Drugs have been a contentious issue since humanity’s first use of them. Some of the earliest documentation of this is seen in the Bible, which warns against the effects of ethanol, the chief drug in alcoholic beverages. Now it seems that the number of debates has exploded exponentially, with the most popular fights being over performance enhancers and marijuana use. While the data in these cases is often incomplete, little-known controversies have arisen over two drugs – Plan B and buprenorphine – in which the available science is robust. Plan B On December 16, 2003, a meeting was conducted by the Nonprescription Drugs Advisory Committee (NDAC) in a joint session with the Advisory Committee for Reproductive Health Drugs (ACRHD). [9,15] NDAC and ACRHD, both advisory panels for the United States Food and Drug Administration (FDA), were stocked with pharmacists, physicians, and scientists in order to expertly guide the FDA’s Center for Drug Evaluation and Research on the topic of Plan B, an emergency contraceptive available through prescription since July of 1999. [9,15] The final vote: 23 to 4. The conclusion: Plan B should be available over-the-counter. [9,15] In a single stunning, unprecedented move in May of 2004, the Food and Drug Administration overruled the findings of its advisory committee, citing a lack of information on Plan B’s safety. [9] Interestingly, the joint session actually found that there was more than enough evidence proving the safety of Plan B [9]; one committee member even went so far as to declare that it was the “safest product that we have seen brought before us.” [15] What happened? Plan B is an emergency oral contraceptive; in other words, it is meant to be used to prevent pregnancy within 72 hours of unprotected sexual intercourse. [1,7,9] The regimen is simple, utilizing two pills taken 12 hours apart. The sole active ingredient is the drug levonorgestrel, which is essentially a synthetic progesterone that mostly acts by preventing ovulation. [2,7] Without ovulation, there can be no fetus, and because Plan B acts before pregnancy, its use is not considered an act of abortion. The FDA’s Durham-Humphrey Drug Amendment Act of 1951 clearly states that all medicines that are not “dangerous, addictive, or complex to use” should be attainable over-the-counter. [9,15] Plan B fits these parameters snugly. [9] The safety evidence accumulated by the joint committee could be summed up into several major points: the drug is nontoxic and safer than most over-the-counter medications; it has no effect on an already pregnant woman or her fetus; it is easy to use and administer; and no deaths, suicides, or serious incidents have occurred as a result of overdose. [3,9]

The contentions of the anti-emergency contraceptive advocates do have some ground, though they generally constitute the minority of mainstream scientific literature. Dr. David Hager, an advisor on the ACRHD panel, claimed that there was a distinct lack of information about the effect of Plan B on adolescents, and he had a point. [15] After considering this for some time, the majority of the two committees’ members felt that age was not an issue, citing physiological reasons; Plan B should act on a young girl the same as it would on an adult woman due to the high degree of similarity between their sexual biology. [15] Dr. Leslie Clapp, of the NDAC panel, pointed out that “morbidity and mortality associated with teen pregnancies is quite high,” [15] and blocking the availability of the drug would only exacerbate this. [3,15] For the most part, scientific information is not lacking on Plan B. However, long-term studies have not yet come to fruition, and demographic information is only slowly developing that could increase the beneficial use of the drug. [1,8,11] For proponents of emergency contraceptives, they will be pleased to know that the drug is available over the counter now due to pressure generated in part by women’s rights organizations. Buprenorphine Few compounds have been found to be as clinically useful in the treatment of opioid addiction as buprenorphine. Because it is structurally and functionally similar to morphine, it can be called a “narcotic” or “opiate.” [2] It is sold by several pharmaceutical manufacturers under a variety of names. For several decades it has been available for use in analgesia, and beginning in 1996, was approved for its current role in the treatment of opioid addiction. [4] Buprenorphine may be a narcotic, but it has properties distinctly different from that of morphine and similar opiates. It is 25 to 40 times more potent as an analgesic than narcotics (like morphine, codeine, Vicodin, or Oxycodone) which means that far less buprenorphine is necessary to illicit the same effects. [7,17] These effects include analgesia and euphoria – an important factor in addiction. They make people feel good. Likewise, buprenorphine feels good too – to a point. [17] After a certain large amount, the more buprenorphine someone uses, typically the worse they should feel. [7,17] Narcotics tend to have a negative side-effect that only worsens with increasing dose: respiratory depression. At high doses, people’s breathing slows and may stop altogether (respiratory arrest.) The risk of respiratory depression with buprenorphine is significantly removed because buprenorphine acts partially to prevent it. [7]

In terms of withdrawal, buprenorphine tends to have symptoms similar to but much less serious than morphine and other narcotics. [7] Therefore, it has a remarkably lower abuse potential, which means that it is also more difficult to overdose on. In contrast, other opioidaddiction treatments, like methadone and fentanyl, are highly addictive and the mortality associated with these can be quite high. [17] This is especially grave because these medicines are meant to treat people already addicted to opiates and who may require higher doses to achieve their high. [4] Drugs can be organized into “schedules” according to several attributes, summarized in Table 1. The schedules, and their criteria, are defined in the United States’ Controlled Substances Act and (with some differences) in the United Nations’ Psychotropic Substance Convention. In the face of heavy scientific opposition, recent attempts have been made to reclassify buprenorphine (a Schedule III since 1989) as a Schedule II drug in the United States and abroad. [4-6] The rescheduling of a drug is of no minor consequence, since the higher up the scale it goes, the less available it becomes. [4] Many countries abide by the international laws set forth by the 1961 Single Convention on Narcotic Drugs and the 1971 Psychotropic Substance Convention, so signatory countries would be forced to comply should the United Nations change buprenorphine’s status. [4,12,13] Throughout the world, the abundance of buprenorphine can be attributed to its existence as a Schedule III drug, which makes it far more available than other opioidaddiction treatments such as methadone and fentanyl (both schedule II) that can be used only in specialized care centers. [4,5] This large presence over the past several decades has resulted in a large repertoire of scientific information. Studies in France concluded that buprenorphine can be credited with significantly reducing heroine overdose mortality, since 90% of opioid replacement therapy in that country is done with the drug. [4] By contrast, mortality associated with methadone, another opioid-addiction treatment, was substantially higher. Overall, the French documented a “dramatic, positive impact” [4] as a result of buprenorphine’s high availability. Many other studies support the notion that the benefits of buprenorphine vastly outweigh the risks. [5,10,17] Should buprenorphine be rescheduled, its availability would decrease because the laws governing Schedule II substances are far more stringent than Schedule III. [4,12,13,16] People who could once obtain the drug from their doctor would suddenly find themselves in a stigmatized treatment center. [4,5]

Developing nations that lack the infrastructure to accommodate the new regulations would find themselves without any significant drug therapy; India, with a high number of heroine addicts, would be without any sort treatment at all. [4] Heroine-related mortality would probably increase considerably, as would the prevalence of diseases like HIV. [4] Opponents or buprenorphine cite its prevalence as a street drug, called “poor man’s heroin,” in countries like Finland, Scotland, and Spain. [6] Purportedly, it has even become a cheap alternative to heroin in India. [6] Whether this is because of the drug’s availability or as a result of poor medicinal regulations is still unknown (in Norway, patients were getting away with multiple prescriptions.) [6] Still, one study in the United States has shown that abuse is extremely low even in places where the potential is quite high. [10] For the time being, buprenorphine continues to exist as a Schedule III drug. What should be done about all of this? Unfortunately, that can only be answered by personal convictions. In the case of Plan B, the issue is one of science versus morality. Scientifically, the answer is very clear, but the answer is morally complicated since no one can agree on what constitutes rightfulness. What is right? What is moral? If anything, hopefully the precedent of Plan B will serve as a reminder to those planning the future policies of buprenorphine. Ultimately, the controversies over these two drugs should show one thing: strong science should not be ignored.

Scott Barraza is a student at Arizona State University.

References:
[1] ACOG Practice Bulletin. “Emergency Oral Contraception.” International Journal of Gynecology and Obstetrics. 78 (2002): 191-98.
[2] Block, John H., and Beale M. John, eds. Organic Medicinal and Pharmaceutical Chemistry. 11th ed. USA: Lippincott Williams and Wilkins, 2004.
[3] Committee on Adolescence. “Emergency Contraception.” Pediatrics. 116 (2004): 1026-035.
[4] Costa e Silva, J. A. “Medicines and the Drug Control Treaties: Is Buprenorphine For Opioid Addiction At Risk of Being Lost?” Human Psychopharmacology: Clinical and Experimental. 19 (2004): 215-24.
[5] Fiellin, David A., Herbert Kleber, and Et al. “Consensus Statement on the Office- Based Treatment of Opioid Dependence Using Buprenorphine.” Journal of Substance Abuse Treatment. 27 (2004): 153-59.
[6] Fox, David M. Hogan and Hartson LLP. “Docket No. 01P-0560 (CP/1).” Letter to FDA. 10 Apr. 2002. Columbia Square, Washington DC.
[7] Hardman, Joel G., and Lee E. Limbird, eds. The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill, 2001.
[8] Merchant, Roland C, Jennifer A. Damergis, and Et al. “Contraceptive Usage, Knowledge, and Correlates of Usage Among Female Emergency Department Patients.” Contraception. 74 (2006): 201-07.
[9] Ranney, Megan L., Erin M. Gee, and Roland C. Merchant. “Nonprescription Availability of Emergency Contraception in the United States.” Annals of Emergency Medicine. 47 (2006): 461-471.
[10] Smith, Meredith Y., J ELise Bailey, and Et al. “Abuse of Buprenorphine in the United States.” Journal of Addictive Diseases. 26 (2007): 107-11.
[11] Thomas, J. “Emergency Department Patients May Need Contraceptive Outreach.” Perspective on Sexual and Reproductive Health. 39 (2007): 63-64.
[12] United Nations. Single Convention on Narcotic Drugs. 1961.
[13] United Nations. Convention on Psychotropic Substances. 1971.
[14] United States of America. Food and Drug Administration. Center for Drug Evaluation and Research. NDAC in joint session with ACRHD. “Final Questions to the Committee.”
[15] United States of America. Food and Drug Administration. Center for Drug Evaluation and Research. NDAC in joint session with ACRHD. “Minutes from Tuesday, December 16, 2003.”
[16] United States of America. Food and Drug Administration. “Controlled Substances Act.”
[17] Yassen, Ashraf, Erik Olofsen, and Et al. “Pharmacokinetic-Pharmacodynamic Modeling of the Effectiveness and Safety of Buprenorphine and Fentanyl in Rats.” Pharmaceutical Research. 25 (2008): 183-93.
[18] http://www.istockphoto.com