Effects of frequent marijuana use on memory-related regional cerebral blood flow

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Abstract

It is uncertain whether frequent marijuana use adversely affects human brain function. Using positron emission tomography (PET), memory-related regional cerebral blood flow was compared in frequent marijuana users and nonusing control subjects after 26+ h of monitored abstention. Memory-related blood flow in marijuana users, relative to control subjects, showed decreases in prefrontal cortex, increases in memory-relevant regions of cerebellum, and altered lateralization in hippocampus. Marijuana users differed most in brain activity related to episodic memory encoding. In learning a word list to criterion over multiple trials, marijuana users, relative to control subjects, required means of 2.7 more presentations during initial learning and 3.1 more presentations during subsequent relearning. In single-trial recall, marijuana users appeared to rely more on short-term memory, recalling 23% more than control subjects from the end of a list, but 19% less from the middle. These findings indicate altered memory-related brain function in marijuana users.

Introduction

Marijuana has remained the most widely used illicit drug for decades. Adverse effects of frequent marijuana use on human brain function and cognition are of serious concern. Remarkably few studies have examined effects of frequent marijuana use on human brain function (Solowij, 1998), and many were conducted years ago with less sophisticated techniques.

In a previous study, we found that long-term, frequent (7+ times weekly) users of marijuana, relative to nonusing control subjects, showed impairments in some aspects of memory, as well as impairments on achievement tests assessing verbal expression and mathematics (Block and Ghoneim, 1993). This study, in contrast to virtually all other studies of mental abilities of drug users, controlled for the possibility that the marijuana users were poorer intellectually before they started using marijuana by matching marijuana users and nonusers on their scores during the fourth grade on the Iowa Tests of Basic Skills (Hieronymus et al., 1982), achievement tests that have been administered in almost all Iowa communities for decades.

In the present study, we expanded this line of research by having frequent marijuana users perform memory tests while we used positron emission tomography (PET) with [15O]water to measure normalized regional brain blood flow (subsequently abbreviated rCBF—an abbreviation that is used here to include the normalization process described below). The memory tests differed in their relative demands on encoding into episodic memory and retrieval from episodic memory. Episodic memory is a form of memory that enables people to remember personally experienced events (in contrast to impersonal general knowledge). Encoding processes that occur during the event initiate memory storage. Later, retrieval processes operate on the stored information and lead to conscious remembering (Tulving et al., 1994a). Prefrontal rCBF changes were of special interest in the present study because a prominent memory model, Endel Tulving's “hemispheric encoding/retrieval asymmetry” model Nyberg et al., 1996, Tulving et al., 1994a, postulates differential prefrontal lateralization of episodic memory encoding and retrieval. Tulving et al. (1994b) observed activation of right dorsolateral prefrontal cortex during episodic memory retrieval. Reviewing other studies Nyberg et al., 1996, Tulving et al., 1994a, he observed that left prefrontal regions are differentially more involved in episodic memory encoding, whereas right prefrontal regions are differentially more involved in episodic memory retrieval.

Hippocampal rCBF changes were also of special interest because the hippocampus has one of the highest densities of cannabinoid receptors (Herkenham et al., 1990) and may play a major role in mediating some cannabinoid effects on memory in animals Hampson and Deadwyler, 1998, Solowij, 1998. Effects of marijuana use on hippocampal rCBF have not been studied.

Section snippets

Subjects

Subjects were 18 frequent marijuana users and 13 nonusing control subjects. The marijuana users were using marijuana 7+ times weekly on average (mean±S.E., 18±2 times), and had been using at about this rate for the last 2+ years (mean, 3.9±0.4 years). Control subjects had never used marijuana (N=10), or only once or twice in their lives (N=3), and had never used any other illegal drugs. All subjects were right ear-dominant according to a dichotic screening test and right-handed, had adequate

Comparability of the groups

The groups did not differ in gender distribution or mean age, height, weight, total intracranial volume, volumes of major brain regions, or hippocampal volume. Marijuana users had slightly (1.1 years) less education than control subjects, but the groups did not differ in mental abilities prior to the onset of marijuana use, estimated by grade equivalent composite scores on the Iowa Tests of Basic Skills (Hieronymus et al., 1982) achievement tests administered when the subjects attended the

Discussion

Marijuana users, relative to control subjects, showed decreased memory-related prefrontal activations and an absence of memory-related lateralization of hippocampal activity, as well as differences in cerebellum and other brain regions. Important prefrontal Nyberg et al., 1996, Tulving et al., 1994a and hippocampal (Lepage et al., 1998) roles in some aspects of episodic memory storage and retrieval have been demonstrated.

Acknowledgements

This research was supported by grants DA10554, NIDA, NIH, and RR00059, General Clinical Research Centers Program, NCRR, NIH. We would like to express our appreciation to Linda Smith and Michael Daugherty for assisting in data collection and Karen Cretsinger and Helen Keefe for trimming the traces of the hippocampus. Thanks also to the PET Center nursing and technological staff (Jo Clark, Dean Clermont, Suzanne Kaprich, Julie Koeppel, John Richmond, Robin Thompson, and Christine Ward).

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    Present address: Alzheimer's Research Unit, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA 02129, USA.

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