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Does Heavy Marijuana Use Impair Human Cognition and Brain Function?
In this issue of The Journal, Pope and
Yurgelun-Todd[ref. 1] report that frequent marijuana users,
relative to less frequent users, show impairments in mental flexibility
and abstraction, as well as some aspects of learning. Their study is
important and timely. Following well over a decade of generally
declining use, marijuana's popularity has increased markedly among US
youth in the last 3 to 4 years,[ref. 2] prompting renewed concerns
about the drug's possible health consequences. In December 1994, US
Department of Health and Human Services Secretary Donna Shalala
announced a department-wide initiative on marijuana, as part of which
the National Institute on Drug Abuse (NIDA) last year convened the
first-ever National Conference on Marijuana Use: Prevention, Treatment,
and Research. At this conference, Shalala and NIDA Director Alan
Leshner emphasized that marijuana use has significant health
consequences and that scientific information about the drug's dangers
should be communicated to youth and parents.[ref. 3,4]
In this environment, and considering that the target organ
for marijuana is the brain, it is remarkable that there is so little
scientific information to communicate about adverse effects of chronic
marijuana use on human cognition or brain function. Some antidrug
messages contain exaggerated claims concerning such adverse effects,
but more responsible disseminators of information to the public have
little ammunition. For example, in NIDA's informational pamphlet,
Marijuana: Facts for Teens,[ref. 5] introduced at the
national conference, the question, "What are the long-term effects of
marijuana use?" is addressed with respect to several organ systems,
but the brain is not mentioned. Later, in response to the question,
"What does marijuana do to the brain?" no actual research on the
human brain is mentioned.
Many studies have examined cognitive effects of chronic marijuana use,
with mixed results. Both studies reporting adverse effects and those
observing few or no effects have frequently suffered from
methodological flaws. Some studies have not required a sufficient
period of abstinence from marijuana before cognitive testing to ensure
that test results were unaffected by recent use. The study by Pope and
Yurgelun-Todd[ref. 1] is noteworthy for incorporating a rigorously
supervised, 19-hour abstinence period before testing. A crucial
requirement for studying performance of heavy marijuana users is
comparison with an appropriately matched control group. Groups of heavy
marijuana users and controls should be matched on some measure of
intellectual ability obtained before the onset of drug use. Yet only
one study reporting adverse effects of chronic marijuana use has
incorporated such matching.[ref. 6] Other important methodological
shortcomings of previous studies are discussed in a recent review by
Pope et al.[ref. 7] Despite the many contradictory reports,
concern about cognitive impairments associated with heavy marijuana use
appears justified, based on the impairments observed in several of the
methodologically stronger studies.[ref. 1,6,8]
It will be interesting to see whether reporters exaggerate the findings
of Pope and Yurgelun-Todd.[ref. 1] Physicians should not. There is
far more extensive, consistent evidence of cognitive deficits
associated with heavy use of alcohol relative to marijuana. Most of the
cognitive impairments observed by Pope and Yurgelun-Todd are not large
relative to normal cognitive variability among individuals; such
impairments would not make a heavy marijuana user "stand out from the
crowd." This does not mean that such deficits lack practical
significance; they could plausibly have detrimental effects on the
scholastic performance of the heavy marijuana users who were studied,
all of whom were college students and many of whom presumably aspired
to intellectually challenging careers. With continued use of marijuana,
moreover, the impairments might increase over the years.
The most plausible interpretation of the findings of Pope and
Yurgelun-Todd[ref. 1] and other similar findings is that heavy
marijuana use produces alterations of brain structure or function that
outlast the direct effects due to presence of the drug in the brain.
The authors note that impairments may alternatively be due to a "drug
residue" of cannabinoids lingering in the brain after acute
intoxication has subsided or to withdrawal. While neither of these
somewhat incompatible alternative interpretations can be excluded,
there is no compelling evidence to support either. Pope and
Yurgelun-Todd's post hoc analyses that incline them toward the drug
residue interpretation are unconvincing. The few reports of cognitive
effects of marijuana lingering on the day after smoking have not proven
reliably reproducible, even by the original
investigators.[ref. 9,10] The only controlled studies
demonstrating withdrawal symptoms with cannabinoids in humans have
required around-the-clock administration of large oral
doses.[ref. 11] There is at least some evidence of cognitive
deficits persisting for prolonged periods following cessation of
marijuana use, consistent with marijuana-induced brain
alterations.[ref. 8,12]
The few studies that have examined effects of chronic marijuana use
with neuroimaging techniques have produced mixed results. All but one
incompletely reported study[ref. 13] were conducted years ago.
Abilities of neuroimaging techniques to detect subtle changes in brain
structure and function have improved enormously in recent years. It is
now possible to evaluate changes in regional cerebral blood flow
associated with specific cognitive activities. Alterations of auditory
evoked potentials during a selective attention test have been reported
in heavy marijuana users.[ref. 12,14] This finding suggests
altered brain function, but does not localize the regions showing
abnormalities. Studies with neuroimaging technologies such as positron
emission tomography, providing high-resolution measurements of regional
brain activity during performance of varying cognitive tests, offer the
best chance of clarifying the specific effects of heavy marijuana use
on cognition and brain function. The recent resurgence in marijuana use
among US youth provides a compelling motivation for conducting such
studies.
Robert I. Block, PhD
Corresponding author: Robert I. Block, PhD, Department of Anesthesia,
Westlawn 340, University of Iowa College of Medicine, Iowa City, IA
52242.
From the Department of Anesthesia, University of Iowa College of
Medicine, Iowa City.
This work was supported in part by National Institute on Drug Abuse
grant No. 5 ROI DA03988-06.
Editorials represent the opinions of the authors and The Journal and not those of the American Medical Association
References
1. Pope HG Jr, Yurgelun-Todd D. The residual cognitive
effects of heavy marijuana use in college students. JAMA.
1996;275:521-527.
2. University of Michigan. Drug use rises again in 1995
among American teens [press release from the Monitoring the Future
study, December 11, 1995]. Ann Arbor: University of Michigan; 1995.
3. Shalala DE. Remarks at the First National Conference on
Marijuana Use: Prevention, Treatment, and Research. Arlington, Va; July
19, 1995.
4. Leshner AI. Remarks at the First National Conference on
Marijuana Use: Prevention, Treatment, and Research. Arlington, Va; July
19, 1995.
5. National Institute on Drug Abuse. Marijuana: Facts
for Teens. Rockville, Md: National Institute on Drug Abuse; 1995.
6. Block RI, Ghoneim MM. Effects of chronic marijuana use
on human cognition. Psychopharmacology. 1993;110:219-228.
7. Pope HG Jr, Gruber AJ, Yurgelun-Todd D. The residual
neuropsychological effects of cannabis: the current status of research.
Drug Alcohol Depend. 1995;38:25-34.
8. Schwartz RH, Gruenewald PJ, Klitzner M, Fedio P.
Short-term memory impairment in cannabis-dependent adolescents.
AJDC. 1989;143:1214-1219.
9. Yesavage JA, Leirer VO, Denari M, Hollister LE.
Carry-over effects of marijuana intoxication on aircraft pilot
performance: a preliminary report. Am J Psychiatry.
1985;142:1325-1329.
10. Leirer VO, Yesavage JA, Morrow DG. Marijuana, aging,
and task difficulty effects on pilot performance. Aviat Space
Environ Med. 1989;60:1145-1152.
11. Jones RT, Benowitz N, Bachman J. Clinical studies of
cannabis tolerance and dependence. Ann N Y Acad Sci.
1976;282:221-239.
12. Solowij N. Do cognitive impairments recover following
cessation of cannabis use? Life Sci. 1995;56:2119-2126.
13. Volkow ND, Fowler JS. Use of positron emission
tomography to study drugs of abuse. In: Nahas GG, Latour C, eds.
Cannabis: Physiopathology, Epidemiology, Detection. Boca
Raton, Fla: CRC Press; 1993:21-43.
14. Solowij N, Michie PT, Fox AM. Effects of long-term
cannabis use on selective attention: an event-related potential study.
Pharmacol Biochem Behav. 1991;40:683-688.
This Editorial represents the opinions of the authors and The Journal of the American Medical Association and not those of the American Medical Association.
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