Effects of frequent cannabis use on hippocampal activity during an associative memory task

Interest is growing in the neurotoxic potential of cannabis on human brain function. We studied non-acute effects of frequent cannabis use on hippocampus-dependent associative memory, investigated with functional Magnetic Resonance Imaging (fMRI) in 20 frequent cannabis users and 20 non-users matched for age, gender and IQ. Structural changes in the (para)hippocampal region were measured using voxel-based morphometry (VBM). Cannabis users displayed lower activation than non-users in brain regions involved in associative learning, particularly in the (para)hippocampal regions and the right dorsolateral prefrontal cortex, despite normal performance. VBM-analysis of the (para)hippocampal regions revealed no differences in brain tissue composition between cannabis users and non-users. No relation was found between (para)hippocampal tissue composition and the magnitude of brain activity in the (para)hippocampal area. Therefore, lower brain activation may not signify neurocognitive impairment, but could be the expression of a non-cognitive variable related to frequent cannabis use, for example changes in cerebral perfusion or differences in vigilance.

[1]  D. Yurgelun-Todd,et al.  Lack of hippocampal volume change in long-term heavy cannabis users. , 2005, The American journal on addictions.

[2]  Nancy C Andreasen,et al.  Effects of Smoking Marijuana on Brain Perfusion and Cognition , 2002, Neuropsychopharmacology.

[3]  Karl J. Friston,et al.  Why Voxel-Based Morphometry Should Be Used , 2001, NeuroImage.

[4]  N. Ramsey,et al.  The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance , 2005, International Journal of Methods in Psychiatric Research.

[5]  Karl J. Friston,et al.  Analysis of fMRI Time-Series Revisited—Again , 1995, NeuroImage.

[6]  N. Ramsey,et al.  Working memory capacity in schizophrenia: a parametric fMRI study , 2004, Schizophrenia Research.

[7]  C. Brignell,et al.  Cognitive and subjective dose-response effects of acute oral Δ9-tetrahydrocannabinol (THC) in infrequent cannabis users , 2002, Psychopharmacology.

[8]  Daniel S. O'Leary,et al.  Cerebellar hypoactivity in frequent marijuana users , 2000, Neuroreport.

[9]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[10]  N. Ramsey,et al.  Phase Navigator Correction in 3D fMRI Improves Detection of Brain Activation: Quantitative Assessment with a Graded Motor Activation Procedure , 1998, NeuroImage.

[11]  H. Pope Cannabis, cognition, and residual confounding. , 2002, JAMA.

[12]  John K. Robinson,et al.  Changes in hippocampal morphology following chronic treatment with the synthetic cannabinoid WIN 55,212-2 , 2000, Brain Research.

[13]  D. Storm,et al.  Hippocampal Neurotoxicity of Δ9-Tetrahydrocannabinol , 1998, The Journal of Neuroscience.

[14]  H. Kalant,et al.  Adverse effects of cannabis on health: an update of the literature since 1996 , 2004, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[15]  Thomas Babor,et al.  Cognitive functioning of long-term heavy cannabis users seeking treatment. , 2002, JAMA.

[16]  T. Turkington,et al.  Brain Morphological Changes and Early Marijuana Use , 2000, Journal of addictive diseases.

[17]  I. Grant,et al.  Non-acute (residual) neurocognitive effects of cannabis use: A meta-analytic study , 2003, Journal of the International Neuropsychological Society.

[18]  D. Hosmer,et al.  Applied Logistic Regression , 1991 .

[19]  J. May,et al.  Is There a Functional Neural Correlate of Individual Differences in Cardiovascular Reactivity? , 2005, Psychosomatic medicine.

[20]  L. Iversen,et al.  Cannabis and the brain. , 2003, Brain : a journal of neurology.

[21]  Marilyn A Huestis,et al.  Cognitive Measures in Long‐Term Cannabis Users , 2002, Journal of clinical pharmacology.

[22]  Karen I. Bolla,et al.  Neural substrates of faulty decision-making in abstinent marijuana users , 2005, NeuroImage.

[23]  M. D’Esposito,et al.  The neural basis of the central executive system of working memory , 1995, Nature.

[24]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[25]  H Eichenbaum,et al.  Functional organization of the hippocampal memory system. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[26]  K I Bolla,et al.  Dose-related neurocognitive effects of marijuana use , 2002, Neurology.

[27]  M. Naus,et al.  Cognitive correlates of long-term cannabis use in Costa Rican men. , 1996, Archives of general psychiatry.

[28]  Peter A. Bandettini,et al.  Task-Independent Functional Brain Activity Correlation with Skin Conductance Changes: An fMRI Study , 2002, NeuroImage.

[29]  John A Matochik,et al.  Altered brain tissue composition in heavy marijuana users. , 2005, Drug and alcohol dependence.

[30]  P. Reuter World drug report , 1998 .

[31]  D. Collins,et al.  Automatic 3D Intersubject Registration of MR Volumetric Data in Standardized Talairach Space , 1994, Journal of computer assisted tomography.

[32]  Robert I. Block,et al.  Effects of chronic marijuana use on human cognition , 2005, Psychopharmacology.

[33]  M. Torrens Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[34]  R. Cabeza,et al.  Imaging Cognition II: An Empirical Review of 275 PET and fMRI Studies , 2000, Journal of Cognitive Neuroscience.

[35]  Karen I. Bolla,et al.  Abnormal brain activity in prefrontal brain regions in abstinent marijuana users , 2004, NeuroImage.

[36]  Gen Kanayama,et al.  Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study , 2004, Psychopharmacology.

[37]  K. Pugh,et al.  Impact of Cannabis Use on Brain Function in Adolescents , 2004, Annals of the New York Academy of Sciences.

[38]  Stephan Arndt,et al.  Effects of frequent marijuana use on memory-related regional cerebral blood flow , 2002, Pharmacology Biochemistry and Behavior.

[39]  Jean-Lud Cadet,et al.  Frontal cortical tissue composition in abstinent cocaine abusers: a magnetic resonance imaging study , 2003, NeuroImage.

[40]  A. Ameri The effects of cannabinoids on the brain , 1999, Progress in Neurobiology.

[41]  B. Weber,et al.  Human hippocampus establishes associations in memory , 1997, Hippocampus.

[42]  Francis Eustache,et al.  The Functional Neuroanatomy of Episodic Memory: The Role of the Frontal Lobes, the Hippocampal Formation, and Other Areas , 1998, NeuroImage.

[43]  N. Ramsey,et al.  Long-term effects of frequent cannabis use on working memory and attention: an fMRI study , 2006, Psychopharmacology.

[44]  Florin Dolcos,et al.  Similarities and Differences in the Neural Correlates of Episodic Memory Retrieval and Working Memory , 2002, NeuroImage.

[45]  R. Herning,et al.  Cerebrovascular perfusion in marijuana users during a month of monitored abstinence , 2005, Neurology.

[46]  C. Lyketsos,et al.  Cannabis use and cognitive decline in persons under 65 years of age. , 1999, American journal of epidemiology.