Does Heavy Marijuana Use Impair Human Cognition and Brain Function?

Editorials represent the opinions of the authors and The Journal and not those of the American Medical Association.

In this issue of The Journal, Pope and Yurgelun-Todd (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, (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. (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, (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 (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. (6) Other important methodological shortcomings of previous studies are discussed in a recent review by Pope et al. (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. (1,6,8).

It will be interesting to see whether reporters exaggerate the findings of Pope and Yurgelun-Todd. (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 (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 by 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. (9,10) The only controlled studies demonstrating withdrawal symptoms with cannabinoids in humans have required around-the-clock administration of large oral doses. (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. (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 (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. (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

This work was supported in part by National Institute on Drug Abuse grant No. 5 ROI DA03988-06.

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.

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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.