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HomeMy WebLinkAboutCOM 0749.050 1998-2000 $ 'I ~ • • Pubdate: Sat, 15 Jul 2000 Source: Las Vegas Weekly (NV) Copyright: 2000 Radiant City Publications, LLC Contact: lasvega n,lasvegasweekly.com Address: P.O. Box 230657, Las Vegas, NV 89123 -0011 Fax: (702) 990 -2424 Website: http:/ /www.lasvegasweekly.com/ Author. Raymond Cushing INAHAZE Nearly Three Decades Ago The Government Knew Marijuana Could Help Cure Cancer, The Rest Of Us Are Just Finding Out Now The term medical marijuana took on dramatic new meaning in February when researchers in Madrid announced they had destroyed incurable brain cancer tumors in rats by injecting them with THC, the active ingredient in cannabis. The Madrid study marks only the second time that THC has been administered to tumor - bearing animals; the first was a Virginia investigation 26 years ago. In both studies, the THC shrank or destroyed tumors in a majority of the test subjects. Most Americans don't know anything about the Madrid discovery. Virtually no U.S. newspapers carried the story, which ran only once on the AP and UPI news wires, on Feb. 29. The ominous part: This isn't the first time scientists have discovered that THC shrinks tumors. In 1974, researchers at the Medical College of Virginia, who had been funded by the National Institute of Health to find evidence that marijuana damages the immune system, found instead that THC slowed the growth of three kinds of cancer in mice - -lung and breast cancer, and a virus- induced leukemia. The ED quickly shut down the Virginia study and all further cannabis /tumor research, according to Jack Herer, who reports on the events in his book, The Emperor Wears No Clothes. In 1976, President Gerald Ford put an end to all public cannabis research and granted exclusive research rights to major pharmaceutical companies, who set out -- unsuccessfully - -to develop synthetic forms of THC that would deliver all the medical benefits without the "high." C Comm. No. 7 0 90 File No. Ref. To:. Cain y Ref. Date JUL 2 6 2000 • • The Madrid researchers reported in the March issue of Nature Medicine that they injected the brains of 45 rats with cancer cells, producing tumors whose presence they confirmed through magnetic resonance imaging (MRI). On the 12th day they injected 15 of the rats with THC and 15 with Win - 55,212 -2 - -a synthetic compound similar to THC. "All the rats left untreated uniformly died 12 -18 days after gloom (brain cancer) cell inoculation ... Cannabinoid (THC)- treated rats survived significantly longer than control rats. THC administration was ineffective in three rats, which died by days 16 -18. Nine of the THC - treated rats surpassed the time of death of untreated rats, and survived up to 19 -35 days. Moreover, the tumor was completely eradicated in three of the treated rats." The rats treated with Win - 55,212-2 showed similar results. The Spanish researchers, led by Dr. Manuel Guzman of Complu- tense University, also irrigated healthy rats' brains with large doses of THC for seven days, to test for harmful biochemical or neurological effects. They found none. "Careful MRI analysis of all those tumor -free rats showed no sign of damage related to necrosis, edema, infection or trauma ... We also examined other potential side effects of cannabinoid administration. In both tumor -free and tumor - bearing rats, cannabinoid administration induced no substantial change in behavioral parameters such as motor coordination or physical activity. Food and water intake as well as body weight gain were unaffected during and after cannabinoid delivery. Likewise, the general hematological profiles of cannabinoid - treated rats were normal. Thus, neither biochemical parameters nor markers of tissue damage changed substantially during the 7 -day delivery period or for at least two months after cannabinoid treatment ended." Guznian's investigation is the only time since the 1974 Virginia study that THC has been administered to live tumor - bearing animals. (The Spanish researchers cite a 1998 study in which cannabinoids inhibited breast cancer cell proliferation, but that was a "petri dish" experiment that didn't involve live subjects.) Guzman says he has heard of the Virginia study, but has never been able to locate literature on it. Hence, the Nature Medicine article • characterizes the new study as the first on tumor -laden animals and doesn't cite the 1974 Virginia investigation. "I am aware of the existence of that research. In fact I have attempted many times to obtain the journal article on the original investigation by these people, but it has proven impossible." Guzman says. In 1983 the Reagan /Bush Administration tried to persuade American universities and researchers to destroy all 1966 -76 cannabis research work, including compendiums in libraries, reports Jack *fern, who states, "We know that large amounts of information have since disappeared." Guzman provided the title of the work— "Antineoplastic activity of cannabinoids," an article in a 1975 Journal of the National Cancer Institute- -and this writer obtained a copy at the UC medical school library in Davis and faxed it to Madrid. The summary of the Virginia study begins, "Lewis lung adenocarcinoma growth was retarded by the oral administration of tetrahydrocannabinol (THC) and cannabinol (CBN) "- -two types of cannabinoids, a family of active components in marijuana. "Mice treated for 20 consecutive days with THC and CBN had reduced primary tumor size." The 1975 journal article doesn't mention breast cancer tumors. But an article in the Washington Post, dated Aug. 18, 1974 - -the only newspaper story ever to appear about the 1974 study - -does mention THC's effects on breast cancer. Under the headline, "Cancer Curb Is Studied," it read in part: "The active chemical agent in marijuana curbs the growth of three kinds of cancer in mice and may also suppress the immunity reaction that causes rejection of organ transplants, a Medical College of Virginia team has discovered." The researchers "found that THC slowed the growth of lung cancers, breast cancers and a virus- induced leukemia in laboratory mice, and prolonged their lives by as much as 36 percent." Guzman was eloquent in his response after he was faxed the clipping from the Washington Post of a quarter century ago. In translation, he wrote: "It's extremely interesting to me, the hope that the project seemed to awaken at that moment, and the sad evolution of events during the years foll:wing the discovery, until now we once again 'draw • back the veil' over the anti - tumoral power of THC, 25 years later. Unfortunately, the world bumps along between such moments of hope and long periods of intellectual castration." News coverage of the Madrid discovery has been virtually nonexistent in this country. The news broke quietly on Feb. 29 with a story that ran once on the UPI wire about the Nature Medicine article. I stumbled on it through a link that appeared briefly on the Drudge Report web page. The New York Times, Washington Post and Los Angeles Times all ignored the story, even though its news worthiness is indisputable: a benign substance occurring in nature destroys deadly brain tumors. If that's not page one, what is? Arttineoplastic Activity o annabinolds 3. ' A. E. Munson, L. S. Harris, M. A. Friedman; W. L. Dewey, and R. A. Carchman a SUMMARY —Lewis lung adenocarclnom• growth was retarded carcinoma, leukemia 1.1210, and 6-tropie Friend leu- by the oral administration of A'•telrahydrocannabinol (.Y•THC), kcmi;,. • a`•lelrahydrocannabinol (aa•THC), and cannablnol (CON), but In vivo syilcros.- -Lewis lung tumor: For the nlainte• not cannabldiol (CBD). Animals treated for 10 consecutive days mince of the Lewis lung carcinoma. approximately with A°•71 beginning the day after tumor Implantation, 1 -mitt' pieces of honor were transplanted into C57111./6 demonstrated a dose- dependant action of retarded tumor mice with a 15•gatige Irocar. In experiments involving growth. Mice treated for 20 consecutive days with A "•THC and chemotherapy, 11• to 18•sla•old tumors were excised, CEIN had reduced primary tumor size. CBD showed no Inhlbl- neared of debris and necrotic tissue., and cueinto small Tory effect on tumor growth et 14, 21, or 28 days. a °•TIIC, fragments (-z.: 1 nun'). Tumor !issue was then placed in a'•THC, and CBN increased the mean survival time (36 °4 at 0.25? Irypsin in Dulbecco•s medium with 100 U pcnici• 100 mg /kg, 25% it 200 mg /kg, and 27% •t 50 mg /kg. re- tin /nil and 100 l,g srreptonlycin /nil. After 90 minutes' spectively), whereas C8D did not. a' -THC administered orally incuh ;muff :it 22° C. Irypsin action was slopped by the daily until death In doses of 50, 100, or 200 mg /kg did not addition of complete medium containing hea l•inacti• Increase the Ilfe•spens of (C5713L/6 x 1313A /2)FI (1IDE)) mice valet' fetal calf serum (final concentration, 20 %). Cells hosting the L1210 murine leukemia. However, a "•THC admin• were washed two times in complete medium, enumerated Istered daily for 10 days significantly Inhibited Friend lea- in a Coulter couuler (Model Z11 Or 011 a hemOE)•lontetrr, kemia virus- Induced spienomegaly by 71% al 200 mg /kg as and resuspended in seruln•free nletliunl at a concert a• compared to 90.2% for actlnomycin D. Eapeurnents with bone lion of 5 x 10' cells /ml. Next 1 X 10' cells were injected marrow and Isolated Lewis lung cells Incubated In vitro with int into the right hind gluteus muscle, and drugs admin. a'•THC and A "•THC showed ■ dose-dependent (10' - 10. 1 ) is1cu as descl ibed in ' Ilestills.'• Standard regimens pro. Inhibition (80 -20 %, respectively) of lrltlated mymidine and vidcd for 10 consecutive daily doses beginning 24 hours ''C•uridlne uptake Into these cells. COD was active only In after rumor inoculation. Body weights were recorded he. high concentrations (10-9. - N•li Cancer inst 55: 597 - 602, fur a tumor inoculation and weekly for 2 weeks. Tumor 1975. sire was measured weekly for the duration of the ex(scri• meat and converted to mg tumor weight, as described Investigations into the physiologic processes affected by Alayo (J0). by the psychoactive constituents of Marihuana [A'.ictra• Friend leukemia: 6•Tropic Friend leukemia virus hydrocannabinol (A'.THC) and p'-ICtrahydrocaunabi,iol (FIN) was maintained in ItALII /c slice, and drug evalu• (.1': r11C)j purified from Canrtnbu tabus are extensive actor perfunnel' in the same animals. pools of virus welt (1). However, only recently have attempts been Made to pie reed (emu the plasma of slice given FLV and stored elucidate the biochemical basis for their cylotoxic or at -70° C. hl experiments will) FLV, 0.2 nil of a 1/20 cytostatic activity. Leucluenberger et al. (2) demon- - dilution of plasma (derived from F1.V• infected mice) in sinned That human lung cultures exposed to marihuana luediunl was inoculated ip into IIALII /c spice. Cannabi• smoke showed alterations in DNA synthesis, with the holds \rate administered orally daily for 10 consecti- appearance of anaphase bridges. Zimmerman and Mc- tire days beginning 21 flours after virus inoculation. Clean (J), studying nlacromolccillar synthesis in Tenn- Twcnt•(our hours after the last thug administration, the hymen'', indicated that very low concentrations of A'- mice were killed by cervical dislocation, and the spleens TI IC inhibited RNA, DNA, and protein synthesis and removed and weighed. Mice not given FLV were treated produced cytolysis. Stenche•er et al. (1) showed an in- as described above, to evaluate possible drug•induced crease in the number of damage! or broken chromo- s)ICumnrga1y. sorties 111 chronic users of marihuana. A'•1ftC adnainis. 1.1210 leukemia: The murine leukemia L.1210 was 'erect iv inhibited bone marrow Ieukopoicsis (5), and maintained in 1)6;1 /2 mice by weekly transfers of 111' Kolodny et al. (6) reported that marihuana may impair cells derived from the peritoneal cavity. 111 these experi• testosterone secretion and spermatogenesis. Furthermore, mews, 10' leukemia cells were inoculated ip 11110 • Naha% et al. (7) showed that in chronic marihuana users (057111. /6 x D11A /2)F, (I1DF,) mice, and the ;nice were there is a decreased lymphocyte reactivity to ntitugens :is treated daily for 10 consecutive clays beginning 24 flours measured by Ihy'mitline uptake. These and other (8) after tumor cell inoculation. Mean survival time was observations suggest that marihuana 0'.'1'11C) interferes used as an index of drug activity. with vital cell biochemical processes, though no definite In vitro roll sysfenu.— I.esvis lung tumor: We obtained mechanism has yet been established, A preliminary re• isolated Lewis lung tumor cells by subjecting Trim' sec. port from this laboratory (9) indicated that the ability of tions of tumor to 0.25% Irypsin at 22° C and stirring for .}' •TIIC to interfere with normal cell functions might 60-90 minutes. After Irypsinization, the cells were centri• prove efficacious against neoplasms. This report repre- sents an effort, to lest various c: in several 1 limited December 2fi, 1974: accepted May JQ, 1975. ill vivo and ill vitro tumor systems l0 determine the a Supppiorl <d by Public Health 6ffvicc giant DA00190 Irmo Ihr kinds of tumor's that are sensitive to these colnpoullitlf Nallnu+l hl Ui n,tr on thug Ahua<, Health ben i[ra k Mama' and reveal !heir possible biochemical sites of action(s). health Adminimalinn: by a grant from the Alexandre 311i1 \lava gavel Ste■+all "rr Ull Puud; and by III inariluhonal gum Iron the MATERIALS AND METHODS American Cancer Suci<ay. a Depanmau of Pharmacology and the klCV /VCU Cancer Cell. The tumor systems used 1YCrC 111C Lewis full . 1t'CIIO- Ire, klydiial College of \ Virginia Commonwealth Uni,a• g my Richmond, Va. 23298. IOURNAI. OF TIIE NATIONAL CANCER INSTITUTE. VOL. SS, NO 3, SEr'1 r.3lnr• 1973 597 FIRLT TklrtE( PAGE'S -„_. 98 • MUNSON ET L. ' k fuged (1,000 rpm for 10 min) and washed twice in Dud- C1-13 CH becco's medium containing 20% hea -t l•inactivated fetal calf 1 3 serum. hey were then reconstituted to 10' re!Is /ml in OH 0 OH Lulbecco•s Mediuus containing, for every 500 ntl, 5 rut of 200 rant glutamine, 5,000 U penicillin, and 5,010pg strep- \ tornycin. Tumor cells (3-6 nil) were dispensed into 25 m1 �'` Erlenmeyer flasks and preincubated with either the drug I C5H11(n) is CgHllln) or the drug vehicle for 15 minutes in a 1)ubnolf metabolic g shaker at 37 C in an atmosphere of 5;i. CO, -95% 0,.. C• -THC p -THC p -THC pi -[){C After preincnbaiion, 10 pl tritiated lhynsidinc ('I.LTDR) (10 pCi, 57 Ci /mntole; New England Nuclear Corp., Bos- ton, Mass.) was added to each Bask and incubated for vari• ous tithes, after which I•nsl aliquots were removed and CH CH placed in 10x75•min Zest tubes containing 1 nil 10% trichloroacefit acid (TCA) at 9° C. The TC•prccipi• (-1,,, OH OH fated samples were then filtered on 0.45-p Millipore fil- ters and washed twice wins 5 ml of IU%'TCA at 1° C. t The filters were transferred to liquid scintillation vials . C H (n) and counted in a toluene cocktail containing Liquifluor. 5 II \ C (New England Nuclear Corp.) (9 liters toluene to 160 nil OH Liquifluor). Samples were then counted in a liquid Cannabinal (CBN) Connabidiol (CBD) scintilla lur. Bone marrow: Bone marrow cells were derived from Ti rricear 1 unures of Mc lour major ca ne abi voids. the tibias and fibulas of BU:, mice. One nil Dulbecco's medium containing 1 U heparin /ml was forced through subscuues were stirred with a lass rod in a sonicator The until a good suspension 10 was achieved. desired Sufficient distilled each one by a 1 inl syringe with a 26.gauge needle. cells were washed three tunes, nucleated cells Were enu `viler was niai added ui make the desired dilution. Con• merited on a hemocytonseter, and cell viability was anti-- cenuitions were routinely checked with a gas chronml• ograph. tained by await blue exclusion. Cell number was ad. When Enwlphor- alcohol was used as the cehi• jutted to 101 cells /ml with he iarin.hee Dulbecco's cle, the desired amount of cannabinoid was sonicated medium and incubated at 9° C for 15 minuses. Bone in a .solution of equal volumes by absolute ethanol and � ins) into 25 -ins Enwlldior (EI G20: CA Corp., New fork, N.l'.) and marrow cells were then dispensed (3 -5 i Erlenmeyer flasks contalidng the toast drug or the drug then diluted with 0.15 r< NaCI for a final ratio of 1:1:9 vehicle. 'Phis preinutbation period was followed by she (ethanol: Emulphor:NaCI). addition of 10 pi 'H•TDR and the procedures done as outlined for use isolated Lewis lung cells. RESULTS 0 L1210: L1210 cells were derived from DBA /2 mice as Effects of C•nnebinolds on Murine Tumors • described above. They were obtained from DIIA /2 mice a•.1 as - TIIC, and cannabinol (CIIN) all inhibited and inoculated 7 days before the experiment by the primary Lewis lung tumor growth, whereas cannabidiol peritoneal cavity being flushed with 10 nil Dulbecco's (CBI)) enhanced tumor growth. Oral administration of medium containing heparin (5 pimp. The cells were 25, 50, or 100 mg "1'IIC /kg inhibited primary tumor washed three times in medium, and the final medium wash did not contain heparin. The cells were resus- 2o b)• 98, 72, and (a 1 )Iien m red 12 pend mice ed at 10' cells /ml and treated as described above. 1 mice given gi post tumor T11C inoculation had a 3y had a 31 sable ; redusii I . On ri 19. n Cells Were routinely counted with a hem tumor r o ocytometer for si. On day 30, primary tumor aim i was n 6 s the determination of cell viability with trypan blue; for le and onl s /k that • Lewis lung tumor and LI210 cells, a Coulter apparatus a g m ica and only those given 100 m ar•THC g had Pl a (Mode 7.11,) was also used. significant increase in survival time (36 ;). All onici reagents were of the highest quality grade Mice treated with as:I'HC showed a slight weight loss • g 1 y g over the 2•weck period (average loss, 0.3 g at 50 ing /kg available. Actinonsycin I), 5•fluorouracil (5.FU), and and 0.1 g at 1110 nig /kg), This can be compared to cyclo• cytosine arabinoside (ara -C) were provided by the Drug phosphamisle, which caused weight loss approaching 20% Development Branch, National Cancer Institute (NCI). (table 2). Connabinoids. — The structures of the four coinpounda ar.T11C activity was similar to that of as•THC when are shown in text-figure 1. All occur naturally in nsari. administered orally daily moil death (table 2). However, livana and were chemically synthesized. These drugs as with a• -T I1 C, primary tumor growth approached con• were provided by the National Institute on Drug Abuse trol values after 3 weeks. When measured 12 days Irosi or the Sheehan Institute for Research, Cambridge, Massa• tumor inoculation, all doses (50-400 mg /kg) of as.TI1G chusetts. In the preparation of the drugs, the cannabi• inhibited primary tumor growth between 40 and 6(1"6. noids were complexed to albumin or sohshilired in Significant inhibition was also seen on day 21, which was Enmiphor- alcohol. Both preparations produced similar comparable to cyclophospharnicle•ireatetl nsice. Although s antitumor activity. With albumin, the cannabinoids were this was not the optimum regimen (or cyclopliospliatniie. prepared in the following manner: A stock solution of it was time positive control protocol provided by the NCI 150 mg cannabinoid per ml absolute ethanol was made. (1/). All mice given as.THC survived significantly longer Six ml of this solution was placed in a 200.m! fink. The than controls, except those treated with 100 mg /kg. Alice •, C11131101 was evaporated off under a stream of nitrogen given 50, 200, and 400 nig /kg iv-T1 had an increases! and 2.100 nig lyophilized bovine scrum albumin (BSA) life•span of 22.6, 24.6, and 27.2 %, respectively, as rota• added. After the additions of 20 ml distilled water, the pared to 33% for mice seated with 20 mg cyclophus• 1, ANTICANCER ACTIVITY OF CANNABIN 599 / - TABLE 1. -Effed of C' -TIIC on tumor growth and seminal time of mice hosting Lewis lung tnrcinomra • 'furnnr weighta (g) at Treatment Dose Body weight - - - -- hlean aurviv al Increased mg /kg 'change (g) • 12 days • 10 Jnyn • 30 Jaye • time (Jaye) life•epan, % C ontrol (USA 7.5%) - +1.5 892 ±150 8,456x252 5,8871±673 25.8 ±1.3 (8) (3) i p••TIIC 25 +0.9 468 2, 363 146 ' 4,337 ±270 30.3 ±2.0 17.4 I (8) (8) (4) 1 p' - T1IC 50 -0.3 253±118 2,168 ±105' 4,861 27.4±0.0 0.2 (8) ( (I) p'•TIIC • 100 -0. 221 ±98' 2,307 ±362' 4,066 ±312' 35.0 ±1.1 ' 30 (71 (7) (7) - • Groups 01 mice wise Inoculated Im w11b 1 %10' Lewis lung tells end tinted orally for 10 Jaye with d• -TIIC. a Whole body weight change alter IU d.y. of treatment. , Pon tumor Implants: tumor •rlahts wefts derived 'rum mruurement of m•io, • nU minor a ,t.. V.luta ate mean. Sac: number of mire ate indicated in por,nlh, • P <0.03 as compared to control.. TABLE 2. -Effect of A' -7I1C on h growth and nrnilnl time of Rol, mice hosting Leath lnnp carcinoma • Tumor weight,' (g) at Treatment Done Body weight mg /kg change (g) ' 12 days • 21 da •n' Aline (Jaya) e- span, time (Jaya) lilts -gpnn, r • Control (USA 7.5%) - -1.6 621 ±30 4,880 ±380 30.5 ±0.9 (30) (30) p •TIIC 60 -0,9 279x46 3,204 ±271 31.4±1.7' 22.6 d' -TUC IOU -3.4 104x36 d 2,211 *236' 34.3 ±1.0 12.4 (7) (7) p' -TUC , 200 -1.6 174±53 3,185 ±390' 38.0 *1.0' 24.6 (0) (6) o••TIIC • 400 - 3.3 235±78 3,104 ±413' 38.8 ±1.2' 27.2 CydaphwphamiJe 20 -4.0 (G) . (6) I 0 2,040 ±194 40.631.8' 33.0 Pyran copolymer 60 o•r OH +0.3 1.. ±39 . 1,870 ±174 42.5 ±3.3 39.3 (8) (8) • Croupe of male BOP' mice were Inoculated Im .Ith 10' Lee It hag carcinoma tells and lusted Dully J•ily lilt!, 3' - TIIC until death. Cyclophosph.mbu awl Pyr.n (stub liter were administered Ip for 10 consecutive days beginning 11 hours •I err tumult Inocul. nun. ' Whole body weight changes due 10 days of treatment. ,. • Post rumor Implants: tumor weights •ere derived from measurement of m•iur •nd minor tumor ••es. Values are meant ±•g;' number of mice art ledi- wed in portnlAun. , P <0.03.e compared to control 1 1 TABLE 3. -Effect of CIIN on tumor growth and •Taunt time in ltDF, mire hotting Lruis lung carcinoma • tl 1 . 11111111" w eighth (g) al T reatment \ l gnu sat n•i vnl 3 ur remee 1 T Ulna Hotly weight mg/kg change (g) • 14 day, • 24 dnya • time (days) life•span, • Control (USA 7.5%) +3.3 1,2$S ±146 5,520 *566 26.6 ±1.3 (21) (21) CIIN 25 • -11.6 1 ±146 6,74:1 ±376 29.0 ±1.2 12 (N) \ CIIN 50 -11.6 875 ±115 5,700 ±201 33.7 ±1.0 27 • _2 (6) (6) CItN IOU .6 200±99 4,943 ±462 27.8 ±0.0 3.5 ( (7) • • Croups of mite Inoculated I•n with 1 x IU' 1..l. lung cell. and Ira trd orally d•lly suit, '-TIIC or CON until dr•lh. 1 Whole body weight changes slier y • ler 10 Mays nl treatment. - • Pon tumor Implants; lamer nights were Jade td Iron measurement of major and n,inor tumor ern. Veber err marmot; number of mice err indl• rated in parr..IAran. • P <0.03 a compared to controls. • phainide /kg. Pyran copolymer, an inimunopolcntiator was observed on day 21; however, these animals did stn. (/2) when administered at 50 nig /kg, also significantly vivc 27 "; longer. increased the survival time of the animals (99.3 %). CItU, adminislcred at 25 or 200 nsg /kg daily until CIIN, administered by gavage daily until death, deal- death, showed 110 tumor-inhibitory properties as meas. onsirated antitumor activity against the Lewis lung carci• urea by primary Lewis hung tumor site or survival time nonsa when evaluated on Clay 11 post tumor inoculation (cable •I). In this experiment, CBD• treated mice showed 1 (table 3). Primary tumor growth was inhibited by 77 at enhanced primary tumor growth. However, the control doses of 100 mg /kg on day 11 but only by 11% on day 24. tumor growth rate in this experiment was decreased as At 50 nig /kg, CIIN inhibited rilnary' tumor growth by compared 10 the previous studies. only 32% when measured on day 11, and no inhibition Survival time of IIUF, mice hosting 1.1210 leukemia ' • , \.Ii.N.AI 2'P. va a .L AS, , $4„,2•••"•-••1•:4;41....-4:1,.:# . 1.-. Y" nr .. • • (' t e � . :• Ys 1 b.• .. ,-. .rah.,.., :.! ,x,,,..» qtr +.a•fx, Y •,. , Y .... .-. M arij uana Use and Mortality • • • • A B , , S' T R. A C T. Stephen Sidnev, MD, Jerome E. Beck DrPll, Irene S. 7 MA, Charles P Quesenberry, lc PhD, and Gary D. Friedman, AID Objectives. The purpose of this study was to examine the relation- Introduction confidence interval ICU = 0.8, 1.9) after ship of marijuana use to morality. adjusunent for social background. Methods. The study population Marijuana is the most commonly We report here the findings of a composed 65 171 Kaiser Pemtan• used illegal drug in the United States. study of the relationship of marijuana use • ente Medical Care Program enroll- Over 65 million Americans (31% of the to morality in a cohort of over 65 (X).) tees, aged 15 through 49 years. who US population aged 12 and older) Sir ' of a large prepaid health plan. completed questionnaires about estimated to have used marijuana: its Data on marijuana use in this cohort were smoking habits. including marijuana mean retail sales value in the United collected before the "war on drugs" use, between 1979 and 1985. Mortal- Sates is approximately 510 billion.' escalated in the latter half of the 19815, ity follow -up was conducted through Respite its longstanding popularity :aid which may have resulted in underreport - 1991. increasing use among youth in recent ing of illegal drug use .° Mortality is one of Results. Compared with nonuse ycars2 we still know little about long- several health outcomes being studied: or experimentation (lifetime use six term health risks associated with mrl- other endpoints include cancer incidence or fewer times), current marijuana Juana use. Harvard policy analyse Nlark and outpatient utilization fur respiratory • use was nu( associated with a signifi- Kleiman recently concluded that "aside illnesses and injuries. We hypothesized cantly increased risk of non- acquired from the almost self - evident proposition that marijuana use would be associated intnunodeliekncy syndrome (AIDS) that smoking anything is probably bad for with increased risk of respiratory diseae mortality in ran (relative risk [RR) = the tunes, the quarter century since large and injury. 1.12.95%confidence interval )CI) = numbers of Americans began to use 0.89. 1.39) or of total mortality in marijuana has produced remarkably little h'fethuds women (KR = 1.09. 95% 0 = 0.80, laboratory or epidemiological evidence of 1.48). Current marijuana use was serious health damage done by the Smelly Population associated with increased risk of drug." 4P25rt Similar appraisals of the A cohort of 65 171 men and women AIDS morality in then (RR = 1.90. health effects of cannabis were offered in aged 15 through 49 years (mean age. 33 95% CI = 133, 2.73). an association the two most comprehensive reviews years) completed detailed self - adnunis• that probably was not causal but most (rum the 19805. More currently, Hall tered research questionnaires on tobacco. likely represented uncontrolled con - and coauthors concluded that while there marijuana. and alcohol use from nud- founding by male homosexual behav- are no well- established health or psycho- 1979 through 1985. The subjects were iota This interpretation was supported logical effects of chronic cannabis use. the undergoing mulmphasie health checkups by the lack of association of mari- following were considered to he probable in the San Francisco (until 1980) and juana use with AIDS mortality in major adverse effects: respiratory diseases Oakland Kaiser Permanence facilities. men from a Kaiser Pennanente AIDS associated with smoking as the method of Mortality was followed through Decerat- daabau. Relative risks for ever use adminisration, including chronic bronchi- bet 31, 1991, for a mean length of 10.0 uf marijuana were similar. tis and premaltgnamt histopathological years. Conclusion. Marijuana use in a changes in the lung; development of a prepaid health care -based study co- cannabis dependence syndrome: and subtle Stephen Sidney. Irene S. kkawa Charles P. bon had fink effect on non-AIDS forms of cognitive impair menl."P'a' Qucsenbcry. Jr. and Gary D. Friedman art wan mortality in men and on total mortal- The only other large - scale study of to Div ision of Resca,th. Kaiser Pemunenhe ity in women. (Am .1 Public Health. ma use and mortality was der- Medial Care Program tNumem California Region), Oakland. Calif. Jerome E. Beck is with 1997 :87:585 -5901 forced in a col of 45 540 male the School of Public Health. University of Swedish conscripts, aged 18 through 20 Caldomua, Berkeley. years at baseline and followed for 15 kequests for reprints should be sir to years.' In this sooty, the relative risk (RR) Stephen Sidney. MI), Division of Research • Kaiser Permanente Medical Care Program 3505 for mortality associated with marijuana Broadway. Oakland. CA 94o 11. use Inane than 50 Woes) was 1.2 (95`-f This paper was 'accepted lune 28, 1990. • Sidney n al. • • DaJnilinns of Use TABLE 1- Sociodemographic Characteristics of a Cohort of Kaiser Current marijuana smoking was dc• Perrnanente Medical Care Program Members (n = 65 171), by Sex and Marijuana Use Status: Oakland and San Francisco, June lined by admission to smoking currendv 1979 through December 1985 and more than six times ever. Fomhcr marijuana smoking was defined by denial Marijuana Use °n of current smoking but admission to having smoked more than six tilnes ever. No. Never Experimental Former Current Nonsmoking was defined as never having Men 14 407 smoked. Experimenters were defined as (n = 9103( (n = 5304) in = 6114) (n = 7560) Ihosc admitting to having ever smoked from one through six times. Ever users Age at entry y included current and former users but 15 968 32.1 17.5 17.1 33,4 .20 7 802 21.6 16.3 25.2 36.9 excluded experimenters. Smoking dura• 30 11 619 27.9 18.6 25.1 28.4 ' Lion was expressed as total years of usc. 40 7 692 50.3 22.1 13.6 13.7 Smoking frequency was expressed as less Race than once per month once or twice per White 16 175 26.4 19.1 24.7 29.8 month. once or twice per week. and daily Black 6 622 30.4 190 19.9 30.8 or almost daily. Asian 3 075 65.3 16.7 11.4 6.6 Hispanic 1 353 37.3 21.3 19.2 22.2 Persons were classified as current. Other/unknown 856 36,6 18.6 21.3 23.6 former, or never smokers and users of Education alcoholic beverages on the basis of their High school a less 4788 35.7 18.1 18.1 26.2 questionnaire responses, Cunene and Technical or business 1 113 37.9 18.9 18.2 25.1 former smokers were categorized by X1001 frequency number of cigarettes r da Some coa re uenc ege 8 406 28.8 16.6 22.2 30.4 4 y ( g• cremes a Y) College graduate 6 424 34.8 18.3 21.9 25.0 and duration (years) of smoking. Current Postgraduate 6 793 31.5 20.3 23.9 24.3 alcohol users were categorized by usual Unknown 557 31.4 19.4 26.6 22.6 numbers of drinks consumed per day. Marital status Never married 9 159 22.0 16.7 24.3 37.1 ,bfonaliry Follow -Up Married 12 949 43.9 19.6 18.7 17.9 Remarried 1 777 27.2 24.0 24.3 24.5 Monality was ascertained through Separated 951 21.0 18.2 22.7 36.1 1991 by computer - mooching study cohon Divorced 2 660 20.6 19.8 24.9 34.6 Widowed . 71 42.3 29.6 14.1 14.1 members with the Kaiser Pcrinanenie Unknown 514 28.4 17.7 29.2 24.7 Medical Care Program membership file Total 28 081 32.4 18.9 21.8 26.9 as of 1992 and extracting a list of subjects 6Cf who were no longer members. Fmrn this l d Wome list we accepted as confirmed deaths (n = 15 952) (n = 7913) (n = 6657) (n = 6566) those a cenainaxl in previous research Age at entry, y studies. The mortality status of the remain - 15-19 1 773 33.6 22.1 19.4 24.9 ing study subjects who were no longer 20-29 12 414 30.9 21.1 22.6 25.3 30 14 240 40.1 22.3 20.1 17.5 members was ascertained by computer- 40 8 663 67.0 19.8 7.5 5.7 matching names and other demographic • Race data with the California death file, using White 18 323 30.9 23.3 24.1 21.8 the California Automated Mortality Link• Black 11 689 48.5 21.6 13.1 16.8 age and information System (CAM• Asian 4 154 74.7 13.3 7.2 4.8 LIS). Death cenilicale Specified under - Hispanic 1 807 56.8 18.3 12.1 12.8 lying causes of death (International 1117 44.9 21.3 16.9 16.9 Y g Education Classification of Diseases, 9th rev. Hgn scrod or less 7 927 52.4 19.8 13.0 14.9 1C0-9) were used for coding. Centers for Technical or business 1 945 48.4 22.3 13.0 16.3 Disease Control and Prevention criteria school were used to code acquired imntuntdeli• Some college 12019 41.2 21.5 18.0 19.4 ciency syndrome (AIDS) prior to the College graduate 7 918 43.3 20.3 19.1 17.3 Postgraduate 6 524 33.3 23.9 23.4 19.5 introduction of specific disease axles Unknown 757 41.0 21.9 23.3 13.9 associated with the human inununodefi• Marital status ciency virus (HIV) in I9S7'.y Never roamed .11 559 29.9 21.1 22.9 26.2 Deaths of subjects who left Califur- Mamed 15 550 56.4 19.4 13.6 10.7 nia were investigated by linking pertinent Remarried 2009 38.6 26.8 20.2 14.3 Social Security numbers to a Pension Separated • 1 521 36.4 23.9 16.4 23.3 genefilslnfonnaliun Calif) tl:ua Drvorced 5 340 35.4 24.9 19 3 20 4 Wdowed 416 64.2 17.6 9.4 8.9 base that included mortality data from the Unknown 695 36.1 23.3 24.3 16.3 stale of California Center for Health • Total 37 090 43.0 21.3 17.8 17.7 Statistics, the Social Security Administra- tion. the Department of Defense. the Civil Arwil IOU V'.J 9,,7 No 4 • • ?Lrijunu Lx' •usi N 2- Relative Risk of Death for Ever Users and Current Users of Marijuana, by Sex and Cause of Death: Kaiser Permanente Medieai Caro Program Members (n 65 171), Oakland and San Francisco, June 1979 through December 1985 Ever Users _ - Current Users No. Deaths in Nonsmokers./ Nonsmokers/ Reference Full ModeP Occasional Drinkers° Full MooeP Occasional Drinkers° Group Cause of No. -- ----- ---- -- No. - (Nonusers' Deals Deaths RR (95% 0) RR (95% CI) Deaths RR (95% CI) RR (95% CI) E°perinlenlers) -__ Men - ;� 7n I . AIDS 152 1.80 (1.29, 2.52) 2 34 (1 32. 4.14) 104 1,90 (1.33, 2.73) 1.91 (1.02, 3.55) 55 . Non -AIDS 266 1.11 (0.92, 1.34) 1.25 (0.82, 1.89) 153 1,12 (0.89, 1.39) 1.15 (0.67, 1.97) 315 Neoplasms 45 0,78 (0.52, 1.16) 0.46 (0 15, 1_41) 30 0.97 (0.61, 1,55) 0.75 (0.21, 2.69) 90 Circulatory disease 60 1.08 (0.75, 1.55) 1.36 (0.58, 3.19) 37 1.22 (0.60. 1.87) 1.80 (0.68, 4,73) 102 Injury/poisoning 92 1.24 (0.87, 1.75) 1,65 (0.64. 3.23) 47 0 99 (0.65, 1.50) 1,23 (0 51, 2.95) 72 Other causes ' 69 1.47 (0.98, 2.22) 1.71 (0.62, 4.68) 39 1.39 (0.86. 2.24) 0.66 (0.14, 3.451 51 Unknown 12 ... ... 6 ... ... 7 Total • 430 1.28 (1.09, 1.50) 1.58 (1.14, 2.18) 265 1.33(1.11, 1.59) 1.50 (1.01, 2.22) 377 Women !(,.>J ps, 6 f 7 , i 12rk erg t / Neoplasms 36 0.82 (0.54, 1.22) 0.70 (0.31, 1.58) 19� 0.06 (0.51, 1.45) 0.56 (0.17, 1.90) 155 Circulatory disease 13 0.68 (0.35. 1.33) 0.34 (0.04. 2.90) 10' 0.96 (0.46, 2.02) 0.70 (0.08, 5,95) 64 Inluryipxtisonirg 28 1.39 (0.79, 2.44) 1.40 (0.65, 3.04) 19 1.86 (0.99, 3.51) 2.04 (0.85, 4.91) 38 Other causes' 16 0.76 (0.39, 1.46) 0.40 (0.05, 3.35) 10 0.95 (0.45. 2.04) 0.84 (0.10, 7.23) 50 Unknown 4 ... ... 3 ... .,. 4 Total 97 0.90 (0.69, 1.16) 0.81 (0.49, 1.34) 61 1.09 (0.80, 1.48) 1.03 (0.55, 1.90) 311 Now, RR = relative risk, CI = confidence interval. w6 'Adjusted for age, race. education, marital status, obesity, cigarette smoking, and alodnul use. °Adjusted for age, race, education, mental status, and obesity, Includes 3AID5 Wachs. "No. deaths in current users is included in no. deaths in ever users. Service Commission. and the Railroad deuce intervals were obtained from These were about twice as likely to be ever users ' Retirement Hoard. While Social Security ;nixiels. Age- squared terns were en- as their married counterparts. Su-jodenu- numbers were available for about two tered into Cox proportional hazards mod- graphic patterns were generally similar thirds of the study cuhon. only 27 of 1215 els t0 determine whether here was a for current marijuana use. deaths (2.2%) were ascertained by out -of- nonlinear relationship between age and Current marijuana users were twice state search. Since cansess of death were mortality and were included when signiti- as likely as never users In be curlew unavailable for out -of -state deaths. these cant. Interactions between marijuana and tobacco cigarette smokers and nearly 2.5 deaths were included in analyses of total tobacco use and between marijuana and li as likely w be alcohol drinkers. - Rte mortality but excluded in subcategory alcohol use were tes(ed in the selected percauage of cutienl ;Waken was 21'.)' mortality analyses. rnalels (total monaljly. AIDS munaljty for never marijuana users. 31% fin The overall age - specific motility linen only], non -AIDS mortality [men experimenters. 32'h- for former users. and rates of this group were about three onlyl, and mortality from injuries/poison - 42% for current users. The corresponding quarters as large as the corresponding ings) by including cross - product terns in percentages of those consuming one or 1987 United States rates. a discrepancy our proportional h:¢alds mulels. None of more drink per day were l . _ 3I' wr attnbute to the probable better health the interactions were statistically si_mif- and 39Ca. While few nlaijuana users were and predominantly employed status of our cant ( < .05). nonusers of alcohol, a substantial propor- insured population and to our inability to tj0n of ever Illariju:ula user\ 125 ° r of men. ascertain mortality in subjects without R e s uliS 30'.'o of wotnenl and current marijuana Social Security numbers who had left users (22% of men- 28% of women) were California. Sociodentographic characteristics of nonsmokers of tobacco cigarettes and :L iv '• the sample are shown in Table I. The occasional (less than once per nim ' cohort consisted of 38'f nonusers. 20% drinkers. • SAS programs were used for stalisti- eaperinlenters. 204 former user. and We compared risks of rnonality as- cal analysts.'' Cox proportional hazards 22% current users.lhr percentage of ever ,o dated with ever and current use relative models were used to examine the pate users was highest in the 20- through 29- 10 never ore.spennlental use of marijuana. effect of socludemographic charactenstics year -old age group. Ever use of marijuana There were SU7 deaths among men arid and use of marijuana tobacco. and was more common among men than 408 deaths among woolen in this cohort. alcohol on nit:ru ty risk: estimates of among women and was highest Milting We performed analyses for total rnonal- relative risks and associated 95'.'n coati- Whites. Never- married men and women jtv, AIDS linen only ).neoplcome, ' Sid ucy et al. • • TABLE 3—Rlsk of Mortality Associated with Current Cigarette, Alcohol, and Marijuana Use: Kaiser Permanence Medical Care Program Members (n = 65 1711, Oakland and San Ftancisco, June 1979 through December 1985 Curren) Marijuana Use' Current Consumption al Three or — Cigarene Smoking' More AlcohoLC Dunks per Day° Al Least Once a Week Daily RR (959a CI) - -_ — Rf9 (95`,0 CI) - -- RR (95 °= 0) RR (95'ro CI) Men AIDS 1.64 (1.15, 2.34) 0 94 (0 60, 1 47) 2.09 (1.42. 3 06) 1.65 (0.97, 2.82) Non -AIDS 1.76 (1.40, 2.20) 1.21 (0 94. 1.86) 1.17 (0.91, 1.51) 1.31 (0.93. 1.84) Total mortality 1.75 ( 1 . 4 5 , 2 . 1 1 ) 1 . 1 3 (0.91. 1 401 1.46 (1.19, t 79) 1.43 (1.08, 1.901 , Women: Total monaliry 1.58 (1.25, 2.011 1.90 (1.31, 2.76) 1.23 (0.84, 1.80) 1.44 (0.00. 2.56) _ _ I Note. The model was adjusted 1o1 age. race, education. marital status. nbe il'y. Cigarette smoking. and alcohol use. RR = relative risk, GI = conhuence interval. •Retacve to nonsmoking. - r to occasional alcohol use. °Relaljve to nonuser /experimental user status. • I 10ry disease, injury or poisoning. "other were not an artifact resulting from incom- Lion of whether analynic control for causes" of mortality, and lolal nun -AIDS piece control of the effects of cigarette marital status was insufficient to adjust foil mortality (men only) (Table 21. smoking or alcohol use. The results of an confounding lifestyle factors. particularly analysis of mortality excluding subjects male homosexual behavior. Marijuana Use in Relation who died within the bust 5 years of To address this question. the study to Mortal:1 follow -up (data not shown) were similar cotton was linked to the Nonhem Cali fur. For men, ever use of marijuana was to the overall results shown in Table 2. nia Kaiser I'cnnanente Medical Care associated with a significantly increased suggesting that the overall results were Program AIDS Database. which revealed risk of total mortality (28%) and AIDS uncompromised by the possibility that 214 men with a diagnosis of AIDS after mortality (8U%) and a nonsignificant (P> serious illness occurring before the multi- deieniiination of their marijuana use .05) increase (I I%) in risk of non -AIDS phasic health checkup affected subjects' status. The prevalence or current man- atonality. Relative risks associated with decision to use marijuana. juana use al the nine of the checkup (507; ) ever marijuana use for these mon;dity Duration of use in current marijuana in These AIDS patients was substantially categories were similar or higher in users was not consistently related to the higher than the prevalence in unntarned nonsmokers/occasional drinkers (a group risk of AIDS atonality in men or to total men in the toad study cotton 138%1. in which marijuana use could be evalu- mon:tlity in women, and had an inverse For these 214 AIDS patients. current aced without uncontrolled confounding by tendency in relationship to mud and marijuana use was ;rsxwiated with a cigarette and substantial alcohol use). Of non -AIDS atonality in men (data not nonsignificant decrease: in relative risk for note was the nearly significant 47% in- shown). A continuous duration -of -use total mortality (RR = 0.78, 95 e Cl = crease in "other causes" of monality, variable was not significant when added 0.47. 1.30) and lur AIDS mortality examination of which revealed higher to the full models for each mortality (RR = 0.71, 95% 0 = 0.41. 1.231. As • proportions of deaths from infectious outcome. miming that most of the unmarried men diseases and from alcohol and drug abuse Marijuana use at least once a week who developed AIDJS were homosexual in ever users than in never users/ was associated with slightly hither relit- or bisexual. these findings supported We experimenters. Current marijuana use was rive risks of atonality than less frequent hypothesis that the prevalence ol mari- also associated with a significantly in- use. The addition of frequency of use jutna use was higher in homosexual and creased risk in men of total mortality improved the lit of the model (P < .05) bisexual men in the cohort. a group al high (33 %) and AIDS morality (90%). only for total monaliry in men (kR = 1.25, risk for AIDS mortality. Therefore. male In women. there were no signihcnt 959i 0 = 0.97, 1.62, for toed monaliry homosexual behavior. a critical confound- increases or decreases in mortality risk among those who used less than once a ing variable. could not be controlled for in associated with ever or current marijuana week and RR = 1.46. 955; CI = 1.19. complete cohort monalily;nalyses. use. Current use was associated with a 1.79, among those who used at least once nearly significant 86% increase in atonal- . a week, relative to nonuserslexrcrintent- Comparative h'ic'ks of /irhurcn,. • Icy from injury or poisoning. which could mil. Alcohol, and b9w'ijuunn Use not be attributed to any specific category ;U h lortnfiry The relative risks of total mortality in of injury. men and women. and of AIDS and Relative risks associated with Mari- The vat( majority of AIDS deaths non -AIDS mortality in men. associated juana use among nonsmokers/occasional (172/207 = 83%) occurred among never with current cigarette smoking. vonsuntp- drinkers were generally similar 10 (hose married men. CLUTCH( marijuana use was lion of ttuee or more dunks per day. urd for the complete cohort. suggesting that nearly twice as high in never manned as in current marijuana use are shown in Table increased risks in the complete cotton warned men (Table 11. rising the titles 3. 13xcept fur AIDS rnortaluy. the risks I • "qv A rri - n• ■•■nrll ld P1. 11 ^'J1h ANO t'hr' Via N1 No • . \Lrijualm tar and Mortality associated with marijuana use were lower and occasirwal alcohol drinker, a sub- maxinwrn age reached. 63 years); a lack than those for tobacco cigarette smoking. group unlikely to concur many parenteral of information regarding other illegal Compared with consumption of three or drug user. Additional evidence against drug use: and potential underascenain- °tre drinks per day. marijuana use was nuutju;ua as a mat ken for parentcrd drug meat of mortality (noted carlien. Esu- associated with a higher risk of total use was the finding of only one case of mates of marijuana use were similar to mortality and AIDS mortality in men and infective entice:miuu to Kaiser Ferman- dose obtained during this period by the a lower risk of total mortality in women. ente hospitalization records of the AIDS National Household Survey on Drug decedents. Abuse. Inc most authoritative source of Discussion 'The lack of incre: scd atonality illegal drug use infommation for US during Inc tint 5 years of follow •up adults.=' The lack of longitudinal data The main overall findings were an suggests that therapeutic rise of marijuana regarding use status is common to many increased risk of toted mortality associated at baseline for AIDS - rr•Lucd symptoms cohort studies. It seems unlikely that with marijuana use in men but not in has little. if any. explanatory effect on Inc "ever" marijuana use status would have women. The increased risk of total association between ucrriju;na use and changed substantially over tithe. because morality in men was explained by Inc AIDS. Furthermore, the majority of AIDS relatively few adults in this cohort are strong relationship between marijuana use patients initiated marijuana use long likely to have initiated marijuana use • and AIDS mortality. Marijuana use was before Inc onset of clinical disease: nearly during follow -up in a period (Inc 1980s) unassoeiated with non -AIDS mortality in two thirds (b59rt of AIDS patients re- when there was a marked secular decline men. honed initiation before t976, when IiIV in .elf- reported marijuana use in Inc • The question of the effect of Milli- infection in the San Francisco Bay area United States.' It is possible that relation - juana use on AIDS mortality is an was either nonexistent or ncgligiblc. -= ships between marijuana use and mortal- important one. Marijuana use has been While marijuana and its psychotic- icy might he found with longer -term advocated as a therapeutic adjunct to rive cannabanoids possess known Muria- follow -up or later in life. It is likely that if ameliorate the nausea and loss of appetite nosuppressive qualities, there is no consen- information on subjects' use of other commonly associated with the wasting sus as to whether typical doses result in illegal drugs had been available, adjust - syndrome in AIDS." We have provided clinical irttmunosuppression in humans!' orient for other thug use would have substantial evidence that Inc increased Marijuana rise has been associated with a lowered Inc relative risk estimates for risk of AIDS mortality in the total study higher prevalence of seropositivity for marijuana use. cohort probably resulted from uncon- HIV in some cross - sectional studies of As noted earlier, relatively few ad- trolled confounding by homosexual bchav- homosexual and bisexual men!"'' but it verse clinical health affects from Inc ion. Other studies have reported a substan- has not been shown to bc an independent chronic use of marijuana have been tially higher prevalence of marijuana use predictor of semconvcrstun. nor does it documented inhmnans."P The criminal- in homosexual and bisexual men, support- increase the risk of AIDS in scropositive ization of marijuana use may itself be a ing Inc hypothesis that marijuana use is a men.=' health hazard. since it may expose the marker for homosexuality or bisexual- The nearly significant increase in consumer to violence and criminal activ- ity. mortality risk from injury or poisoning for ity.y" While reducing the prevalence of There are several other potential female current marijuana users was consis- drug abuse is a laudable goal, we must explanations • for Inc increased risk of tent with our hypothesis the marijuana recognize that marijuana use is wide - AIDS in marijuana users. Marijuana use is a risk factor for death due to injury. spread despite the long -tern, multibillion smoking night theoretically place AIDS Marijuana is known to decrease psycho- dollar War on Drugs. Therefore, medical patients at increased risk of infection motor performance: some studies have guidelines regarding its prudent use should because of its irritative effects on the implicated its use in motor vehicle be established. akin to the commonsense respiratory system or because of infec- crashes. "Pr•' Slarijuana use is also guidelines that apply to alcohol use. tious contaminants (e.g., fungi) in magi- strongly associated with alcohol use. Unfortunately. clinical research on (mien- juana. Other potential explanations in- another major risk for accidental death. teal therapeutic uses for marijuana has elude marijuana as a marker of high -risk There were tcxi few deaths to meaning - been difficult to accomplish in the United sexual behavior or intravenous drug use fully study the other main hypothesis. that States, despite reasonable evidence for Inc initiation of marijuana use as a result of marijuana use would be associated with efficacy of tctrahydrucannabinol 1 /1(Th having HIV or AIDS, rather than preced- increased respiratory disease morality. and marijuana as antienetic and anuglau- ing Inc disease: and possible inhnunosup- Another study performed on a suhgroup coma agents and the suggestive evidence pressive properties of marijuana of this cohort showed that daily or for their efficacy in the treatment of The use of alcohol and nonmedical near -daily marijuana users who were not other medical conditions. including psychoactive drugs, including marijuana. tobacco cigarette smoker, had a 19% AIDS.'rP''! °-' is associated with risky sexual behavior higher risk of outpatient visits for respira- In numuar thus study showed little. such as unprotected intercourse!u but tory disorders than nonusers of bah if any. effect of marijuana use on nun- methodological limitations have made it substances. AIDS nonahry in men and on total mot- impossible to detennune causality!' Mari- The major limitations of this study alloy in women. The increased risk of juana use may serve to a certain extent as include its reliance on self-repon for AIDS tonality in male marijuana user a marker of intravenous drug use. How- ascertainment of marijuana use slams: the probably did not reflect a causal relation• ever, the relative risk of AIDS mortality inability to study changes in marijuana ship. but most likely represented uncon- associated with marijuana. use did not use status during follow -up. a lack of trolled confounding by male homosexual diminish when the analysis was limited to lengthy follow -up into the geriatric age behavior. The risk of mortality associated men who were nonsmokers of tobacco range (maximum follow -up. 12.5 year: with marijuana use was lower than that • h .. ,., „ n,,, ,,,i ,•i p:d t t,,.,nt, iso r . • Sidney et al. asm coaled with tobacco Cigarette s11)04- Gnvenllneni I'ublislulie Scn,ce. 1954. 2(1. Ostrow DC). Substance use and HIS'. inc. ❑ N:aunal Ihu1. Sualcg). \U. 25. transmitting behaviors among gay and 8- Andremsun S. Allrtticl, 1' Cunnahls and hlsexuul men. In: Ruljes Id..Siotsxla Z. IuunLiih among vuun(• 11 ICH :1 lunptwdu C,acr WC. eds. "I'iu Contest of 11/1 Rol Acknowledgments 111 sluts ul SS. ■iuii iuus,npI.. Scam( l among (Drug awn and 'heir .Sr lima 'Ibis research was supported t) gram RUI . M.d I'rnrl }L'+ -15 Ponnen. Rockville. Md. National Insumie 0.k0(1(4/9 111118 the National INIAUle 011 0 Suliit ■ S. I". WVncv tai .i��rcl>am data till Ihup Abuse: 1494. N1DA Research ter:udlo}: ne141.. o imai uvula use and M Ih 141, Abuse. DI Friedman is supported in pan h■ 1 na f soppy). 1965 -I 115 iu.,r.'rur 1)ru, pain R35 C.4497b from We National Cancer I`rnl. "_.115 -1J t 21. Iciph BC :. Stall K. Substance use and risk Inshore. The collection of data on alcohol use Ili Foenn Ci. SLLInIt S. I'nlul M Snalknnl, se AUDI 1X211Jnui ILK eaposwc to 111V. wa suplslne.J b) a grata' from The Ak issues in rtreWosluln into xcuu'm. and Ilneru•r Medh ::d Kc search Foundation IIJalu Kohl's anyone d 'fnd H.14t�pn „a: ex :unu reel. 1479 methodology. _ m i 'nit 14.'4 J ±Ibo5:051 -656. pleceubon. Am ''sterol. 1991 :48:10:1. more. MII. 11. KlaNk■ Al.. Ano.uoug MA. Friedman 11k16. fl,e authors acknowledge Othsuunna GO Risk ul r. oiiuvas;ul:u mortality In 22. 9afle IoW. Darrow WW. fcbcntcIg DE et N - d Karns. Sic +r Wilson. and Mas:ume Sadly 1, oLe,s u, nunolnnk alcohol Janke >. r .. al The acyotted Inununudelinencv .yyro for mmpu(er pulpranunutg and Leo liurlr' for ers. Am J Giulio,. 19():lde 1237 - 1242. mume in a cohort oltanrxuexual men. Amt consultation rrparding die Use Of the Kaiser I'_. rt•Iluno M. Pcmle,m G. Prom f)13. South I Per manenlc AIDS database. R. Mom Alert 1 165:1111,_ 10-2 14. k. 'flee Calitsuum automated 1031114 11 23. Hollisicr LE. Marijuana and Immump. 1 linkage system. am 1 Public Health R ofCrcncfsS l' hnurti,e Dnrgs 1912: ? - 11'_1 :1 S'i -114. 1984( 24 -1310. I. Prrhmm Errirnn,rs from the 1•114 his- 13. Vermund S. Rising 111 V'relalct nxdalus 24. Kasluw RA, Blackwelder WC. Ostrow r oma/ fl;mlehnld Sunrr. Advance kcr'n in young Americans. JAMA. 19'93:269: DC. el al. No evidence lur a rule of alcohol No Ill. Rockville. Md: Substance Abuse 7034 -1015 Editorial. tar odder psychoactive drugs in acederawtp :aid Menial Ileahl, Sen'ICeS AJnhn °tn- 1 4. //row I/naed Stoves. 19.5'9 ilv :uuvilIc. umnmmddlcienCy in HIV -I positive inJi- non. 1995. Md. National Centel for I lcalth Smbsbcs: viduals: a relcsn Innis the mulucemn 2. 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