One Month of Cannabis Abstinence in Adolescents and Young Adults Is Associated With Improved Memory

Randi Melissa Schuster, Jodi Gilman, David Schoenfeld, John Evenden, Maya Hareli, Christine Ulysse, Emily Nip, Ailish Hanly, Haiyue Zhang, A Eden Evins, Randi Melissa Schuster, Jodi Gilman, David Schoenfeld, John Evenden, Maya Hareli, Christine Ulysse, Emily Nip, Ailish Hanly, Haiyue Zhang, A Eden Evins

Abstract

Objective: Associations between adolescent cannabis use and poor neurocognitive functioning have been reported from cross-sectional studies that cannot determine causality. Prospective designs can assess whether extended cannabis abstinence has a beneficial effect on cognition.

Methods: Eighty-eight adolescents and young adults (aged 16-25 years) who used cannabis regularly were recruited from the community and a local high school between July 2015 and December 2016. Participants were randomly assigned to 4 weeks of cannabis abstinence, verified by decreasing 11-nor-9-carboxy-∆⁹-tetrahydrocannabinol urine concentration (MJ-Abst; n = 62), or a monitoring control condition with no abstinence requirement (MJ-Mon; n = 26). Attention and memory were assessed at baseline and weekly for 4 weeks with the Cambridge Neuropsychological Test Automated Battery.

Results: Among MJ-Abst participants, 55 (88.7%) met a priori criteria for biochemically confirmed 30-day continuous abstinence. There was an effect of abstinence on verbal memory (P = .002) that was consistent across 4 weeks of abstinence, with no time-by-abstinence interaction, and was driven by improved verbal learning in the first week of abstinence. MJ-Abst participants had better memory overall and at weeks 1, 2, 3 than MJ-Mon participants, and only MJ-Abst participants improved in memory from baseline to week 1. There was no effect of abstinence on attention: both groups improved similarly, consistent with a practice effect.

Conclusions: This study suggests that cannabis abstinence is associated with improvements in verbal learning that appear to occur largely in the first week following last use. Future studies are needed to determine whether the improvement in cognition with abstinence is associated with improvement in academic and other functional outcomes.

Trial registration: ClinicalTrials.gov identifier: NCT03276221.

© Copyright 2018 Physicians Postgraduate Press, Inc.

Figures

Figure 1.
Figure 1.
A total of 592 valid urine specimens were collected during the study period, and 93.2% (n = 552) of the specimens had THCCOOH levels that were quantifiable based on available laboratory methods (range of creatinine-unadjusted THCCOH levels in quantifiable samples: 0 – 3920ng/ml; range of creatinine-adjusted THCCOH levels in quantifiable samples: 0 – 1765.8ng/mg). Urine creatinine-adjusted THCCOOH concentrations declined during four weeks of monitored cannabis abstinence only among those randomized to 4 weeks of cannabis abstinence (MJ-Abst). Values are presented for specimens where quantifiable THCCOOH and creatinine were available. All values represent means and standard errors.
Figure 2.
Figure 2.
A. Attention improved similarly in MJ-Abst and MJ-Mon across the 4-week assessment period. All values represent means and standard errors. B. Memory improved only in MJ-Abst, and this improvement occurred in the first week of cannabis abstinence. All values represent means and standard errors.

References

    1. Johnston LD, O’Malley PM, Miech RA, Bachman JG, Schulenberg JE. Monitoring the Future national survey results on drug use, 1975–2016: Overview, key findings on adolescent drug use. Ann Arbor: Institute for Social Research; 2017.
    1. Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, et al.: Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 1999; 2:861–8633.
    1. Sowell ER, Thompson PM, Holmes CJ, Batth R, Jernigan TL, Toga AW: Localizing age-related changes in brain structure between childhood and adolescence using statistical parametric mapping. NeuroImage 1999;9(6 Pt 1):587–597.
    1. Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, et al.: Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci USA 2004;101:8174–8179.
    1. Benes FM, Turtle M, Khan Y, Farol P: Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood. JAMA Psychiatry 1994;51:477–484.
    1. Durston S, Hulshoff Pol HE, Casey BJ, Giedd JN, Buitelaar JK, van Engeland H: Anatomical MRI of the developing human brain: what have we learned? J Am Acad Child Adolesc Psychiatry 2001;40:1012–1020.
    1. Giedd JN: Structural magnetic resonance imaging of the adolescent brain. Ann N Y Acad Sci 2004;1021:77–85.
    1. Jernigan TL, Gamst AC: Changes in volume with age--consistency and interpretation of observed effects. Neurobiol Aging 2005;26:1271–1274; discussion 5–8.
    1. Pfefferbaum A, Mathalon DH, Sullivan EV, Rawles JM, Zipursky RB, Lim KO: A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol 1994;51:874–887.
    1. Bava S, Tapert SF:Adolescent brain development and the risk for alcohol and other drug problems. Neuropsychol Rev 2010;20:398–413.
    1. Viveros MP, Llorente R, Suarez J, Llorente-Berzal A, Lopez-Gallardo M, de Fonseca FR: The endocannabinoid system in critical neurodevelopmental periods: sex differences and neuropsychiatric implications. J Psychopharmacol 2012;26:164–176.
    1. Harte LC, Dow-Edwards D: Sexually dimorphic alterations in locomotion and reversal learning after adolescent tetrahydrocannabinol exposure in the rat. Neurotoxicol Teratol 2010;32:515–524.
    1. O’Shea M, Singh ME, McGregor IS, Mallet PE: Chronic cannabinoid exposure produces lasting memory impairment and increased anxiety in adolescent but not adult rats. J Psychopharmacol 2004;18:502–508.
    1. Quinn HR, Matsumoto I, Callaghan PD, Long LE, Arnold JC, Gunasekaran N, et al.: Adolescent rats find repeated Delta(9)-THC less aversive than adult rats but display greater residual cognitive deficits and changes in hippocampal protein expression following exposure. Neuropsychopharmacology 2008;33:1113–1126.
    1. Rubino T, Realini N, Braida D, Guidi S, Capurro V, Vigano D, et al.: Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus 2009;19:763–772.
    1. Gruber SA, Silveri MM, Dahlgren MK, Yurgelun-Todd D: Why so impulsive? White matter alterations are associated with impulsivity in chronic marijuana smokers. Exp Clin Psychopharm 2011;19:231–242.
    1. Schuster RM, Hoeppner SS, Evins AE, Gilman JM: Early onset marijuana use is associated with learning inefficiencies. Neuropsychology 2016;30:405–415.
    1. Gruber SA, Sagar KA, Dahlgren MK, Racine M, Lukas SE: Age of onset of marijuana use and executive function. Psychol Addict Behav 2012;26:496–506.
    1. Crane NA, Schuster RM, Mermelstein RJ, Gonzalez R: Neuropsychological sex differences associated with age of initiated use among young adult cannabis users. J Clin Exp Neuropsychol 2015;37:389–401.
    1. Hanson KL, Winward JL, Schweinsburg AD, Medina KL, Brown SA, Tapert SF: Longitudinal study of cognition among adolescent marijuana users over three weeks of abstinence. Addict Behav 2010;35:970–976.
    1. Roten A, Baker NL, Gray KM: Cognitive performance in a placebo-controlled pharmacotherapy trial for youth with marijuana dependence. Addict Behav. 2015;45:119–23.
    1. Schuster RM, Hanly A, Gilman J, Budney A, Vandrey R, Evins AE: A contingency management method for 30-days abstinence in non-treatment seeking young adult cannabis users. Drug Alcohol Depend 2016;167:199–206.
    1. Petry NM: A comprehensive guide to the application of contingency management procedures in clinical settings. Drug Alcohol Depend 2000;58(1–2):9–25.
    1. Huestis MA, Cone EJ: Differentiating new marijuana use from residual drug excretion in occasional marijuana users. J Anal Toxicol 1998;22:445–454.
    1. Schwilke EW, Gullberg RG, Darwin WD, Chiang CN, Cadet JL, Gorelick DA, et al.: Differentiating new cannabis use from residual urinary cannabinoid excretion in chronic, daily cannabis users. Addiction 2011;106:499–506.
    1. Wechsler D: Wechsler Abbreviated Scale of Intelligence. New York, NY: The Psychological Corporation: Harcourt Brace & Company; 1999.
    1. Wechsler D: Wechsler Test of Adult Reading. San Antonio, TX: Pearson; 2001.
    1. Adamson SJ, Sellman JD: A prototype screening instrument for cannabis use disorder: the Cannabis Use Disorders Identification Test (CUDIT) in an alcohol-dependent clinical sample. Drug Alcohol Rev 2003;22:309–315.
    1. Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M: Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption--II. Addiction 1993;88:791–804.
    1. Robinson SM, Sobell LC, Sobell MB, Leo GI: Reliability of the Timeline Followback for cocaine, cannabis, and cigarette use. Psychol Addict Behav 2014;28:154–162.
    1. First MB, Spitzer RL, Gibbon M, Williams JBW: Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-Patient Edition. New York, New York Biometrics Research, New York State Psychiatric Institute; 2002.
    1. Medina KL, Hanson KL, Schweinsburg AD, Cohen-Zion M, Nagel BJ, Tapert SF: Neuropsychological functioning in adolescent marijuana users: subtle deficits detectable after a month of abstinence. J Int Neuropsychol Soc 2007;13:807–820.
    1. Schwartz RH, Gruenewald PJ, Klitzner M, Fedio P: Short-term memory impairment in cannabis-dependent adolescents. Am J Dis Child 1989;143:1214–1219.
    1. Solowij N, Jones KA, Rozman ME, Davis SM, Ciarrochi J, Heaven PC, et al.: Verbal learning and memory in adolescent cannabis users, alcohol users and non-users. Psychopharmacology 2011;216:131–144.
    1. Thoma RJ, Monnig MA, Lysne PA, Ruhl DA, Pommy JA, Bogenschutz M, et al.: Adolescent substance abuse: the effects of alcohol and marijuana on neuropsychological performance. Alcohol Clin Exp Res 2011;35:39–46.
    1. Crane NA, Schuster RM, Fusar-Poli P, Gonzalez R: Effects of cannabis on neurocognitive functioning: recent advances, neurodevelopmental influences, and sex differences. Neuropsychol Rev 2013;23:117–137.
    1. Grant I, Gonzalez R, Carey CL, Natarajan L, Wolfson T: Non-acute (residual) neurocognitive effects of cannabis use: a meta-analytic study. J Int Neuropsychol Soc 2003;9:679–689.
    1. Schweinsburg AD, Brown SA, Tapert SF: The influence of marijuana use on neurocognitive functioning in adolescents. Curr Drug Abuse Rev 2008;1:99–111.
    1. Ranganathan M, Radhakrishnan R, Addy PH, Schnakenberg-Martin AM, Williams AH, Carbuto M, et al.: Tetrahydrocannabinol (THC) impairs encoding but not retrieval of verbal information. Prog Neuropsychopharmacol Biol Psychiatry 2017;79(Pt B):176–183.
    1. Dickerson BC, Eichenbaum H: The episodic memory system: neurocircuitry and disorders. Neuropsychopharmacology 2010;35:86–104.
    1. Uncapher MR, Wagner AD : Posterior parietal cortex and episodic encoding: insights from fMRI subsequent memory effects and dual-attention theory. Neurobiol Learn Mem 2009;91:139–154.
    1. Bhattacharyya S, Fusar-Poli P, Borgwardt S, Martin-Santos R, Nosarti C, O’Carroll C, et al.: Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis. JAMA Psychiatry 2009;66:442–451.
    1. Bossong MG, Jager G, van Hell HH, Zuurman L, Jansma JM, Mehta MA, et al.: Effects of Delta9-tetrahydrocannabinol administration on human encoding and recall memory function: a pharmacological FMRI study. J Cogn Neurosci 2012;24:588–599.
    1. Ashtari M, Avants B, Cyckowski L, Cervellione KL, Roofeh D, Cook P, et al.: Medial temporal structures and memory functions in adolescents with heavy cannabis use. J Psychiatr Res 2011;45:1055–1066.
    1. Churchwell JC, Lopez-Larson M, Yurgelun-Todd DA: Altered frontal cortical volume and decision making in adolescent cannabis users. Front Psychol 2010;1:225.
    1. Medina KL, Nagel BJ, Tapert SF: Abnormal cerebellar morphometry in abstinent adolescent marijuana users. Psychiatry Res 2010;182:152–159.
    1. Yucel M, Zalesky A, Takagi MJ, Bora E, Fornito A, Ditchfield M, et al.: White-matter abnormalities in adolescents with long-term inhalant and cannabis use: a diffusion magnetic resonance imaging study. J Psychiatry Neurosci 2010;35:409–412.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera