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PCP: Proof We Don't Need Schedule I
Rocking it out in Schedule II for decades with no currently accepted medical use.
What drug has three letters and:
has not been used medically in humans since the 1960s; but
is in Schedule II?
PCP: A Brief History
Pharmaceutical company Parke-Davis synthesized PCP in the late 1950s and marketed the drug as a surgical anesthetic called Sernyl. Although safe and effective for that purpose, it caused “an intense, prolonged emergence delirium that ultimately made it undesirable for human use.” So, just a few years after it entered the market, it exited. Use in humans was discontinued in 1967.
PCP’s use as a wild animal anesthetic continued under brand name Sernylan. But after the 1970s PCP “epidemic” (see below), Sernylan was discontinued as well.
Because of the intolerable side effects in humans, Parke-Davis wanted a new drug, one that wouldn’t make patients as sick. It sought a drug with similar anesthetic potential but fewer side-effects and shorter action. Naturally, it looked to PCP analogs. And soon after, consultant and organic chemist Calvin Stevens stumbled upon Ketamine, a PCP analog with one-tenth the potency.
Both PCP and Ketamine are dissociatives that act as N-methyl-d-aspartate (NMDA) receptor antagonists. But unlike PCP, ketamine can rapidly produce analgesia with a limited duration of effect that can be safely used with repeated administrations.
(Interestingly, for those paying attention, early research involving Sernyl may have foreshadowed the usefulness of NMDA antagonists, such as Ketamine, in treating depression and anxiety. For example, one study noted improvement in 25 out of 32 psychiatric patients administered Sernyl with anxiety symptoms.)
Despite the fact that in 1970, PCP had no accepted medical use in humans and very limited medical use in animals, in the initial set of schedules, Congress placed PCP in Schedule III. That would soon change.
The PCP Problem
PCP first emerged as a street drug in 1960s San Francisco. But its popularity on the streets didn’t take off until the 1970s. And by the late 1970s, it became a drug of concern. PCP in the late 70s was what LSD had been in the 60s and what crack would be in the 80s. In some areas, PCP abuse ranked second only to that of marijuana.
The sharp increase in abuse caused DEA to act.
In late 1977, DEA moved PCP out of schedule III. Surprisingly, however, it did not heed the recommendation of the National Institute of Drug Abuse, which had recommended DEA put PCP in Schedule I. Despite no approved uses in humans, DEA put PCP into Schedule II. Why? The explanation of the Assistant Secretary of Health at HHS in the Federal Register is worth reproducing in full:
The Bureau of Drugs and the Bureau of Veterinary Medicine within the Food and Drug Administration have reviewed the data on phencyclidine and agree with the conclusion of the Drug Enforcement Administration that this compound and its salts should be moved to Schedule II. I concur with the scientific and medical evaluation and recommend that action be initiated to move phencyclidine and its salts from Schedule III to Schedule II of the Controlled Substances Act. A summary of the basis for the recommendation including the medical and scientific findings required under Section 201 of the Controlled Substances Act is enclosed. The National Institute of Drug Abuse has also reviewed the data and recommended that phencyclidine be placed in Schedule I to assure the most stringent controls possible. The only regulatory difference between Schedules I and II relates to the ability of licensed practitioners to use the drug in medical practice. Phencyclidine is not approved for any medical use in humans, but it is a valuable anesthetic in the veterinary care of primates. It is used in zoos and wild animal centers, and to our knowledge, diversion from legitimate users has not been a significant source of supply to the illicit market. Consequently, neither the Food and Drug Administration nor I conclude that placement of phencyclidine in Schedule I is appropriate at this time.
There are two critical items to unpack from this paragraph.
First, the bolded statement: “The only regulatory difference between Schedules I and II relates to the ability of licensed practitioners to use the drug in medical practice.” As we have repeatedly explained in this newsletter and elsewhere, Schedules I and II controls are almost entirely the same. In the AIMS case, we reproduced a chart from a 1975 article in the Drug Enforcement Administration periodical proving that point (page 16). But you don’t have to take our word—or DEA’s word. It is right there from HHS in the Federal Register. There are only two material differences between Schedule I and II: significant red-tape to engage in research and the ability of licensed practitioners to use the drug in medical practice.
Once one realizes that the difference between Schedules I and II largely amounts to whether licensed practitioners can use the drug in medical practice, one understands a great deal about the CSA and why the CSA fails today. In brief, today, the federal government uses Schedule I “no currently accepted medical use” to set federal law and prohibit states from implementing their own medical programs, such as medical marijuana programs. Absent a change in federal policy, the same will come to be true with psilocybin. It is inevitable. But when enacted in 1970, the “accepted medical use” prong of the scheduling criteria acted not as a grant of federal authority but as an important limitation: it was supposed to prevent the federal government from intruding on the ability of licensed practitioners to use the drug in accepted medical practice, which is traditionally handled at the state level.
Second, note how HHS in 1977 concluded that PCP’s use in a very discrete, limited setting – in zoos and wild animal centers – didn’t create a risk of diversion. That’s pretty sober when it comes to the War on Drugs, and it makes total sense. Zoos and wild animal centers obtaining and using PCP for a very limited purpose are CSA registrants that would be monitored by DEA. As a Schedule II drug, DEA also gets to impose quotas. It can track where that limited PCP is going. Of course there isn’t a serious diversion risk in allowing some zoos and animal centers to sporadically use PCP to anaesthetize apes.
No doubt, one could extend this same logic to other settings. For example, in AIMS, we argued that DEA could permit terminally ill patients to access psilocybin at end-of-life without a serious risk of diversion. On page 29 of its brief in AIMS, DEA argued otherwise:
Application of the CSA to restrict the use of psilocybin by patients with life-threatening conditions thus furthers the CSA’s main objectives “to conquer drug abuse and to control the legitimate and illegitimate traffic in controlled substances.”
I need not belabor the point. Somewhere in the War on Drugs, common sense got lost amidst fear and paranoia.
But lest we think that use as a “valuable anesthetic in the veterinary care of primates” as a “currently accepted medical use” was unusual, it is not. In fact, there are a couple other drugs in Schedule II that have no approved human uses, but have limited medical uses in animals. Like the exceedingly powerful fentanyl analog carfentanil used for big game control.
Shortly after DEA’s scheduling action, the two legitimate manufacturers of PCP for use in animals did not believe they could comply with the more stringent Schedule II requirements. So they voluntarily removed their products from the market.
"A Killer Drug on the Rise"
The rise in PCP use prompted additional governmental scrutiny. After rescheduling, the conversation continued.
In August 1978, Congress convened hearings entitled "PCP - A Killer Drug on the Rise" to focus national attention on the PCP problem and explore legislative solutions and the “relatively new phenomenon in drug abuse, namely, the illicit use of legitimate chemicals.”
One witness, Dr. Boerne, expressed reservations with overreacting:
I think one of the key issues with PCP is to make our response a measured one that expresses appropriate concern, without overreacting and developing hysteria about it and without doing anything that would draw undue publicity to the drug and thus increase its use.
I think our well-intentioned efforts in the past with regard to some other drugs, such as LSD, have in fact ended up causing the drug to be used more widely than it would have been had the publicity and concern by the Federal Government not been so great.
He then explained the “price” of rescheduling:
You also pay a price when you reschedule drugs. Although it is limited, PCP does have a legitimate use. It is used as an animal tranquilizer by veterinarians. Apparently it is very effective. I think that we do not want to go so far in our concern to restrict the elicit use of PCP that we place an intolerable burden on veterinarians who are using it legitimately.
At the same time, one of the precursors, piperidine, has very widespread medical use. Again, we do not want to put an inordinate burden on manufacturers or physicians who are using other drugs derived from these precursors for legitim ate medical purposes. I think we have to balance the burden that we impose on manufacturers and on the medical community against the risk from PCP itself.
If they are for legitimate medical purposes, then you have a doctor or a member of the medical profession who is able to get the drugs. So it seems to me that it could be fairly easily controlled by the standard medical procedure for dispensing prescriptions.
Boerne then explained his opposition to pending legislation:
Some of the drugs derived from these precursors have very legitimate medical uses, and we don’t in any way want to infringe on the right of the American people to get adequate medical care. I have some concern about just passing laws in the drug area, merely for the sake of passing laws. I think if we can’t have some confidence that this legislation is going to have some significant impact on the PCP problem, then there is no point in passing the legislation.
Meanwhile, in the executive branch, the government convened an interdepartmental initiative to address the increasing abuse of PCP. Members of the initiative included NIDA, DEA, FDA, and the National Institute for Mental Health, all under the auspices of the White House Office of Drug Abuse Policy. The agencies engaged in a number of health initiatives, including publishing reports on the dangers of PCP. DEA set up a “Special Action Office” on June 1, 1978 with “program goals” such as meeting targets for PCP-related arrests and laboratory raids.
The agencies also coordinated to identify, prepare, and test PCP analogs for scheduling. They attempted to “anticipate” traffickers’ illicit activities by synthesizing PCP analogs to show that several of the closely-related chemicals all possessed PCP-like activity to support a case to “generically schedule all chemically related substances.”
Interestingly, “[i]n view of the lack of an approved NDA and consequently ‘no current medical use in treatment in the U.S.’, FDA, DEA, and NIDA considere[d] the appropriateness and feasibility of rescheduling PCP to Schedule I.” But that never happened. On November 10, 1978, the President signed a law that enhanced criminal penalties for PCP. But PCP remains on Schedule II to this very day.
The PCP arc teaches several important lessons deeply relevant to today’s drug policy conversation. And these lessons can provide reformers some ammunition to critique the current system and combat common talking points.
First, a familiar refrain: the DEA and federal government generally have more flexibility and discretion in scheduling and rescheduling drugs than they let on. The CSA may seem inflexible—and they may say it is inflexible—but when you look at the law and study it, it has some play with the joints. The law isn’t inflexible; government officials are.
Second, note how DEA put PCP into Schedule II in 1978. Following that Schedule II placement, PCP use rates leveled off at the end of the 1970s and into in the early 1980s and declined. And then once the crack epidemic hit—but with no rescheduling or relevant changes to legislation—PCP use declined quite rapidly into the late 1980s. As a Schedule II drug.
From a legal standpoint and supply/demand, this makes sense. DEA has all the same regulatory controls under Schedule II as Schedule I. One cannot point to anything material about Schedule I that decreases diversion any more than a Schedule II classification. The reason Adderall (Schedule II) is more available than Schedule I drugs has nothing to do with it being a Schedule I drug, but the fact that millions of Adderall is made and circulates as prescription medicine. In contrast, nobody makes PCP as a Schedule II drug.
In short—we don’t need and never have needed a Schedule I regulatory classification to combat abuse and diversion. PCP helps prove the point.
Indeed, every single drug in Schedule I could be moved to Schedule II and almost nothing would change. Drugs with legitimate medical uses (like Adderall) would be available; drugs without medical uses (like PCP) would not. Two things change: (1) research gets easier and (2) DEA, a law enforcement agency, doesn’t get to decide whether and when drugs have “accepted medical uses.”
Abolishing Schedule I may seem radical. But it is an supremely elegant fix that could set right the very worst aspects of the CSA and does next to nothing to increase abuse and diversion.
Third, PCP-in-Schedule-II underscores a prominent absurdity in modern drug law. Marijuana is used medicinally in around 75% of the country and 91% of voting adults support medical marijuana use. That drug, however, has “no currently accepted medical use in treatment in the United States,” due to an unlawful convoluted pharmaceutical-oriented test. A drug that hasn’t been legally administered in humans since the 1960s is more available from a regulatory standpoint than marijuana. If I were at an oversight hearing trying to make a point, I’d be talking about PCP.
Fourth, and importantly, the PCP story provides valuable lessons into drug development. Because of its undesirable side-effects, PCP never turned out to be much of anything in medicine. But a small tweak to the phencyclidine molecule eliminated the worst effects, maintained nearly all of medical utility, and produced a powerhouse: ketamine. The discovery of ketamine occurred in 1962, before drug control laws—and schedule I—made this type of research and experimentation far more difficult.
The next generation’s miracle medicines could be one molecule away from existing Schedule I drugs, with research on them held back by bad policy and draconian, unjustifiable regulation.
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