cannabisnews.com: MDs Balk At Dispensing Marijuana MDs Balk At Dispensing Marijuana Posted by CN Staff on July 11, 2003 at 07:47:52 PT By Brian Laghi Source: Globe and Mail Ottawa -- Doctors who have already taken a risk by helping their patients get authorization to use marijuana are balking at a federal request to store and dispense the drug. "I won't do it," said Brian Cornelson, a doctor who has in the past signed affidavits on behalf of patients who need the drug."This whole idea of having us dispense is ludicrous." Dr. Cornelson made his comments yesterday as at least one patient filled out the required forms to get the drug. The Toronto man, who is HIV positive, was able to find a doctor who agreed to handle the drug. However, Dr. Cornelson and other physicians interviewed said the federal government plan is nonetheless worrisome on many fronts.They said they are concerned about being burgled and/or pressured by patients to release the drug.Moreover, they will be bucking the recommendations of the Canadian Medical Association, whose leadership said this week they shouldn't dispense the drug.Doctors who have signed affidavits to help patients obtain affidavits have already done so despite the concerns of the Canadian Medical Protective Association, which defends doctors against litigation.The organization is concerned about future lawsuits from patients who might suffer unintended side effects from the drug.Dr. Cornelson, who operates a practice in Toronto, said doctors who agree to dispense the drug will be concerned that news they are doing so will get out and they will become robbery targets. He added that doctors are also in a quandary over the quantity of marijuana individual patients need to ameliorate the symptoms of their disease."We're being put in a position of regulating something we have no knowledge of in terms of dosage," he said."If this is the best they can come up with -- the Health Canada people -- they must be smoking it themselves."Under the plan, Ottawa is preparing to release the drug in 30-gram packets to those individuals who need medical marijuana and can't grow it themselves or can't find others to do so. The drug will cost patients $5 a gram. Ottawa is also prepared to make marijuana seeds available.Another doctor said he is willing to dispense the drug but only under extraordinary conditions."I don't think it's an optimum situation, but I guess under exceptional circumstances I might," Mark Latowsky said.Dr. Latowsky, who has also supported applications for the drug, said the federal government should have the marijuana distributed through pharmacies."Doctors should write a prescription for it, the patient should pick up the prescription, go to the pharmacist, the pharmacist should dispense however much the physician is prescribing and the physician should follow the patient just like any other patient."A spokesman for the federal government, Jirina Vlk, said the Health Department decided against going the pharmacy route because the program is an interim one and it was felt that widespread distribution was not warranted.Ottawa has said it could take as little as a week for the drug to be delivered to authorized patients, a prediction that will immediately be tested by a Toronto man, who said yesterday he had found a doctor to accept the drug on his behalf.Jari Dvorak, 62, said he needs the drug to help with nausea and felt lucky to have found a doctor."He was concerned," said Mr. Dvorak, who is HIV-positive. "But I guess I am an exception with an exceptional doctor."The organization that defends doctors against lawsuits has already expressed concern about physicians who help patients get exemptions.Note: Doctors fret over burglaries, being hassled by patients to release the drug.Source: Globe and Mail (Canada)Author: Brian LaghiPublished: Friday, July 11, 2003 - Page A7 Copyright: 2003 The Globe and Mail CompanyContact: letters globeandmail.caWebsite: http://www.globeandmail.com/Related Articles & Web Site:Canadians for Safe Accesshttp://www.safeaccess.ca/Ottawa Pot Plan Unworkable: Doctors http://cannabisnews.com/news/thread16819.shtmlPatients Seek Relief On Price of Medical Pot http://cannabisnews.com/news/thread16813.shtmlCanada To Supply Marijuana To Seriously Ill http://cannabisnews.com/news/thread16809.shtml Home Comment Email Register Recent Comments Help Comment #2 posted by goneposthole on July 11, 2003 at 08:43:34 PT this may interest those Canadian doctors Anticancer activity of cannabinoids (materials and methods omitted)Journal of the National Cancer Institute, Vol. 55, No. 3, September 1975, pp.597-602 By A.E. Munson, L.S. Harris, M.A. Friedman, W.L. Dewey, and R.A. Carchman Department of Pharmacology and the MCV/VCU Cancer Center, Medical College of Virginia, Virginia Commonwealth University. Richmond, Va. 23298 Supported by Public Health Service grant DA00490 from the National Institute on Drug Abuse, Health Services & Mental Health Administration; by a grant from the Alexander and Margaret Stewart Trust Fund; and by an institutional grant from the American Cancer Society. Summary --- Lewis lung adenocarcinoma growth was retarded by the oral administration of delta-9-tetrahydrocannabinol, delta-8-tetrahydrocannabinol, and cannabinol (CBN), but not cannabidiol (CBD). Animals treated for 10 consecutive days with delta-9-THC, beginning the day after tumor implantation, demonstrated a dose-dependent action of retarded tumor growth. Mice treated for 20 consecutive days with delta-8-THC and CBN had reduced primary tumor size. CBD showed no inhibitory effect on tumor growth at 14, 21, or 28 days. Delta-9-THC, delta-8-THC, and CBN increased the mean survival time (36% at 100 mg/kg, 25% at 200 mg/kg, and 27% at 50 mg/kg;, respectively), whereas CBD did not. Delta-9-THC administered orally daily until death in doses of 50, 100, or 200 mg/kg did not increase the life-spans of (C57BL/6 X DBA/2) F (BDF) mice hosting the L1210 murine leukemia. However, delta-9-THC administered daily for 10 days significantly inhibited Friend leukemia virus-induced splenomegaly by 71% at 200 mg/kg as compared to 90.2% for actinomycin D. Experiments with bone marrow and isolated Lewis lung cells incubated in vitro with delta-8-THC and delta-9-THC showed a dose-dependent (10 -4 10 -7) inhibition (80-20%, respectively) of tritiated thymidine and 14C -uridine uptake into these cells. CBD was active only in high concentrations (10 -4). ----J Natl Cancer Inst 55: 597-602, 1975. Investigations into the physiologic processes affected by the psychoactive constitutuents of marihuana [delta-9-tetrahydrocannabinol (delta-9-THC) and delta-8-tetrahydrocannabinol (delta-8-THC)] purified from Cannabis sativa are extensive (1). However, only recently have attempts been made to elucidate the biochemical basis for their cytotoxic or cytostatic activity. Leuchtenberger et al. (2) demonstrated that human lung cultures exposed to marihuana smoke showed alterations in DNA synthesis, with the appearance of anaphase bridges. Zimmerman and McClean (3), studying macromolecular synthesis in Tetrahymena, indicated that very low concentrations of delta-9-THC inhibited RNA, DNA, and protein synthesis and produced cytolysis. Stenchever et al. (4) showed an increase in the number of damaged or broken chromosomes in chronic users of marihuana. Delta-9-THC administered iv inhibited bone marrow leukopoieses (5), and Kolodny et al. (6) reported that marihuana ;may impair testosterone secretion and spermatogenesis. Furthermore, Nahas et al. (7) showed that in chronic marihuana users there is a decreased lymphocyte reactivity to mitogens as measured by thymidine uptake. These and other (8) observations suggest that marihuana (delta-9-THC) interferes with vital cell biochemical processes, though no definite mechanism has yet been established. A preliminary report from this laboratory (9) indicated that the ability of delta-9-THC to interfere with normal cell functions might prove efficacious against neoplasms. This report represents an effort to test various cannabinoids in several in vivo and in vitro tumor systems to determine the kinds of tumors that are sensitive to these compounds and reveal their possible biochemical sites of action(s). RESULTS Effects of Cannabinoids on Murine Tumors Delta-9-THC, delta-8-THC, and cannabinol (CBN) all inhibited primary Lewis lung tumor growth, whereas cannabidiol (CBD) enhanced tumor growth. Oral administration of 25, 50, or 100 mg delta-9-THC/kg inhibited primary tumor growth by 48, 72, and 75% respectively, when measured 12 days post tumor inoculation (table 1). On day 19, mice given delta-9-THC had a 34% reduction in primary tumor size. On day 30, primary tumor size was 76% that of controls and only those given 100 mg delta-9-THC/kg had a significant increase in survival time (36%). Mice treated with a delta-9-THC showed a slight weight loss over the 2-week period (average loss, 0.3 g at 50 mg/kg and 0.1 g at 100 mg/kg). This can be compared to cyclo-ohosphamide, which caused weight loss approaching 20% (table 2). Delta-8-THC activity was similar to that of delta-9-THC when administered orally daily until death (table 2). However, as with delta-9-THC, primary tumor growth approached control values after 3 weeks. When measured 12 days post tumor inoculation, all doses (50-400 mg/kg) of delta-8-THC inhibited primary tumor growth between 40 and 60%. Significant inhibition was also seen on day 21, which was comparable to cyclophosphamide-treated mice. Although this was not the optimum regim;en for cyclophosphamide, it was the positive control protocol provided by the NCI (11). All mice given delta-8-THC survived significantly longer than controls, except those treated with 100 mg/kg. Mice given 50, 200, and 400 mg/kg delta-8-THC had an increased life-span of 22.6, 24.6, and [Image] 27.2%, respectively, as compared to 33% for mice treated with 20 mg cyclophosphamide/kg. Pyran copolymer, an immunopotentiator (12) when administered at 50 mg/kg, also significantly increased the survival time of the animals (39.3%). CBN, administered by gavage daily until death, demonstrated antitumor activity against the Lewis lung carcinoma when evaluated on day 14 post tumor inoculation (table 3). Primary tumor growth was inhibited by 77%, at doses of 100 mg/kg on day 14 but only by 11% on day 24. At 50 mg/kg on day 14 but only by 11% on day 24. At 50 mg/kg, CBN inhibited primary tumor growth by only 32% when measured on day 14, and no inhibition was observed on day 24; however, these animals did survive 27% longer. CBD, administered at 25 or 200 mg/kg daily until death, showed no tumor-inhibitory properties as measured by primary Lewis lung tumor size or survival time (table 4). In this experiment, CBD-treated mice showed enhanced primary tumor growth. However, the control tumor growth rate in this experiment was decreased as compared to the previous studies. Survival time of BDF 1 mice hosting L1210 leukemia was not prolonged by delta-9-THC treatment (table 5). Mice treated with delta-9-THC at doses of 50, 100, and 200 mg/kg administered orally daily until death, survived 8.5, 7.8, and 8.6 days, respectively, as compared to 8.6 days for mice treated with the diluent. However, delta-9-THC inhigited FLV-induced splenomegaly by 71% at 200 mg/kg as compared to 90.2% for the positive control actinomycin D (0.25 mg/kg). Although there was a dose-related inhibition, only the high dose was statistically significant (table 6). Effect of Cannabinoids on Isolated Cells In Vitro Isolated cells incubated in vitro represent a simple, reliable, and, hopefully, predictive method for the monitoring of the effects of agents on several biochemical parameters at the same time. The incorporation of 3H-TDR into TCA-precipitable counts in isolated Lewis lung cells is shown in text-figure 2. Similar types of curves were seen for bone marrow and L1210 cells. In all instances, for 15-45 minutes there was a linear increase in 3H-TDR uptake into the TCA-precipitable fraction. Qualitatively, similar data (not shown) were seen after a pulse with 14C-uridine. Actinomycin D (1 mcg/ml) preferentially inhibited 14C-uridine incorporation after uridine uptake had decreased to less than 30% that of control (data not shown). This is indirect evidence that we were measuring RNA synthesis. Experiments (data not shown) done with 5-FU (10 -4 M) indicated that, in isolated bone marrow cells, both thymidine uptake with time by delta-9-THC (10 -5 M) on Lewis lung cells is depicted in text-figure 2. In this experiment, delta-9-THC caused a nonlinear uptake of 3H-TDR. At 30 minutes, uptake of 3H-TDR into the acid-precipitable fraction was about 50% that of control Longer incubations (i.e., 60 min) did not significantly change the uptake pattern for control and de;ta-9-THC treated tumor cells. The effect of several cannabinoids on the uptake of 3H-TDR into cells incubated in vitro indicated that delta-9-THC, delta-8-THC, and CBN produced a dose-dependent inhibition of radiolabel uptake in the three cell types (table 7). These results, presented as percent inhibition of radiolabel uptake as compared to control, represented an effectof cannabinoids on one aspect of macromolecular synthesis. CBD was the least active of the cannabinoids, but showed its greatest activity in the L1210 leukemia cells. Other data (not shown) indicate that these compounds similarly effect the uptake of 14C-uridine into the acid-precipitable fraction. Ara-C markedly inhibited 3H-TDR uptake more dramatically than did the cannabinoids (table 7). Note that delta-9-THC exhibited inhibitory properties in the isolated Lewis lung tumor and L1210 cells at concentrations that did not interfere with thymidine uptake into bone marrow cells. At certain concentrations of CBD (2,5 X 10 -6 and 2.5 X 10 -7M), radiolabel uptake was consistently stimulated in bone marrow cells and in several experiments with the isolated Lewis lung cells. DISCUSSION We investigated four cannabinoids for antineoplastic activity against three animal tumor models in vivo and for cytotoxic or cystostatic activity in two tumor cell lines and bone marrow cells in vitro. The cannabinoids (delta-9-THC, delta-8-THC, and CBN) active in vivo against the Lewis lung tumor cells are also active in the in vitro systems. The differential sensitivity of delta-9-THC against Lewis lung cells versus bone marrow cells is unique in that delta-8-THC and CBN are equally active in these systems. Johnson and Wiersma (5) reported that delta-9-THC administered iv caused a reduction in bone marrow metamyelocytes and an increase in lymphocytes. It is unclear from the data whether this is a depression of myelopoiesis or if it represents a lymphocyte infiltration into the bone marrow. The use of isolated bone marrow cells, which represent a nonneoplastic rapidly proliferating tissue, enables the rapid evaluation and assessment of drug sensititity and specificity, and thereby may predict toxicity related to bone marrow suppression. CBD showed noninhibitory activity either against the Lewis lung cells in vivo or Lewis lung and bone marrow cells in vitro at 10 -5M an 10 -6M, respectively. Indeed, the tumor growth rate in mice treated with CBD was significantly increased over controls. This may, in part, be the consequence of the observation made in vitro (i.e., 10 -7M CBD stimulated thymidine uptake), which may be reflected by an increased rate of tumor growth. One problem related to the use of cannabinoids is the development of tolerance to many of its behavioral effects (13). It also appears that tolerance functions in the chemotherapy of neoplsms in that the growth of the Lewis lung tumor is initially markedly inhibited but, by 3 weeks, approaches that of vehicle-treated mice (tables 1, 3). This, in part, may reflect drug regimens, doses used, increased drug metabolism, or conversion to metabolites with antagonistic actions to delta-9-THC. It may also represent some tumor cell modifications rendering the cell insensitive to these drugs. Of further interest was the lack of activity of delta-9-THC against the L1210 in vivo, whereas the invitro L1210 studies indicated that delta-9-THC could effectively inhibit thymidine uptake. The apparent reason for this discrepancy may be related to the high growth fraction and the short doubling time of this tumor. The in vitro data do not indicate that the cannabinids possess that degree of activity; e.g., ara-C, which "cures"L1210 mice, is several orders of magnitude more potent on a molar basis than delta-9-THC in vitro. Inhibition of tumor growth and increased animal survival after treatment with delta-9-THC may, in part, be due to the ability of the drug to inhibit nucleic acid synthesis. Preliminary data with Lewis lung cells grown in tissue culture indicate that 10 -5M delta-9-THC inhibits by 50% the uptake of 3H-TDR into acid-precipitable counts over a 4-hour incubation period. Simultaneous determination of acid-soluble fractions did not show any inhibitory effects on radiolabeled uptake. Therefore, delta-9-THC may be acting at site(s) distal to the uptake of precursor. We are currently evaluating the acid-soluble pool to see if phosphorylation of precursor is involved in the action of delta-9-THC. These results lend further support to increasing evidence that, in addition to the well-known behavioral effects of delta-9-THC, this agent modifies other cell responses that may have greater biologic significance in that they have antineoplastic activity. The high doses of delta-9-THC (i.e., 200 mg/kg) are not tolerable in humans. On a body-surface basis, this would be about 17 mg/m(2) for mice. Extrapolation to a 60-kg man would require 1,020 mg for comparable dosage. The highest doses administered to man have been 250-300 mg (14). Whether only cannabinoids active in the central nervous system (CNS) exhibit this antineoplastic property is not the question, since CBN, which lacks marihuana-like psychoactivity, is quite active in our systems (15). With structure-activity investigations, more active agents may be designed and synthesized which are devoid of or have reduced CNS activity. That these compounds readily cross the blood-brain barrier and do not possess many of the toxic manifestations of presently used cytotoxic agents, makes them an appealing group of drugs to study. [ Post Comment ] Comment #1 posted by FoM on July 11, 2003 at 08:32:32 PT Related Article from Snipped Source Medical Pot Offer Horrifies MDBCMA head decries federal marijuana shipments to doctors. Pamela Fayerman and Mark Kennedy, CanWest News Service The federal government will immediately begin to ship medical marijuana to physicians who prescribe pot to their patients -- a move the head of the B.C. Medical Association calls "horrifying and mind-boggling.""It boggles the mind. It sounds like a scheme thought up by a bureaucrat trying to make doctors' lives more difficult," BCMA president Dr. John Turner said Wednesday."I mean what would a doctor do with 10 totes of marijuana in the office cupboard? You would have to hope nobody breaks into your office. I think most doctors would be absolutely horrified by this." Not only is the federal government willing to ship directly to doctors but it will do so at bargain-basement prices. Hundreds of chronically ill patients who currently qualify for "medical marijuana" under Health Canada's program had better rush their order though, because within weeks, the government may revoke its official drug supplier status and resume its policy of keeping its stash -- grown at an old mine site in Flin Flon, Man. -- under lock and key.The marijuana is being offered to Canadians at $5 a gram, enough for about one or two joints, compared to the black market street value prices of $10 to $25 a gram. It will be regularly distributed by courier to a patient's doctor in 30-gram bags and be limited to the amount that the physician says is required to treat the condition. As well, the government will sell marijuana seeds -- $20 for a packet of 30 -- to sick Canadians to grow their own.Federal Health Minister Anne McLellan, who announced the plan Wednesday, made it clear she is lukewarm about the new system. "Keep in mind that it was never the intention for us to supply the product," she told reporters.She said the government wants to be convinced first of the medical benefits of marijuana, but its hand was forced by a court ruling earlier this year that essentially required it to meet a deadline to become a drug supplier -- at least for now.Snipped:Complete Article: http://www.canada.com/health/story.html?id=8890C497-6BDB-41E5-BE5F-DD414F0B4A48 [ Post Comment ] Post Comment