Morphinelike arousal by methadone during sleep

Abstract

Methadone was investigated to see if it induced an insomnia comparable to that after single doses of morphine. After one adaptation night, the sleep of seven male nondependent opiate addicts was studied after intramuscular methadone (7.5, 15, or 30 mg/70 kg), morphine (10 or 20 mg/70 kg), and placebo at weekly intervals in a randomized double-blind crossover design. Drug effects were measured on several sleep and wakefulness patterns. Methadone is equipotent to morphine in its increase of wakefulness, drowsiness, muscle tension, shifts in sleep-waking state, and latency to rapid eye movement sleep (REMS) and its decrease of sleep efficiency, delta sleep, and REMS. This similarity of methadone to morphine in acute arousal from sleep is in contrast to the differences between these two drugs during long-term administration, when morphine induces a small but persistent arousal and methadone does not.

Morphine‐like insomnia from heroin in nondependent human addicts.

“…Morphine also slows alpha frequency and produces slower frequencies in some humans at a 20 mg i.m. dosage (Andrews, 1941;1943 (Kay et al, 1969;Pickworth et al, 1981). Morphine (7.5, 15, 30 mg/70 kg) produces a dose-related increase in insomnia and muscle tension in nondependent opiate addicts (Kay et al, 1969); it also produces a doserelated decrease in REM sleep and delta sleep.…”

“…Persistence, although attenuated, of this arousal effect is seen during chronic administration of morphine (Kay, 1975b). Methadone produces a comparable dose-related insomnia in nondependent opiate addicts (Pickworth, Neidert & Kay, 1981), with almost complete tolerance developing during chronic administration of methadone (Kay, 1975a). Heroin (diacetylmorphine) effects on sleep have not been studied as extensively as those of morphine or methadone.…”

Pharmacovigilance of the Analgesic Therapy

“…This is likely due to the interference of this class of molecules with the action or binding of sleeprelated neurotransmitters, such as noradrenaline, serotonin, acetyl choline, dopamine, histamine and gamma-aminobutyric acid [22]. Although this effect appears to be limited to the depth of sleep and duration of the REM (Rapid eye movement) phase rather than the quality of sleep itself [23,24], this factor might be worth considering when opioid treatments worsen sleep disturbances derived from an underlying condition.…”

Rare and Serious Side Effects in Chronic Pain after Opioids

“…However, few experimental studies have come out with contradictory results. Administration of opioids can lead to disturbed sleep pattern in numerous ways such as decrease in total sleep time, disturbed arousal-sleep pattern and imbalance between deep sleep and Rapid Eye Movement (REM) sleep [50][51][52]. However, the most controversial fact in these studies was related to the general condition of the cancer patients as the different stages of oncologic process can interfere with normal sleep pattern.…”