High Times, July 1994, pp. 18-21 Marinol: The Little Synthetic That Couldn't After dogs on Nabilone started having convulsions and dropping dead, the first attempts at producing synthetic THC were scrapped. Enter Marinol, a drug never intended for human use and one with many dangerous side effects. By Elsa Scott Sam Skipper is a handsome man with black hair, blue eyes and a theatrical style that is well known in La Mesa, California. But in 1991, two years after the freelance gardener was diagnosed with HIV, his famous energy began to wane. "From August to December, I lost nineteen pounds," says Skipper. "When I went to the doctor, he said, `It's obvious you're suffering from wasting syndrome.'" Wasting syndrome, or anorexia-cachexia, afflicts 70 to 90 percent of AIDS patients, robbing them of their appetite. The resulting malnutrition can be more deadly than the virus itself. But there is only one drug that is commonly prescribed for the treatment of wasting syndrome: Marinol, the synthetic form of THC, the most psychoactive component of marijuana. When Skipper tried a friend's Marinol, it passed through him without any effect. "But marijuana is wonderful," says Skipper. "It relaxes me, it takes away my pain. It makes me hungry and thirsty, so I eat and drink more, and that builds up my immune system." After watching his lover suffer through AZT treatment, Skipper refused synthetic medication altogether. "I took it on myself to eat," he says - with the help of some homegrown sinsemilla. He liked to eat the buds fresh, or blend them into "peanut-butter balls" for breakfast, or cook them down into what he calls "cannabis tar." "You take a little bit of that on your finger and chase it with milk," he says. The pot made Skipper hungry, and he started to gain back his weight. Blood tests taken last fall show that he has a high T-cell count (1210, which is 400 above normal), and also carries the antibodies to Hepatitis A, B, and C. "My immune system functions quite well," he declares. At 164 pounds, he feels fat. But the US government isn't interested in Skipper's weight gain - only his criminality. In the spring of 1993, a local narcotics task force raided his home twice, seizing crops of about 40 plants each. He was charged with possession and cultivation, and went to trial in San Diego Superior Court last October. In a landmark decision, the jury accepted his medical-necessity defense. Skipper was free until January, when the judge threw him in jail for violating an earlier probation. There he was knifed and lost eight pounds before his release on March 3. His case is now on appeal. After one look at this man, the San Diego jury understood something the US government cannot bring itself to admit: that it is more important to help AIDS patients eat than it is to punish them for smoking marijuana. Today, millions of Americans suffer from medical conditions that can be alleviated by marijuana. Doctors have witnessed that smoking marijuana, among other things, promotes weight gain for AIDS patients and reduces vomiting for cancer patients undergoing chemotherapy. But for cancer and AIDS patients, the US government has one answer: Marinol, or THC in a gel cap. Marinol has been approved by the FDA as a treatment for nausea and wasting syndrome, and the government claims it is superior to the "crude drug" marijuana. But the ban on marijuana isn't really driven by concerns over public health. Instead, it serves the interests of business and pharmacology. Unlike marijuana, which can be grown cheaply by the masses, Marinol is produced by pharmaceutical companies that manufacture and distribute it for profit. And unlike hemp seeds, which reproduce in the presence of light, water and a green thumb, Marinol is hatched in a lab, the product of chemicals and machines. The story begins in 1985, when Unimed, now located in Buffalo, IL, bought the patent for Marinol from the National Cancer Institute. In order to produce the artificial cannabinoid THC, Unimed purchases a raw material known as termpene olivitol from Hoffmann-LaRoche, and sends it to a laboratory in Southern California. There, the crude oil is treated by a process known as liquid chromatography. If you push enough termpene olivitol through a silica gel column, you get 99 percent THC. Another lab takes that THC and mixes it with sesame oil, then seals it in gel caps, in doses of 2.5, 5 and 10 milligrams. These caps are shipped to Roxane Laboratories in Columbus, Ohio, where they are packaged and distributed to your local drug store. A month's prescription costs between $150 and $180. The only problem is that the pill, which looks like a vitamin cap, isn't all that popular in the sick wards. There are three main objections. First, vomiting patients have trouble swallowing a pill. Then, if a patient does swallow the pill, the good effects don't kick in for hours. And when the pill finally starts to work - buckle up. "A 2.5 milligram Marinol pill absolutely knocked me out," reports one man with AIDS. "I wound up lying on the sofa for days, just totally drugged and unproductive." Marinol has unpleasant side effects - as can be expected from a pill that is 99 percent THC. An April 1986 product insert from Roxane warned that Marinol elicits "disturbing psychiatric symptoms," and that even patients on low doses might experience "a full-blown picture of psychosis." The latter phrase has disappeared from recent product inserts, but experts say nothing has changed. "It's way too psychoactive," says Robert Randall, the glaucoma patient who was the first American to obtain marijuana legally from the government. "When I took Marinol, I found it anxiety-provoking and intense, like I had wandered into a short story by Flannery O'Connor." Marinol - "I wound up lying on the sofa for

days, just totally drugged and unproductive." In 1992, Randall traveled around the country. "I talked to hundreds of AIDS patients," he says, "and only one preferred Marinol to marijuana." It's not just that marijuana helps them gain weight - it's that Marinol is so scary. "A lot of guys start crying spontaneously when they're on THC," says Randall. "Then there's the girl who took Marinol, looked at her mother and saw the angel of death." Randall snorts. "How unpleasant would that be if you were sitting in a hospital, dying?" It's not unusual for AIDS patients who start smoking marijuana to gain 20 or 30 pounds. And many of them told Randall that Marinol didn't even make them hungry. Randall's informal poll is backed up by Dr. Robert Gorter of San Francisco, who has studied AIDS patients extensively. Writing in the journal of the Physicians Association for AIDS Care in 1992, Gorter stated, "Again and again patients have testified that they preferred marijuana above dronabinol [the scientific name for Marinol] for its appetite-stimulating effect." Naturally, Roxane Labs has done studies that prove Marinol is effective as an appetite stimulant. "We went to a lot of trouble," says Dr. Kirk Shepard, Roxane's director of medical affairs. "It's very difficult to do clinical trials for patients who are very ill. But we did properly controlled, randomized studies over the past few years and have proved that, statistically, there was a benefit for the majority of patients." Dr. Shepard is willing to admit that marijuana can be an effective treatment for cancer and glaucoma. "With chemotherapy, I would say yes, there are some studies that show that marijuana is effective," he says. But for AIDS patients with a loss of appetite, he says, "there's just no data" to show that marijuana can be safe and effective. Most doctors leave it to the patients to decide whether or not a drug works. But the DEA doesn't trust patients' judgment. In the government's 1992 decision to ban medical marijuana, a DEA administrator wrote, "Sick people are not objective, scientific observers, especially when it comes to their own health." The decision was backed by Robert Bonner, the head of the Public Health Service under George Bush, who declared, "There is not a shred of evidence that smoking marijuana assists a person with AIDS." Some advocates of medical marijuana believe the best strategy for getting marijuana to AIDS patients is to conduct studies that will definitively prove its effectiveness. Randall scoffs at the need for such studies. Recalling the late Kenny and Barbra Jenks, the Florida AIDS patients who received legal government marijuana, he says, "What's to prove? Two people have AIDS. They smoke pot, they gain weight. End of story." Advocates of clinical trials say the US government should supply the natural marijuana - and it's not as if Uncle Sam doesn't know how. Since 1969, a team of white coats has been cultivating the flowering tops of female cannabis plants in Oxford, MS. The notorious "pot farm," hidden on five acres of bottomland, is funded by the National Institute on Drug Abuse (NIDA) and run by the University of Mississippi. It continues to produce a limited quantity of low-grade marijuana each year. After the plants are analyzed for THC content, they're shipped in barrels to the Research Triangle Institute in North Carolina, where the dried leaves are rolled at a cost of $2 per joint. The joints are stored and frozen, pending delivery. Back in the 1970s, these machine-rolled cigarettes were considered the best way to give THC to cancer patients who needed it. But there was concern about whether it was advisable from a political point of view. On May 9, 1978, a group of doctors met at the National Cancer Institute to discuss whether the THC cigarette merited further study. At the time, there was a THC pill available for research, but no pill had passed the tests needed for FDA approval. According to minutes of the NCI meeting, Dr. Monroe Wall of the Research Triangle Institute said that his THC cigarette "is now highly standardized and is a reliable and reproducible method of administering the drug." Several doctors at the meeting noted that absorption of the THC pill was "erratic" and "unpredictable," They agreed that "all in all, the cigarette may be the best means of administering the drug." Meanwhile, the news was spreading that marijuana could provide relief for cancer patients. In 1978, New Mexico passed the first state law recognizing the medical value of marijuana. Over the next few years, more than 30 states passed similar legislation. "By the summer of 1980," says Bob Randall, "there was building pressure on the federal government to provide marijuana through an experimental program." California requested one million joints. The burgeoning demand for THC put the government in a pinch. But the bureaucrats rejected the obvious solution, which would be to increase production on the "pot farm." The idea that NIDA could grow enough marijuana to accommodate the needs of sick people is what the drug warriors call an "imponderable" - meaning simply that they refuse to think about it. And so the search began for a pharmaceutical substitute. In the late 1970s, says Bob Randall, "Everyone had decided that nabilone was the great white drug" that would replace marijuana. Nabilone is manufactured by Eli Lilly under the trade name Cesamet; its active ingredient is hexahydro-cannabinol. By 1978, the drug was being tested on cancer patients, and Lilly officials were predicting FDA approval within a year. "They had it on double-tracking with humans and animals," Randall says, "until suddenly, dogs on nabilone started having convulsions and dropping dead." [photo caption:]

Sam Skipper Enjoys A Bowl Of Buds To

Ward Off AIDS Wasting Syndrome. Enter Marinol. Tested on rats and other animals in the 1970s, it was never meant for human consumption. But after Cesamet bombed, the bureaucrats decided to give it a chance. In October 1980, the NCI began distributing Marinol free of charge to 20,000 patients at 800 hospitals. One of the 2,600 doctors who participated in the program was Dr. Ivan Silverberg, an oncologist in San Francisco. Silverberg, one of the first doctors to use chemotherapy on lymphoma patients, had been an early champion of medical marijuana. Nevertheless, he entered the NCI program, and began prescribing THC to his cancer patients. After a year, Randall says, "One of Ivan's patients walked into his office and threw the bottle at him, accusing him of trying to poison her." He subsequently dropped out of the program. During the early '80s, studies were conducted in six states, offering smokeable marijuana to cancer patients who had not responded to traditional antivomiting medication. And while thousands of patients found marijuana consistently safer and more effective than synthetic THC, the government rejected the studies. They had already found a foster home for Marinol. Back when Ronald Reagan was elected, Unimed was just a fledgling company in Somerville, NJ. Its executives didn't have the money to develop pharmaceuticals on their own, so they developed a strategy to purchase experimental drugs from university and government studies, then market the drugs for a profit. In 1981, the government agreed to sell the Marinol patent to Unimed, and Unimed applied to the FDA for permission to market the pill as a treatment for nausea. In November 1984, the FDA rejected Unimed's application because clinical tests that had been done on the drug were deficient. But Unimed hustled up some more data, and by June 1985, the FDA delivered its approval. A year later, the DEA gave it a green light. In 1987, two years after Unimed bought the Marinol patent from the NCI, the little company was flush with profits from the pill: $1.5 million in one year alone. In 1990, Unimed executives said they were anticipating a potential windfall of $80 million a year from the poor saps with cancer, and up to $1 billion a year from victims of the HIV virus. Marinol sales have never reached expectations. In fact, the company's annual revenues have never topped $3 million. In 1992, soon after the FDA approved Marinol for wasting syndrome, Roxane's publicity department went into overdrive, printing out glossy pamphlets for AIDS patients. The pamphlets offer advice on weight gain ("Enjoy an ice cream sundae frequently!") and dining enjoyment ("Use a tablecloth and china; invite a friend to share your meal"). But the most bizarre tip involves marijuana: "Do not smoke marijuana while using Marinol. This can cause an overdose." It's simply ludicrous to suggest that a patient who is taking gel caps of 99 percent THC is going to overdose by smoking a cigarette averaging 5 to 10 percent THC. The product insert for Marinol dated December 1992 makes no mention of interactions between Marinol and smoked marijuana. Besides, you can't overdose to death on pot. According to pharmacologist Andrew Weil, researchers have tried to kill dogs with an overdose of marijuana, and the dogs simply won't die. You might die if you ate 40 aspirins or 10 raw potatoes, but not if you ate 10 pounds of pot. Synthetic THC is another story: swallowing a handful of pills can leave a patient unconscious. The 1992 product insert offers this advice for treating a Marinol overdose: "A potentially serious oral ingestion, if recent, should be managed with gut decontamination. In unconscious patients with a secure airway, instill activated charcoal via a nasogastric tube. A saline cathartic or sorbitol may be added to the first dose of activated charcoal." Does that sound risky? Let's move on to the potential for developing a habit. According to the December 1992 product insert, Marinol can be "habit-forming" - in other words, a patient who stops taking it abruptly may go through four days of withdrawal. Typical symptoms include irritability, insomnia, anorexia, hiccups and diarrhea. Sleep disturbances may last for weeks. What about cancer? Of course, anything you smoke may be damaging to your lungs. And one of the medical raps against marijuana is that it involves smoking a combination of 421 chemicals: 61 cannabinoids, a host of amino acids, proteins, and sugars - and at least one known carcinogen, benzopyrene. No one knows what that does to your lungs, but according to Dr. Donald Tashkin, one of the government's anti-marijuana experts, recent laboratory studies have linked marijuana smoke with "accelerated malignant changes in hamster lung cells," with "increased mutations," "microscopic abnormalities," and "increased risks of respiratory tract malignancy." Those links sound a bit tentative. But even NORML executive director Dick Cowan concedes that marijuana may be carcinogenic. "We have never claimed marijuana is harmless," he says. "I encourage people to use a water pipe to reduce the possible damage to the respiratory system." You would think, with all the government-funded tests to see if marijuana can be linked to cancer, the same would be done for Marinol. But no one seems to care. According to the 1992 product insert, "Carcinogenicity studies have not been performed with dronabinol." Aside from lung cancer, smoking marijuana poses another potential risk for people with compromised immune systems. The government has long been telling pot-smokers that they risk "salmonella and fungal spore contamination." And a recent study conducted at Johns Hopkins School of Public Health found that smoking marijuana, crack, or other drugs is "significantly associated" with bacterial pneumonia among patients with HIV. The government has not produced a single case of a pneumonia or lung cancer contracted from smoking marijuana. But the risks are authentic, and Sam Skipper has taken precautions. He smokes from a large collection of water pipes. Skipper is also keen to the risk of fungus and bacteria. "There are no contaminants in homegrown," he points out. "But sometimes when I buy marijuana, I sterilize it myself. Marijuana is not water-soluble, so you can actually wash it in a pan, and then stick it in the microwave and dry it. You lose about a third, but you end up with sterilized cannabis." Finally, it's worth reviewing the side effects of marijuana and Marinol. While there are numerous side effects from smoking marijuana (euphoria, laughter, anxiety, dry mouth, red eyes, sleepiness, clumsiness, the munchies), countless patients who have used marijuana in a medical setting have testified that they experienced no adverse side effects. People who take Marinol, on the other hand, frequently complain about the "disturbing psychiatric symptoms" that are common side effects of the drug. According to a 1985 edition of The Medical Letter, the side effects of Marinol are "disorientation, depression, paranoia, hallucinations and manic psychosis." The 1992 product insert for Marinol scatters these symptoms throughout the section marked ADVERSE REACTIONS ("amnesia," "depersonalization," "hallucination," "paranoid reaction," "depression"), but saves psychosis for a passing reference in the section called OVERDOSAGE: "Patients experiencing depressive, hallucinatory or psychotic reactions should be placed in a quiet area and offered reassurance." [photo caption:]

Marinol Sales

Have Never Reached

Expectations. In Fact,

The Company's Annual

Revenues Have Never

Topped $3 Million. [The accompanying photo shows the label from a bottle of Marinol. Its text reads: NDC 0054-2602-11

25 Capsules

5 mg

MARINOL ®

(DRONABINOL)

(Warning: May be habit

forming)

See Package Insert for

Complete Prescribing

Information

Keep Tightly Closed

Store in a Cool Place

DEA ORDER FORM REQUIRED

Mfg. by

Banner Gelatin Products Corp.

Chatsworth, CA 91311

Distributed by

Roxane

Laboratories, Inc.

Columbus, Ohio 43216 The side effects of marijuana pale beside those of other drugs commonly prescribed by doctors in the US. The standard drugs used in chemotherapy can cause deafness, kidney failure and cancer; those used to treat nausea can cause ulcers, secondary infections and psychosis; the eye drops and pills used to treat glaucoma can cause depression, heart failure, numbness and kidney stones; and the medications commonly given to paraplegics can cause kidney failure, hepatitis and seizures. In 1987, after reviewing the evidence, DEA administrative law judge Francis Young declared, "Marijuana, in its natural form, is one of the safest therapeutically active substances known to man." But don't ask why the government is so afraid of medical marijuana. Even Bob Randall doesn't have an answer. "I think it's odd we've got a government that's willing to secretly give you plutonium," he says, "but it won't give you marijuana when you want it. That seems a little twisted to me." Fortunately, the sick people who need marijuana are not alone in their struggle. In the last few years, cancer and AIDS doctors have begun to speak out, asserting a physician's right to prescribe any drug that might work. Last spring, the Lymphoma Foundation and the Physicians Association for AIDS Care joined a lawsuit on behalf of medical marijuana. The 1,000 members of PAAC, which is based in Chicago, treat nearly 250,000 people with HIV, so they have firsthand experience with marijuana as a treatment for wasting syndrome. "First," says PAAC's executive director Gordon Nary, "physicians should try the drugs that have been FDA-approved." Of course, not all drugs work for all patients. Before suggesting marijuana, he says, doctors should "alert patients who have a compromised immune system to the risks" of fungal infection. But when you're treating someone whose life is at stake, Nary sighs, "It's simply a matter of appropriate medicine and human decency to allow compassionate use of any drug, experimental or on somebody's blackballed list." [End] Portland NORML notes: Roxane Laboratories, Inc. set up a Web site for Marinol in 1998 at http://www.marinol.com/. About this page ... to the Articles page. This URL: http://www.pdxnorml.org/HT_Marinol_0794.html