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 Cannabis and Cannabidiol By Fred Gardner AIDS Treatment News #305 Notes: (1) Robert Gorter, M.D., is associate clinical professor at the University of California San Francisco Medical Center (Department of Family and Community Medicine), and also the medical director of the European Institute for Oncological and Immunological Research, a nonprofit with headquarters in Berlin and offices in Milan and Amsterdam.
 (2) Cannabidiol (CBD) is a non-psychoactive ingredient of the
hemp plant which is being studied for potential medical uses
including treatment of head injury and certain strokes, as an
anti-psychotic, and as an anti-inflammatory. (3) The
references to "Anthroposophical" refer to Anthroposophy, a
movement founded in 1924 by Rudolph Steiner (1861-1925). JSJ]
Robert Gorter, M.D., is organizing clinical trials of a cannabis extract, hoping to establish that it leads to weight gain in HIV and cancer patients. In July he attended the annual meeting of the International Cannabinoid Research Society, where he apprised colleagues of his progress and caught up on theirs. We debriefed him in San Francisco in early August. Fred Gardner: What is your interest in cannabis? Dr. Gorter: My interest in cannabis goes back to the early 1970s. I studied medicine in Amsterdam in the 1960s and I lived in a commune where almost everybody "blowed" every day- -but I never did. And usually in the middle of the night, people would meet in the kitchen and have fried eggs and snacks; they said that when you smoke, it stimulates your appetite. When I settled down as an Anthroposophical family practitioner in Amsterdam in 1973, I had many cancer patients in my practice. Many had loss of appetite and severe weight loss. Many older people from Holland had never smoked pot. So we made an oral preparation for them. We grew cannabis in a city park, until it was discovered. We made an alcohol extract of cannabis, and my patients took half a teaspoon a day twice a day, and they loved it. Almost all reported appetite stimulation after about a week. There was a clear mood elevation--they felt better. And many patients who were using opiates for pain control said they needed much less opiates with small amounts of cannabis. Most people gained weight, but not all. If patients were close to dying, weight gain was not seen. Gardner: For how many years were you treating cancer patients in Amsterdam with cannabis? Dr. Gorter: From 1973 to 1983. At that time cannabis was also available as an injectable from Weleder, an Anthroposophical company that distributes natural medicines. I've used it as an injectable for backaches and muscle cramps and people with insomnia. But for stimulating appetite the injections did not work well; the patients needed a larger dose, delivered orally. Gardner: And then you came to UCSF in 1983? Dr. Gorter: In the Nancy Reagan years, I felt insecure about telling patients about medical effects of cannabis. But if people asked me, of course I would tell them what I knew. Then, in 1986, Marinol(R) (dronabinol) was developed, so right away I could prescribe Marinol for appetite stimulation. I have also tried it with patients with chronic pain. But many people had side effects. My patients who had experience with both cannabis and Marinol almost always preferred cannabis, because Marinol had more side effects, including headaches and a hung-over feeling. In 1989 I set up an efficacy trial of Marinol as an appetite stimulant in AIDS patients. Gardner: What happened? Dr. Gorter: After a delay it was conducted in Texas. In 1991 Marinol received approval of an additional indication for appetite stimulation in HIV infection. In 1992 I took a sabbatical and went to Europe to conduct a clinical trial of Iscador in HIV patients. To make a long story short, I was offered an opportunity to establish the European Institute for Oncological and Immunological Research in Berlin, and since then I have been flying back and forth. Gardner: What became of your cannabis-vs.-Marinol study? Dr. Gorter: We decided to start a clinical trial in Europe to study Marinol against placebo and then compare cannabis against placebo and then cannabis against Marinol for its efficacy, toxicity and so on. It took me about two years of lobbying, but then the German government and the Dutch government agreed that it was time to have these studies done. Both governments have given me an official okay to conduct such a trial in about 800 AIDS and cancer patients. Our institute has developed an oral preparation of cannabis which we have named Cannador--from 'cannabis' plus 'dor/doron' for gift. Gardner: You will not be testing smoked cannabis? Dr. Gorter: For the elderly, in a hospital setting or a hospice, smoking raises all kinds of problems. And smoking cannabis is so strongly associated with recreational drug use, that it is not palatable to people in the government. A clean, standardized extract works better. Ours will be a whole-plant extract made from male and female plants, and standardized for its THC and other cannabinoid contents by thin-layer chromatography. We will process it in a fatty medium for packaging in a soft-gel capsule. [Note: THC, or tetrahydrocannabinol, is the main psychoactive ingredient in marijuana.] Gardner: Do the male and female plants have significantly different components? Dr. Gorter: Yes. Cannabis contains at least 600 different components; among them 64 different cannabinoids have been identified, and everybody agrees that there are more. And there are 10 times as many other substances. They differ from year to year depending on the soil, the weather, the degree of sexual separation, and other factors. The highest concentration of THC is in the glands of the female plant. Gardner: Donald Abrams, M.D., told SYNAPSE you were planning a study in the U.S. involving cannabis and appetite in HIV patients.
It was decided that we could go straight to a phase III trial, because so much is known already about safety. But in February of this year we had a conference call from the same FDA committee but with a different chair; she said, "You have to do a phase I trial." We ended agreeing to do a combined phase I/II trial. I am now raising money for that trial and hopefully it will be conducted in the spring of next year. In the late fall we will start with the phase III trial at 18 universities in Germany, the Netherlands, Austria and Switzerland. There will be 360 cancer patients and 360 AIDS patients who have lost at least 5% of their body weight in the last six months, and who are candidates for appetite stimulation, and have been free of cannabis for at least four weeks (so we can test the efficacy of our preparation). So soon we will have both studies running parallel--a phase III trial in Europe and a phase I/II in the US. [Phase I tests toxicity in humans; phase II tries to determine an optimum dose. Phase III is an efficacy trial against placebo or other medications--the key step in obtaining a license to market the drug. Phase IV trials, conducted after market approval, involve thousands of patients followed over time to assess long-term toxicity.] Gardner: From what source are you obtaining your cannabis? Dr. Gorter: The cannabis used in the U.S. will come from NIDA [the National Institute on Drug Abuse, which has authorized Professor Mahmoud ElSohly, a commercial grower employed by the University of Mississippi, to cultivate marijuana on their farmland for sale to the federal government.] The cannabis to be used in Europe will be purchased by the Dutch government, also from NIDA. Gardner: NIDA's marijuana is reportedly weak and stale. Dr. Gorter: I trust ElSohly to provide a suitable product. In any case, the concentrations we get in the extraction process are what matters, and we can control that. We will soon start in Amsterdam and in England trials of Cannador on multiple sclerosis patients. Gardner: There were references at the International Cannabinoid Research Society meeting to the immunosuppressant activity of THC. Dr. Gorter: Only in high doses in animal studies that do not correspond to the pattern of human use. After a while you see a drop of blood pressure and immune dysfunction. Animals are generally given 125 milligrams of THC per kilogram body weight. That would be for humans 7 or 8 thousand milligrams per day. The average amount in a joint is about 10-15 milligrams; so 8 thousand milligrams is beyond every form of human use. Cannabidiol Dr. Gorter: In Berlin we will develop another form of Cannador with a much higher content of CBD (cannabidiol), and do a pilot project on patients with epilepsy. CBD counters, to some extent, the psychoactive effects of THC. Gardner: How do you adjust to get a plant heavy on CBD and light on THC? Dr. Gorter: You grow plants with high content of CBD. No problem. Gardner: Does ElSohly have that kind of sophistication? Dr. Gorter: We will collaborate and share our expertise. For More Information AIDS Treatment News Published twice monthly Subscription and Editorial Office: P.O. Box 411256 San Francisco, CA 94141 800/TREAT-1-2 toll-free U.S. and Canada 415/255-0588 regular office number Fax: 415/255-4659 E-mail: aidsnews@aidsnews.org
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