Human sleep during chronic morphine intoxication

Abstract

The sleep of 6 opiate addicts was studied for 11 nights during 3 phases of a chronic morphine cycle. The control phase consisted of 5 consecutive nights before morphine administration. The induction phase consisted of 1 night at 21-36 days after the onset of morphine administration, when the daily dose was 140-220 mg. The stable dose phase consisted of 5 consecutive nights after the subjects had received 240 mg of morphine daily for 8-19 weeks. No sleep could be studied during the withdrawal phase. Sleep was continuously monitored with EEG, EMG and EOG. Chronic morphine produces signs of a small but persistent sleep disturbance: delta sleep (early night) becomes less stable and shifts toward later in the night, waking state increases during the middle of the night, RME sleep (expecially its activated EEG without eye movements) decreases, the RMES cycle increases, and burst of delta activity (with mean duration of 5-6 sec) increase. Although this disturbance persists throughout the night, it is much less than that seen after single doses of morphine in a previous study. With chronic morphine, therefore, partial tolerance develops to the sleep disturbance produced by morphine. The small but persistent nocturnal arousal during chronic morphine contrasts with the sedation seen during chronic methadone. Both opioids produce an increase in delta bursts during chronic administration, which might be an EEG phenomenon specific to chronic opioid intake.

Sleep Impairments in Rats Implanted with Morphine Pellets

“…PS observed during the 10 days after implantation corroborates the physical dependence measured by precipitating withdrawal with naloxone [9]. The decrease in PS duration during dependence was previously observed in humans [5] and suggests an action of morphine at the medial pontine reticular formation level [1].…”

“…In the rat, morphine dependence was often evaluated by disturbing the animal by modifying its external environment, hotplate test [6], in acting physically on its body, tail-flick latency test [7], or in acting chemically, injection of a morphine antagonist [1,4]. Though morphine addiction can be obtained by repeated morphine injection [5,8], one of the most widely employed techniques to induce morphine dependence is the subcutaneous implantation of morphine pellets [3,4,[9][10][11]. Looking at previous publications, only one study has been performed on sleep in pellet-implanted rats [12].…”

“…Many studies have been performed on the effects of morphine in different species: cat [1], dog [2], mouse [3], rat [4] and human [5]. In the rat, morphine dependence was often evaluated by disturbing the animal by modifying its external environment, hotplate test [6], in acting physically on its body, tail-flick latency test [7], or in acting chemically, injection of a morphine antagonist [1,4].…”

Sleep and GABA levels in the oral part of rat pontine reticular formation are decreased by local and systemic administration of morphine

“…Unfortunately, opioids have numerous side effects including sleep disruption (Kay et al, 1969, Kay, 1975. In healthy human volunteers, clinically relevant doses of opioids increase light sleep (stage 2), decrease deep sleep (stage 4), and decrease rapid eye movement (REM) sleep (Walder et al, 2001, Shaw et al, 2005.…”

Remifentanil Inhibits Rapid Eye Movement Sleep but Not the Nocturnal Melatonin Surge in Humans

“…Early studies in former opioid-dependent prisoners [7][8][9][10][11] and a recent study in opioid-naive healthy volunteers 12 demonstrated that morphine and other opioids dosedependently inhibit sleep, especially slow wave sleep (SWS) and rapid eye movement (REM) sleep. In all of these studies, the dose of opioid was administered before the sleep recording period.…”