The Relationship Between Methamphetamine Use and Increased Dental Disease

BackgroundMethamphetamine (MA) use has been linked anecdotally to rampant dental disease. The authors sought to determine the relative prevalence of dental comorbidities in MA users, verify whether MA users have more quantifiable dental disease and report having more dental problems than nonusers and establish the influence of mode of MA administration on oral health outcomes.MethodsParticipating physicians provided comprehensive medical and oral assessments for adults dependent on MA (n = 301). Trained interviewers collected patients' self-reports regarding oral health and substance-use behaviors. The authors used propensity score matching to create a matched comparison group of nonusers from participants in the the Third National Health and Nutrition Examination Survey (NHANES III).ResultsDental or oral disease was one of the most prevalent (41.3 percent) medical cormorbidities in MA users who otherwise were generally healthy. On average, MA users had significantly more missing teeth than did matched NHANES III control participants (4.58 versus 1.96, P < .001) and were more likely to report having oral health problems (P < .001). Significant subsets of MA users expressed concerns with their dental appearance (28.6 percent), problems with broken or loose teeth (23.3 percent) and tooth grinding (bruxism) or erosion (22.3 percent). The intravenous use of MA was significantly more likely to be associated with missing teeth than was smoking MA (odds ratio = 2.47; 95 percent confidence interval = 1.3–4.8).ConclusionsOvert dental disease is one of the key distinguishing comorbidities in MA users. MA users have demonstrably higher rates of dental disease and report long-term unmet oral health needs. Contrary to common perception, users who smoke or inhale MA have lower rates of dental disease than do those who inject the drug. Many MA users are concerned with the cosmetic aspects of their dental disease, and these concerns could be used as behavioral triggers for targeted interventions.Clinical ImplicationsDental disease may provide a temporally stable MA-specific medical marker with discriminant utility in identifying MA users. Dentists can play a crucial role in the early detection of MA use and participate in the collaborative care of MA users.     

Impact of Canadian federal methamphetamine precursor and essential chemical regulations on methamphetamine-related acute-care hospital admissions

Background

In response to its domestic methamphetamine problems and an emerging international consensus that methamphetamine precursor and essential chemicals should be controlled, Canada regulated its import/export of ephedrine and pseudoephedrine (precursor chemicals) in January 2003, its domestic distribution of those chemicals in July 2003, and its import/export and manufacturing of essential chemicals (e.g., toluene) in January 2004. This study examines the regulations’ impact on the problem of methamphetamine-related hospital admissions in Canada.

Methods

ARIMA-based intervention time-series analysis was used to assess impacts on monthly counts of Canada's methamphetamine-related acute-care hospital admissions (04/1996 to 03/2005). Cocaine-, heroin/opioid-, and alcohol-related hospital admissions were examined as quasi-control time-series.

Results

No impact was found for the January 2003 regulation. The July 2003 and January 2004 regulations were associated with 20% and 21% increases, respectively, in methamphetamine-related admissions. No impacts on the quasi-control time-series were found.

Conclusions

This study indicates that Canada's regulations were not associated with reductions in methamphetamine-related hospital admissions. The January 2003 regulation's focus on imports/exports rather than domestic distribution may help explain its lack of impact. In contrast, the two other regulations had salient domestic foci – domestic precursor sales (July 2003) and domestic essential chemical manufacturing (January 2004). Both regulations, however, were associated with increases in admissions, rather than declines. Government reports indicate that a shift in methamphetamine production, from smaller-scale operators to more sophisticated crime organizations (groups better able to circumvent the regulations), occurred around the times of the regulations. Such a shift could increase supply and possibly admissions.     

The association of methamphetamine use and cardiomyopathy in young patients

Purpose

Methamphetamine is the most widespread illegally used stimulant in the United States. Previously published case reports and series suggest a potential association between methamphetamine exposure and cardiomyopathy. The objective of this study is to demonstrate an association between methamphetamine use and cardiomyopathy.

Subject and Methods

Case-control study based on chart review of discharges from a tertiary care medical center from January 2001 to June 2004. Patients were ≤45 years old. Cases included patients with a discharge diagnosis of either cardiomyopathy or heart failure. Controls included hospitalized patients who had an echocardiographic assessment of left ventricular function with ejection fraction ≥55% and no wall motion abnormalities.

Results

One hundred and seven cases and 114 controls were identified. Both groups had similar gender distribution, length of hospital stay, rates of health insurance, prevalence of coronary artery disease, diabetes mellitus, hypertension, cigarette smoking, alcohol abuse, and marijuana and cocaine use. Cases were older than controls (mean age: 38 vs 35 years; P=.008), had higher body mass index (BMI) (mean BMI: 37 vs 30 kg/m²; P<.001), and higher prevalence of renal failure (13% vs 4.4%; P=.03). Methamphetamine users had a 3.7-fold increased odds ratio [95% confidence interval, 1.8-7.8] for cardiomyopathy, adjusting for age, body mass index, and renal failure.

Conclusions

Methamphetamine use was associated with cardiomyopathy in young patients.     

Brain levels of neuropeptides in human chronic methamphetamine users

Animal data show that neuropeptide systems in the dopamine-rich brain areas of the striatum (caudate, putamen, and nucleus accumbens) are influenced by exposure to psychostimulants, suggesting that neuropeptides are involved in mediating aspects of behavioral responses to drugs of abuse. To establish in an exploratory study whether levels of neuropeptides are altered in brain of human methamphetamine users, we measured tissue concentrations of dynorphin, metenkephalin, neuropeptide Y, neurotensin, and substance P in autopsied brains of 16 chronic methamphetamine users and 17 matched control subjects. As expected, levels of most neuropeptides were enriched in dopamine-linked brain regions such as the nucleus accumbens and striatum of normal human brain. In contrast to animal findings of increased neuropeptide levels following short-term methamphetamine exposure, striatal neuropeptide concentrations were either normal or moderately decreased in the methamphetamine users. In other examined dopamine-poor cortical and subcortical brain areas, neuropeptide levels were generally either normal or variably reduced. Although the neuropeptide differences might be explained by methamphetamine-induced damage to neuropeptide-containing neurons, our human data are consistent with the possibility that, at least in the human striatum, long-term methamphetamine exposure leads to an adaptive process that is distinct from that which increases neuropeptide levels after acute methamphetamine exposure.     

A long-term ecstasy-related change in visual perception

Rationale The present study provides the first evidence of the long-term consequences of ecstasy use on visual processes thought to reflect serotonergic functions in the occipital lobe. Methylenedioxymethamphetamine (“ecstasy”) is known to cause lasting changes to the serotonin system in animals, and convergent evidence suggests that similar changes occur in human ecstasy users. Other research suggests that serotonin may be involved in lateral inhibition between orientation sensitive neurons in the occipital lobe, and that disruption to the serotonin system causes an increase in the magnitude of the tilt aftereffect illusion that is known depend on those neurons. Objectives The aim of the present study was to determine if ecstasy users have detectable changes in occipital lobe behavioural functioning, as revealed by the tilt aftereffect illusion. Materials and methods Thirty ecstasy users and 34 non-drug using controls were compared on the magnitude of the tilt aftereffect illusion following adaptation to stimuli oriented at 15 and 40° from vertical. Results Ecstasy users who had not used amphetamines for 115 days or more had a larger average tilt aftereffect than non-drug using controls after adaptation to 40° stimuli but not after adaptation to 15° stimuli. Additionally, there was no difference between non-drug using controls and ecstasy users who had used amphetamines within the last 61 days at either adaptation angle. Conclusions The results were consistent with the proposal that ecstasy-related damage to the serotonin system causes behavioural changes on tests of visual perception processes that are thought to reflect serotonergic functions in the occipital lobe. An erratum to this article can be found at     

Involvement of free radicals followed by the activation of phospholipase A2 in the mechanism that underlies the combined effects of methamphetamine and morphine on subacute toxicity or lethality in mice: comparison of the therapeutic potential of fullerene, mepacrine, and cooling

An increase in polydrug abuse is a major problem worldwide. The coadministration of methamphetamine and morphine increased subacute toxicity or lethality in rodents. However, the underlying mechanisms by which lethality is increased by the coadministration of methamphetamine and morphine are not yet fully understood. Coadministered methamphetamine and morphine induced lethality by more than 80% in BALB/c mice, accompanied by the rupture of cells in the kidney and liver, and an increase in poly (ADP-ribose) polymerase (PARP)-immunoreactive cells in the heart, kidney and liver. The lethal effect and the increase in the incidence of rupture or PARP-immunoreactive cells induced by the coadministration of methamphetamine and morphine was significantly attenuated by pretreatment with mepacrine (phospholipase A(2) inhibitor) or fullerene (a radical scavenger), or by cooling from 30 to 90 min after drug administration. Furthermore, based on the results of the electron spin resonance spin-trapping technique, hydroxyl radicals were increased by the administration of methamphetamine and morphine, and these increased hydroxyl radicals were potently attenuated by fullerene and cooling. These results suggest that hydroxyl radicals plays an important role in the increased lethality induced by the coadministration of methamphetamine plus morphine. The potency of cooling or drugs for decreasing the subacute toxicity or lethality induced by the coadministration of methamphetamine and morphine was in the order fullerene=cooling>mepacrine. These results indicate that fullerene and cooling are beneficial for preventing death that is induced by the coadministration of methamphetamine and morphine.     

Thai War on Drugs: measuring changes in methamphetamine and other substance use by school students through matched cross sectional surveys

In 2003 the Thai government announced a radical shift in drug policy with the implementation of a War on Drugs. Although consequences of this controversial measure (e.g. drug dealer deaths) have received widespread attention relatively little work has evaluated changes in substance use. We used two anonymous representative samples of secondary school students to compare drug use in Northeast Thailand before (1998; n=4217) and after (2004/5; n=3489) the War on Drugs. Results indicate that reported levels of current illicit drug use reduced significantly between 1998 and 2004/5 (for methamphetamine from 4.2% to 0.9%). By examining trends in year of first methamphetamine use we identify that observed reductions in drug initiation are temporally consistent with the War on Drugs. However, while prevalence of alcohol use has also fallen, there was a three-fold increase in daily alcohol use. We suggest that this rise, combined with other negative impacts of 'wars' on drugs, means drug control requires a public health perspective that sees eliminating drug use as part of a wider strategy that has improvement in population health, not just drug prevention, as its core objective.     

The acetylcholine fiber density of the neocortex is altered by isolated rearing and early methamphetamine intoxication in rodents

Alterations in the cholinergic physiology of the brain were the first to be observed when research on environmental influences on postnatal brain development began 35 years ago. Since then, the effects of isolated rearing (IR) or early pharmacological insults have been shown not only on the physiology, but also the anatomy of a variety of transmitter systems. The cholinergic fiber density, however, still remained to be assessed. We therefore used a histochemical procedure to stain cholinergic fibers in the brains of young adult gerbils reared either in groups in enriched environments or isolated in standard makrolon cages. Half of the animals from each rearing condition had received a single high dose of methamphetamine on postnatal day 14. Fiber densities were measured by computerized image analysis in the medial and orbital prefrontal cortex (PFC), dysgranular and granular insular cortex, sensorimotor cortices, and the entorhinal cortex of both hemispheres. Isolation rearing increased the cholinergic fiber densities in the prefrontal cortices of the left hemisphere and in the entorhinal cortex of the right hemisphere by about 10%, with no effect in the respective contralateral side. The early methamphetamine intoxication showed no influence in prefrontal and entorhinal cortices, but diminished the acetylcholine (ACh) innervation of the forelimb area of cortex in both hemispheres in IR gerbils and of the left hemisphere in ER gerbils, and reduced the acetylcholine innervation in the hindlimb area in both sides in both rearing groups. These results demonstrate that (a) cholinergic fiber density is differentially regulated in different cortical areas and (b) the plasticity of the cholinergic system can only be understood in the interplay with other neuromodulatory innervations.     

mRNA expression of the Nurr1 and NGFI-B nuclear receptor families following acute and chronic administration of methamphetamine

Nur-related 1 (Nurr1) and nerve growth factor inducible-B (NGFI-B) constitute closely related subgroups of the nuclear receptor superfamily. One to three hours after 4 mg/kg acute methamphetamine (METH) administration, the levels of Nurr1 mRNA were significantly higher in the prelimbic (PrL), primary motor (M1) and primary somatosensory (S1) cortices and ventral tegmental area (VTA), as compared with the basal level. Pretreatment with 0.5 mg/kg of SCH23390 prevented the acute METH-induced increase in Nurr1 mRNA levels in these brain regions. One to three hours after 4-mg/kg acute METH administration, the levels of NGFI-B mRNA increased significantly in the PrL, M1, S1, striatum, and nucleus accumbens core (AcbC). Pretreatment with either 0.5 mg/kg of MK-801 or 0.5 mg/kg of SCH23390 prevented the acute METH-induced increase in NGFI-B mRNA levels in these brain regions. The levels of mRNAs were determined 3 h after a challenge injection of either saline or 4 mg/kg METH at the three-week withdrawal point in rats which had previously been exposed to either saline or METH (4 mg/kg/day) for 2 weeks. After the saline challenge, the group chronically exposed to METH displayed significantly higher levels of Nurr1 mRNA in the PrL, S1 and VTA, and of NGFI-B mRNA in the PrL, M1, S1, striatum and AcbC than did the group chronically treated with saline. The groups chronically exposed to METH failed to increase Nurr1 mRNA in the VTA, and NGFI-B mRNA in the AcbC, when challenged with 4 mg/kg METH. These results suggest that Nurr1 and NGFI-B mRNA play differential roles upon exposure to METH.     

Acute anhydrous ammonia injury from accidents during illicit methamphetamine production

BACKGROUND: Anhydrous ammonia (AA), a chemical commonly used in agriculture, is a key component in illicit methamphetamine production. Although injuries associated with AA exposure are well studied, AA injuries associated with incidents during illicit methamphetamine production have not been adequately described in the literature. OBJECTIVE: This study better characterizes AA injuries occurring in an agricultural region where illicit methamphetamine production is common. METHODS: We performed a cross-sectional study based on a chart review of 49 patients who were admitted to a tertiary hospital in Illinois with known or suspected exposures to chemical agents. Indices of morbidity were compared between injuries resulting from exposure to AA and injuries from other chemicals, and between AA injuries from incidents during illicit methamphetamine production and AA injuries from other causes. RESULTS: AA was the most common cause of chemical injury (41%; n=20/49). Incidents during illicit methamphetamine production were the most common cause of AA injury (75%; n=15/20). AA injury was associated with significantly greater morbidity compared to non-AA chemical injury. In addition, methamphetamine-related AA injury was associated with significantly greater morbidity compared to non-methamphetamine-related AA injury. CONCLUSION: Chemical burns during illicit methamphetamine production were the most common cause of both chemical and AA-related injury in our agricultural population and these injuries were associated with greater morbidity during hospitalization.