Method for treating drug or alcohol dependency
Provided herein is a method for weaning a subject suffering from a drug addiction or addictive behaviors involving opioid signaling by sequentially blocking peripheral and CNS opioid receptors and modulating opioid dependence.
1 . A method for weaning a drug-dependent subject from a drug dependency, wherein the drug dependency is an opioid addiction and wherein the subject is taking an opioid agonist as part of pain therapy, under opioid use disorder, or in a maintenance program, comprising the sequential steps of:
a) oral administration of a dose of 0.5 to 10 mg of 6-beta-naltrexol, once or twice daily for 2-4 days, followed by a dose of 2 to 20 mg once or twice daily for 4-8 days to block a peripheral opioid receptor in said subject;
b) oral administration of 4-50 mg of 6-beta-naltrexol, once or twice daily for at least 1-4 weeks, and reduction of the 6-beta-naltrexol dose until first signs of abstinence symptoms emerge, thereby stabilizing the peripheral opioid receptor signaling by maintaining administration of the 6-beta-naltrexol at doses sufficient to block peripheral but not central opioid receptors, to prevent peripheral opioid adverse effects and reduce opioid-induced hyperalgesia and dependence, during reduction of the dosage of the opioid agonist;
c) oral administration of 6-beta-naltrexol in an increasing amount to block a CNS opioid receptor in said subject, and during reduction and cessation of opioid agonist treatment at a rate that elicits only mild, tolerable abstinence symptoms, thereby weaning said subject from said opioid addiction, wherein the 6-beta-naltrexol is for oral administration in a dose of 10-80 mg twice daily for 4-8 days, then in a dose of 20-120 mg once or twice daily for 1-4 weeks, and further escalation to a maintenance dose of 40-300 mg once or twice daily; and
d) administration of 6-beta-naltrexol of the maintenance dose to block central opioid receptors during periods of high relapse risk and at an intermediate dose sufficient to block activation of peripheral opioid receptors long-term.
2 . The method according to claim 1 , wherein the peripheral opioid receptor is the mu opioid receptor.
3 . The method according to claim 1 , wherein in step a) blocking of said peripheral opioid receptors is measured by restoration of bowel activity in opioid use disorder without central opioid withdrawal symptoms.
4 . The method according to claim 1 , further comprising implementation of a long-term opioid antagonist maintenance regimen until the risk of recidivism is considered low.
5 . The method according to claim 4 , wherein, in the long-term opioid antagonist maintenance regimen, the 6-beta-naltrexol is for administration at a dosage range of 40-300 mg per day orally.
6 . The method according to claim 4 , wherein in the long-term opioid antagonist maintenance regimen, the 6-beta-naltrexol is for administration at a dosage of 100 mg per day orally.
7 . The method according to claim 4 , wherein for long-term maintenance with reduced risk of recidivism, the dosage of 6-beta-naltrexol is reduced to 4-50 mg per day.