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Harrison G. Pope, Jr, MD; Amanda J. Gruber, MD; James I. Hudson, MD, SM; Marilyn A. Huestis, PhD; Deborah Yurgelun-Todd, PhD

Arch Gen Psychiatry. 2001;58:909-915.

Background  Although cannabis is the most widely used illicit drug in the United States, its long-term cognitive effects remain inadequately studied.

Methods  We recruited individuals aged 30 to 55 years in 3 groups: (1) 63 current heavy users who had smoked cannabis at least 5000 times in their lives and who were smoking daily at study entry; (2) 45 former heavy users who had also smoked at least 5000 times but fewer than 12 times in the last 3 months; and (3) 72 control subjects who had smoked no more than 50 times in their lives. Subjects underwent a 28-day washout from cannabis use, monitored by observed urine samples. On days 0, 1, 7, and 28, we administered a neuropsychological test battery to assess general intellectual function, abstraction ability, sustained attention, verbal fluency, and ability to learn and recall new verbal and visuospatial information. Test results were analyzed by repeated-measures regression analysis, adjusting for potentially confounding variables.

Results  At days 0, 1, and 7, current heavy users scored significantly below control subjects on recall of word lists, and this deficit was associated with users' urinary 11-nor-9-carboxy-9-tetrahydrocannabinol concentrations at study entry. By day 28, however, there were virtually no significant differences among the groups on any of the test results, and no significant associations between cumulative lifetime cannabis use and test scores.

Conclusion  Some cognitive deficits appear detectable at least 7 days after heavy cannabis use but appear reversible and related to recent cannabis exposure rather than irreversible and related to cumulative lifetime use.

From the Biological Psychiatry Laboratory, McLean Hospital, and the Department of Psychiatry, Harvard Medical School, Belmont, Mass (Drs Pope, Gruber, Hudson, and Yurgelun-Todd); and the Intramural Research Program, National Institute on Drug Abuse, Baltimore, Md (Dr Huestis).

Corresponding author: Harrison G. Pope, Jr, MD, McLean Hospital, Harvard Medical School, 115 Mill St, Belmont, MA 02478.

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