Calcium Carbonate Attenuates Withdrawal and Reduces Craving: A Randomized Controlled Trial in Alcohol-Dependent Patients

Abstract

<b><i>Introduction:</i></b> Preclinical studies have shown that calcium seems to be the active component of the anti-craving drug acamprosate (Ca<sup>2+</sup> bis-acetyl-homotaurinate). Clinical effects in humans have also indicated an association between increased calcium plasma concentration due to acamprosate treatment and better outcome relating to time to relapse and cumulative abstinence. In contrast, low calcium concentration in alcohol-dependent patients was related with craving for alcohol. The main goal of the trial was to investigate whether an oral calcium administration is able to affect craving, withdrawal, and relapse risk in alcohol-dependent patients. <b><i>Methods:</i></b> We conducted a single-blind, randomized, monocentric, controlled clinical two-arm trial in alcohol-dependent patients (Clinical Trials Registration: DRKS00011293). A total of 55 alcohol-dependent subjects received calcium carbonate (800 mg + 5 μg vitamin D) versus sodium bicarbonate (1,000 mg) daily during the 14 days of inpatient alcohol-withdrawal treatment. <b><i>Results:</i></b> Based on an intention-to-treat protocol, withdrawal intensity (assessed with CIWA-Ar) in the calcium carbonate group attenuated faster than in the sodium bicarbonate subgroup. Alcohol craving (assessed with OCDS) in the calcium carbonate subgroup was also significantly reduced versus the sodium bicarbonate subgroup. <b><i>Conclusion:</i></b> Our data support earlier findings and show that treatment with calcium carbonate during alcohol withdrawal reduces symptoms of alcohol withdrawal as well as alcohol craving in a controlled clinical pilot study. Mode of actions will need to be determined to allow the further development of pharmacological interventions beyond Ca<sup>2+</sup> bis-acetyl-homotaurinate.

Acamprosate reduces ethanol intake in the rat by a combined action of different drug components

“…Furthermore, acamprosate has failed to produce a signi cant reduction in time to rst heavy drinking day in several human trials [29][30][31] raising the question of whether a decline of e cacy is also seen in some human populations. Given the present in vivo microdialysis results of the enhanced effects following co-administration of calcium and sodium acamprosate in rats, and the recently observed positive association between craving and calcium plasma concentrations in human studies 32,33 , the main question of the current voluntary ethanol consumption study was if sodium acamprosate would add on to the effect of calcium with regards to reducing ethanol intake. In concurrence with the results in the microdialysis study, the combined administration of calcium and sodium acamprosate demonstrated potentiated effects and signi cantly reduced the ethanol intake during the whole treatment period, as compared to vehicle treated controls.…”

“…However, ethanol is known to temporarily lower plasma calcium concentrations in a dose-dependent manner by decreasing secretion of parathyroid hormone and accelerating calcium excretion into the urine [35][36][37] . The effect of calcium treatment has been investigated and showed that increased calcium concentrations in alcohol-dependent individuals was associated with attenuation in the intensity of alcohol withdrawal symptoms 33 . Elevated plasma calcium levels also correlated with decreased alcohol craving in dependent patients undergoing detoxi cation treatment 32 .…”