Opioid Abuse Medication

Updated: Sep 05, 2023
  • Author: David W Dixon, DO; Chief Editor: Glen L Xiong, MD  more...
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Medication Summary

The goals of pharmacotherapy are to treat the addiction of the chemical substances that cause them.


Opioid analgesics

Class Summary

Two uses for opioid analgesics are as follows: (1) Oral substitution therapy or maintenance therapy or opioid agonist therapy (OAT) refers to substitution of an oral opioid for injected heroin, with the goal of reducing harmful behaviors associated with heroin use. (2) Detoxification, or controlled withdrawal with the goal of abstinence, is based on the principle of cross-tolerance in which one opioid is replaced with another and then slowly withdrawn.

Methadone (Dolophine)

Inhibits ascending pain pathways, diminishing the perception of and response to pain. There are inpatient facilities and a few, specialized, licensed, outpatient, drug treatment programs that provide opioid detoxification using methadone. Also a preferred agent for opioid agonist maintenance. Some experts feel that laboratory measures of plasma levels should be used to adjust the dose and that 400 ng/mL seems sufficient to stop craving and drug hunger.

Benefits include good treatment retention, psychosocial adjustment, and reduced criminal activity.


Analgesics, Opioid Partial Agonist

Class Summary

The sublingual product is used predominantly for induction dosing followed by maintenance with buprenorphine/naloxone SL. The buprenorphine subdermal implant may be considered for maintenance therapy of opioid addiction in patients who have achieved prolonged clinical stability on low-to-moderate buprenorphine/naloxone doses. Additionally, a once-monthly SC injection is also an option.


Partial opioid agonist and potent antagonist, is a potent analgesic that can be administered once a day to block withdrawal symptoms. The agonist effect is limited by a ceiling effect (ie, higher doses [>12-16 mg] do not produce more analgesia). The sublingual tablet is used for initial detoxification treatment of opioid addiction. It is administered in a stepwise regimen over 4-5 days before switching to maintenance treatment with buprenorphine/naloxone. Stabilization with buprenorphine transmucosal also precedes maintenance with a long-acting buprenorphine product (eg, once monthly SC injection, every 6 month subdermal implant).

Buprenorphine subdermal implant (Probuphine)

Semisynthetic narcotic mixed agonist-antagonist analgesic; exerts partial agonistic effects at the mu opioid receptor in the CNS and antagonistic effects at the kappa opioid receptor. The implant is indicated for the maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low-to-moderate doses of a transmucosal buprenorphine-containing product. The implants are inserted in the upper arm and provide 6 months of continuous buprenorphine.

Buprenorphine, long-acting injection (Sublocade)

Once monthly SC injection that forms a solid mass upon contact with body fluids from the Atrigel delivery mechanism. Must be administered in a healthcare setting to avoid inadvertent IV administration that could result in death. The half-life is 43-60 days. It is indicated for treatment of moderate-to-severe opioid use disorder (OUD) in adults who have initiated treatment with a transmucosal buprenorphine-containing product and have been on a stable dose of transmucosal buprenorphine treatment for ≥7 days.


Opioid Partial Agonist/Opioid Antagonist

Class Summary

This combination is used predominantly for maintenance dosing following initial induction dosing with buprenorphine SL. The sublingual tablet or film (Suboxone, Zubsolv) or the buccal film (Bunavail) may be used for induction for short-acting opioids (eg, heroin) but NOT for patients dependent on long-acting opioids (eg, methadone) because of risk for abrupt withdrawal symptoms.

Buprenorphine/naloxone (Bunavail, Suboxone, Zubsolv)

Buprenorphine is a semisynthetic narcotic mixed agonist-antagonist analgesic. Naloxone is a potent antagonist at the mu opioid receptors and produces opioid withdrawal signs and symptoms in individuals physically dependent on full opioid agonists when administered parenterally.


Opioid Antagonists

Class Summary

Reverses opioid effects by inhibiting opioid agonists at receptor sites.

Naloxone (Zimhi)

Pure opioid antagonist. Used to reverse opioid intoxication.

If patients do not respond to multiple doses of naloxone, consider alternative causes of unconsciousness. Need of ongoing substance abuse treatment should be established while caring for overdose. The injectable solution is available as a generic in vials and syringes (0.4 mg/mL, 1 mg/mL) for IV/IM/SC administration. A high-dose (5 mg/0.5 mL; Zimhi) IM/SC injectable solution in a prefilled syringe is also available. In pharmacokinetic studies, a single IM dose of 5 mg provided significantly higher peak plasma concentration and AUC compared with a single 2-mg IM injection.

Naloxone intranasal (Kloxxado, Narcan Nasal Spray, RiVive)

Competitive opioid antagonist that antagonizes opioid effects by competing for the same receptor sites. The intranasal form is indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. The brand name product (ie, Narcan Nasal Spray) was the first opioid antagonist granted OTC designation in March 2023 and delivers a 4-mg dose. A second OTC product (ie, RiVive) was approved in July 2023 that delivers a 3-mg dose. A higher concentration intranasal product (ie, Kloxxado) is available by prescription that delivers 8 mg/actuation. Generics that deliver 4 mg/actuation are also prescription. 

Naltrexone (ReVia, Vivitrol)

Used in combination with clonidine for rapid (4-5 d) detoxification.

Very effective long-acting opioid antagonist that was thought to be an ideal maintenance agent because it blocks receptor sites and, hence, opioid reinforcing properties. However, clinical results are not very promising when compared with methadone maintenance. Craving may continue during naltrexone maintenance. For groups of patients such as health care professionals or business executives for whom external incentives to stay away from drugs are important, naltrexone therapy has been very effective.

Indicated for prevention of relapse to opioid dependence following opioid detoxification.


Alpha 2 adrenergic agonists

Class Summary

Used for mitigation of withdrawal symptoms to facilitate abrupt opioid discontinuation.

Lofexidine (Lucemyra)

Central alpha-2 adrenergic agonist that binds to receptors on adrenergic neurons, resulting in reduced release of norepinephrine and decreased sympathetic tone. This action suppresses autonomic-mediated signs and symptoms of withdrawal. Indicated for short-term mitigation of withdrawal symptoms to facilitate abrupt opioid discontinuation in adults.

Clonidine (Catapres)

May reduce norepinephrine release. In opioid withdrawal, seems to be most effective in suppressing autonomically mediated signs and symptoms of abstinence but less effective for subjective symptoms.

Used in higher doses for detoxification than for treating hypertension. Benzodiazepines may be beneficial as adjuvant therapy for muscle cramps and insomnia. Clonidine in combination with naltrexone, which is a potent long-acting narcotic antagonist, also is referred to as rapid detoxification. Treatment is initiated after confirmation of physical dependence by the naloxone challenge test. This drug combination is designed to shorten the time of withdrawal to 5 d.

Clonidine may also be beneficial in prolonging the duration of abstinence in patients concurrently receiving buprenorphine for maintenance therapy. Daily life stress may also be partially decoupled from opioid craving in patients receiving clonidine. However, although clonidine may prolong the time to relapse, it may not prevent it entirely. Clonidine alone and in combination has been demonstrated to be feasible in primary care settings as an outpatient treatment.