The effect of chronic opioid vs. cannabinoid exposure on the expression of tolerance to morphine- or WIN-55,212-2-induced analgesia and hypothermia in the guinea pig

Maguma, Hercules T.; Taylor, David A.

doi:10.1016/j.ejphar.2011.04.010

Cited by 10 publications

(10 citation statements)

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“…The current study examined how the antinociceptive effects of opioids and cannabinoids are changed during chronic treatment with relatively large doses of morphine alone that result in dependence, as evidenced by the emergence of withdrawal signs when treatment was discontinued. This important first step is necessitated by inconsistent development of cross-tolerance to cannabinoids in morphine-treated rodents (Basilico et al 1999;Maguma and Taylor 2011;Yesilyurt and Dogrul 2004).…”

Section: Discussionmentioning

confidence: 99%

“…In morphine-tolerant rodents, the antinociceptive potency of cannabinoids is also decreased under some, but not all, conditions (Basilico et al 1999;Maguma and Taylor 2011;Yesilyurt and Dogrul 2004); however, antinociceptive tolerance does not develop during chronic treatment with a combination of morphine and a cannabinoid (Cichewicz and Welch 2003;Fischer et al 2010;Smith et al 2007). The current study begins to address in nonhuman primates whether tolerance and dependence are likely to impact the use of combinations of opioids and cannabinoids for treating pain.…”

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confidence: 94%

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Cross-tolerance to cannabinoids in morphine-tolerant rhesus monkeys

2015

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Tolerance developed to the antinociceptive effects of morphine and cross-tolerance developed to cannabinoids under conditions that produced modest physical dependence. Compared with the doses examined in this study, much smaller doses of opioids have antinociceptive effects when given with cannabinoids; it is possible that tolerance will not develop to chronic treatment with opioid/cannabinoid mixtures.

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Section: Discussionmentioning

confidence: 99%

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confidence: 94%

Cross-tolerance to cannabinoids in morphine-tolerant rhesus monkeys

2015

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“…First, the hypothermic effect produced by morphine is very modest in magnitude compared to that of other agents such as cannabinoids (Maguma and Taylor, 2011). The essential role of receptor activation that results in a robust physiological response and adaptation responsible for the development of tolerance is well documented (Taylor and Fleming, 2001) and has been further reinforced by previous studies showing that chronic use of sub-effective doses of opioids does not induce tolerance (Welch and Eads, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…We have also previously shown that chronic parenteral treatment with morphine leads to the development of tolerance to the analgesic effects of acute morphine (Maguma and Taylor, 2011) but did not determine whether similar tolerance developed after pellet implantation or explore the time course over which the change occurred. The goal of the present study was to test the hypothesis that chronic in vivo exposure to opioids through pellet implantation would produce a qualitatively similar progression in the appearance, maintenance, and disappearance of enhanced sensitivity to excitatory and reduced sensitivity to inhibitory agents in the LM/MP, and to the analgesic and hypothermic effect of morphine in vivo .…”

Section: Introductionmentioning

confidence: 96%

Time Course of Altered Sensitivity to Inhibitory and Excitatory Agonist Responses in the Longitudinal Muscle–Myenteric Plexus and Analgesia in the Guinea Pig after Chronic Morphine Treatment

Barrett¹,

Maguma²,

Taylor³

2012

Front. Pharmacol.

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Tolerance that develops after chronic morphine exposure has been proposed to be an adaptive response that develops and decays over a defined time course. The present study examined the development of tolerance to the acute hypothermic and analgesic effects of morphine and correlated the time course for the desensitization in vivo with the reduced responsiveness to DAMGO and 2-CADO and increased responsiveness to nicotine of the longitudinal muscle/myenteric plexus (LM/MP) preparation in vitro. Assessment was performed at various times after morphine or placebo pellet implantation. Morphine produced a modest hypothermic response to which no tolerance developed. However, the development of tolerance to the analgesic effect of morphine, the inhibitory effect of DAMGO and CADO on neurogenic twitches of the LM/MP and hypersensitivity to the contractile response to nicotine was observed to occur in a time-dependent manner. The alterations in sensitivity to DAMGO, nicotine, and responsiveness to morphine analgesia occurred between days 4 and 10 and returned to normal by day 14 post-implantation. In contrast, sensitivity of LM/MP preparations to 2-CADO displayed a similar time-dependent onset but the tolerance persisted beyond 14 days after implantation. These data suggest that the heterologous tolerance that develops after chronic morphine treatment is time-dependent and persistent but, ultimately returns to normal in the absence of any intervention. Furthermore, the data suggest that the basis of the adaptive phenomenon may involve multiple cellular mechanisms including the modulation of cell excitability and normal physiology but the consequences of the adaptation extend to all effects of the agonist.

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“…These adverse effects are particularly important for opioid/cannabinoid combinations because cross-tolerance develops between these two drug classes. For example, the antinociceptive potency of cannabinoids is decreased in morphine-tolerant monkeys (Gerak et al, 2015) and in some morphine-tolerant rats (Basilico et al, 1999;Yesilyurt and Dogrul, 2004;Maguma and Taylor, 2011). When opioids and cannabinoids are combined, tolerance and cross-tolerance might develop concurrently and produce a greater decrease in antinociceptive potency than would be observed when either drug is given alone; however, some studies in rodents receiving morphine and cannabinoids concurrently report that antinociceptive tolerance is not greater for the combination (Cichewicz and Welch, 2003;Smith et al, 2007;Fischer et al, 2010).…”

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confidence: 99%

Combined Treatment with Morphine and 9-Tetrahydrocannabinol in Rhesus Monkeys: Antinociceptive Tolerance and Withdrawal

Gerak

2016

Journal of Pharmacology and Experimental Therapeutics

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Opioid receptor agonists are effective for treating pain; however, tolerance and dependence can develop with repeated use. Combining opioids with cannabinoids can enhance their analgesic potency, although it is less clear whether combined treatment alters opioid tolerance and dependence. In this study, four monkeys received 3.2 mg/kg morphine alone or in combination with 1 mg/kg D 9 -tetrahydrocannabinol (THC) twice daily; the antinociceptive effects (warm water tail withdrawal) of morphine, the cannabinoid receptor agonists WIN 55,212, and the k opioid receptor agonist U-50,488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzenacetamide methanesulfonate) were examined before, during, and after treatment. To determine whether concurrent THC treatment altered morphine dependence, behavioral signs indicative of withdrawal were monitored when treatment was discontinued. Before treatment, each drug increased tail withdrawal latency to 20 seconds (maximum possible effect). During treatment, latencies did not reach 20 seconds for morphine or the cannabinoids up to doses 3-to 10-fold larger than those that were fully effective before treatment. Rightward and downward shifts in antinociceptive dose-effect curves were greater for monkeys receiving the morphine/THC combination than monkeys receiving morphine alone. When treatment was discontinued, heart rate and directly observable withdrawal signs increased, although they were generally similar in monkeys that received morphine alone or with THC. These results demonstrated that antinociceptive tolerance was greater during treatment with the combination, and although treatment conditions were sufficient to result in the development of dependence on morphine, withdrawal was not markedly altered by concurrent treatment with THC. Thus, THC can enhance some (antinociception, tolerance) but not all (dependence) effects of morphine.

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The effect of chronic opioid vs. cannabinoid exposure on the expression of tolerance to morphine- or WIN-55,212-2-induced analgesia and hypothermia in the guinea pig

Cited by 10 publications

References 42 publications

Cross-tolerance to cannabinoids in morphine-tolerant rhesus monkeys

Cross-tolerance to cannabinoids in morphine-tolerant rhesus monkeys

Time Course of Altered Sensitivity to Inhibitory and Excitatory Agonist Responses in the Longitudinal Muscle–Myenteric Plexus and Analgesia in the Guinea Pig after Chronic Morphine Treatment

Combined Treatment with Morphine and 9-Tetrahydrocannabinol in Rhesus Monkeys: Antinociceptive Tolerance and Withdrawal

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