The Association between Serum Magnesium Levels and Depression in an Adult Primary Care Population.

Depression is common, places a large burden on the patient, their family and community, and is often difficult to treat. Magnesium supplementation is associated with improved depressive symptoms, but because the mechanism is unknown, it is unclear whether serum magnesium levels act as a biological predictor of the treatment outcome. Therefore, we sought to describe the relationship between serum magnesium and the Patient Health Questionnaire (PHQ, a measure of depression) scores. A cross-sectional analysis of medical records from 3604 adults (mean age 62 years; 42% men) seen in primary care clinics between 2015 and 2018, with at least one completed PHQ were included. The relationship between serum magnesium and depression using univariate analyses showed a significant effect when measured by the PHQ-2 (-0.19 points/mg/dL; 95% CI -0.31, -0.07; P = 0.001) and the PHQ-9 (-0.93 points/mg/dL; 95% CI -1.81, -0.06; P = 0.037). This relationship was strengthened after adjusting for covariates (age, gender, race, time between serum magnesium and PHQ tests, and presence of diabetes and chronic kidney disease) (PHQ-2: -0.25 points/mg/dL; 95% CI -3.33, -0.09; P < 0.001 and PHQ-9: -1.09 95% CI -1.96 -0.21; P = 0.015). For adults seen in primary care, lower serum magnesium levels are associated with depressive symptoms, supporting the use of supplemental magnesium as therapy. Serum magnesium may help identify the biological mechanism of depressive symptoms and identify patients likely to respond to magnesium supplementation.

Magnesium status and attention deficit hyperactivity disorder (ADHD): A meta-analysis.

Current research suggests conflicting evidence surrounding the association between serum magnesium levels and the diagnosis of attention deficit hyperactivity disorder (ADHD). This systematic review and meta-analysis aims to explore, summarize and quantify the published literature addressing this topic. We conducted an exhaustive literature search on Scopus and PubMed for all the relevant observational studies published up to August 2018. A meta-analysis using a random-effects model was used to summarize the overall association between serum magnesium level and ADHD from the available data. We identified seven studies which reported the mean and standard deviation (SD) of magnesium concentration in both ADHD and control groups. The random-effects meta-analysis showed that subjects with ADHD had 0.105 mmol/l (95% CI: -0.188, -0.022; P < 0.013) lower serum magnesium levels compared with to their healthy controls. Moreover, we observed striking and statistically significant heterogeneity among the included studies (I2 = 96.2%, P = 0.0103). The evidence from this meta-analysis supports the theory that an inverse relationship between serum magnesium deficiency and ADHD exists. High heterogeneity amongst the included studies suggests that there is a residual need for observational and community-based studies to further investigate this issue.

The Role of Elements in Anxiety.

Elements (bioelements) are necessary factors required for the physiological function of organisms. They are critically involved in fundamental processes of life. Extra- and intracellular message and metabolic pathway factors as well as structural components include one or many elements in their functional structure. Recent years have seen an intensification in terms of knowledge gained about the roles of elements in anxiety disorders. In this chapter we present a review of the most important current data concerning the involvement of zinc, magnesium, copper, lithium, iron, and manganese, and their deficiency, in the pathophysiology and treatment of anxiety.

[Magnesium deficiency and stress: Issues of their relationship, diagnostic tests, and approaches to therapy].

Magnesium plays an important role in the functions of the central nervous system. It takes part in the regulation of the cell membrane, the transmembrane transport of calcium and sodium ions, and metabolic reactions that produce, accumulate, transfer, and utilize energy, free radicals, and their oxidation products. The magnesium-containing substances include many sequestered antigens, such as glial fibrillary acidic protein, S100, and neuron-specific enolase; magnesium may act as a neuroprotector that is able to modulate the regulation of blood-brain barrier permeability. Investigations have demonstrated a relationship between the manifestations of stress reactions (anxiety, autonomic dysfunction, and maladjustment) and magnesium deficiency (MD). Thus, mental and physical stresses cause an increase in magnesium elimination from the body. MD in turn enhances a response to stress, by paradoxically aggravating its sequels. Compensation for MD increases the ability of the nervous system to resist stress. The valid diagnosis of MD present difficulties; namely, a blood magnesium concentration decrease below 0.8 mmol/l is evidence of MD; but the constant blood level of magnesium may be long maintained due to its release from the bone tissue depot. So it is necessary to keep in mind the clinical manifestations of MD. The authors have developed and tested a simple rapid MD assessment test and a stress resistance self-rating test. The proposed tests will help to screen stress resistance and MD in outpatient settings.

Hypomagnesaemia linked to depression: a systematic review and meta-analysis.

BACKGROUND: The reported risk of depression in patients with hypomagnesaemia is controversial. AIM: The objective of this meta-analysis was to assess the association between depression and hypomagnesaemia. METHODS: A literature search was performed using MEDLINE, EMBASE, Cochrane Database and clinicaltrials.gov from inception through October 2014. Studies that reported odds ratios, relative risks or hazard ratios comparing the risk of depression in patients with hypomagnesaemia were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Six observational studies (three cohort studies, two cross-sectional studies and a case-control study) with a total of 19,137 patients were identified and included in the data analysis. The pooled RR of depression in patients with hypomagnesaemia was 1.34 (95% CI, 1.01-1.79, I(2) = 33%). The association between depression and hypomagnesaemia was marginally insignificant after the sensitivity analysis including only cohort and case-control studies, with a pooled RR of 1.38 (95% CI, 0.92-2.07, I(2) = 24%). CONCLUSION: Our study demonstrates a potential association between hypomagnesaemia and depression. Further studies assessing the benefits of treatment of hypomagnesaemia in patients with depression are needed.

Dietary magnesium deficiency affects gut microbiota and anxiety-like behaviour in C57BL/6N mice.

OBJECTIVE: Magnesium deficiency has been associated with anxiety in humans, and rodent studies have demonstrated the gut microbiota to impact behaviour. METHODS: We investigated the impact of 6 weeks of dietary magnesium deficiency on gut microbiota composition and anxiety-like behaviour and whether there was a link between the two. A total of 20 C57BL/6 mice, fed either a standard diet or a magnesium-deficient diet for 6 weeks, were tested using the light-dark box anxiety test. Gut microbiota composition was analysed by denaturation gradient gel electrophoresis. RESULTS: We demonstrated that the gut microbiota composition correlated significantly with the behaviour of dietary unchallenged mice. A magnesium-deficient diet altered the gut microbiota, and was associated with altered anxiety-like behaviour, measured by decreased latency to enter the light box. CONCLUSION: Magnesium deficiency altered behavior. The duration of magnesium deficiency is suggested to influence behaviour in the evaluated test.

Dietary magnesium deficiency alters gut microbiota and leads to depressive-like behaviour.

OBJECTIVE: Gut microbiota (GM) has previously been associated with alterations in rodent behaviour, and since the GM is affected by the diet, the composition of the diet may be an important factor contributing to behavioural changes. Interestingly, a magnesium restricted diet has been shown to induce anxiety and depressive-like behaviour in humans and rodents, and it could be suggested that magnesium deficiency may mediate the effects through an altered GM. METHODS: The present study therefore fed C57BL/6 mice with a standard diet or a magnesium deficient diet (MgD) for 6 weeks, followed by behavioural testing in the forced swim test (FST) to evaluate depressive-like behaviour. An intraperitoneal glucose tolerance test (GTT) was performed 2 day after the FST to assess metabolic alterations. Neuroinflammatory markers were analysed from hippocampus. GM composition was analysed and correlated to the behaviour and hippocampal markers. RESULTS: It was found that mice exposed to MgD for 6 weeks were more immobile than control mice in the FST, suggesting an increased depressive-like behaviour. No significant difference was detected in the GTT. GM composition correlated positively with the behaviour of undisturbed C57BL/6 mice, feeding MgD diet altered the microbial composition. The altered GM correlated positively to the hippocampal interleukin-6. CONCLUSION: In conclusion, we hypothesise that imbalances of the microbiota-gut-brain axis induced by consuming a MgD diet, contributes to the development of depressive-like behaviour.

[Role of magnesium in nerve tissue].

The role of magnesium on nerve tissue was discussed. Two main topics of "magnesium and neural activity" and "magnesium-therapy and brain neurons" were described together with introducing our research on rat cultured neurons of cortex and hippocampus.

Effect of magnesium chloride on psychomotor activity, emotional status, and acute behavioural responses to clonidine, d-amphetamine, arecoline, nicotine, apomorphine, and L-5-hydroxytryptophan.

BACKGROUND: The beneficial effects of magnesium (Mg) salts on central manifestations of Mg deficiency are well known. Mg replacement therapy can be effective to prevent some of the serious depression-like and anxiety-related behaviour sequelae of Mg deficiency. However, few experimental studies have been undertaken on Mg-deficiency-induced behavioural changes. Even fewer studies have been carried out on acute behavioural responses to clonidine, D-amphetamine, arecoline, nicotine, apomorphine, and L-5-hydroxytryptophan (HTP), which might characterize possible neuromediator changes in Mg deficiency. The effects of correcting Mg deficiency by magnesium chloride (MgCl2 · 6H2O) and the combination of this salt with vitamin B6, on the behavioural manifestations of Mg deficiency have never been described as well. OBJECTIVE: The aims of this study were: to estimate effect of MgCl2 · 6H2O alone and in combination with vitamin B6 on acute behavioural responses to agonists or blockers of the main neurotransmitter systems in CNS, psychomotor activity and emotional status of rats fed with Mg-deficient diet for 49 days. In our study open field test has shown that in Mg-deficient rats locomotor activity and vertical activity, number of visiting and residence time in central squares were decreased significantly. In the elevated plus maze test, the number of visiting open arms and residence time of rats were significantly less as compared with the control group. In the forced swimming test, time immobile was significantly increased by 44.29% and time of swimming was decreased by 52.79% compared to control. RESULTS: In our study Mg-deficient rats were more sensitive to d-amphetamine-induced motor stereotypes. Mg deficiency antagonized 5-hydroxytryptophan-induced head-twitch response and arecoline-induced tremor. Supplement of MgCl2 · 6H2O with vitamin B6 administered to a Mg-deficient rat increased the Mg level in plasma and erythrocytes. Furthermore, this increase was in relation to vitamin B6 given to the animal. Mg supplementation alone and in combination with pyridoxine normalized acute behavioural responses to d-amphetamine, 5-hydroxytryptophan, and arecoline in Mg deficient rats with a return to pre-deficient levels observed in the Mg sufficient group. DISCUSSION: Combination of Mg salts and pyridoxine hydrochloride can be effective at treating some behavior form of primary Mg deficiency.

Phase 2 study examining magnesium-dependent tinnitus.

BACKGROUND: Recent studies in noise-induced and idiopathic sensorineural hearing loss have suggested that magnesium supplementation may lessen both hearing loss and the severity of tinnitus in patients. Further epidemiological evidence indicates that all age groups of Americans fall short of the recommended daily allowance for magnesium by 100 mg daily. PURPOSE: The purpose of this study was to examine any potential benefit in lessening the severity of tinnitus in patients taking supplemental magnesium. RESEARCH DESIGN: The study was a single-arm, open-label, before-and-after study of oral magnesium (532 mg per day) in 26 patients for 3 months. Tinnitus severity was evaluated and recorded daily by the patient using the Tinnitus Distress Rating (TDR) scale of 0 (no tinnitus) to 10 (worst possible tinnitus). The Tinnitus Handicap Inventory (THI) was administered before and at the end of the study, and scores were converted to the grades of the 5-item Tinnitus Severity Scale (TSS). The purpose of this phase 2 study was to investigate whether the treatment was effective at all, and, as such, a placebo control was not performed. All data were collected at Mayo Clinic in Scottsdale, Arizona, between March 6 and December 10, 2008. STUDY SAMPLE: Patients with moderate to very severe tinnitus (TDR score of 3 through 8). INTERVENTION: Daily magnesium supplementation, 532 mg; patient completion of the THI; and daily self-report of TDR. DATA COLLECTION AND ANALYSIS: The main outcome measures were mean TDR scale scores and THI scores as converted to TSS grades. The primary analysis was done on the basis of intention to treat. RESULTS: Twenty-six patients were enrolled; 19 completed the study. The extent of handicap, as measured by THI/TSS, for subjects with slight or greater impairment was significantly decreased (P=.03). Patients who ranked slight or greater on the THI/TSS before intervention showed a significant decrease in the severity of their tinnitus at post-testing (P=.008). CONCLUSION: The results suggest that magnesium may have a beneficial effect on perception of tinnitus-related handicap when scored with the THI.

Features of central neurotransmission in animals in conditions of dietary magnesium deficiency and after its correction.

Magnesium is important in the regulation of neurotransmitter metabolism and the modulation of receptor function in the CNS, including neurotransmitters and receptors involved in the pathogenesis of many mental disorders. The aim of the present work was to perform a pharmacological evaluation of the central mechanisms of action of magnesium salts in the clofelin, phenamine, arecoline, nicotine, apomorphine, and 5-hydroxytryptophan tests in conditions of dietary magnesium deficiency. After reaching the magnesium deficiency state, animals were given oral (via tube) magnesium L-asparaginate and magnesium chloride lone and in combination with vitamin B(6), as well as the reference agent Magne B6. Our assessments of phenamine stereotypy in magnesium-deficient animals showed reductions in the latent period by an average of 14.89% and a significant increase in the duration of phenamine stereotypy by an average of 19.44% (from 268.23 +/- 8.17 to 320.36 +/- 19.90 min) as compared with intact rats. Studies of hyperkinesia induced by 5-hydroxytryptophan showed a two-fold reduction in its extent in the magnesium-deficient group (p

[The characterization of central neuromediation in rats fed with magnesium-deprived diet before and after magnesium replenishment].

Magnesium (Mg) has been proposed to take part in biochemical dysregulation contributing to psychiatric disorders. The aims of this study was to estimate acute behavioural responses to clonidine (0.1 mg/kg i.p.), d-amphetamine (5 mg/kg, i.p), arecoline (15 mg/kg i.p), nicotine (6 mg/kg i.p.), apomorphine (1.5 mg/kg i.p.) and L-5-hydroxytryptophan (300 mg/kg i.p.) in rats fed with Mg-deprivated diet for 49 days and then treated with organic and inorganic Mg salts (50 mg Mg per kg) ether alone or in combination with pyridoxine (5 mg vitamin B6 per kg). In our study Mg-deficient rats were more sensitive to d-amphetamine-induced motor stereotypes compared with control rats; time of onset of the stereotypies insignificantly decreased by 14.89% and duration of the stereotypies significantly increased by 19.44% (320.36 +/- 19.90 vs. 268.23 +/- 8.17 minutes; p = 0.043). Mg deficiency did not modulate sensitivity to nicotine-induced seizure. The time between nicotine injection and emergence of clonic seizure (seizure latency) in the controls and Mg-deficient rats were 0.80 +/- 0.26 and 0.96 +/- 0.21 minutes respectively. Duration of the seizures in the controls and Mg-deficient rats were 64.93 +/- 7.20 and 79.32 +/- 8.13 minutes. In our study, Mg deficiency did not affect on clonidine- and apomorphine-induced hypothermia. Clonidine produced similar decreases in rectal temperature in controls and Mg-deficient group. In experiments using apomorphine, values of hypothermia were similar to those observed with clonidine. Mg deficiency antagonized 5-hydroxytryptophan-induced head-twitch response. The number of head twitches produced by 5-hydroxytryptophan was significantly (p = 0.49) decreased: twofold in magnesium-deficient rats (1.23 +/- 0.44 per minute) as compared with controls (2.42 +/- 0.52 per minute). Arecoline-induced tremor was comparably less expressed in Mg-deficient rats than in controls. The time between arecoline injection and time of onset of the tremor in the controls and Mg-deficient rats were 92.75 +/- 19.35 and 245.17 +/- 121.86 seconds respectively (p < or = 0.035). Duration of the tremors in the controls and Mg-deficient rats were 1175.58 +/- 127.87 and 703.83 +/- 89.33 seconds (p = 0.015). Magnesium salts (Mg chloride, Mg L-aspartate alone and in combination with B6) were administered through gastric tube during twenty days up to complete compensation oferythrocyte and plasma Mg levels in all experimental groups. In our study administration of Mg salts resulted in normalization of acute behavioural responses in Mg-deficient rats to d-amphetamine, arecoline, and L-5-hydroxytryptophan. Behavioural responses in rats treated with both Mg chloride and Mg L-aspartate in combinations with B6 were comparable with those observed in MagneB6 treatment.

Reproductive and neurobehavioral outcome of drinking purified water under magnesium deficiency in the rat's diet.

Taking magnesium deficient diet and drinking soft water (including purified water, essentially mineral free) are common consumed in the world. The present study was conducted to assess the potential combined influence of maternal drinking purified water and taking magnesium deficient diet on postnatal development and behavior in the offspring of exposed rats. Sprague-Dawley (SD) rat were assigned to four groups: group 1 fed with control diet (Mg(2+) 0.4 g/kg) and control water (Mg(2+) 12.7 mg/L), group 2 fed with control diet and purified water (Mg(2+) 0.015 mg/L), group 3 fed with magnesium deficient diet (Mg(2+) 0.2 g/kg) and control water, group 4 fed with magnesium deficient diet and purified water from 5 weeks of age of the F0 generation to 3 weeks of the F1 generation, respectively. Reproductive and neurobehavioral parameters were measured. Maternal body weights significantly decreased during treatment (before mating) and lactation periods in the group fed with magnesium deficient diet and purified water. There were no significant differences of the reproductive outcome in the groups. Offspring's body weight, development of reflexes significantly reduced in the group 4. Although it was no significant difference in the four groups, the data showed a trend toward a decreased risk for offspring body weight, neurobehavioral development as follows: group 1>group 2>group 3>group 4. Therefore, purified water cannot obviously affect the reproductive outcome when magnesium is sufficient or half of the estimated average requirement (EAR) in the diet. However, drinking purified water can decrease maternal magnesium level slightly, induce offspring's development retardation, especially when the magnesium deficiency in the diet. Furthermore, magnesium deficiency in the diet (half of the EAR) can produce growth delay and reflex development retardation in F1-offspring. Therefore, drinking purified water should be carefully considered, especially for susceptible population.

[Potentiation of Delta9-tetrahydrocannabinol (THC) effects by magnesium deficiency in the rat]. / Potentialisation des effets du Delta9-tétrahydrocannabinol (THC) par la carence magnésique chez le rat.

Aggressive behavior can be classified into three major categories: defense, social attack and predatory behavior. The predatory behavior of rats, which prompts them to prey on mice (muricidal behavior) may be induced by injection of high doses (11 mg/kg) of Delta9-tetrahydrocannabinol (THC) or by acute magnesium deficiency. We have studied the effect of a single injection of low doses of THC (2, 4 or 8 mg/kg) in rats with a severe (50 ppm magnesium diet) or moderate (150 ppm) magnesium deficiency. The combination of moderate magnesium deficiency with low doses of THC induced muricidal behavior in all the rats and an increase in aggressiveness at the doses of 4 or 8 mg/kg of THC. Hyperaggressiveness increased with magnesium deficiency severity. Serotonin is probably involved in aggressiveness induced by both moderate magnesium deficiency and low doses of THC, but implication of other neurotransmitters and magnesium deficiency-induced alterations of CB1-and/or CB2-receptor expression are not excluded.

Magnesium (mg) retention and mood effects after intravenous mg infusion in premenstrual dysphoric disorder.

BACKGROUND: Conflicting data exist regarding the presence of magnesium (Mg) deficiency and the therapeutic efficacy of Mg in premenstrual syndrome or premenstrual dysphoric disorder (PMDD). METHODS: The % Mg retention was determined using 24-hour urinary Mg excretion and the total dose of Mg given intravenously. In women with (n = 17) and without (n = 14) prospectively diagnosed PMDD, several blood measures of Mg and mood were obtained before, immediately after, and the day following an intravenous Mg (.1 mmol/kg) loading dose. A positive mood response was seen under open conditions; as open Mg infusion improved mood, subsequent PMDD patients (n = 10) were randomized in a double-blind, placebo-controlled, crossover fashion. RESULTS: Patients (31.5%) and control subjects (27.5%) retained comparable mean percentages of Mg. Neither group differed in measures of mean Mg before, immediately after, or the day following Mg infusion. Although there was a time effect for all mood measures in the patient group (p < .01 for all), there was neither a treatment nor time-by-treatment effect. CONCLUSIONS: Contrary to prior reports, we found no evidence of Mg deficiency in women with PMDD compared with control subjects. Furthermore, Mg was not superior to placebo in the mitigation of mood symptoms in women with PMDD.

[Magnesium deficiency--benefits of "life salt nuti ma-su"].

One of essential minerals magnesium tastes bitter, so human love to remove magnesium from salt. But magnesium is also essential for cell functions in the body. Salts are getting purifying only NaCl from sea water. It means other minerals are gone out. So other essential minerals easily are getting to deficiency in the body. Recently the technique of purification of salt from sea water has developed. But the contents of magnesium other than [NaCl] is getting decrease. So deficiency symptom is easily occurred. The important role of magnesium is control of higher function of nervous system, behavior, memory and learning in the human. So we have to intake a lot of magnesium from many kinds of salts including sea water.

Magnesium-deficient diet alters depression- and anxiety-related behavior in mice--influence of desipramine and Hypericum perforatum extract.

A relation between magnesium (Mg) status and mood disorders has been suggested, but evidence remains inconsistent. Therefore, we examined in mice whether Mg-depletion would alter behavior evaluated in established animal models of depression and anxiety and whether these effects would be sensitive to antidepressants. Compared to control mice fed with normal diet, mice receiving a low Mg diet (10% of daily requirement) for several weeks displayed increased immobility time in the forced swim test, indicating enhanced depression-like behavior. In addition, the partial Mg-depletion increased anxiety-related behavior in the light/dark and open field test, while locomotor activity or motor coordination was not influenced. Chronic oral administration of desipramine (30 mg/kg/day), or Hypericum extract LI160 (Hyp, 380 mg/kg/day) prevented the "pro-depression-like" forced swim behavior in Mg-depleted mice. Furthermore, the increase in anxiety-related behavior of Mg-depleted mice was abolished in both the open field and light dark test by Hyp. Taken together, we report that Mg-depletion leads to enhanced depression- and anxiety-related behavior in mice, which was further validated by the reversibility of the behavioral changes by known antidepressant and anxiolytic substances. Further, the utility of Mg-depletion as a new screening model for clinically active antidepressant and anxiolytic drugs is suggested.

Magnesium deficiency reveals the neurotoxicity of delta-9-tetrahydrocannabinol (THC) low doses in rats.

In the present study, muricide behaviour (MB) was studied in Long Evans rats in various situations. The MB pattern of each experimental group was compared, in 6 successive assays 1 hr-delayed to that of natural killer rats (NK). The percentage of NK rats was 11% in the strain used. In the 11 mg THC/kg b.w. treated naive rats, a significant additional percentage of rats (59%) became muricidal. The durations of the 3 MB phases were significantly increased as a result of an increased aggressiveness in the 1st assay but returned progressively to NK values on the 6th assay, in parallel with the physiological elimination of THC. This result indicates a true killing training in those non killer rats that became muricidal under THC. A severe magnesium deficiency induced by a 50 ppm magnesium-deficient diet induced 100% MB whereas a 150 ppm magnesium deficiency did not induce additional MB. In the severe deficiency, the MB pattern was rather similar to that of NK with the exception of the attack on the living mouse which was doubled probably because of magnesium-induced hyperexcitability responsible for a lower attack efficiency. In both 50 but also 150 ppm magnesium-deficient rats, a single injection of THC at low doses (2, 4 or 8 mg THC/kg b.w.) which is without aggressive effect in control rats, induced a 100% MB, the pattern of which was all the more severe as the magnesium deficiency was important or the THC dose higher. The pattern showed an important decrease in the two first phases and a dramatic increase in the attack on the dead mouse, suggesting that the combination of both treatments provoked severe central damage with a compulsive killing behavior. Consequently, it appears that a magnesium deficiency, even a moderate one, may aggravate the neurotoxicity of THC at low doses and, reciprocally, that low doses of THC may reveal the potential neurotoxicity of a moderate magnesium deficiency.

THC aggravates rat muricide behavior induced by two levels of magnesium deficiency.

A severe magnesium deprivation induces an interspecific aggressive behavior (muricidal behavior, MB) in different strains of rats. Delta9-tetrahydrocannabinol (THC) is also known to induce MB even after a single injection (11 mg/kg) in starving, isolated rats. In the present work, we investigated the MB behavior, for six successive assays 1 h delayed, of two groups of male Long-Evans rats fed 50- or 150-ppm Mg(2+)-deficient diets, for 42 days after a single injection of THC at doses (2, 4 or 8 mg/kg) that did not induce aggressiveness in control rats. This treatment led to Mg(2+) plasma levels of 5+/-0.3 and 12.3+/-0.9 mg/ml vs. 21+/-1.5 mg/ml initially. In the 50-ppm Mg-deficient rat group, all the rats were muricidal but the MB pattern was severely aggravated by THC. In the 150-ppm Mg-deficient rat group, no rat was muricidal but all doses of THC induced a 100% MB. In addition, by quantifying the three phases of MB, we showed through six consecutive hourly muricidal assays, that the two first phases (attack latency and attack on the living mouse) decreased progressively, whereas the third phase (attack on the dead mouse) increased dramatically. This indicates firstly that Mg-deprivation decreases the responsiveness threshold of rats to THC. Secondly, these very low doses of THC induced an aggravation of MB and an acquired hyper-aggressiveness in both 50- and 150-ppm Mg-deficient rats, probably involving different neurotransmitters, mainly serotonin, which is decreased by both treatments.