Abstract
Introduction
The endogenous cannabinoid system is sensitive to the introduction of exogenous cannabinoids such as delta-9-tetrahydrocannabinol, which are known to impact upon memory functioning. We sought to examine the impact of chronic cannabis use upon memory-related brain function via examination of the subsequent memory effect (SME) of the event-related potential (ERP).
Methods
The SME is predictive of recall outcome and originates in structures that are dense with cannabinoid receptors (hippocampus and parahippocampus). The SME and performance on a verbal memory task were compared between 24 cannabis users (mean 17 years of near daily use) in the unintoxicated state and 24 non-using controls. The task involved the presentation of word lists, each with a short delay before recall. ERPs were recorded during encoding and later averaged by outcome (correctly recalled/not recalled).
Results
Cannabis users showed poorer recall and altered patterns of SME activation: specifically, attenuation of the negative N4 and an increase in the late positive component. Duration of cannabis use and age of initial use correlated significantly with SME amplitudes. A longer history of use also correlated with greater recall that was related to N4 expression.
Discussion
The results indicate that relative to non-using controls, chronic users of cannabis have altered memory-related brain activation in the form of dysfunctional SME production and/or poorer neural efficiency, which is associated with deficits in memory recall. Greater alteration was associated with a longer history of cannabis use and an earlier onset of use. Neuroadaptation to the effects of chronic exposure may additionally play a role.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Blanchet S, Gagnon G, Bastien C (2007) Event-related potential study of dynamic neural mechanisms of semantic organizational strategies in verbal learning. Brain Res 1170:59–70
Block RI, O’Leary DS, Hichwa RD, Augustinack JC, Ponto LLB, Ghoneim MM, Arndt S, Hurtig RR, Watkins GL, Hall JA, Nathan PE, Andreasen NC (2002) Effects of frequent marijuana use on memory-related regional cerebral blood flow. Pharmacol Biochem Behav 72:237–250
Bolla KI, Brown K, Eldreth D, Tate K, Cadet JL (2002) Dose-related neurocognitive effects of marijuana use. Neurology 59:1337–1343
Ceballos NA, Houston RJ, Smith ND, Bauer LO, Taylor RE (2005) N400 as an index of semantic expectancies: differential effects of alcohol and cocaine dependence. Prog Neuropsychopharmacol Biol Psychiatry 29:936–943
Ceballos NA, Bauer LO, Houston RJ (2009) Recent EEG and ERP findings in substance abusers. Clin EEG Neurosci 40:122–128
Dunn BR, Dunn DA, Languis M, Andrews D (1998) The relation of ERP components to complex memory processing. Brain Cogn 36:355–376
Felder CC, Nielsen A, Briley EM, Palkovits M, Priller J, Axelrod J, Nguyen DN, Richardson JM, Riggin RM, Koppel GA, Paul SM, Becker GW (1996) Isolation and measurement of the endogenous cannabinoid receptor agonist, anandamide, in brain and peripheral tissues of human and rat. FEBS Lett 393:231–235
Fernandez G, Weyerts H, Tendolkar I, Smid H, Scholz M, Heinze H (1998) Event-related potentials of verbal encoding into episodic memory: dissociation between the effects of subsequent memory performance and distinctiveness. Psychophysiology 35:709–720
Fletcher PC, Honey GD (2006) Schizophrenia, ketamine and cannabis: evidence of overlapping memory deficits. Trends Cogn Sci 10:167–174
Friedman D, Johnson R Jr (2000) Event-related potential (ERP) studies of memory encoding and retrieval: a selective review. Microsc Res Tech 51:6–28
Grant I, Gonzalez R, Carey CL, Natarajan L, Wolfson T (2003) Non-acute (residual) neurocognitive effects of cannabis use: a meta-analytic study. J Int Neuropsychol Soc 9:679–689
Hoffman AF, Oz M, Caulder T, Lupica CR (2003) Functional tolerance and blockade of long-term depression at synapses in the nucleus accumbens after chronic cannabinoid exposure. J Neurosci 23:4815–4820
Ilan AB, Smith M, Gevins A (2004) Effects of marijuana on neurophysiological signals of working and episodic memory. Psychopharmacology (Berl) 176:214–222
Ilan AB, Gevins A, Coleman M, ElSohly MA, de Wit H (2005) Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids. Behav Pharmacol 16:487–497
Jacobsen LK, Mencl WE, Westerveld M, Pugh KR (2004) Impact of cannabis use on brain function in adolescents. Ann N Y Acad Sci 1021:384–390
Jacobsen LK, Pugh KR, Constable RT, Westerveld M, Mencl WE (2007) Functional correlates of verbal memory deficits emerging during nicotine withdrawal in abstinent adolescent cannabis users. Biol Psychiatry 61:31–40
Jager G, Kahn RS, Van den Brink W, Van Ree JM, Ramsey NF (2006) Long-term effects of frequent cannabis use on working memory and attention: an fMRI study. Psychopharmacology (Berl) 185:358–368
Johnstone SJ, Clarke AR (2009) Dysfunctional response preparation and inhibition during a visual Go/Nogo task in children with two subtypes of attention-deficit hyperactivity disorder. Psychiatry Res 166:223–237
Kempel P, Lampe K, Parnefjord R, Hennig J, Kunert H (2003) Auditory-evoked potentials and selective attention: different ways of information processing in cannabis users and controls. Neuropsychobiology 48:95–101
Leweke M, Kampmann C, Radwan M, Dietrich D, Johannes S, Emrich H, Munte T (1998) The effects of tetrahydrocannabinol on the recognition of emotionally charged words: an analysis using event-related brain potentials. Neuropsychobiology 37:104–111
Messinis L, Kyprianidou A, Malefaki S, Papathanasopoulos P (2006) Neuropsychological deficits in long-term frequent cannabis users. Neurology 66:737–739
Musshoff F, Madea B (2006) Review of biologic matrices (urine, blood, hair) as indicators of recent or ongoing cannabis use. Ther Drug Monit 28:155–163
Nelson HE, Willison JR (1991) National adult reading test (NART): test manual, 2nd edn. NFER-Nelson, Windsor
Nielsen-Bohlman L, Knight R (1995) Prefrontal alterations during memory processing in aging. Cereb Cortex 5:541–549
Olichney JM, Taylor JR, Gatherwright J, Salmon DP, Bressler AJ, Kutas M, Iragui-Madoz VJ (2008) Patients with MCI and N400 or P600 abnormalities are at very high risk for conversion to dementia. Neurology 70:1763–1770
Onaivi ES, Ishiguro H, Zhang PW, Lin Z, Akinshola BE, Leonard CM, Chirwa SS, Gong J, Uhl GR (2006) Endocannabinoid receptor genetics and marijuana use. In: Onaivi ES, Sugiura T, Di Marzo V (eds) Endocannabinoids: the brain and body’s marijuana and beyond. CRC, Boca Raton
Otten LJ, Sveen J, Quayle AH (2007) Distinct patterns of neural activity during memory formation of nonwords versus words. J Cogn Neurosci 19:1776–1789
Paller K, Kutas M, Mayes AR (1987) Neural correlates of encoding in an incidental learning paradigm. Electroencephalogr Clin Neurophysiol 67:360–371
Patrick G, Straumanis JJ, Struve FA, Fitz-Gerald MJ, Leavitt J, Manno JE (1999) Reduced P50 auditory gating response in psychiatrically normal chronic marihuana users: a pilot study. Biol Psychiatry 45:1307–1312
Pope HG, Yurgelun-Todd D (1996) The residual cognitive effects of heavy marijuana use in college students. JAMA 275:521–527
Pope HG, Gruber AJ, Hudson JI, Huestis MA, Yurgelun-Todd D (2001) Neuropsychological performance in long-term cannabis users. Arch Gen Psychiatry 58:909–915
Ramaekers J, Kauert G, Theunissen E, Toennes S, Moeller M (2009) Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users. J Psychopharmacol 23:266–277
Ranganathan M, D’Souza DC (2006) The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology (Berl) 188:425–444
Rentzsch J, Penzhorn A, Kernbichler K, Plöckl D, Gómez-Carrillo de Castro A, Gallinat J, Jockers-Scherübl MC (2007) Differential impact of heavy cannabis use on sensory gating in schizophrenic patients and otherwise healthy controls. Exp Neurol 205:241–249
Roser P, Stadelmann AM, Arning L, Gallinat J, Epplen JT, Juckel G (2008) Acute effects of delta 9-tetrahydrocannabinol on the auditory event-related mismatch negativity depending on genetic variations in the dysbindin, neuregulin, and G72 gene. Int J Neuropsychopharmacol 11:256
Semlitsch HV, Anderer P, Schuster P, Presslich O (1986) A solution for reliable and valid reduction of ocular artifacts, applied to the P300 ERP. Psychophysiology 23:695–703
Sim-Selley LJ (2003) Regulation of cannabinoid CB1 receptors in the central nervous system by chronic cannabinoids. Crit Rev Neurobiol 15:91–118
Skosnik PD, Krishnan GP, Vohs JL, O’Donnell BF (2006) The effect of cannabis use and gender on the visual steady state evoked potential. Clin Neurophysiol 117:144–156
Skosnik PD, Park S, Dobbs L, Gardner WL (2008) Affect processing and positive syndrome schizotypy in cannabis users. Psychiatry Res 157:279–282
Solowij N (1995) Do cognitive impairments recover following cessation of cannabis use? Life Sci 56:2119–2126
Solowij N (1998) Cannabis and cognitive functioning. Cambridge University Press, New York
Solowij N, Battisti R (2008) The chronic effects of cannabis on memory in humans: a review. Curr Drug Abuse Rev 1:81–98
Solowij N, Michie PT, Fox AM (1991) Effects of long-term cannabis use on selective attention: an event-related potential study. Pharmacol Biochem Behav 40:683–688
Solowij N, Grenyer BFS, Chesher G, Lewis J (1995a) Biopsychosocial changes associated with cessation of cannabis use: a single case study of acute and chronic cognitive effects, withdrawal and treatment. Life Sci 56:2127–2134
Solowij N, Michie PT, Fox AM (1995b) Differential impairments of selective attention due to frequency and duration of cannabis use. Biol Psychiatry 37:731–739
Solowij N, Stephens RS, Roffman RA, Babor T, Kadden R, Miller M, Christiansen K, McRee B, Vendetti J (2002) Cognitive functioning of long-term heavy cannabis users seeking treatment. JAMA 287:1123–1131
Solowij N, Yücel M, Lorenzetti V, Lubman DI (2009) Structural brain alterations in cannabis users: association with cognitive deficits and psychiatric symptoms. In: Ritsner MS (ed) The handbook of neuropsychiatric biomarkers, endophenotypes and genes neuroanatomical and neuroimaging endophenotypes and biomarkers. Springer, Netherlands
Tabachnick BG, Fidell LS (2000) Using multivariate statistics, 4th edn. Allyn and Bacon, Boston
Wölfling K, Flor H, Gruesser SM (2008) Psychophysiological responses to drug-associated stimuli in chronic heavy cannabis use. Eur J NeuroSci 27:976–983
Yücel M, Solowij N, Respondek C, Whittle S, Fornito A, Pantelis C, Lubman DI (2008) Regional brain abnormalities associated with long-term heavy cannabis use. Arch Gen Psychiatry 65:694–701
Author information
Authors and Affiliations
Corresponding author
Additional information
This research project was funded by a University of Wollongong University Research Council Small Grant.
Rights and permissions
About this article
Cite this article
Battisti, R.A., Roodenrys, S., Johnstone, S.J. et al. Chronic use of cannabis and poor neural efficiency in verbal memory ability. Psychopharmacology 209, 319–330 (2010). https://doi.org/10.1007/s00213-010-1800-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-010-1800-4