The effects of cannabis on heart rate variability and well-being in young men.

INTRODUCTION: The effects of cannabis use on the autonomic regulation of the heart had been identified in tests with volunteers. We studied these effects of cannabis use on young adults in everyday life. METHODS: We measured heart rate variability (HRV) and well-being (WHO-5 score) in young men during a routine medical examination. Seventy-two men were identified with a positive drug screening test solely for tetrahydrocannabinol. The comparison group consisted of 72 men, matched according to age and body mass index, who used no illicit drugs or pharmaceuticals. RESULTS: In the cannabis group, HRV was significantly increased compared to the control group. The median value of root mean square of successive differences (RMSSD) at rest was 56.2 ms in the drug users and 48.6 ms in the controls (p<0.05). The ratio of low-to-high frequency was higher in the controls (median 1.87 vs. 1.62; p<0.05). Psychological well-being, measured by WHO-5 score was significantly lower in cannabis users. DISCUSSION: Our data support the hypothesis that the use of cannabis leads to a change in cardiovascular sympathovagal balance.

Cardiac effects of vagus nerve stimulation in patients with major depression.

INTRODUCTION: Changes in the heart rate variability are well known among patients with depression. Amongst others, a modulation of the autonomic nervous system is discussed. An investigation of heart rate variability during terms of stimulation could give some insight in the central nervous effect of vagus nerve stimulation (VNS) and possible cardiac side effects. METHODS: The effects of VNS on heart rate (HR) and heart rate variability were studied (HRV) during stimulation in nine patients with major depression according to ICD-10. RESULTS: When comparing treated depressive patients with a sex- and age-matched healthy control group, the analysis of heart rate revealed significantly (t=2.8; df=16, p=0.012) elevated heart rates during completely switched off conditions, during switched on VNS programme in stimulation-free intervals (5 min period) (t=3.0; p=0.009) and during stimulation conditions (30 s) (t=2.8, Levene corrected, p=0.015). The RMSSD (root mean square of successive differences) as a measure of the HRV increased significantly in switched on conditions during stimulation (30 s) in six patients compared to stimulation-free intervals (t=-4.7; df=5, p=0.006) and baseline. DISCUSSION: Clinically relevant cardiac effects were not observed throughout the study. VNS induces reversible changes in heart rate variability in patients with major depression during stimulation conditions.

The effects of venlafaxine on cognitive functions and quantitative EEG in healthy volunteers.

Antidepressants that selectively block serotonin uptake may cause unwanted effects on cognitive functions such as impairment of vigilance and memory. A double-blind, randomized, placebo-controlled cross-over trial was performed to examine the effects of venlafaxine, a selective serotonin and noradrenaline reuptake inhibitor (SSNRI), on cognitive functions and quantitative EEG (qEEG) in humans. 12 healthy male subjects aged 23-32 years (26+/-3 years mean+/-sd) orally received 37.5 mg venlafaxine b.i.d. for 7 days and subsequently 75 mg b.i.d. for another 7 days. After a 14-day wash-out phase, placebo was administered to the subjects for 14 days under randomized double-blind cross-over conditions. Venlafaxine did not influence cognitive functions such as choice reaction, memory, psychomotor performance and subjective mood. Placebo resulted in an increase in slow alpha power (p<0.05) whereas venlafaxine had no effect on qEEG. In conclusion, multiple dosing with venlafaxine did not influence cognitive functions in healthy humans.

The effects of moclobemide on autonomic and cognitive functions in healthy volunteers.

BACKGROUND: Moclobemide, a reversible and selective inhibitor of the MAO-A isoenzyme, is marketed as an antidepressant that lacks autonomic and cognitive side effects. However, only few and inconclusive quantitative data on the effects of moclobemide on autonomic and cognitive functions have been reported in the literature. Therefore, a double-blind, randomized, placebo-controlled crossover trial was performed. METHODS: Twelve healthy male volunteers (age 22-29 years) received orally 150 mg moclobemide b.i.d. and placebo for 14 days each. Heart rate variability (HRV) and skin conductance response (SCR) following sudden deep breath were employed as parameters for autonomic function. Quantitative EEG (qEEG) and psychometric tests served as parameters for cognitive function. Measurements were performed before the start of drug administration and repeatedly on the last treatment day. RESULTS: Parameters of HRV and SCR were not changed by multiple dosing with moclobemide (P > 0.05). Neither cognitive functions such as flicker fusion frequency, memory, choice reaction time, and psychomotor performance nor qEEG was significantly influenced, but subjective tiredness was decreased at all time points of measurement after multiple dosing with moclobemide (P < 0.05). CONCLUSIONS: In conclusion, moclobemide does not appear to influence autonomic functions or cognitive functions when given subchronically to healthy humans. In contrast, changes in subjective mood hint at a subtle activating effect.

Do preceding vasoconstrictions influence the 'inspiratory gasp test'?

Diabetic or other neuropathies can affect the autonomic innervations of vessels and heart. Using non-invasive and inexpensive autonomic tests, one can detect autonomic neuropathy. One of these tests is the inspiratory gasp response (IGR). It appears as a short reduction of skin blood volume (SBV) following deep inspiration (DI). Unfortunately, because of a high degree of variability of the study results, the clinical merits of this test have been questioned. However, there remains vagueness about underlying mechanisms or pitfalls. The aim of the study was to identify preceding vasoconstrictor episodes as putative pitfalls in assessing IGR. With regard to the hypothesis that a preceding vasoconstrictor episode may affect the amplitude of the following one, we investigated SBV in fingertips of 25 healthy test subjects (14 females, 11 males; mean age 24 years), using the photoplethysmographic technique. After adaptation to environmental conditions the subjects were instructed to perform five DI in various time lags (90, 30, 20 and 180 s). We found that the shorter the time interval to a preceding IGR, the lower the amplitude of the following IGR. After an interval of 180 s, the amplitude increased again. We conclude that this newly observed phenomenon might explain the contradictory results of the IGR test found in some earlier studies. We suppose that reduced IGR may depend on alterations in peripheral norepinephrinergic transmission processes (e.g. emptying of norepinephrine reservoirs). In clinical studies it should be ruled out that a diagnostically assessed IGR is influenced by a preceding vasoconstrictor episode.

Autonomic responses of blood vessels and sweat glands in patients with schizophrenia treated with olanzapine or clozapine.

RATIONALE: Data comparing the in vivo effects on autonomic nervous system function of standard clinical doses of olanzapine and clozapine are sparse. OBJECTIVE: The goal of this study was to compare the skin conductance response (which is peripherally mediated via muscarinic m3-receptors) and the inspiratory gasp response (which is peripherally mediated via adrenergic receptors) between healthy controls and schizophrenics treated with clozapine or olanzapine. METHODS: Twenty patients with schizophrenia (according to DSM-III-R criteria) treated with either clozapine (200-500 mg/day) or olanzapine (10-20 mg/day) as well as ten matched controls underwent simultaneous recordings of the skin conductance response (SCR) of sweat glands and of the inspiratory gasp response (IGR) of acral blood vessels. A single, deep inspiration was used as the stimulus. Group differences for the SCR amplitudes and the post-IGR redilation times were compared using the Mann-Whitney test. RESULTS: Both clozapine- and olanzapine-treated patients showed a significant SCR reduction compared to controls. Interestingly, the reduction in SCR was significantly larger in the clozapine group compared to the olanzapine group (P<0.05). Moreover, only clozapine-treated patients showed a statistical trend towards a longer IGR redilation time compared to controls. CONCLUSION: The significantly stronger SCR reduction amongst clozapine-treated compared to olanzapine-treated patients suggests that olanzapine at a standard clinical dose exhibits a significantly smaller anticholinergic effect at peripheral m3-receptors in vivo compared to clozapine. The prolongation of IGR redilation can be explained by a prolonged release of noradrenaline due to the alpha2-antagonistic effect of clozapine.