[Congressional Record (Bound Edition), Volume 156 (2010), Part 13]
[House]
[Pages 19350-19352]
[From the U.S. Government Publishing Office, www.gpo.gov]




                   MEDICINAL MARIJUANA IS A MISNOMER

  (Mr. KAGEN asked and was given permission to address the House for 1 
minute and to revise and extend his remarks.)
  Mr. KAGEN. Mr. Speaker, I rise this morning, before everyone begins 
their conversations about tax cuts, about jobs, about immigration, to 
raise a serious health concern. You know, when I was brought up in 
northeast Wisconsin, my father taught me that if it's good for 
business, it's going to happen; I would just like it to be legal. And 
the subject I am going to mention here is the idea, the false idea of 
medicinal marijuana.
  There is nothing safe about smoking. There is nothing safe about 
smoking an illicit product called marijuana. Marijuana is universally 
contaminated with a mold spore Aspergillus, Mucor, Penicillium, and 
other items that will harm human health.
  This House, this body has do what's best for people. We need a 
healthy economy and we need healthy people at work. So don't make the 
mistake of thinking at any point in time that there is something safe 
about smoking medicinal marijuana, which is a misnomer.
  So I look forward later today to passing House Resolution 1540 that 
addresses the illicit production of marijuana on Federal lands.

               Marijuana Smoking and Fungal Sensitization

  (Steven L. Kagen, M.D., Viswanath P. Kurup, Ph.D., Peter G. Sohnle, 
            M.D., and Jordan N. Fink, M.D. Milwaukee, Wis.)

     The possible role of marijuana (MJ) in inducing sensitization 
     to Aspergillus organisms was studied in 28 MJ smokers by 
     evaluating their clinical status and immune responses to 
     microorganisms isolated from MJ. The spectrum of illnesses 
     included one patient with systemic aspergillosis and seven 
     patients with a history of bronchospasm after the smoking of 
     MJ. Twenty-one smokers were asymptomatic. Fungi were 
     identified in 13 of 14 MJ samples and included Aspergillus 
     fumigatus, A. flavus, A. niger, Mucor, Penicillium, and 
     thermophilic actinomycetes. Precipitins to Aspergillus 
     antigens were found in 13 of 23 smokers and in one of 10 
     controls, while significant blastogenesis to Aspergillus was 
     demonstrated in only three of 23 MJ smokers. When samples 
     were smoked into an Andersen air sampler, A. fumigatus passed 
     easily through contaminated MJ cigarettes. Thus the use of MJ 
     assumes the risks of both fungal exposure and infection, as 
     well as the possible induction of a variety of immunologic 
     lung disorders. (J Allergy Clin Immunol 71:389, 1983.)
       The recreational and medicinal use of MJ has reached 
     epidemic proportions. The National Institute on Drug Abuse 
     has documented that nearly one in 10 American high school 
     seniors use MJ on a daily basis.\1\ Furthermore, a survey of 
     adult and pediatric oncology centers reveals that a 
     substantial population of patients receiving cancer 
     chemotherapy are now encouraged to use MJ as an 
     antiemetic.\2\
       The medicinal use of MJ, however, is not without risks. MJ 
     may contain toxic substances such as Agent Orange, 
     phencyclidine, or paraquat, and outbreaks of salmonellosis 
     and hepatitis B have been traced to MJ.3-5 
     Similarly, Aspergillus has been cultured from MJ and has been 
     considered the likely source of infection in patients who 
     have developed invasive pulmonary and allergic 
     bronchopulmonary aspergillosis.6-8 Due to the 
     widespread use of MJ by normal and immunodeficient 
     individuals, we thought it important to evaluate its possible 
     role as a source of exposure and sensitization to Aspergillus 
     organisms. Preliminary results of our investigations revealed 
     that MJ contains pathogenic, inhalable Aspergillus organisms 
     that may sensitize the user.9,}10 This article 
     presents additional in vitro studies and further documents 
     the spectrum of fungal organisms present in MJ.

                         Materials and Methods


                                Subjects

       A total of 28 subjects were randomly selected to be 
     evaluated for immunologic reactivity toward A. fumigatus, to 
     which they may have been exposed while smoking MJ. Medical 
     histories, physical examinations, cultures of their MJ, and 
     serologic studies were performed. Ten age-matched individuals 
     who denied ever having smoked MJ served as controls.


                                Cultures

       Samples of MJ were plated directly onto SGA, SGA with 
     antibiotics, TSA, and TSA with novobiocin. SGA plates were 
     incubated at room temperature and at 37 deg. C, while TSA 
     plates were incubated at 55 deg. C. Plates were observed 
     daily for growth of organisms. Any growth appearing was 
     subcultured, purified, and identified according to standard 
     methods.11,}12


                          Immunologic studies

       Precipitins. Serum precipitins against A. fumigants, A. 
     flavus, and A. niger, the predominant cultured organisms, 
     were evaluated by agar gel diffusion as previously 
     described.13,}14 Serum precipitin assays were also 
     performed with routine culture filtrate antigens from 
     Thermoactinomyces candidus and T. vulgaris, Mucor, and 
     Penicillium species to better assess the significance of 
     circulating precipitins to Aspergillus antigens in MJ 
     smokers.
     Abbreviations used
       MJ: Marijuana
       SGA: Sabouraud's glucose agar
       TSA: Trypticase soy agar
       CPM: Counts per minute
       Con-A: Concanavalin A

[[Page 19351]]

       PMN: Polymorphonuclear
       THC: Delta-9-tetrahydrocannabinol

       Lymphocyte transformation. Lymphocytes were obtained from 
     peripheral blood by Hypaque-Ficoll centrifugation and 
     suspended at 0.25 x 106 cells/ml in 0.4 ml of RPMI 
     tissue culture medium (Gibco, Inc., Grand Island, N.Y.), 
     using 15% pooled human plasma, with penicillin, streptomycin, 
     and glutamine added. The cells were cultured with or without 
     stimulants in a humidified atmosphere containing 5% 
     CO2, for 5 days, at which time 1 mCi of \3\H-
     thymidine was added. Twenty-four hours later the cells were 
     harvested onto glass fiber filters. The incorporation of 
     \3\H-thymidine was counted by scintillation counting and data 
     were expressed as either total CPM or stimulation ratios (CPM 
     experimental/CPM control). A positive result is defined as 
     CPM >3000 and stimulation ratios >4.0, as previously 
     described.\15\ Antigens and mitogens employed included Con-A 
     (Miles Laboratories, Inc., Elkhart, Indiana), A. fumigatus, 
     A. niger, and A. flavus. The optimal final concentrations of 
     mitogens were determined in preliminary experiments with 
     either human or guinea pig lymphocytes (A. fumigatus, 5 mg/
     ml; A. niger, 50 mg/m1; Con-A, 10 mg/m1).


                           Fungal inhalation

       MJ cigarettes were obtained from patients and attached to 
     an Andersen air sampler via rubber tubing. The cigarettes 
     were then lit and the smoke was drawn into the sampler, 
     deposited onto plates, and cultured. Additional unlit MJ 
     cigarettes were similarly assessed. Control samplings of 
     laboratory air were also obtained.


                                RESULTS

       The results are summarized in Tables I and II.


                                Subjects

       The study population consisted of 16 female and 12 male 
     patients, ranging in age from 17 to 36 yr, including 18 
     tobacco cigarette smokers. The duration of MJ use varied from 
     6 mo to 14 yr, with a mean of 9 yr. The total number of MJ 
     cigarettes smoked was estimated by multiplying the daily 
     average by total duration expressed in days. Patient 1 had 
     systemic aspergillosis and presented with complaints of 
     fatigue, night sweats, and coughing episodes associated with 
     MJ use. The chest film revealed bilateral interstitial 
     infiltrates, and A. niger was cultured from sputum, nasal 
     secretions, skin pustules, urine, and an open lung biopsy. 
     Hematologic studies, immunoglobulin levels, and complement 
     components were normal, and he was later found to have a 
     defective PMN oxidative enzyme system.
       Patients 2, 3, 4, 6, 27, and 28 admitted experiencing cough 
     and wheezing after MJ exposure. Additionally, patient 6 
     experienced a ``chest cold'' for 2 mo, which included cough, 
     thick brown sputum, and body aches, all of which disappeared 
     shortly after discontinuing the use of 60 to 70 MJ cigarettes 
     weekly. The remaining 21 patients had no history of immediate 
     or delayed respiratory symptoms with MJ use.


                                Cultures

       Thirteen of 14 MJ samples contained potentially pathogenic 
     fungi in various combinations. The flora consisted of A . 
     fumigatus, A. flavus, A. niger, Mucor, Penicillium, and 
     thermophilic actinomycete species in varying densities, but 
     with Aspergillus predominating.


                          Immunologic studies

       Thirteen of 23 MJ-smoking subjects had precipitins against 
     at least one of the Aspergillus antigens. In the control 
     sample of 10 MJ-nonsmoking individuals, one had a precipitin 
     line against A. fumigatus and A. niger (p < 0.02). There were 
     no differences between the MJ-smoking group and the control 
     group with regard to precipitins to antigens other than 
     Aspergillus (Table II).
       Significant blast transformation to A. niger in the MJ-
     smoking group occurred in only three of 23 subjects, whereas 
     all demonstrated significant blastogenesis to Con-A, a 
     nonspecific mitogen.


                           Fungal inhalation

       Fungal inhalation studies with MJ sample 25 revealed that 
     both lit and unlit cigarettes allowed the passage of fungal 
     spores. A. fumigatus in particular traveled through the MJ 
     cigarettes unimpeded in both lit and unlit conditions. 
     Control samplings of laboratory air were repeatedly negative 
     for fungal growth.


                               DISCUSSION

       MJ can now be found in nearly every high school in America, 
     and in a growing number of medical communities. Several 
     clinical trials employing THC and other cannabinoids present 
     in MJ have demonstrated its potentially significant 
     antiemetic effect.16-21 Because serum levels of 
     THC are best attained via inhalation, it has been advocated 
     that THC and MJ be inhaled by oncology patients shortly prior 
     to receiving' cancer chemotherapy.18, 22 Our 
     studies, however, have shown that illicit MJ must now be 
     assumed to contain pathogenic inhalable fungi. As such, its 
     use by immunosuppressed oncology patients should be 
     discouraged.
       The spectrum of fungi found in MJ included the following 
     organisms: Aspergillus fumigatus, Aspergillus niger, 
     Aspergillus flavus, Mucor, Penicillium spp, Thermoactinomyces 
     candidus, and Thermoactinomyces vulgaris. When inhaled, these 
     organisms are known to cause a variety of immune lung 
     disorders, ranging from asthma, allergic bronchopulmonary 
     aspergillosis and hypersensitivity pneumonitis to invasive 
     systemic fungal infections in immunoincompetent hosts. In 
     addition to identifying these fungi, we have demonstrated 
     that A. fumigatus may be inhaled in contaminated MJ cigarette 
     smoke.

                                    TABLE II. PRECIPITINS TO ROUTINE ANTIGENS
----------------------------------------------------------------------------------------------------------------
                                                                        T.         T.                Penicillium
                                                                     vulgaris   candidus    Mucor        spp
----------------------------------------------------------------------------------------------------------------
MJ smokers........................................................       4/28       9/28       3/28        5/28
Controls..........................................................        2/9        4/9        3/9         2/9
----------------------------------------------------------------------------------------------------------------

       The presence of circulating precipitins to any given 
     antigen is generally taken to mean that a significant 
     immunologic exposure to that antigen has taken place. 
     Aspergillus precipitins may thus arise from re peated 
     antigenic inhalation, active colonization, or previous 
     clinical or subclinical fungal infections. Of 23 MJ-smoking 
     patients tested, 13 had precipitins to Aspergillus antigens. 
     This 52% incidence is significantly greater than both our 
     control group (p < 0.02) and the normal 3% to 10% incidence 
     in populations reported by Chmelik et al?29 
     Furthermore, there was no correlation between the presence of 
     precipitins and the total estimated MJ exposure. Since 13 of 
     14 MJ samples contained at least one Aspergillus species and 
     the contaminated MJ cigarettes were shown to deliver viable 
     organisms, it is not unreasonable to assume that our patients 
     acquired their precipitins from smoking MJ. We were, however, 
     unable to determine whether pulmonary infections or 
     colonizations were present in these patients, although both 
     occurrences were possible.
       In vitro cellular immune responses to Aspergillus antigens 
     in aspergillosis, in contradistinction to serum precipitins, 
     rarely correlate with disease activity.30 
     Substantiating this, we found no correlation between 
     blastogenesis to Aspergillus antigens and the presence of 
     serum precipitins (Table I). Of special interest was the 
     finding that our index case (patient I) possessed adequate 
     cellular immune responses to A. fumigatus and A. niger 
     antigens despite his disseminating systemic aspergillosis. 
     Perhaps, because of his malfunctioning PMN enzyme system, he 
     was unable to either completely metabolize Aspergillus 
     antigens or sufficiently inhibit hyphal growth. The fungus 
     would then be able to proliferate even though an active 
     cellular immune response existed.
       As illustrated by this patient, diseases induced by the 
     inhalation of viable fungal spores depend primarily on the 
     host's innate immune and metabolic capabilities. A defect in 
     PMN metabolism, coexistent with fungal inhalation, may lead 
     to the development of either systemic invasive mycoses or a 
     fungus ball. We anticipate that future reports may continue 
     to substantiate the already increasing incidence of systemic 
     aspergillosis, especially if oncology patients continue to be 
     exposed to MJ smoke.
       The use of MJ thus assumes the risks of both fungal 
     exposure and infection, as well as the possible induction of 
     a variety of immune and infectious lung disorders. Given the 
     extraordinary number of individuals estimated to be MJ 
     smokers, the occurrence of these illnesses may well become 
     more commonplace.
       We thank Abe Resnick and Trudy Scribner for their technical 
     assistance and Anita H. Balistreri, Julie Kaepernick, and 
     Catherine A. Walther for their typing and editorial 
     assistance.


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