Dextroamphetamine with Morphine: Respiratory Effects

Abstract

The combination of dextroamphetamine and morphine has been shown to be synergistic for analgesia and antagonistic for most other effects. However, the claim that dextroamphetamine antagonizes the respiratory depression caused by morphine has not been well substantiated. In this double-blind study, we investigated respiratory effects, including resting respiration, isohypercapnic ventilation, CO2 response, dose response, and duration of these effects with dextroamphetamine alone and in combination with morphine. Dextroamphetamine alone (0.215 mg/kg) caused increases in minute ventilation and a leftward shift of the CO2 response curve that lasted for less than 2 hours. Dextroamphetamine combined with low-dose morphine (0.15 mg/kg) antagonized respiratory depression throughout the 5-hour observation period. Dextroamphetamine combined with high-dose morphine (0.30 mg/kg) was unable to completely antagonize depressed ventilation, and some residual effects of morphine persisted at 23 hours.

Agonist-Like or Antagonist-Like Treatment for Cocaine Dependence with Methadone for Heroin Dependence: Two Double-Blind Randomized Clinical Trials

“…Even under well-controlled preclinical laboratory, and clinical laboratory settings (Foltin and Fischman, 1992, substantial 'individual differences' emerge and this is observed in clinical settings. Some data emerge from pain treatment where the opioid and stimulant combination is used effectively (Forrest et al, 1977;Bourke et al, 1983;McManus and Panzarella, 1986;Payne, 1997 personal communication). Still, in a human laboratory study with concurrent IM morphine and d-amphetamine administration to nondependent individuals, Jasinski and Preston (1986) observed greater euphoria and mutual antagonism of side effects.…”

Ventilatory Effects of Fentanyl, Heroin, andd-Methamphetamine, Alone and in Mixtures in Male Rats Breathing Normal Air

“…The different patterns and time-effect functions of stimulant drugs on ventilation in the present study (monophasic increases for dmethamphetamine under the normal air conditions) and a previous study (bi-phasic changes for (±)methamphetamine and d-amphetamine under hypercapnic conditions; Elder et al, 2023) might be related to the use of different CO 2 levels in the two studies (normal air in the current study and hypercapnic in the previous study); however, d-amphetamine (0.046-0.215 mg/kg, i.v.) produced only monophasic increases in V E relative to placebo in humans even under hypercapnic conditions (3%-7% CO 2 ; Bourke et al, 1983). Another difference between the current study using rats and the previous study using mice, is that the experiments were conducted in the light cycle in the current study and in the dark cycle in the previous study (Elder et al, 2023).…”

“…d-Amphetamine also increases V E in humans under hypercapnic conditions (3-7% CO 2 ) that increase ventilation (Bourke et al, 1983). Clinical studies have shown that d-amphetamine can attenuate the ventilatory depressant effect of morphine under both normal air and hypercapnic conditions (Bourke et al, 1983;Jasinski and Preston, 1986). In rats breathing normal air, d-amphetamine attenuates fentanyl-induced changes in ex vivo respiratory parameters (i.e., increase in partial pressure CO2 and decrease in percent oxygen saturation; Moody et al, 2020).…”

“…For example, d-methamphetamine and d-amphetamine increase f in human subjects breathing normal air (Martin et al, 1971) and d-amphetamine also increases f in rats breathing normal air (Schierok et al, 2000). d-Amphetamine also increases V E in humans under hypercapnic conditions (3-7% CO 2 ) that increase ventilation (Bourke et al, 1983). Clinical studies have shown that d-amphetamine can attenuate the ventilatory depressant effect of morphine under both normal air and hypercapnic conditions (Bourke et al, 1983;Jasinski and Preston, 1986).…”

Drug Interactions of Clinical Significance with Opioid Analgesics

“…A double-blind study of 7 volunteers examined the respiratory effects of combined dexamphetamine (0.215 mg/kg) and morphine (0.15 mg/kg) alone and in combination (Bourke et al 1983). Dexamphetamine, itself a respiratory stimulant, was able to sufficiently antagonise the respiratory depression caused by morphine.…”