Abstract: The present invention provides compounds of formula (I): NR1R2SOOYR3 (I) or a pharmaceutically acceptable salt thereof. The present invention also provides pharmaceutical compositions comprising a compound of formula (I), and use of the com-pounds and the pharmaceutical compositions for treating or ameliorating opioid withdrawal syndrome in a subject.

Abstract: Methods of reducing symptoms of opioid withdrawal syndrome and risk of relapse to drug seeking are provided. The method comprises administering to the subject an effective amount of probenecid.

Abstract: A method of screening a compound or a composition for use in modulating opioid withdrawal symptoms in a mammal. The method comprises the steps of: selecting a group of test animals; separating the group into two subgroups; inducing Panx1 activation or expression in both subgroups; dosing a first subgroup with a candidate compound; dosing a second subgroup with a placebo; measuring ATP released in spinal microglia of test animals in the first subgroup and in the spinal microglia of test animals in the second subgroup; quantifying the difference in ATP released in spinal microglia of test animals in the first subgroup and in the spinal microglia of test animals in the second subgroup; if the difference in the ATP released in the first subgroup and the APT released in the second subgroup is greater than 25%, then formulating the candidate compound into a pharmaceutical composition.

Abstract: A method of screening a compound or a composition for use in modulating opioid withdrawal symptoms in a mammal. The method comprises the steps of: selecting a group of test animals; separating the group into two subgroups; inducing Panx1 activation or expression in both subgroups; dosing a first subgroup with a candidate compound; dosing a second subgroup with a placebo; measuring ATP released in spinal microglia of test animals in the first subgroup and in the spinal microglia of test animals in the second subgroup; quantifying the difference in ATP released in spinal microglia of test animals in the first subgroup and in the spinal microglia of test animals in the second subgroup; if the difference in the ATP released in the first subgroup and the APT released in the second subgroup is greater than 25%, then formulating the candidate compound into a pharmaceutical composition.

Abstract: Combination therapies of an opioid receptor agonist and a cannabinoid receptor antagonist in an amount effective to potentiate a therapeutic activity of the opioid receptor agonist and/or inhibit, delay, reduce and/or reverse tolerance to the opioid receptor agonist are provided. Also provided are methods for use of these combination therapies in potentiating a therapeutic activity of an opioid receptor agonist and/or inhibiting, delaying or reducing development of acute and/or chronic tolerance to opioid receptor agonists and treating conditions treatable by opioid receptor agonist therapy in a subject. In addition, a method for reversing opioid receptor agonist tolerance and/or restoring therapeutic effect of an opioid receptor agonist in a subject via administration of a cannabinoid receptor antagonist is provided.