The influence of oral alcohol intake on the effects of the 35% CO2 challenge in healthy volunteers

Alcohol use disorders and Panic Disorder (PD) show a high degree of comorbidity which seems to be related to both psychological and biological factors. First, alcohol consumption could lower anxiety both by diverting attention from anxiogenic cues and by the expectation of having an anxiolytic effect. Second, the effect of alcohol could be linked to its pharmacological properties. Although numerous studies have been devoted to the pharmacology of alcohol and the underlying mechanism of alcoholism, only a small number has examined the causes underlying its comorbidity with other disorders, such as PD, using experimental methodologies. The present study aims to evaluate the anxiolytic effect of a small oral dose of alcohol in experimental panic induced by a 35% CO2 challenge. The study was conducted according to a placebo-controlled, double-blind, randomised, cross-over design. Eight healthy volunteers were enrolled (power = 95%: 5 males, 3 females; mean age: 36.6 years). All subjects were physically and mentally healthy and did not have a history of psychiatric disorders. Thirty minutes after the subjects finished their alcohol or placebo intake the blood alcohol concentration was assessed, and they underwent the 35% CO2 challenge. The dose of alcohol used was small to keep the subjects as far as possible below the threshold of any clinically relevant intoxication. Before and after the inhalation, the following assessments were made: the State Trait Anxiety Inventory (STAI-1), the Profile Of Mood States (POMS), the Zung Self rating Scale for Anxiety (SAS), a Visual Analogue Scale of Anxiety (VAAS), and the Panic Symptom List (PSL). After alcohol intake, subjects presented a significant reduction of state anxiety associated with the challenge procedure. The PSL score was significantly lower after alcohol intake (p = 0.032) if compared with the placebo. The VAAS was also lower in the alcohol condition, however without reaching statistical significance (p = 0.111). No statistically significant differences were found between the two testing days concerning the biological variables (blood pressure, heart rate) and the pre-challenge score of the PSL and the VAAS. None of the subjects reported a panic attack following the 35% CO2 challenge. Related to the small dose of alcohol used, baseline anxiety did not vary significantly from the alcohol test day to the placebo test day. This means that the blunted response to CO2 observed after alcohol intake cannot be related to a decreased anticipatory anxiety, but to a specific inhibitory effect of ethanol on experimental panic. In conclusion, moderate doses of alcohol (Blood Alcohol Concentration = 0.41 ± 0.05 mg/ml) decrease the response to the 35% CO2 challenge in healthy volunteers. These results are in agreement with the literature and confirm a direct pharmacological anxiolytic effect of alcohol at moderate doses. Furthermore, it supports the view that this property may reinforce the drinking behaviour among those with high levels of anxiety. Further investigations are necessary especially referring to a larger sample including a clinical population of PD patients, using IV administration of ethanol, in order to eliminate any bias due to the act of drinking.