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While film director Roman Polanski fights extradition to the United States, time is taken here to remember Quaalude—the drug that a 43-year-old Polanski allegedly gave to a 13-year-old girl before he had sex with her in 1977.*

Quaalude is the trade name for methaqualone, a chemical developed in the 1950s in India as an antimalarial compound. Contemporaneous data also indicated that the drug provided "good hypnotic activity" and had "low toxicity" when compared with widely used barbiturate sedatives. Consequently, during the 1960s, the drug became a popular prescription alternative to potentially addictive agents like secobarbital (Seconal; Eli Lilly) for the treatment of insomnia.

In the United States, the drug was first sold by Pennsylvania-based William H. Rorer, Inc, which applied the trademark Quaalude to its tablets in 1965. The company incorporated the double-a into the brand name as a way of capitalizing on the success of its antiacid product, Maalox (which is now owned by Novartis Consumer Health). The recommended therapeutic dosage for Quaalude was 150 or 300 mg.

Reports of physiologic addiction to and overdose of methaqualone were published repeatedly in the medical literature, beginning in the late 1960s (for example, here and here). Among Americans, abuse of Quaalude exploded during the 1970s, especially among young adults and teens—who often combined the drug with alcohol for a really soporific buzz. The activity was known as "luding out." The drug also gained a word-of-mouth reputation as an aphrodisiac and enhancer of sexual pleasure (eg, "The Love Drug" or "Heroin for Lovers"); although these effects were overstated, if not outrightly made up. As one young user described her Quaalude experience to the Washington Post in 1978: "I fell asleep."

With the rise of its legitimate and recreational popularity, the unpatented methaqualone was also legally manufactured in the United States by Anar-Stone Laboratories, which called its capsule Sopor (in 75-, 150-, and 300-mg doses). Other American manufacturers of methaqualone compounds included Parke-Davis (Parest) and Wallace (Optimil).

A 1972 Chicago Tribune report ("A Sedative Gains in Drug Culture") indicated that the street cost of methaqualone was 25 or 50 cents per pill. Slang names for the drug included "Rorers" and "seven-fourteens." These terms were derived from the stamp on the branded Quaalude tablet, "Rorer 714." In her grand jury testimony, Polanski's 13-year-old victim reported that the director gave her part of a tablet (dose unknown) that had "Rorer 714" on it.**

According to a 2006 "Frontline" report, high methaqualone demand in the United States was supplied not only by drug firms, but through rogue domestic labs and counterfeit South American operations. In 1981, recreational use of methaqualone was so widespread that it ranked second to marijuana in popularity. The DEA estimated that 80%-90% of the world's methaqualone production was diverted to the illegal drug business. (The DoJ cites the emergence of "stress clinics" in New York, New Jersey, and Florida—essentially B&M equivalents of today's dubious online pharmacies—for the boost of methaqualone abuse in the early 1980s.) 

"Frontline" credits the DEA's Gene Haislip with shutting down the illicit methaqualone business in the United States. Haislip successfully convinced foreign manufacturers of the methaqualone powder and their resident countries to stop production. And without the powder, South American producers, like those in Colombia, could no longer pound out pills for export. Simultaneously US physicians began prescribing other hypnotics as sleep aids, and law enforcement shut down the stress clinics. Then in 1984, federal legislation banned the domestic production and sale of methaqualone; in other words, the compound was designated a Schedule I drug.

South Africa is the current hotbed of methaqualone abuse. There the drug is consumed in the form of Mandrax (which combines 250 mg of methaqualone with 25 mg of diphenhydramine). The tablet is typically crushed and snorted or smoked with cannibis.

* Polanski also allegedly plied the girl with champagne. For relevant court records, including Polanski's contemporaneous guilty plea to having sex with a minor, start at thesmokinggun.com.

** Rorer 714 t-shirts were a popular counterculture item.

Image of methaqualone pills attributed to Indiana Prevention Resource Center.

Not sure which is more shocking: The report that at least 20 non-OTC drugs were recovered from Michael Jackson's home or the fact that ABC News is sourcing The Sun on this one. Maybe ABC's reporters were impressed by alleged autopsy information printed last week by the tabloid—namely that Jackson's arms were riddled with needle marks. Yesterday ABC reported the same ("Jackson's arms were scarred with track marks"), citing "investigators."

On the basis of reportage from ABC and The Sun, the partial, cobbled-together list of drugs (save propofol [Diprivan]) found in Jackson's home includes the following (in alphabetical order):

1. Demerol: Generic names, meperidine and pethidine. A fast-acting opioid available in injectable and oral formulations. Legitimate use has become unpopular during the last 2 decades, owing to the drug's potential neurotoxicity and abuse potential. Jackson allegedly took Demerol daily and possibly several times a day.
2. Dilaudid: Generic name, hydromorphone. A morphine derivative available in injectable and oral formulations. Typically used for pain management.
3. Fentanyl: A highly potent synthetic opioid available in injectable, transdermal patch, and "lollipop" formulations. Typically used in anesthesia induction and pain management.
4. Lidocaine: Presumably in the form of low-concentration vials to produce local anesthesia. Possibly used in conjunction with propofol to reduce injection-associated pain.
5. Methadone: A synthetic oral opioid. Most commonly used as a maintenance medication when kicking opioid addiction.
6. OxyContin: Generic name, oxycodone. A wildly popular, semi-synthetic oral opioid. Jackson allegedly took the medication daily.
7. Paxil: Generic name, paroxetine. An orally administered, selective serotonin-reuptake inhibitor (SSRI). Indicated for the treatment of depression, OCD, panic disorder, anxiety disorders, and PTSD.
8. Percocet: Generic ingredients, oxycodone (same as OxyContin) and acetaminophen (eg, Tylenol). Typically prescribed short term for pain relief.
9. Soma: Generic name, carisoprodol (a metabolite of meprobamate, aka Miltown). An orally administered, centrally acting muscle relaxant that potentiates opioid-induced analgesia.
10. Versed: Generic name, midazolam. A very-short-acting benzodiazepine in oral and injectable formulations. Typically used as a premedication before surgical or medical procedures.
11. Vicodin: Generic ingredients, hydrocodone and acetaminophen. Orally administered and should be prescribed short term for pain relief. (N.B.—I've witnessed physicians dispense this drug like Pez candy.)
12. Xanax: Generic name, alprazolam. An orally administered, short-acting benzodiazepine. Prescribed for anxiety and/or sedation.
13. Zoloft: Generic name, sertraline. An orally administered SSRI. Indicated for the treatment of depression, OCD, panic disorder, anxiety disorder, PTSD, and premenstrual dysphoric disorder (which Jackson presumably did not have).

There are a number of permutations for lethal combinations of these drugs, some of which can kill all by themselves. Perhaps more surprising than Jackson's death is his survival—given the duration of his alleged polypharmacy use and dependence.

OCD = obsessive-compulsive disorder; OTC = over the counter; PTSD = posttraumatic stress disorder.

Props must be given to TMZ. Multiple news sources have been citing the entertainment news-gossip web site in the widespread coverage of Michael Jackson's suspect death.

The latest: Edward Chernoff, criminal defense lawyer for Conrad Murray (Michael Jackson's doctor), won't confirm or deny that Murray gave Jackson propofol (trade name, Diprivan). In a phone interview last night, Chernoff reportedly told TMZ, "I have no statement on whether the Dr. prescribed or administered Propofol." Although the lawyer was apparently willing to repeat that Murray did not administer Demerol or OxyContin to Jackson.

In its update, TMZ implies that Chernoff is now backtracking somewhat on last night's statements and "can't speak for anything that was in the [Jackson] home."

Image of Diprivan formulations from APP.

Sources are now implicating propofol (Diprivan; sanofi-aventis) in Michael Jackson's death. TMZ reports that police recovered the anesthesia inducer at Jackson's rented home. And ABC News interviewed Jackson's nutritionist, Cherilyn Lee, who stated that the singer asked her for Diprivan, by trade name, 3 months ago. Jackson's alleged intention, bizarre as it may sound, was to be put to sleep at home under the guidance of an anesthesiologist.

In use for more than 2 decades, Diprivan is a rapidly acting (within 40 seconds) IV sedative-hypnotic that is FDA approved for the induction and maintenance of anesthesia and for sedation in an intensive care unit (in both cases, patients are mechanically ventilated). According to the prescribing information, the induction dosage for ICU sedation begins at 5 microg/kg/min and should be titrated (by increments of 5-10 microg/kg/min) to the desired clinical effect. Maintenance rates are generally 5-50 microg/kg/min or higher for adults.*

For anesthesia induction, the typical dosage is 40 mg every 10 seconds in healthy adults younger than 55 years of age; maintenance of anesthesia can be achieved by intermittent boluses of 20-50 mg. However, slow infusion or injection techniques are recommended to avoid apnea and hypotension. Diprivan dosages should be reduced in patients who have received large doses of narcotics.

Common adverse events with Diprivan use include bradycardia or other arrhythmias, hypotension, and apnea. Burning pain or stinging at the injection site, which is also common, may be reduced by preinjecting the vein with a 1% lidocaine solution (1 mL).

Subanesthetic doses of Diprivan may have the potential for abuse by inducing euphoria. Diprivan's abuse potential is particularly high among physicians who have access to the drug—namely, anesthesiologists. An e-mail survey in 2007 indicated that Diprivan abuse has increased substantially in academic anesthesia departments during the last 10 years. Among the 25 reported abusers in the survey, 16 (64%) were resident physicians. Seven (28%) abusers died; 6 of the deceased were resident physicians. In academic centers where abuse occurred, none had established pharmacy protocols to account for the drug (as is done routinely with opiate medications).

In 2008, an anesthesia nurse was convicted of killing a University of Florida student, with whom he was infatuated, by injecting her with propofol in her home. The victim's propofol blood level was 4.3 microg/mL. The expected propofol concentration after a bolus induction dose of 2.5 mg/kg (175 mg for a 70-kg man) is 1.3-6.8 microg/mL.

If a vial or vials of Diprivan were indeed recovered from Jackson's home, it seems almost certain that the medication was palmed by someone who had access, rather than formally prescribed.

Addendum: It also appears that Diprivan can be purchased through online pharmacies. For instance, drugdelivery.ca offers a 50-mL prefilled syringe for $122.99 USD. The completion of a patient questionnaire is necessary (along with payment); it is not clear that a valid prescription is required.

* So for a 70-kg man (~154 lbs), 0.35 mg/min would be administered for induction, and the maintenance dosage ranges from 0.35 to 3.5 mg/min. Vials of Diprivan contain 10 mg/mL and come in 20-, 50-, and 100-mL vials.

Image of Diprivan formulations from APP.

07/04/09 update: Yesterday the AP, citing an anonymous law enforcement official, confirmed that Diprivan was found in Jackson's rented home. CNN also reported that Neil Ratner, an anesthesiologist, traveled with Jackson during his HIStory tour in the mid-90s. Ratner's NY medical license was suspended in 2002 after being convicted of insurance fraud.

D'oh! Just when you thought you dodged an IOC bullet, the overseer of the Olympic Games announced yesterday that it will further analyze blood and urine samples collected from athletes at this summer's Beijing games. First on the retroactive testing list is Roche's long-acting red-cell booster Mircera.* But the IOC also warns that it will store the Beijing samples for 8 years to enable additional analyses when new drug tests become available.

In Beijing, 4770 doping tests were conducted on blood or urine, covering the period from July 27th to August 24th. But only 6 out of approximately 11,000 athletes suffered sanctions as a result of positive tests, an unexpected, low number (Table). Therefore the IOC will retest samples with a recently validated assay for Mircera. The announcement comes on the heels of news this week that 3 more Tour de France racers tested positively for the substance.

Disqualified Athlete		Country	Sport	Highest Placement	Detected Substance
1	Lyudmila Blonska	Ukraine	Heptathlon	2nd	methyltestosterone
2	Igor Razoronov	Ukraine	Weightlifting	6th	nandrolone
3	Fani Halkia	Greece	Hurdles	—	methyltrienolone
4	Jong Su Kim	North Korea	Shooting	2nd	propanolol
5	Isabel Moreno	Spain	Cycling	—	Epo
6	Thi Ngan Thuong Do	Vietnam	Gymnastics	15th	furosemide

(IOC decisions regarding 3 other alleged Olympic doping cases, Belarussian hammer throwers Vadim Devyatovskiy and Ivan Tiskhan [testosterone] and Polish kayaker Adam Seroczynski [clenbuterol], are pending.)

* A pegylated version of recombinant erythropoietin.

Image of a freakishly bulked-up Lyudmila Blonska from Wikipedia.

A rise in the use of crack by older veterans was reported yesterday by South Carolina psychiatrist Diana Thorne at the ongoing annual meeting of the American Psychiatric Association in Washington, DC. MedPage Today covered the presentation, in which Thorne reported data for 114 men and 3 women, all of whom are older than 50 years and addicted to the rock form of cocaine. She called the group, whose aging members may spend a 20-spot for a couple of rocks to smoke under the broadleaf trees in the southern state's capital, "the old man's crack club."

Most of the addicts also abuse alcohol, still the number-one substance of abuse among her patient cohort; but Thorne has seen crack cocaine supplant marijuana as the second most-preferred drug among the veterans (most of whom served in Vietnam) during the last several years. For 17 of her patients, crack was a first-time experience after the age of 50.

Photo of crack pipe from iStockPhoto.