General Information

Buprenorphine, a partial opioid agonist, is a chemical derivative of thebaine. During the 1980s, Reckitt & Colman began marketing buprenorphine hydrochloride under the name Buprenex. Buprenex is primarily found in 0.324 mg/ml injectable formulations. 0.324 mg buprenorphine hydrochloride is equivalent to 0.3 mg buprenorphine. On October 7th, 2002, the DEA rescheduled the drug from Schedule V to Schedule III. A day later, the FDA approved the drug as a treatment for opiate/opioid addiction, under the brand names Suboxone and Subutex. Two street names for the buprenorphine/naloxone compound are "bupe" and "sub(s)."

Chemical Name. 17-(cyclopropylmethyl)-alpha-(1,1-dimethylethyl)-4,5-epoxy- 18,19-dihydro-3-hydroxy-6-methoxy-alpha-methyl-6,14- ethenomorphinan-7-methanol
Classification. Partial opioid agonist.
Primary Uses. Analgesia, opiate dependency treatment.
Other Names. Buprenex, Suboxone, Subutex, Temgesic.

Suboxone

- SUBOXONE sublingual tablets contain buprenorphine hydrochloride and naloxone hydrochloride dihydrate at a ratio of 4:1. These tablets contain Acesulfame K sweetener as well as a lemon/lime flavoring (2 mg buprenorphine HCl/0.5 mg naloxone HCl dihydrate or 8 mg buprenorphine HCl/2 mg naloxone HCl dihydrate).

- SUBUTEX sublingual tablets only contain buprenorphine hydrochloride (2 mg buprenorphine or 8 mg buprenorphine).

The Naloxone Myth? Many folks believe that naloxone is in Suboxone to block the effects of other opiates; however, this is untrue. The naloxone contained in Suboxone is intended to deter users from injecting it, but there are an increasing number of reports that prove otherwise. Many users claim to have injected Suboxone without precipitating rapid withdrawal. It is never safe to inject a pill which is not meant for injection. The binders and fillers contained within could lead to fatal complications. When Suboxone is administered sublingually, naloxone does not produce a significant amount of effects, though the amount in the bloodstream is measurable.

Blocking Effects. The reason it is nearly impossible to obtain effects from other opiates while taking Suboxone/Subutex is due to its higher binding affinity to opioid receptors (compared with other opiates: morphine, oxycodone, heroin, etc.) coupled with its incredibly long half-life. Buprenorphine can render other opiates unusable for three days. Sometimes this can lead to an overdose. For example, Pete takes Subutex for a few days, but then wants to get high. He waits 24 hours after his last dose of buprenorphine, then takes his regular dose of opiates, but barely feels it. Pete continues to take more and more until he takes too much. It is hard to monitor how the body is handling the mixture when it is nearly impossible to feel it.

Miracle Pill? Suboxone/Subutex is approved for short-term and long-term opioid maintenance. Some users stay on it for 21 days, while other remain on the drug for a few years. Your mileage may vary. When buprenorphine was first approved for treatment of opioid dependency, people thought of it as the "miracle pill." The fact is, when taking Suboxone or Subutex, an opioid (though only a partial opioid agonist) is still in the body, and the body and mind are still dependent on a drug. There is no easy way out, but buprenorphine can soften the fall.

See also: Suboxone vs. Methadone, Suboxone/Subutex FAQ

Pharmacology and Pharmacokinetics

Buprenorphine has a very high binding affinity to the mu-opioid receptor; however, due to the fact that it is only a partial opioid agonist, it does not produce the same "high" or "rush" of full agonists (Ex. morphine, oxycodone, heroin). These two properties must be carefully considered for two reasons. Most importantly, it complicates situations involving overdosage. For individuals dependent on full-agonist opioids, if there is not sufficient time between the last dose of the full-agonist and the dosing of buprenorphine, it can trigger withdrawal syndrome.

Buprenorphine/buprenorphine hydrochloride can be administered via intravenous or intramuscular injection, transdermal patch, or sublingual tablet. The drug is broken down into norbuprenorphine (an active metabolite) and glucuronidation. This is completed by N-dealkylation mediated by cytochrome P-450 3A4 isozyme. The average elimination half-life of buprenorphine is 37 hours.

Buprenorphine Pharmacology and Pharmacokinetics for Various Routes of Administration^{[1] [2] [3]}

Law

In the United States, buprenorphine is a Schedule III substance, making it illegal to use/possess without a prescription. Schedule III substances, such as codeine, hydrocodone (when combined w/ nonnarcotic active ingredient), and Marinol (synthetic THC), meet the following criteria according to the Controlled Substances Act:

1. The drug or other substance has a potential for abuse less than the drugs or other substances in Schedules I and II.
2. The drug or other substance has a currently accepted medical use in treatment in the United States.
3. Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence.

Side Effects

Sedation
Nausea
Vomiting
Dizziness
Headache
Constipation
Sweating
Insomnia
Urinary retention
Miosis
Confusion
Euphoria or dysphoria

Withdrawal

Buprenorphine withdrawal is generally milder than that of a full agonist, but lasts longer because of its long half-life. Total duration can be up to two weeks, with symptoms lingering for a few months thereafter. Possible symptoms are listed below:

• Depression/dysphoric mood
• Nausea and vomiting
• Muscle aches and cramps
• Insomnia
• Mild fever
• Lacrimation
• Rhinorrhea
• Sweating
• Piloerection
• Diarrhea
• Yawning
• Craving

Recommended Reading

• Buprenorphine for depression?
• Suboxone / Subutex FAQ
• Suboxone vs. Methadone
• Experiences > Treatment with Suboxone? Go for it!
• Drug Rehabilitation

Additional Reading (External Links)

• Severe opiate withdrawal in a heroin user precipitated by a massive buprenorphine dose
  "By diverting his dispensed medication, our patient collected 11 buprenorphine tablets (8 mg each), which he took in one day. The result was not respiratory depression, but instead severe opiate withdrawal lasting four days — this scenario has not previously been reported. This case highlights features of the unique pharmacology of buprenorphine and some key issues for its use in the management of heroin dependence."

Sources

[1] Mendelson J, Upton RA, Everhart ET, Jacob P 3rd, Jones RT. Bioavailability of sublingual buprenorphine. J Clin Pharmacol [Entrez PubMed]. 1997 Jan;37(1):31-7. [ link ]

[2] Brewster D, Humphrey MJ, Mcleavy MA. The systemic bioavailability of buprenorphine by various routes of administration. J Pharm Pharmacol [Entrez PubMed]. 1981 Aug;33(8):500-6. [ link ]

[3] James J. Kuhlman, Jr., Shairose Lalani, Joseph Magluilo, Jr., Barry Levine, William D. Darwin, Rolley E. Johnson, and Edward J. Cone. Human Pharmacokinetics of Intravenous, Sublingual, and Buccal Buprenorphine. Journal of Analytical Toxicology, Volume 20, Number 6, October 1996, pp. 369-378. [ link ]