Although much progress has been made to treat pain, morphine and related opioids are still the most effective analgesics. However, their use is limited by concerns about abuse and the development of dependence during chronic administration. The utility and safety of morphine- like opioids may be improved by combining them with other drugs that increase analgesia through different (non-opioid) mechanisms. For example, combinations of opioids and drugs acting on serotonin (5-HT) systems (for example, SSRIs [fluoxetine]) are commonly used to treat pain. Also, combinations of opioids and 9-tetrahydrocannabinol (THC), which are used recreationally, might have advantages to treat pain. However, it is not clear if these drugs increase only the analgesic effects of opioids, or also their abuse- and dependence-related effects. Studies described in this revised application continue a history under this grant of examining opioids alone and with other drugs. In addition, they build on exciting preliminary findings that THC and drugs acting on 5-HT systems markedly increase the analgesic effects of morphine, but attenuate its discriminative stimulus effects. Drug discrimination and antinociception procedures will be used to characterize behavioral effects of morphine in combination with THC and other cannabinoid receptor agonists (Aim I) and in combination with drugs acting on 5-HT systems (Aim II). Receptor selective agonists and antagonists will help to examine which receptors mediate these interactions, and chronic dosing studies will investigate how these interactions are affected by chronic treatment. Studies under Aim III examine how THC and fluoxetine modify the reinforcing effects of heroin and the development of dependence on morphine. Collectively, these experiments examine interactions between morphine and cannabinoid or 5-HT drugs to determine whether their combination increases pain relief without increasing, and possibly decreasing, abuse and dependence.
Opioids are not effective for treating pain in many patients and their clinical use is limited by concerns about abuse and dependence. This grant examines interactions between morphine and serotonergic (e.g., fluoxetine) or cannabinoid (e.g., THC) drugs to determine whether the combination enhances their ability to alleviate pain without increasing, and possibly decreasing, their abuse and dependence.
|Collins, Gregory T; Gerak, Lisa R; France, Charles P (2018) The behavioral pharmacology and therapeutic potential of lorcaserin for substance use disorders. Neuropharmacology 142:63-71|
|Gerak, Lisa R; Collins, Gregory T; Maguire, David R et al. (2018) Effects of lorcaserin on reinstatement of responding previously maintained by cocaine or remifentanil in rhesus monkeys. Exp Clin Psychopharmacol :|
|Minervini, Vanessa; France, Charles P (2018) Effects of morphine/CP55940 mixtures on an impulsive choice task in rhesus monkeys. Behav Pharmacol 29:60-70|
|Gerak, Lisa R; Maguire, David R; Woods, James H et al. (2018) Reversal and prevention of the respiratory-depressant effects of heroin by the novel µ opioid receptor antagonist methocinnamox in rhesus monkeys. J Pharmacol Exp Ther :|
|Weed, Peter F; Gerak, Lisa R; France, Charles P (2018) Ventilatory-depressant effects of opioids alone and in combination with cannabinoids in rhesus monkeys. Eur J Pharmacol 833:94-99|
|Maguire, David R; France, Charles P (2018) Reinforcing effects of opioid/cannabinoid mixtures in rhesus monkeys responding under a food/drug choice procedure. Psychopharmacology (Berl) 235:2357-2365|
|Weed, Peter F; France, Charles P; Gerak, Lisa R (2017) Preference for an Opioid/Benzodiazepine Mixture over an Opioid Alone Using a Concurrent Choice Procedure in Rhesus Monkeys. J Pharmacol Exp Ther 362:59-66|
|Maguire, David R; Gerak, Lisa R; France, Charles P (2016) Effect of daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys. Behav Pharmacol 27:155-64|
|Gerak, L R; France, C P (2016) Combined Treatment with Morphine and ?9-Tetrahydrocannabinol in Rhesus Monkeys: Antinociceptive Tolerance and Withdrawal. J Pharmacol Exp Ther 357:357-66|
|Maguire, David R; France, Charles P (2016) Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys. Behav Pharmacol 27:249-57|
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