and integration of impulse flow between distributed multifocal neuronal networks, the partial loss of 5-HT presynapses must be expected to impair the ability of these networks to maintain the integrity of signal flow pattern, and increase the likelihood of switching to unstable information processing. Behavioral responding may therefore become more dominated by activities generated in individual networks, and hitherto "buffered" personality traits and predisposition may become manifested as defined psychiatric syndromes in certain predisposed subjects.

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Section: Acute Effectsmentioning

confidence: 95%

Causes and consequences of the loss of serotonergic presynapses elicited by the consumption of 3,4-methylenedioxymethamphetamine (MDMA, ?ecstasy?) and its congeners

Huether

Zhou

Rüther

1997

J. Neural Transmission

125

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“…Although coronary angiography was normal in these cases, the potential mechanism for AMI after amphetamine abuse is coronary vasospasm, catecholamine-mediated platelet aggregation and increase in myocardial oxygen demand (Bashour, 1994). 'Ecstasy' (3,4-methylenedioxymethamphetamine, MDMA) is another amphetamine-like substance, abuse of which has also been associated with an increased risk of cardiovascular toxicity, including arrhythmias and hypertension (Henry et al, 1992;Gledhill et al, 1993).…”

Section: Risk Factors Associated With Khatmentioning

confidence: 98%

Khat: pharmacological and medical aspects and its social use in Yemen

Al‐Motarreb

Baker

Broadley

2002

Phytotherapy Research

285

251

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Fresh leaves of the khat tree (Catha edulis Forsk.) are chewed for their euphoric properties in East Africa and parts of the Middle East, such as The Yemen. This review describes the history, cultivation and constituents of khat, and the social aspects of khat chewing in Yemen. The major pharmacologically active constituent of the fresh leaves is (--)-S-cathinone. The pharmacology of (--)-S-cathinone in the central nervous system and the peripheral effects are described. (--)-S-Cathinone is regarded as an amphetamine-like sympathomimetic amine and this mechanism of action is discussed in relation to the central stimulant actions and the cardiovascular effects of increasing blood pressure and heart rate. The risk factors associated with khat chewing are described, with emphasis on the reported increased incidence of acute myocardial infarction.

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“…The likelihood of toxicity in individual patients may be related to differences in expression of the metabolic enzymes CYP2D6 and COMT, which are deficient in 5-9% of the population [17]. As discussed above, intracranial hemorrhage has been reported as a complication of MDMA abuse, but all previously reported cases have been in patients who either coingested other sympathomimetic drugs [3][4][5], who had other cerebrovascular abnormalities such as aneurysm, arteriovenous malformation, or vasculitis [4][5][6][7] or vasculitis [8,9]. The likelihood of toxicity is likely to be related to the dose of MDMA ingested, as well.…”

Section: Discussionmentioning

confidence: 98%

“…MDMA ingestion has also been associated with various forms of intracranial hemorrhage, including subarachnoid hemorrhage and intracerebral hemorrhage. To date, all reports of intracranial hemorrhages associated with MDMA ingestion have either been in patients who either coingested MDMA with other stimulant drugs such as cocaine or amphetamines [3][4][5]; or who had pre-existing vascular malformations or aneurysms [4][5][6][7] or vasculitis [8,9]. In this report, we describe three patients who developed MDMA induced intracranial hemorrhage in the absence of any cerebrovascular abnormalities on extensive neuroimaging, including catheter angiography.…”

Section: Introductionmentioning

confidence: 94%