Physical Complications of Substance Abuse: What the Psychiatrist Needs to Know

Michael F Baigent


Curr Opin Psychiatry. 2003;16(3) 

In This Article

Amphetamines, Cocaine and Other Stimulants

Stimulants generally resemble each other in terms of their toxic physical effects.

Psychostimulants are known to cause teeth clenching and bruxism.[31,32] These adverse effects, as well as temporomandibular disorders, were also more common in a group of polydrug users from a methadone clinic than among control individuals, and resulted in symptoms of headache and tooth wear.[31]

Clinically, patients can present with a picture of mild hepatitis and spontaneous recovery is the usual outcome, although some cases have progressed to hepatic failure. 3,4-Methylenedioxy-methamphetamine (MDMA, or 'ecstasy') and related substances are metabolized via CYP2D6, with metabolites then being degraded further, the products of which can be hepatotoxic if there is a drop in the level of free glutathione.[31]

Peripheral release of noradrenaline (norepinephrine) by these substances mediates cardiovascular complications through raised blood pressure (risks rupturing blood vessels) and tachycardia (increases cardiac load, risks heart failure).[31] Intracranial haemorrhages following stimulant use have been caused by hypertension-mediated angiitis, and are also frequently due to rupture of pre-existing abnormal vasculature.[33] MDMA, well within the recreational dose range, was demonstrated to increase the pulse rate by 28 beats/minute, systolic blood pressure by 25 mmHg and cardiac output by 2 l/min without a measurable inotropic effect.[34] This is concerning given that the drug is frequently taken in association with rigorous physical activity on the dance floor. Cocaine, when taken together with or after alcohol, has an additive effect on heart rate, and there is an increase in blood cocaine levels of up to 30%.[35*] Cocaine is associated with ischaemic and haemorrhagic infarction at any level of the neuraxis. It can occur within 3 h of use but mostly within 1 h.[26,36] Drug use is so common a cause of stroke in the young adult that it should be considered in the case of stroke in this age group, even when drug use is denied.[26] Renal infarction and atherosclerosis of the kidney can result from cocaine use[18] and presumably other stimulants. It is thought to exacerbate pre-existing renal disease.

Overactivity, sweating and dysregulated thermostasis can lead the user to excessive water intake and haemodilution. Combining this with inappropriate antidiuretic hormone release can lead to raised intracranial pressure, seizures and obviously death.[26,31] Cocaine lowers the seizure threshold. A correlation between cerebral atrophy and duration of use has now been demonstrated.[26]

The relentless elevation in core body temperature can lead to rhabdomyolsis, myoglobulinuria and renal failure, liver damage and disseminated intravascular coagulation.[18,26,31] Dramatic and often heroic methods to reduce the body temperature are often needed to prevent death.[31]

With respect to MDMA, most cases of serious toxicity or death have occurred at doses of 2-10 times the usual recreational usage. However, as Kalant[31] pointed out, some have occurred within the 'normal' usage range, which reflects the importance of environmental factors as well as drug dose.

There is growing evidence that chronic exposure to toxic substances can cause subtle neuropsychological deficits that may precede neurological deficits.[37*] Salo et al.[38**] compared a small sample of methamphetamine-dependent people with control individuals with respect to performance on the computerized Stroop test. The most significant finding was impairment in the Stroop negative priming task, similar to that observed in patients with Parkinson's disease and with lesions in the anterior cingulate and prefrontal cortex. A study conducted by Volkow et al.[39] of abstinent methamphetamine-dependent patients also revealed damage to part of the brain in a pattern that is similar in some but not all respects to Parkinson's disease pathology. Striatal dopamine transporters were reduced in the methamphetamine-dependent group, which correlated with the outcome measures used for gross motor function (timed gait and grooved pegboard tasks). The same study by Volkow et al. reported in a different paper[40] showed a significantly lower metabolism in the striatum and thalamus in a pattern reminiscent of abnormalities in patients with atypical Parkinson's disease. Volkow et al. concluded that these findings should alert the clinician to the possibility of an increased risk for neurodegenerative conditions as the user's brain ages. Interestingly, however, most extrapyramidal movement disorders in chronic amphetamine users have been transient,[26] which at this stage does not suggest progressive changes to these areas of the brain.


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