Marijuana Research Review is a publication of Drug Watch Oregon.
MARIJUANA RESEARCH REVIEW
Marijuana absent in 1993 scientific review of glaucoma treatment
Glaucoma treatment was thoroughly reviewed in the New England Journal of Medicine, Vol.
328, p. 1103, 1993, by Quigley. Marijuana was not mentioned in the review of effective
medications for treatment of this disorder. For precise control of the intraocular
pressure usually associated with this disease, frequent monitoring of patients receiving a
drug that delivers uniform doses is necessary.
Commentary: Except in rare instances glaucoma is a symptomless disease
until loss of eyesight begins. Most, but not all patients afflicted with glaucoma,
experience increased intraocular pressure which, if left untreated, will lead to
blindness. Since there are many effective medications, and since doses of marijuana by
smoking cannot be controlled, using smoked marijuana to treat glaucoma is potentially
dangerous.
Because the baseline (normal) pressure varies from individual to individual, this disease
and its treatment must be carefully monitored and tailored to each patient. Though
marijuana, like alcohol, can reduce intraocular pressure, the dose cannot be controlled
and risk of damage due to either excessive or inadequate lowering of pressure could lead
to blindness. Further, the side effects associated with marijuana use, such as impairment
of motor skills, are not present with currently available approved therapies. To assure
the best outcome for this disease, frequent monitoring of patients receiving a drug that
delivers uniform doses is necessary.
Suppository form of Delta 9 THC better than oral form for treating
appetite loss
Struwe et al, in the Annals of Pharmacotherapy, vol. 27, pp. 827-831, 1993, reported a
double-blind, randomised placebo-controlled crossover trial with two 5-week treatment
periods separated by a 2-week washout period. Patients received dronabinol (Marina) 5 mg
twice daily before meals, or a placebo. Twelve HlV-infected patients who had lost at least
five pounds participated in the study. Only five patients were able to complete the
protocol because of various side effects of delta 9 THC. In the subjects who completed the
study, there was no statistically significant weight gain, increased serum proteins, or
improved appetite.
Commentary: Smoking marijuana has been alleged to be good for the loss of
appetite seen in AIDS patients. Because inhalation of irritants (which potentially could
be contaminated with fungi) poses a needless and serious endangerment to the already
compromised immune systems of AIDS patients, this practice would appear risky.
Oral delta 9 THC, the synthetic form of the most active cannabinoid in marijuana, would
seem to be a better choice, but recent research on its efficacy was disappointing. Thus,
in a selected group of HIV infected patients, a controlled study failed to support any
effect of delta 9 THC to increase appetite.
Perhaps the recent report by Mattes and associates, in the journal, Pharmacology,
Biochemistry, and Behaviour, vol. 44, pp. 745-747, 1993, of a rectal form of THC which was
well-tolerated, would be of benefit. This drug produced higher and more sustained plasma
levels which should enhance its efficacy as an anti-vomiting drug in chemotherapy and,
perhaps, as an appetite stimulant. This would completely avoid the necessity to have a
smoked form of the drug in which a variable amount of active drug is delivered with each
cigarette and further compromises damaged immune systems.
Marijuana carries serious risk for those under treatment for mental
illness
Tardive dyskinesia is a condition in which abnormal involuntary movements develop,
producing serious necrologic disability. Some patients treated for schizophrenia with
drugs such as chlorpromazine, develop this serious condition as a side effect of therapy.
New research published by Zaretsky in the journal, Schizophrenia Research, Vol. 11, pp.
3-8, 1993, shows that a major risk factor for development of this complication of
neuroleptic therapy is current or past use of cannabis. A study of 51 chronic
neuroleptictreated outpatients with diagnoses of schizophrenia showed that current use of
cannabis far outdistanced any other risk factor such as cigarette smoking, caffeine, or
alcohol use. The authors concluded that even "recreational" use of marijuana or
hashish in patients treated with these drugs was dangerous .
Commentary: This study adds to the current literature confirming that up
to 60% of schizophrenic patients use non-prescription psychoactive drugs. O
Marijuana components damage the ability of human immune cells to
function.
Recent work by Watzl et al, Drugs of Abuse Immunity and Immunodeficiency, 1991, and
Djeu et al, published in the same journal, showed that the major psychoactive component of
marijuana, delta 9 tetrahydrocannabinol (THC) is able to interfere with the function of
white blood cells taken from humans. Both neutrophils, which fight bacterial infection,
and mononuclear cells of the immune system, which fight viruses, were suppressed by
various concentrations of THC.
Schwartz, in the Journal of Hospital and Community Psychiatry, Vol. 38, p. 531, May 1987,
pointed out that marijuana use is a factor in preparing the ground for HIV infection and
that in the list of risk-reducing behaviours for patients with HIV, a significant
preventative step might be to discourage the use of marijuana among those at risk.
It is of interest, as pointed out by Pillia, in the Archives of Toxicology, Vol. 65, pp.
609-617, 1991, that drugs of abuse, as well as alcohol, have immunotoxic properties which
include marked changes in the cellular, humeral, and other components of the immune
defence mechanism.
Commentary: Applying this work to human beings would suggest that
marijuana smoke would depress those immune cells which protect the body from viral or
bacterial infections. This would be particularly dangerous in patients with already
compromised immune systems, such as those with AIDS.
Thus, since a large majority of people with AIDS have a well-established history of drug
and alcohol abuse, Such a compromise of the immune system can render the body more
susceptible to the development of AIDS after HIV infection.
Material used in this publication has been reviewed and commented on by
William M. Bennett, M.D., Professor, Chief of Nephrology, Clinical Pharmacology and
Hypertension at Oregon Health Sciences University, Portland, Oregon.
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Fungal sinus infection associated with marijuana use
Marijuana smoke is often contaminated by the fungus, aspergillus, (Kagen et al, Journal
of Allergy and Clinical Immunology, vol. 71, pp. 389-393, 1983). A report by these authors
showed that 11 of 12 samples they tested demonstrated various species of the fungus,
aspergillus. It then was of great interest when Brummund, in the Journal of the American
Medical Association, vol. 256, pp. 3249-3253, 1986, reported cases of allergic sinus
infection with the same fungus from the recreational use of contaminated marijuana.
Commentary: Fungal sinus infections can be very difficult to treat and
can lead to destruction of the sinuses with involvement of the brain and central nervous
system.
Marijuana implicated in fatal fungal infection
A 34-year-old man who had undergone a bone marrow transplant for chronic leukemia was
reported to have developed a fatal disseminated fungal infection associated with a
contaminated batch of marijuana cigarettes used heavily for several weeks prior to his
admission to the hospital (Chestvol. 94/2, pp. 432-433, 1988).
Commentary: Noting that "Invasive aspergillosis has become a
significant cause of death in immunosuppressed patients" The authors, Hamadeh and
associates, reported the case so that physicians would be aware of this potentially lethal
complication of marijuana use in compromised hosts such as patients with AIDS or
malignancies.
Aspergillus spores are found throughout the environment in soil, air, and vegetable
matter, including tobacco and marijuana. However, smoking contaminated plant material,
puts a concentration of the fungi directly into the lungs and blood stream placing
smokers/ patients without intact immune systems at extreme risk.
Marijuana use impairs function in all areas
Psychological tests measuring intelligence, memory, and other mental functions, were
given to 26 heavy cannabis users and compared with a control group by Varma reported in
the journal Drug and Alcohol Dependence, vol. 21, pp. 147-152, 1988. A heavy cannabis user
was defined as a person consuming cannabis for five years, 20 or more times per month,
with a daily intake equivalent to 150 mg of delta-9 THC, 3 to 5 joints depending on the
concentration.
Commentary: These authors found that the cannabis users, with an average
of 6.8 years of use, were found to react very slowly in performing motor tasks, but more
importantly, suffered disability in personal, social, and vocational areas. They also
indicated a higher score for neurotic and psychotic behaviour. This is consistent with
several other recent studies linking marijuana smoking to behavioural problems.
Marijuana smoking linked to increased lung damage
Marijuana smoke is known to be as irritating as tobacco smoke. Research by Barbers and
associates American Review of Respiratory Marijuana Research Review, Volume 1, No.2, July
1994
Diseases, vol. 135, pp. 1271 -1275, 1987, showed that smoking of both marijuana and
tobacco caused the small oxygen exchanging parts of the lung to shed inflammatory cells.
The smoking of marijuana and tobacco together increased this reaction significantly above
smoking either drug alone, and marijuana caused an adverse effect on the lungs that was
independent of and additive to that of tobacco. 19 healthy non-smokers and 43 healthy
smokers of tobacco and/or marijuana took part in the study.
Commentary: None of these individuals had any previous history of chronic
lung disease. These lung inflammatory changes are early findings in individuals who go on
to develop malignancy, chronic infection, and emphysema in their lungs.
Pre-employment screening for marijuana use makes good economic sense
Zwerling and associates, in the Journal of the American Medicine Association, vol. 264,
pp. 2639-2643, 1990, present a prospective controlled study of the association between
pre-employment drug screening tests and adverse employment outcomes in 2,537 postal
employees. "This was a blind study: the employees, hiring officials, medical
personnel and management officials did not know the results of the urine drug screens at
any time during the study. The study was designed to detect and measure any association
between the presence of marijuana and/or cocaine on a preemployment drug screen and
employment outcomes such as employee turnover, absenteeism, accidents, injuries, and
discipline."
Commentary: The purpose of the study was to substantiate or disprove
claims that drug-abusing employees have substantially more accidents at work, many more
compensable injuries, and use significantly more sick leave than those who do not use
illicit drugs.
The study showed that marijuana users had "55% more industrial accidents, 85% more
injuries and a 78% increase in absenteeism." It also showed that cocaine users had a
145% increase in absenteeism and an 85% increase in injuries. The mean absence rate from
the job was 7.1% for marijuana users compared to 4% for non-users.
The study showed that pre-employment drug screens positive for marijuana and cocaine were
associated with significant adverse employment outcome supporting the use of such
screening for economic and health reasons.
Marijuana continues to be available for scientific research
Since the 1970's more than 10,500 scientific studies have been conducted on marijuana.
The marijuana (cannabis) used in the studies is obtained from the Research Institute of
Pharmaceutical Sciences at the University of Mississippi, who produce a standardised
marijuana specifically for research. Material to be used in clinical trials is shipped to
Research Triangle Institute in North Carolina where it is processed into marijuana
cigarettes. It is then made available for Researchers following proper protocol and
paperwork filed with the National Institute on Drug Abuse, in that form. Questions
regarding the availability of marijuana should be directed to Dr. Rao Rapaka or Dr. Paul
Hillery at NIDA (301-443-4250).
Per Mahmoud A. ElSohly, Ph.D., Project Director, NIDA Marijuana Project. 4/1/93
Material used in this publication has been has been reviewed and
commented on by William M. Bennett, M.D., Professor, Chief of Nephrology, Clinical
Pharmacology and Hypertension at Oregon Health Sciences University, Portland, Oregon.
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MARIJUANA RESEARCH REVIEW
Dangerous side effects of cocaine are amplified when used in
conjunction with marijuana
Drug-using volunteers were used in a study to determine the effect that marijuana
smoking had on their subsequent use of cocaine. Lukas and colleagues (Pharmacology,
Biochemistry and Behaviour, Vol 48:715721, 1994). The study found that the increase in
heart rate due to cocaine was markedly enhanced if preceded by smoking marijuana, and that
the time to the cocaine high was reduced from two minutes to one minute. Most importantly
there was double the amount of drug absorption evident when marijuana use preceded cocaine
use.
Commentary: Many drug users use two or more drugs at the same time. In
analyses of polydrug use, marijuana is the most heavily used illicit drug. Because it
enhances the cocaine experience, it is commonly used in combination with this drug.
People snorting cocaine after smoking marijuana are at greater risk of overdose and more
severe cardiovascular effects from the cocaine. Variability in the nasal effects of both
drugs makes dosing unpredictable and dangerous.
Study on use of THC to treat HlV-wasting syndrome shows no weight gain.
A review of the current treatment for the HIV-wasting syndrome reported on studies with
dronabinol, which has an approved use for anorexia in AIDS patients. Schroeder, Hart, and
Lynch (Annals of Pharmacotherapy, Vol 28:595-597, 1993). Dronabinol, a synthetic form of
THC, the active ingredient in marijuana, was approved by the FDA based on a double-blind
placebo-controlled clinical trial involving 139 AIDS patients in 18 centers.
Patients with a five-pound weight loss, no active infection, and no marijuana use for 30
days were included in the study. Dronabinol was given in a dose of 2.5 mg orally twice a
day to the treatment group with a placebo control group. Patients reported an increase in
appetite after six weeks of therapy. However, there was less than a half-pound weight gain
in treated patients which was not statistically different from the one-pound weight loss
in the placebo group at the end of the six week period.
The authors conclude that the efficacy of dronabinol in reversing the wasting process
associated with AIDS is yet to be determined, and that the subjective increase in appetite
did not necessarily correspond to increased body weight.
Commentary: AIDS wasting is a devastating complication of infection with
the AIDS virus. The drug megestrol has been recently approved by the FDA and is far more
effective than dronabinol in the studies to date.
Likewise, no scientific studies have confirmed a benefit of the use of crude marijuana on
HlV-wasting syndrome. Additionally, for the AIDS patient, smoking a substance with fungal
and bacterial contamination, as well as the inherent damage by the smoke to lungs already
predisposed to infection, would be counterproductive.
Review of anti-nausea drugs show restricted use for synthetic
cannabinoids
Grunder and Hesketh (New England Journal of Medicine, Vol. 329:1790-1795, 1993)
recently reviewed current therapies for chemotherapy-induced vomiting control. The authors
discuss the vomiting response and the neural pathways involved in mediating that response.
Regarding the use of cannabinoids, the authors state that dronabinol and nabilone, the two
cannabinoids that have been evaluated most thoroughly, are active only in patients
receiving mild, not severely, emetogenic chemotherapy.
The authors state that these drugs have serious side effects, however, including
dysphoria, vertigo, hallucinations, sedation, and disorientation, and are seldom selected
as first-line anti-emetic therapy. They point out that while these drugs have limited
usage, some synthetic cannabinoids with no psychotropic activity have anti-emetic
properties, suggesting that there are separate sites of action for the anti-vomiting and
the psychotropic activity.
Commentary: With the availability of newer anti-emetic drugs which are
more potent, more effective and have less side effects in reversing nausea and vomiting
associated with chemotherapy, the use of drugs with major side effects should be avoided.
One common assumption about taking anti-emetics orally is that the patients are already
vomiting and cannot keep the medication down. However, all anti-emetic therapy is given
prior to administration of chemotherapy drugs, before the onset of nausea and vomiting.
Further, if the need for additional anti-emetic medication were indicated it could be
administered in suppository form.
Study looks at immunologic impact of tobacco and marijuana smoke on the
lungs
Wallace and associates, in Chest, Vol. 105:847-852, studied the effect of heavy,
habitual marijuana use and compared it with tobacco smoking on the composition of cells in
the peripheral blood and small airways of the lung.
Cell samples from 14 non-smokers were compared to samples from 14 tobacco smokers, 19
heavy habitual marijuana smokers, and 9 patients who smoked both substances. The tobacco
smokers had lower percentages of cells in their small airways that had the marker for the
CD4 or helper T-cells. Marijuana use had the opposite effect of lowering the CD8 positive
cells, so-called suppressor cells, at the expense of CD4 cells. The authors concluded that
tobacco and marijuana have effects on immune cells and blood lymphocyte populations that
differ from each other, both in type and magnitude.
Commentary: These data are further examples of information from the group
of Tashkin et al which show the effects of tobacco and marijuana smoke on the intrinsic
cells in the lung and the immunologic defenses of the lungs. A combination of tobacco and
marijuana would be devastating in terms of exposure of patients to carcinogens, and also
in damaging the immune response to foreign particles, bacteria, and viruses. Immunologic
alterations that were observed in the study were of potential importance because they
correlated with the adverse health effects of smoking either substance, alone or in
combination.
Material used in this publication has been reviewed and commented on by
William M. Bennett, M.D., Professor of Medicine, Division of Nephrology, Clinical
Pharmacology and Hypertension at Oregon Health Sciences University, Portland, Oregon.
Drug Watch Oregon, P.O. Box 5853, Portland, Oregon. 97228-5853
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Study shows MS patients further impaired by smoking low-THC marijuana.
Greenburg et al, in their paper in Clinical Pharmacology and Therapeutics, Vol.
55:324-328, 1994, performed a double-blind, randomised, placebo-controlled study of
inhaled marijuana smoke on balance and coordination responses in ten adult patients with
spastic multiple sclerosis, and normal volunteers who were matched for age, sex, and
weight. A sophisticated computer controlled video system was used to identify responses.
The study showed that marijuana smoking enhanced the abnormalities already present in MS
patients and that smoking just one marijuana cigarette containing 1.5% delta-9 THC
increased the objective errors in these responses. The authors concluded that marijuana
smoking impairs coordination and balance in patients with spastic MS.
Commentary: This is an objective and well done controlled study which
strongly refutes anecdotes suggesting that marijuana is beneficial for patients with
multiple sclerosis. In the absence of data showing any benefit, this documentation of an
adverse effect is disturbing and should be heeded by those who would consider using smoked
marijuana for treatment of this disorder.
Low doses of THC found to cause learning deficits
Kamine et al, in their article in Behaviour of Pharmacology, Vol 5:71-78, 1994, studied
the effects of delta-9 tetrahydrocannabinol (THC) on the learning and performance ability
of eight healthy subjects (19-32 years of age) all of whom had occasionally used
marijuana, as well as other psychoactive drugs, but were not perceived to be drug
dependent. Subjects were given placebo capsules, and 10 mg. and 20 mg. capsules of THC,
("...roughly equivalent to smoking a marijuana cigarette containing 2.3-3.6%
THC")
Oral THC caused measurable learning deficits which, the authors concluded, might be
disastrous in some environments, such as operating "the cab of a speeding
locomotive." They pointed out that the "learning deficit from a single dose
might become quite relevant if it accumulates over time."
Commentary: In regular marijuana users, the presence of a learning
deficit with a single dose of drugs and five hours of post-therapy monitoring is sobering.
In view of the greatly increased potency of marijuana over the past decade and the recent
rise in its use by teenagers and pre-adolescent children, this should be particularly
alarming to parents and educators. This report contributes to the body of evidence showing
that "recreational use of marijuana is not a benign habit in terms of intellectual
performance."
Marijuana's implication in a number of chronic diseases reflects its
harmful impact on the immune system.
Immune defenses against fungal organisms are triggered by natural killer cells. If this
system is upset, the susceptibility to fungal infections is enhanced. Cusher et al, in
their report in Cellular Immunology (Vol 154:99-108, 1994) incubated human large granular
lymphocytes (human immune cells) with varying concentrations of THC (delta-9
tetrahydrocannabinol). The concentrations used mirrored what would be obtained in the
blood of people smoking marijuana or taking the drug dronabinol. They found that low
levels of THC inhibited tumour necrosis factor thereby weakening the killing activity of
lymphocytes against tumour cells.
Commentary: It is well-known that substance abuse may compromise immune
response to a variety of infectious agents. Marijuana, a widely abused drug around the
world, and its components, have adverse effects on the immune system. This study is
another of a series showing that, in the test tube, concentrations of the major
psychoactive metabolites of marijuana are capable of impairing the ability of human immune
cells to kill tumours and destroy fungal cells. The importance of this report is that the
relatively low concentrations which mimic drug use in humans, cause these profound
depressions of immune activity.
Marijuana not listed in latest review of beneficial treatment for
Multiple Sclerosis
Because of frequent claims that smoking marijuana provides therapeutic benefit to
victims of multiple sclerosis, the extensive and well documented review of all the
effective therapies for treatment of this disease, by G. C. Eber, The Lancet, Vol 343,
January 29, 1994, is included in this publication.
Eber notes in his review that multiple sclerosis (MS) "...is unpredictable, being
characterised by a tendency to relapse and remission and/or to stabilisation without
treatment." He notes that the natural history of the disease is well-defined and
states that trial and error can no longer be reasonably applied to the search for
effective therapies. Eber concludes that although clinical symptoms and anecdotes are
valuable, highly sensitive objective methods are now available in the form of serial MRI
scans to document improvement of the disease with such exciting therapies as
beta-interferon.
Commentary: This extremely complete review of multiple sclerosis therapy
puts to rest any contention that smoked marijuana is good for this disorder and can be
given without side effects. There simply are no data to support the safe or effective use
of either smoked marijuana or dronabinol for treatment of MS. Eber's warning of the need
for objective data when judging a therapy for this complex disease is well worth heeding.
Marijuana use linked to homicide
In terms of life-time use, marijuana was reported to be the most common illicit drug
used by a sample of 268 murderers incarcerated in New York State correctional facilities,
for homicides that occurred in 1984. Spunt et al ("The Role of Marijuana in
Homicide," International Journal of the Addictions, Vol. 29:195-213,1994)
About one-third of prisoners who had used marijuana, had used it in the 24-hour period
before the homicide, and three-quarters of those said they experienced some kind of effect
from the drug when the homicide occurred. The authors speculate that drugs and violence
may be linked in a variety of complex ways.
Commentary: It is clear that abnormal behaviour induced by the use of
psychoactive drugs plays a significant role in violent crimes which are completely
unrelated to either drug profits or trafficking. Many of the murderers interviewed for
this study stated they felt that marijuana use was a factor in their crimes. Recent
well-publicised violent murders, such as the tragic rape and murder of 12 year-old Polly
Klaus, were also committed by people who admitted to being under the influence of
marijuana at the time of their homicides.
Material used in this publication has been reviewed and commented on by William M.
Bennett,M.D., Professor of Medicine, Division of Nephrology, Clinical Pharmacology and
Hypertension at Oregon Health Sciences University, Portland, Oregon
Drug Watch Oregon. P.O. Box 5853, Portland, Oregon 97228-5853
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Cannabis use found to increase frequency of relapse in patients with
schizophrenia
The literature examining the relationship between marijuana use and schizophrenic
symptoms among patients with schizophrenic disorders has been conflicting. The purpose of
this study by Linzen et al (Archives General Psychiatry, Vol. 51, pg. 273-279, 1994), was
to compare cannabis-using schizophrenic patients with schizophrenic non-users. There were
11 mild and 13 heavy cannabis users compared to 69 non-users in a prospective study which
lasted one year. The authors found that significantly more and earlier psychotic relapses
occurred in the cannabis-using group, particularly as use increased. No other factors
could be found to explain this including other street drugs.
Fourteen of the cannabis-using patients, who were experiencing clinical remission from
their schizophrenia, reported an immediate increase in psychiatric symptoms after using
cannabis again.
In all but one of the patients cannabis use also preceded the onset of their first
psychotic symptom. Over the one-year period only 20 percent of the non-using subjects had
a psychotic relapse, as compared to 46 percent for those who used cannabis .
Commentary: This study helps to clarify the relationship between cannabis
use and schizophrenia. While studies such as this cannot prove cause-and-effect
relationships, it is clear that use of cannabis can cause patients with psychiatric
disorders, such as schizophrenia, to have more frequent relapse of symptoms compared to
non-users of cannabis. An important feature of this study was that the groups were matched
for variables, such as the use of other street drugs or alcohol, making these factors not
relevant in interpretation of the results. Findings of this study are consistent with the
observations of prior studies showing that cannabis use prior to illness was an
independent risk factor for schizophrenic symptoms.
Smoking Tobacco or Marijuana Reduces Antioxidant Levels in HlV-infected
Patients
Miguez-Verbano and colleagues from the University of Miami School of Medicine reported
at the American College of Clinical Pharmacology meeting in 1994 that anti-oxidant status
was negatively impacted in 60 non-symptomatic HlV-infected marijuana smokers.
Vitamin E levels were significantly lower in marijuana users, as well as cigarette
smokers, compared to non-smoking HIV infected subjects. Subjects who used both tobacco and
marijuana exhibited frank vitamin E deficiency, although vitamin E intake did not differ
significantly among the groups.
These findings show that marijuana and tobacco smoking have a detrimental effect on
vitamin E status of HlV-infected individuals. This is of concern in light of the important
role of vitamin E in immune processes, including inhibition of viral activation.
Commentary: This well done study shows further evidence that smoking
marijuana contributes to defects in the immune system. The issue of smoking marijuana for
an HlV-infected patient makes absolutely no sense in terms of preserving immune function
to fight the virus that causes the disease. Antioxidant levels also have an important
effect on preventing cardiovascular disease and cancer, both of which would be important
in HlV-infected individuals.
Study examines the use of psychoactive and addictive drugs by
physicians
Lutsky et al studied the current use of psychoactive drugs of abuse by physicians
specialising in medicine, surgery, and anaesthesia, all of whom had trained at the same
academic institution. (Canadian Journal of Anaesthesia 1994/41:7/pp561-7) 1624
questionnaires were sent with a response rate of 58 percent.
Difference in impairment rate among the physicians was not significant: in surgery 14
percent, medicine 20 percent, and anaesthesia 17 percent. Substance abuse was clearly
associated with a family history of substance abuse. Increased stress at various career
stages did not appear to increase substance abuse. Substances most frequently abused were
marijuana 55 percent, amphetamines 33 percent, and benzodiazepines 25 percent.
A number of respondents reported that the use of alcohol and drugs by faculty role models
during their medical training was an important part of their own personal use. Drug
counselling programs and diversion programs were judged inadequate by most respondents.
Commentary: No subset of society is immune from substance abuse in a
modern social context. Obviously, better detection and treatment programs are necessary
for the prevention and control of this problem, which impairs medical judgment and places
patients interests at great risk.
In the United States, only 3 percent of practicing physicians are anesthesiologists, yet
13 percent of physicians being treated for drug dependency are anesthesiologists,
presumably because of the ease of access to these substances in this medical specialty.
The data from this survey pointed out that most drug use started prior to entry into
medical school. The authors suggested that programs aimed at deterrents failed at least
partially because there are no universally acceptable drug screening methods, and because
penalties for drug use are insufficiently severe. Substance abuse by faculty represented
another setback to any prospect for deterring physicians in training.
Study shows two marijuana cigarettes as harmful as 28 of tobacco.
This study by Starr et al followed 25 non-tobacco smoking surfers, in excellent
physical condition, who smoked an average of two marijuana joints per day. The control was
25 male urban smokers from the San Francisco area and 25 non-smoking male Mormons from the
Silicon Valley area. Damage and irritation to the lung cells of the marijuana smokers was
comparable to those who smoked a mean of 28 tobacco cigarettes per day. (Medical Tribune,
page 17,1994)
Commentary: Tobacco smoke is the most widespread factor associated with
premature death due to cancer and cardiovascular disease in the USA. This study shows that
cellular damage to the lungs produced by daily use of two marijuana cigarettes is similar
to that seen in those who smoke nearly a pack and a half of tobacco cigarettes a day.
Material used in this publication has been reviewed and commented on by William M.
Bennett,M.D., Professor of Medicine, Division of Nephrology, Clinical Pharmacology and
Hypertension at Oregon Health Sciences University, Portland, Oregon.
Drug Watch Oregon. P.O. Box 5853, Portland, Oregon 97228-5853
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Increase in unprotected sex in urban minority youth blamed on use of
alcohol or marijuana
It is now established that regular condom use can decrease the spread of AIDS. A recent
study by Ford and Norris (Journal of the Acquired Immune Deficiency Syndrome, Vol
7:389-396, 1994), studied the effects of the use of alcohol and marijuana in the context
of sexual relationships and the impact of these substances on the consistency of condom
use by urban minority youth.
The sample design and field work were conducted by the Survey Research Center of the
Institute for Social Research at the University of Michigan. A total of 1435 interviews
were obtained from Hispanic and African-American young adults, ages 15-24, residing in
low-income areas in Detroit.
Results indicated that when alcohol and marijuana were used with a sexual partner, the
consistency of condom use decreased even when other variables related to sexual history
were controlled. Alcohol use had a greater negative effect on condom use for Hispanic men,
and marijuana for African-American women, than it did for Hispanic women and
African-American men.
The authors concluded that safe sex intervention programs for urban low income minority
youth need to emphasise the risk of AIDS virus exposure that results from substance use,
casual sex, and sex with multiple partners.
Commentary: Aside from the many obvious adverse side effects, use of
alcohol and marijuana among teenagers may contribute to the spread of AIDS.
Clearly, it is counter-productive to give a safe sex message without also pointing out
that the behaviour produced by the use of alcohol and marijuana lessens the likelihood
that safe sex will be performed. This factor is often overlooked in drug prevention
programs and sexual education courses when, in fact, these things should be considered
together.
Delta 9 THC affects metabolism in human blood cells
Delta 9 THC is known to inhibit a variety of immune functions. Diaz and colleagues, in
their paper in the Journal of Pharmacology and Experimental Therapeutics, 268:1289-1296,
1994, show that THC, when incubated with cells from the blood of normal humans, caused
increased release of a variety of metabolites that stimulate acute inflammation. These
metabolites are potent agents that can cause asthma, and which enhance the activity of
other cells which suppress immune defence against virus and other infectious agents.
Commentary: This paper is one of the first to show that normal human
cells, when incubated with concentrations of THC equivalent to that found in the blood of
regular smokers of marijuana, cause immune cells to release compounds which promote
inflammation within the lungs, and at the same time, suppress the natural defenses against
external bacterial and viral agents that cause disease.
While these studies are conducted in the test tube, the implications for smoking marijuana
in humans, particularly those who smoke or with a tendency towards asthma or respiratory
disease are obvious.
Attempt made to use marijuana to treat Tourette's Syndrome
A nurse consultant and a visiting psychiatrist reported on a single case of Tourette's
Syndrome treated successfully with smoked marijuana (Hemming and Yellowlees, Journal of
Psychopharmacology 7-4 1993 pp. 389-391 ).
Tourette's Syndrome is a disorder characterised by multiple motor and vocal tics. The tics
occur many times daily and may include obscenities and other strange behaviours.
Untreated, the disorder tends to be a lifelong disease characterised by remissions and
relapses. Haloperidol (Haldol) is the drug of choice in the treatment of this disorder.
The patient they reported started to smoke marijuana at age 35 to get relief while he
continued his Haldol. The anecdotal improvement prompted the case report. There was no
stopping of the drug to see if symptoms returned, and no rechallenge with marijuana.
Commentary: This report is the type of anecdote used to support claims
for the use of smoked marijuana to treat disease. It is interesting that the standard
treatment of Haldol was continued throughout the period of marijuana use with this
patient, and there was no placebo control or rechallenge involved. There are ways of using
drugs in single patients, known as the "n of 1" method. Efficacy as well as side
effects can be monitored using this method in a single patient. This was not done here. It
is also of interest that there is no objective documentation of improvement in Tourette's
Syndrome in the patient. Neither of the authors has any expertise in neurologic diseases.
Nicotine is also known to potentiate the effects of Haldol in improving motor tics in this
disorder. It is possible that any one of the 4000 components found in marijuana smoke
provided beneficial effects, if, in fact, they did occur.
Study finds self-reporting of Illicit drug use differs greatly from
actual test results.
Self-reporting by users, of the frequency of their drug use, is the measure used In a
variety of studies regarding prevention strategies, needle exchange programs, and effects
of treatment interventions, to indicate the success rate of these programs.
The report by Hindin in the International Journal of the Addictions, 29:771-789, 1994,
highlights the fact that when an objective measurement is done, such as an assay of hair
for actual determination of cocaine, heroine, and marijuana use, the indication is far
greater than that reported by the user.
Among a group of patients followed up post-treatment, only 51 percent of cocaine positive
people and 67 percent of heroin positive people gave an accurate history by their own self
report. The correlation with marijuana was even weaker.
Commentary: The study emphasises the folly of depending on self reporting
as an outcome variable in any study regarding the efficacy of treatment and prevention
programs.
Objective measures of exposure need to be done because of the notorious inaccuracy of self
reporting. This self reporting, with its obvious pitfalls, is, however, currently being
used to prove "efficacy" of needle exchange programs which claim to limit the
spread of HIV by providing "clean" needles to addicts. The purported success of
these programs is based, in part, on self reporting by the addict of whether or not they
shared needles. O
Material used in this publication has been reviewed and commented on by William M.
Bennett,M.D., Professor of Medicine, Division of Nephrology, Clinical Pharmacology and
Hypertension at Oregon Health Sciences University, Portland, Oregon
Drug Watch Oregon. P. O. Box 5853 . Portland, Oregon 97228-5853
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Use of marijuana and other illicit drugs may play role in increase of
genital abnormalities and infertility in males
A report by Auger et al., New England Journal of Medicine. 332:281 -285, 1995, shows
that in some countries, during the past 20 years, there was a decline in the quality of
sperm of fertile men which correlated with an increase in genital abnormalities such as
cancer and cryptorchidism. This effect was independent of the age of the men. In the same
issue of the New England Journal of Medicine, Howards, page 312, pointed out that male
infertility is often related to lifestyle factors such as the use of marijuana, anabolic
steroids, and cocaine.
Commentary: While associations such as these do not prove cause and
effect, it is of interest that illicit drug use could be a major factor in the decline of
fertility among men over the past two decades. The authors of the original paper admit to
not having another explanation and acknowledge that environmental or lifestyle factors
could be playing a major role.
Lower IQ in Toddlers Linked to Prenatal Exposure to Marijuana.
Researchers (Day et al. Neurotoxicology and Teratology 16, 169-175, 1994), found
''significant negative effects of prenatal marijuana exposure on the performance" of
both African-American and Caucasian children in standard intelligence tests. This negative
effect on the child was related to marijuana exposure during the first and second
trimester of pregnancy. On average, children exposed prenatally to marijuana will have a
lower IQ compared to children who are not exposed, even when the effects of various
environmental factors are adjusted for.
Commentary: The children involved in this study were tracked from birth
to three years. The study, which included an equal number of Caucasian and
African-American women, most of whom were single and of lower socioeconomic status,
suggesting that marijuana, not race or other prenatal factors, accounts for these changes.
Sleeping Problems Found in Toddlers Exposed to Marijuana
Prenatal exposure to marijuana showed impairment in sleep pattern and more awake time
after sleep onset in exposed children, at age three, compared to control children (Dahl
and colleagues in the journal, Archives of Pediatric and Adolescent Medicine, 149:145-150,
1995). Sleep deprivation is frequently associated with emotional and behavioural
difficulties and reduced attention span, symptoms which could be associated with other
psychiatric problems as well. Marijuana directly impacts the part of the brain that
regulates sleep and arousal, causing concern that prenatal use of marijuana could affect
the development of that part of the brain, resulting in permanent changes in sleeping
patterns.
Commentary: While studies of prenatal marijuana exposure and long-term
follow-up of children so exposed are rare, the weight of the evidence suggests that this
exposure is not without adverse consequences for the child.
Substance use during Vietnam conflict associated with nine times higher
mortality rate than that for civilians
Price et al., from Washington University School of Medicine, presented long term
follow-up studies on a group of Vietnam veterans, now in their mid-40's, compared to
civilian controls who did not serve in Vietnam. Veterans who tested positive for drugs
upon their return from Southeast Asia, had a nine times higher death rate than that of the
civilian controls. The death rate for veterans who tested negative for drugs was still
four times higher. The authors concluded that substance use in the Vietnam experience
played a key role in the increased mortality.
This is a culmination of a landmark study started in 1972 and consists of 900 soldiers who
had come home from Vietnam the year before. All had been tested for drug use. Three year
follow-up interviews were conducted in 1974 when civilian controls were also added to the
sample. The current study tracks the original participants.
Available data in the present study show that a sizeable percentage of deceased veterans
who tested positive for drugs died of drug and/or alcohol related causes according lo
death certificates. Of the deceased drug positive veterans 37 percent had alcohol or drug
related causes of death, and 14 percent were found to be homicide victims.
While these men tested positive in one single drug test, the authors noted that it was
interesting that this one test seemed to have predicted both the high mortality and a high
risk of certain causes of death. The authors noted that drug use was not the only
statistically significant predictor of premature death, since veterans who tested negative
for drugs still had a four times higher death rate than men of similar age and background
who did not go to Vietnam.
Commentary: This important study should carry major alarm messages for
those who advocate casual drug use and minimalise the impact on the medical and
psychiatric health of the population.
Toxic Psychosis Produced by Marijuana Smoking While on Antabuse
A 36-year-old man who was on Antabuse alcohol treatment smoked marijuana as a
substitute for alcohol. He immediately developed an acute toxic psychosis with
disorientation, lack of reality, and a manic psychosis. This lasted for 48 hours. The
manufacturers of Antabuse have had one previous report of this type of drug interaction
(Lacoursiere et al., American Journal of Psychiatry, 140:242-244, 1983.)
Commentary: People attesting to a relative safety of marijuana forget
that there are interactions between many drugs that may lead to adverse reactions. This
example of an acute toxic psychosis in someone under treatment for alcohol abuse
emphasises the potential for marijuana interactions with prescription and non-prescription
substances.
Material used in this publication has been reviewed and commented on
by William M. Bennett M.D. Professor of Medicine, Division of Nephrology, Clinical
Pharmacology and Hypertension at Oregon Health Sciences University, Portland, Oregon.
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Damaging effects of prenatal marijuana use show up in older children
Subjects of this investigation by Fried P A, reporting on the effects of marijuana used
during pregnancy since 1978 (Life Sciences, 56:2159-2168, 1995) were primarily middle
class, low-risk women who entered the study in their early pregnancy. The offspring have
been assessed repeatedly during the neonatal period and at least annually up unto the age
of 6. While earlier reports of children to age 3 did not reveal an association between
defects associated with in utero exposure to marijuana (memory, language development,
visual perceptual functioning), later follow-up could distinguish between marijuana
exposed children and control children.
Prenatal marijuana exposure showed that at age 4 and older children showed increased
behavioural problems and decreased performance on visual perceptual tasks, language
comprehension sustained attention and memory. The author concluded that the nature and the
timing of the appearance of these deficits was consistent with the notion that prenatal
marijuana exposure adversely affected behaviour that is goal-directed which includes
planning, organised search, and impulse control. These findings suggested to the author
that chronic marijuana use impacted on functioning of the prefrontal lobe in the brain.
Commentary: This study documents that the adverse effects of prenatal exposure may
not become apparent until the child grows old enough to perform high level tests such as
those termed executive functioning. The danger of drawing short-term conclusions from
effects that, while introduced in utero may take a generation to discover, have been amply
documented for other poisons ingested by expectant mothers such as lead, cocaine, and
alcohol. Some authors have suggested that differences in the functioning of children
exposed in utero to marijuana to nonexposed children often disappear by age 2-3. However,
effects of marijuana cannot be determined until enough time has passed so that the
children are expected to perform. Then, and only then, can their performance be accurately
assessed. This prospective study provides valuable insights into the many insidious
problems associated with the use of marijuana.
Prenatal use of tobacco and marijuana by adolescent mothers causes increased damage to
infants
Cornelius et al. studied the effects of tobacco and marijuana use during pregnancy on
length of gestation, growth, and formation of 310 children of adolescent mothers
(Paediatrics 95:738-743). The subjects were interviewed at mid-pregnancy and after
delivery to obtain information on their use of tobacco, marijuana, and other substances
before and during pregnancy. The infants were examined by physicians 24-36 hours after
birth. The average maternal age was 16.
Prenatal tobacco use was associated with reduced birthweight, length, and circumferences
of head and chest, but not the gestational age or the number of physical abnormalities of
the baby. Prenatal marijuana smoking was associated with increased premature birth.
Additionally, some physical abnormalities were associated with the use of marijuana during
the first trimester among the white participants in the study These effects of prenatal
tobacco and marijuana smoke were prominent despite the lower levels of exposure in these
offspring as compared with the offspring of mothers of adult age. The authors concluded
that the risk of adverse effects from use of tobacco or marijuana during pregnancy may be
increased for offspring of adolescent mothers.
Commentary: Under the best of circumstances, infants of adolescent mothers are 2-6
times more likely to be of low birthweight compared to infants of adult women, and these
infants are at increased risk for prematurity, complications, and infant mortality. During
the first year of life, the mortality of children born to teenagers is 2-3 times that of
infants born to older mothers, and there is a 6-told increase of Sudden Infant Death
Syndrome, Hectman L. Teenage mothers and their children: risks and problems: A review,
Canadian Journal of Psychiatry, 34:569-575, 1989. The current study points out that the
use of tobacco or marijuana can be associated with adverse effects on newborns. The
authors found that adolescent mothers who smoked tobacco during pregnancy were more likely
to binge on alcohol and use other illicit drugs in the first trimester. Mothers who smoked
heavily had significantly lower pre-pregnancy weight. Similarly, teenagers who used
marijuana tended to use more tobacco and drink more alcohol, particularly in the crucial
first trimester when the fetal organs are being formed. It is clear that preventive
efforts aimed at eliminating the use of marijuana and tobacco would correlate with
reduction of alcohol intake, further reducing the risk of adverse effects to the children
of these adolescent mothers.
Attention impaired by marijuana use
If attention processes were impaired through chronic use of marijuana, this would be
important to understanding decreases in work performance, memory learning, and every day
tasks, such as driving. Previous research has shown that cannabis use impairs attention
while the user is intoxicated, but the long-term effects of chronic use had not previously
been studied. Subjects in this study by Solowji et al (Biol Psychiatry, 37:731-739, 1995)
were recruited from the general community through advertising. The minimum requirement for
participation as a cannabis user was regular use at least once a month for 3 years. By
criteria established by the American Psychiatric Association, all subjects could be
labelled as cannabis dependent or cannabis abusers. The control group of non-users were
selected to cover the range of the age, years of education, and sex distribution in the
user group. The subjects were excluded if they had a history of any psychiatric or
neurologic disorders, head injury, or the use of any other drugs more than once a month,
or alcohol abuse. The ability to focus attention and filter out irrelevant information was
measured and was found to be impaired progressively by the number of years of marijuana
use, but was unrelated to the frequency of use. With increasing frequency of use the speed
of information processing was delayed significantly but was unaffected by the duration of
use. The results suggested that a chronic build-up of cannabinoid produces both short- and
long-term impairments of brain function compared to control subjects.
Commentary: The data from this well-done study provide an outstanding demonstration
that marijuana use effects brain function, and documents in an objective way what has been
observed for decades, namely that marijuana produces an attention deficit. This study was
controlled for alcohol use, educational level, and l.Q. scores. No subject involved in
other illicit drug activity was included in the sample so that these data are from
individuals who consume marijuana by smoking alone. The data developed in this study
provide evidence that increasing duration of cannabis use leads to progressively impaired
information processing which could lead to distractibility and impairment in any situation
where concentration and focus attention are essential.
Passive exposure to cocaine and marijuana impacts children
In a study by Bhushan et al (American Journal of Public Health, 84:675-686, 1994) over
7,700 infants and young children visiting the Pediatric emergency room of a New York City
hospital for six months in 1992 were screened for evidence of biproducts of marijuana and
cocaine in their urine. Of the approximately 15% who were given a routine urinalysis 245
were randomly selected for further testing. The criteria recommended by NIDA for testing
exposure to drugs was applied in 100 of the cases and no metabolites were detected.
However, when more sensitive measures for cocaine and marijuana biproducts were used to
test the remaining 145 specimens, 11 % tested positive for cocaine or marijuana
metabolites. Since these children were all age 8 and under, the most likely avenue of
ingestion is by passive exposure to smoked forms of the drugs. There is some indication
that passive low level exposure may be cumulative in children.
Commentary: Low level exposures to toxins in the environment can only be detected
by changing the detection threshold to a highly sensitive, but still specific level. This
study shows that use of NIDA limits for exposure would not have picked up the passive
exposure of children whose mothers use smoked marijuana and cocaine in their presence.
Symptoms consistent with cocaine toxicity have been described previously in infants and
toddlers exposed to smoke of cannabinoids and free base cocaine, by Moreland, et al.,
Journal of Forensic Sciences 30:997-1002, 1985. Though these children have no substance
use problems themselves their exposure may predisposed them to such problems in the future
as well as other negative physiological consequences.
Material used in this publication has been has been reviewed and
commented on by William M. Bennett M.D., Professor of Medicine,
Division of Nephrology, Clinical Pharmacology and Hypertension at
Oregon Health Sciences University. Portland. Oregon.
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Marijuana smoking associated with kidney damage
The authors, Lambrecht et al, in Nephron, 70:494496, 1995, report on a 29-year-old man
admitted to the hospital with severe pain in his back. He had smoked marijuana for 10
years, and just prior to admission had smoked several marijuana cigarettes and consumed
several bottles of beer. No other psychotropic drugs were used. An area of damage in the
right kidney resulting from a block in the major branch of the right kidney artery was
detected. Toxicology screening on the urine revealed cannabinoids. All other causes of
acute kidney infarction were excluded. The world's literature on cannabis effects on the
kidney was reviewed by the authors.
Commentary: This report is the first one showing clotting off of an artery to the
kidney resulting from acute marijuana smoking. The cardiovascular effects of marijuana are
well-known and include dilation of peripheral blood vessels resulting in blood pressure
changes and reflex, speeding up of the heart rate. If the heart rate is inadequate, there
may be drops in blood flow to organs such as the kidney with resulting thrombosis of small
arteries. Marijuana is known to be associated with myocardial infarction and stroke
(Zachariah SB, Stroke 22:406-409, 1991; Charles et al. Clinical Toxicology 14:433-438,
1979). It is also possible that the marijuana damaged the blood vessels directly, as has
been suggested for other drugs of abuse, such as amphetamines (Baden et al. New England
Journal of Medicine, 284:111-113, 1971). It is clear from this case report, however, that
a previously healthy male with acute ingestion of marijuana can clog the blood vessels of
a major organ.
British study illuminates negative aspects of regular marijuana use
A self-reporting study of the behaviour of marijuana users attending a community drug
and alcohol clinic was reported on by McBride in Drug and Alcohol Dependence 39:29-32,
1995. One hundred consecutive users were interviewed. All were Caucasian and 85% were
male. The mean age was 28 and their cannabis use had been ongoing for approximately 12.5
years. No one in the sample was employed. All were receiving state benefits. Eighty
percent smoked tobacco cigarettes as well. The author found that the average consumption
of cannabis in the week preceding the interview was 10.5 grams with 60% of interviewees
smoking daily. The average cannabis cigarette comprised 3 cigarette papers, the tobacco
from three-quarters of a king-sized cigarette, and 0.35 grams of cannabis resin. Only 26%
of the sample smoked tobacco in the absence of cannabis. Only 5% of the population took
cannabis by oral ingestion. The amount of money spent on the cannabis averaged £35.00 or
approximately $50.00 per week at current exchange rates. The author concluded that the
high doses of cannabis used, the frequency of use, and the expenditure on the drug
relative to income raised questions about the assumed benign effects of cannabis among
those attending such clinics.
Commentary: Heavy use of cannabis was documented in patients attending drug and
alcohol clinics for which cannabis was not the primary reason for referral to the clinic.
Amphetamines, alcohol, opioids, and benzodiazepines comprised 94% of the cases referred.
This data shows the frequency of cannabis use in combination with tobacco. This makes it
very difficult to interpret self-reporting data about the health effects of tobacco alone.
It is clear that drug-seeking behaviour, even in patients undergoing treatment for drug
and alcohol abuse, is not completely gone since other drugs are being used at the same
time. Perhaps the difficulty in obtaining a higher level of treatment success relates to
this fact. It is also startling to note the amount of money being spent on cannabis by a
population supported by the government and in whom tremendous healthcare resources are
being expended.
Marijuana cigarette triggers severe hypothermia
The symptoms of heatstroke include a body temperature of 104° F or greater, and
delirium, coma, or seizures. Many drugs and chemicals have been associated with
heatstroke, including amphetamines, cocaine, LSD, and PCP. Walter and associates, in
Clinical Toxicology, 34:217-221, report a case of life-threatening hypothermia associated
with the use of marijuana alone. A 24 year-old man with a history of smoking one marijuana
cigarette twice a month for many years left his office immediately after smoking one
marijuana cigarette. He was acclimatised to the environment but had been jogging for only
one week. The temperature was 84° F with a low relative humidity. He had no preexisting
medical conditions. After jogging for 15 minutes, he became acutely ill and collapsed.
Paramedics were called who noted a hot, red, dry skin and an agitated combative condition.
They took him to an emergency department where his rectal temperature was recorded at
107° F. He required aggressive cooling and a tracheal tube for assisted breathing. It
took him 16 hours to return to his usual mental state. All tests were negative except for
urine and blood toxicology screens, which showed cannabinoids. No other drugs associated
with hypothermia were detected.
Commentary: This case report fits with animal studies and some human data showing
that marijuana interferes with normal temperature control. In animal studies, marijuana
has been shown to produce a condition known as poikilothermia, which is a loss of the
ability to regulate temperature control. Marijuana is known to increase heat production in
humans (Hanna et al. Aviation Space Environmental Medicine, 47:634-639, 1976, Rosenberg et
al. Critical Care Medicine, 14:964-969, 1986). Thus, people who smoke marijuana in
environments of high temperature and exert themselves are excessively predisposed to
hypothermia, which can be life threatening. The smoker feels less hot than they really are
because of constriction of skin blood vessels and diminished sweating. The impaired
ability to feel overheated produces a greater chance of developing heatstroke.
THC causes abnormalities in immune molecules
Zhu and colleagues continue a series of investigations into the mechanism of the
immunological effects of the active ingredient in marijuana smoke, tetrahydrocannabinol
(The Journal of Pharmacology and Experimental Therapeutics, 274:10011007, 1995). These
authors had previously reported that interleukin 2, a potent substance released by
activated immune cells (which are necessary for a proper immune response) is suppressed by
ingredients in marijuana smoke. The current studies use a line of cloned natural killer
cells of the immune system which are mixed with varying concentrations of THC. These cells
were blocked in their ability to display this important molecule. The authors suggest that
this effect may account in part, at least, for the THC suppression of the immune response.
Commentary: Further studies by the active immunology group of Klein, et al, at the
University of South Florida, has further explained the way in which the active ingredient
of marijuana can suppress the immune response. Somewhat surprisingly, the liberation of an
important molecule by lymphocytes was not reduced, but instead, the place where it
attaches on activated cells was suppressed. The result of this abnormality is that a
cloned cell line of natural killer cells could not function in their ability to attack
invading foreign molecules. Although these results are done in a test tube, it is
frightening to think what the implications of this work is for patients already
immunosuppressed by the viral disease, AIDS, where part of the viral infection is
impairment of the immune system. Smoking marijuana in this setting would further depress
the body's ability to fight those invading organisms which, ultimately, are the cause the
death of most AIDS patients.
Rectal THC effective as an appetite stimulant
One potential use of delta-9 THC (dronabinol) is as an appetite stimulant in patients
with cancer or AIDS. Mattes et al., Pharmacologic Pharmacology Biochemistry, and
Behaviour, 49:187-195, 1994, reviewed the subject of cannabinoids and appetite
stimulation. They noted that most but not all prior studies showed marijuana to have some
appetite stimulating property. In this study eleven subjects, all of whom were casual
marijuana cigarette users, were observed. The authors compared oral THC with
administration by a rectal suppository. Mean daily food intake was significantly increased
when the patient was routinely using the rectal suppository, but this did not occur with
either an oral capsule or dissolving an oral dose under the tongue.
Commentary: This study confirms the efficacy of rectal suppositories in appetite
stimulation. The drug absorption from the rectal suppository was adequate to accomplish
the therapeutic goal compared to oral or inhalation routes. There was no correlation
between drug efficacy and the age, gender, the drug "high," or plasma drug
levels. This study further supports the possibility of developing a rectal suppository
form of delta-9 THC for use in appetite stimulation in chronically ill patients.
Material used in this publication has been reviewed and commented on
by William M Bennett, M.D., Professor of Medicine, Division of
Nephrology, Clinical Pharmacology and Hypertension at Oregon Health
Sciences University, Portland, Oregon
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Study cites marijuana as factor in increased crime and emergency room episodes
"A substantial proportion of the US population has used illicit drugs, resulting in
increased risk of injury, disease, and death," (BA Rouse, Clinical Chemistry 42:8(B)
1330-1336, 1996). From this perspective, Rouse examined the National Institute of Justice
Drug Use Forecasting (DUF) system and two studies from the Substance Abuse and Mental
Health Services Administration, i.e., the National Household Survey on Drug Abuse and the
Drug Abuse Warning Network (DAWN), to chart the role of illegal or non medical drug use in
emergency room episodes and interactions with the criminal justice system.
The DAWN report showed marijuana use had increased significantly in all age groups and
that in emergency room treatment "most marijuana related episodes also included
mentions of other drugs, particularly alcohol and cocaine." Nonetheless, marijuana
use alone was a significant factor in emergency room visits.
Commentary: In the DUF study on the relationship between drugs and crime it was
noted that since an arrest may occur long after an offence has taken place, determination
as to whether or not drugs were a factor is often minimised. Additionally, only the most
serious offence for which a person was booked was reflected. That being the case, it is
highly likely that drug offences are under reported.
Marijuana users incur Increased health care costs
Marijuana smoke contains carcinogens and more tars than tobacco smoke. However, little
epidimeologic evidence has identified marijuana smoking as a risk factor for health. Polen
et al (Westem Journal of Medicine, Vol. 158, pp 596601, 1993) studied the health effects
of smoking
marijuana by comparing daily marijuana smokers who never smoked tobacco (452 patients)
with a demographically similar group of non-smokers of either substance (450 patients).
Daily marijuana smokers had a 19% increased risk of out patient visits for respiratory
illnesses, a 32% increased risk of injury, and a 9% increased risk of other illnesses
compared to non-smokers. They also had a 50% increased risk of being admitted to the
hospital. These results were adjusted for sex, age, race, education, marital status, and
alcohol consumption.
Commentary: Daily marijuana smoking, even in the absences of tobacco, appears to be
associated with an elevated risk of adverse health outcomes, including an excessive use of
health care resources. Many marijuana smokers also smoke tobacco and the adverse health
consequences of using these two substances together are likely to be multiplied.
Lung cancer causing carcinogen more prevalent in marijuana than tobacco
A breakthrough report published in the journal Science, October 18, 1996, provides the
first true molecular evidence conclusively linking components in tobacco smoking to lung
cancer. A chemical found in tobacco smoking, benzopyrene, causes genetic damage in lung
cells that is identical to the damage observed in the DNA of most malignant tumors of the
lungs.
Although scientists have been convinced in the past that smoking causes lung cancer, the
strong statistical associations did not provide absolute proof. This paper absolutely
pinpoints that mutations in lung cancer cells are caused by benzopyrene. An average
marijuana cigarette contains 30 nanograms of this carcinogen compared to 21 nanograms in
an average tobacco cigarette (Marijuana and Health, National Academy of Sciences,
Institute of Medicine report, 1982). This potent carcinogen suppresses a gene that
controls growth of cells. When this gene is damaged the body becomes more susceptible to
cancer. This gene, P53, is related to half of all human cancers and as many as 70% of lung
cancers.
Commentary: Clearly marijuana smoke contains more of the potent carcinogen
benzopyrene than tobacco smoke. Furthermore, the technique of smoking marijuana by
inhaling deeply and holding the smoke within the lungs presents a chance of much greater
exposure than a conventional tobacco cigarette.
Marijuana interferes with brain's ability to metabolise glucose
Marijuana is the most widely used illicit drug in the United States, but its short and
long term effects on brain metabolism are not clearly understood. Volkow et al (Psychiatry
Research: Neuroimaging, Vol 67, pp 29-38, 1996) studied brain glucose metabolism in daily
marijuana users at baseline and during marijuana intoxication. They used the sophisticated
technique of positron emission tomography (PET scan) which gives a visual picture of the
actively metabolising brain.
The results of eight chronic marijuana users were compared with age and sex matched normal
subjects. They found that THC, the main psychoactive component of marijuana, produced
lower glucose metabolism in the cerebellar part of the brain. A single THC dose in a
chronic user increases metabolism in other specific parts of the brain. This does not
occur in the non-using controls. The activation of chemical metabolism pathways in the
brains of users, as compared to the controls, could lead to the drive and compulsion to
self-administer the drug observed in addicted individuals.
Commentary: This sophisticated use of PET scanning which illustrates individual
regions of the brain and their abilities to metabolise glucose, the main energy source of
the brain, documents an abnormality in chronic users of marijuana. The location of the
abnormality in the cerebellum could account for the motor defects and lack of coordination
previously reported in these subjects. This has obvious implications for public safety and
operation of motor vehicles by marijuana users.
Researcher calls for more studies of impact of marijuana on brain
In an editorial (JAMA 996;275:521-527) Robert I. Block, Ph.D, discusses a study by Pope
& Yurgelun-Todd in the same issue relative to marijuana use and brain function. Dr.
Block laments that there is "so little scientific information to communicate about
adverse effects of chronic marijuana use on human cognition or brain function" He
cites the Pope & Yurgelun-Todd study, which "shows impairment in mental
flexibility and abstraction, as well as some aspects of learning" in frequent
marijuana users, and adds that "With continued use of marijuana...the impairments
might increase over the years."
Block notes that there is evidence of cognitive deficits "persisting for prolonged
periods following cessation of marijuana use, consistent with marijuana-induced brain
alterations," and says that the recent increase in marijuana use by US youth is a
"compelling motivation" to conduct more rigorous testing using the most modern
detection techniques.
Commentary: The editorialist feels that far too few studies have been done on this
aspect of marijuana use and praised the Pope and Yurgelun-Todd study for
"incorporating a rigorously supervised, 19-hour abstinence period before
testing." His suggestion that matched studies must be done to measure intellectual
ability prior to the onset of drug use is seemingly impractical in that it would require
being able to predetermine who would use illicit drugs. However, more well designed and
controlled studies in this area would certainly be useful.
Material used in this publication has been reviewed and
commented on by William M. Bennett M.D., Professor
of Medicine, Division of Nephrology, Clinical
Pharmacology and Hypertension at Oregon Health
Sciences University, Portland, Oregon
DrugWatch Oregon · P. O. Box 5853 · Portland, Oregon 97228-5853
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Costa Rican study observes short term memory loss in long term cannabis users
To test the hypothesis that long term cannabis use is associated with deficits in short
term memory, working memory, and attention span, two groups of long term users (one with
an average age of 45 and the other an average age of 28) were compared to non-users
matched for age and socioeconomic status (Fletcher et al Arch Gen Psychiatry 53:1051
1057,1996).
Polydrug users, or users who did not abstain for the required 72 hours, were excluded
from the study. At follow-up the users had been smoking approximately five joints a day,
two to seven days a week. It was observed that older users (average duration of cannabis
use 34 years) had both impaired short term memory and impaired ability to give attention
to a task compared to non-users. In the younger cohort (average duration of use eight
years) no differences between users and non-users were noted.
Comment: This study confirms observed problems with memory and attention
associated with long term cannabis use. The failure to find these changes in younger, less
chronic users may reflect the need for a cumulative neurotoxic dose threshold to be
exceeded. Again, these patients were abstinent for three days. Performance after recent
doses would likely have been worse. The authors noted that the risks of long-term use are
"likely to be magnified in a more technological society," and that "Certain
occupations may carry particular risk because of safety issues and effects on productivity
and learning.'' They stressed that the findings of the study "suggest a need to focus
on the prevention of cannabis use... to reduce the risk of consumption of drugs..."
Study of marijuana-using college students shows impairment
Pope and Yurgelun-Todd (JAMA 275:521-527, 1996) studied the neuropsyhological test
performance of 65 college undergraduates,19 to 24 hours after a supervised period of
abstinence in a treatment center. All had positive urine for cannabinoids and claimed to
have used marijuana an average of 29 days out of the last 30 . They found that attention
and decision making function, as well as learning and general intellectual function, were
reduced compared to 64 controls who had smoked marijuana a median of 1 day in the previous
30 and had negative urine cannabinoids. Even when baseline intellectual ability and the
use of alcohol were considered, the impairment to heavy users was still significant. The
authors thought this could be due to the effects of marijuana on the brain systems
important for concentration and attention. An accompanying editorial by Block (JAMA
275:560-561,1996) discusses the alternative explanation for the abnormalities, i.e., a
withdrawal syndrome effect.
Comment: Reductions in intellectual functioning during marijuana use have long
been observed and, of course, would impair learning ability in college students. The
control group in this study were light users. It would have been of interest to study
non-users since one would expect the differences to be even more striking. The
editorialist, Robert I. Block, Ph.D., University of lowa College of Medicine, points out
that alcohol also affects cognitive ability. However, the Pope/ Yurgelun-Todd study
controlled for this and observed that "the differences observed in this study were
indeed due to residual effects of marijuana use" and not the effects of alcohol or
other substances.
New Zealand marijuana users view drubs impact on their lives
A survey designed to diagnose the impact of cannabis use on financial position, health,
outlook on life, friendships, home life, and work opportunities (Huw, T., Drag and Alcohol
Dependence 42:201-207,1996), was mailed to 1000 New Zealand subjects, aged 18-35. There
was a 53% response rate to the questionnaire which was based on previous surveys designed
for alcoholism. Of the 528 respondents, 62% claimed never to have used marijuana and did
not complete the survey. Thirty-eight percent (199) admitted some lifetime marijuana use.
Heavy users (108) were people who reported using more than 50 times in their life. Of
these, about half had been daily users (3 - 4 joints per day) at some time. Of heavy
users, 24% experienced panic attacks following use and 15% experienced psychosis.
Twenty-three subjects thought that cannabis had harmed their physical health, citing
frequent nausea and or vomiting, headaches, and persistent coughing as some of the
associated problems. While 70 subjects reported continued use despite problems related to
use, the study concluded that only 58 of them were actually dependent on cannabis.
Comment: The lack of a control group of non users weakens the findings of this
study. However, this may be counterbalanced by the tendency of respondents in
self-administered questionnaires to under-report adverse consequences. As the authors
point out, "In any study, particularly those regarding illegal activities such as
drug use, willingness to participate does not guarantee honesty...There may also be a
tendency for drug users to understate the problems and exaggerate the benefits of drugs in
order to justify continued use." Nonetheless, the 22% of respondents reporting
anxiety/panic attacks, and a 15% prevalence of psychosis, are alarming and need to be
studied further.
Cannabis withdrawal syndrome obsessed by founders of Haight Ashbury Free Clinics
Reporting in the Journal of Substance Misuse, 2:49-53,1997, D. E. Smith and R.
13. Seymour, founders and directors of the Haight Ashbury Free Clinics, review the
neuropharmacology of cannabis and cannabis dependence. They observed that there is
"ample evidence that cannabis is a dangerous substance" and that increased
potency in recent years has increased both the danger and the factors that lead to
physical dependence. They further observed that chronic marijuana users have the profile
of addictive disease, i.e., compulsion! loss of control, and continued use even in the
presence of adverse consequences. Supporting their years of observation, the authors
quoted a statement by NIDA Senior Investigator Billy Martin who said "The fact that
people do seek treatment for marijuana dependence is evidence of marijuana withdrawal in
humans." They also noted that addicted individuals often respond well to recovery
programs like Marijuana Anonymous (similar to Alcoholics Anonymous). The authors stated
that "... it is not uncommon to hear chronic marijuana smokers in long term recovery
comment that it was several years into abstinence before they were truly aware of the
adverse effects marijuana had on their thinking and behaviour."
Comment: It is of interest to note that in the past these two authors often
downplayed the dangers of marijuana use, saw no evidence of the existence of marijuana
addiction, and favoured legalisation. Their personal experience, coupled with significant
inroads in scientific research on marijuana over the past 20 years, has changed that
perspective.
Non-psychoactive cannabinoid derivative can protect injured brain
A non-psychotropic cannabinoid derivative, dexanabinol, has been shown in animals and
humans to provide protection to the brain after injury. Early clinical trials in the
United Kingdom and Israel have shown lack of adverse side effects and reduced injury to
the brain even after a single dose given six hours after the initial event (cited by
Fishrnan, R . H ., The Lancet 348:1436, 1996) . The exact mechanism by which the
synthetic cannabinoid works involves blocking toxic effects of chemicals liberated after
the trauma and also by limiting the effects of free radicals which damage brain cells. The
results of research on dexanabinol were presented by Dr. Mechoulam, a professor of
pharmacology at Hadassah Medical School in Jerusalem, at the November 15, 1996 meeting of
the Society of Neurotrauma .
Comment: A neuroprotective agent would find many uses in clinical medicine. It
is of interest that the useful action of this cannabinoid can be divorced from any
psychoactive properties. The future of cannabinoids as medical treatment will come from
synthetic drugs tailored for therapeutic benefit but lacking the adverse effects of crude
marijuana.
Material used in this publication has been reviewed and
commented on by William M. Bennett M.D., Professor
of Medicine, Division of Nephrology, Clinical
Pharmacology and Hypertension at Oregon Health
Sciences University, Portland, Oregon
DrugWatch Oregon · P. O. Box 5853 · Portland, Oregon 97228-5853
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Marijuana
Research Review. Volume 1, No.1 February, 1994.
