Serum levels of endogenous cannabinoids are associated with arterial blood pressure in depressed women

W.-S. Vanessa Ho1, Matthew N. Hill2, Boris B. Gorzalka2, Cecilia J. Hillard1 & Gregory E. Miller2. 1Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. 2Department of Psychology, University of British Columbia, Vancouver, B.C. Canada V6T 1Z4.

Depression is known to be a risk factor for cardiovascular diseases and predicts poor prognosis for patients with heart failure. However, mechanisms underlying this association remain unclear. Recent animal studies have shown that endogenous cannabinoids (eCBs), anandamide (AEA) and 2-arachidonylglycerol (2-AG) can modulate cardiovascular function and are associated with depression and anxiety disorders. These data lead us to hypothesize that eCBs are a link between depression and cardiovascular function. To explore this hypothesis, we examined the relationship between serum contents of eCBs and resting blood pressure in depressed patients.

A total of 55 adult women from Saint Louis, MO, USA participated in the study, which was approved by the Institutional Review Board of Washington University. Depressed subjects (n=28, age 28.0±1.8) met DSM-IV diagnostic criteria for clinical depression whereas their matched control subjects (based on age and ethnicity; n=27, age 29.0±1.6) had no lifetime history of psychiatric illness. None of the subjects had a history of chronic medical illness; acute infections disease at study entry; or prescribed medication in the past six months, with the exception of oral contraceptives. Serum eCBs contents were determined using solid phase extraction followed by liquid chromatography/mass spectrometry (LC-APCI-MS). Data are given as mean±SEM and analyzed using Pearson correlation tests and Student’s unpaired t-tests.

The average systolic blood pressure is significantly higher in depressed patients than in control subjects (Depressive, 115.1±2.1 mmHg; Control, 108.6±1.5 mmHg; P=0.02). Whilst no significant difference in averaged diastolic pressure was found (Depressive, 69.8±1.3 mmHg; Control, 67.9±1.5 mmHg; P=0.36), 2 out of 28 depressed patients (with systolic/diastolic: 152/91 and 140/84) might be considered for hypertensive treatment. In depressed women, serum AEA (0.8±0.1 pmol/ml) and 2-AG (18.5±2.7 pmol/ml) levels are positively correlated with diastolic (AEA: r=0.46, P=0.01; 2-AG: r=0.62, P<0.01) but not significantly with systolic pressure (AEA: r=0.35, P=0.07; 2-AG: r=0.22, P=0.26). No correlations between eCBs and pressure were found in the control subjects (AEA: 0.7±0.1 pmol/ml, diastolic r=-0.05, P=0.81, systolic r=-0.17, P=0.40; 2-AG: 19.0±2.4 pmol/ml, diastolic r=-0.04, P=0.84; systolic r=0.04, P=0.83).

This study shows that diastolic blood pressure is positively associated with serum level of eCBs, AEA and 2-AG in women with depression. Given the potential involvement of endogenous cannabinoids in patho/physiological cardiovascular and neuronal functions, interrelationships among these agents, cardiovascular parameters and depression warrant future research attention. The current data also confirm previous findings that depression is associated with elevated blood pressure, which is a major risk factor for cardiovascular diseases.

Supported by NIH grants DA016967 and NS41314.