Neuropsychological functioning in adolescent marijuana users: Subtle deficits detectable after a month of abstinence

Medina, Krista Lisdahl; Hanson, Karen L.; Schweinsburg, Alecia D.; Cohen-Zion, Mairav; Nagel, Bonnie J.; Tapert, Susan F.

doi:10.1017/s1355617707071032

Cited by 260 publications

(300 citation statements)

References 102 publications

(115 reference statements)

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“…In addition, the activation of the brain cannabinoid system causes deficits in attention, executive functioning, and short-term memory (Lichtman and Martin, 1996;O'Leary et al, 2002;Medina et al, 2007). It is also demonstrated that object recognition memory was impaired by both endogenous cannabinoid D 9 -THC and synthetic CB 1 receptor agonist WIN 55,212-2 (Schneider and Koch, 2002;Quinn et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Cannabis usage causes deficits in attention, executive functioning, and short-term memory (O'Leary et al, 2002;Medina et al, 2007). We showed earlier that repeated treatment with D 9 -tetrahydrocannabinol (D 9 -THC), the main psychoactive ingredient of marijuana (cannabis), impaired delayed matching-to-sample performance even 24 h after the administration (Miyamoto et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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A Cannabinoid CB1 Receptor Antagonist Ameliorates Impairment of Recognition Memory on Withdrawal from MDMA (Ecstasy)

Nawata

Hiranita

Yamamoto

2009

Neuropsychopharmacol

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( + /À)-3,4-Methylenedioxymethamphetamine (MDMA, 'Ecstasy') abusers have persistent neuropsychiatric deficits including memory impairments after the cessation of abuse. On the other hand, cannabinoid CB 1 receptors have been implicated in learning/memory, and are highly expressed in the hippocampus, a region of the brain believed to have an important function in certain forms of learning and memory. In this study, we clarified the mechanism underlying the cognitive impairment that develops during MDMA withdrawal from the standpoint of the cannabinoid CB 1 receptors. Mice were administered MDMA (10 mg/kg, i.p.) once a day for 7 days. On the 7th day of withdrawal, a novel object recognition task was performed and the amount of cannabinoid CB 1 receptor protein was measured with western blotting. Recognition performance was impaired on the 7th day of withdrawal. This impairment was blocked by AM251, a cannabinoid CB 1 receptor antagonist, administered 30 min before the training trial or co-administered with MDMA. At this time, the level of cannabinoid CB 1 receptor protein increased significantly in the hippocampus but not the prefrontal cortex or striatum. This increase of CB 1 receptor protein in the hippocampus was also blocked by the co-administration of AM251. Furthermore, CB 1 receptor knockout mice showed no impairment of recognition performance on the withdrawal from MDMA. The impairment of recognition memory during withdrawal from MDMA may result from the activation of cannabinoid CB 1 receptors in the hippocampus.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Cannabinoid CB1 Receptor Antagonist Ameliorates Impairment of Recognition Memory on Withdrawal from MDMA (Ecstasy)

Nawata

Hiranita

Yamamoto

2009

Neuropsychopharmacol

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“…In fact, teenagers who frequently smoke marijuana suffer dysfunctions in synaptic pruning processes and display worse performance in learning tests, cognitive flexibility, visual scanning, error commission and working memory (Medina et al , 2007a, 2007b; Nagel et al , 2005). Sometimes, the sum of these mostly cognitive changes is named ‘Amotivational Syndrome’, and it can be the result of chronic THC intoxication or long lasting effects of the abuse of THC for longer periods of time, with unknown pathophysiological mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Chronic exposure to cannabinoids during adolescence causes long‐lasting behavioral deficits in adult mice

et al. 2016

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Regular use of marijuana during adolescence enhances the risk of long‐lasting neurobiological changes in adulthood. The present study was aimed at assessing the effect of long‐term administration of the synthetic cannabinoid WIN55212.2 during adolescence in young adult mice. Adolescent mice aged 5 weeks were subjected daily to the pharmacological action of WIN55212.2 for 3 weeks and were then left undisturbed in their home cage for a 5‐week period and finally evaluated by behavioral testing. Mice that received the drug during adolescence showed memory impairment in the Morris water maze, as well as a dose‐dependent memory impairment in fear conditioning. In addition, the administration of 3 mg/kg WIN55212.2 in adolescence increased adult hippocampal AEA levels and promoted DNA hypermethylation at the intragenic region of the intracellular signaling modulator Rgs7, which was accompanied by a lower rate of mRNA transcription of this gene, suggesting a potential causal relation. Although the concrete mechanisms underlying the behavioral observations remain to be elucidated, we demonstrate that long‐term administration of 3 mg/kg of WIN during adolescence leads to increased endocannabinoid levels and altered Rgs7 expression in adulthood and establish a potential link to epigenetic changes.

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“…In this seminal paper, the authors demonstrated a dramatic drop in intelligence for those with persistent cannabis dependence. Although Meier et al's study has been the largest and most complete longitudinal examination of IQ decline and marijuana use, there is disagreement as to whether this decline is a direct consequence of marijuana involvement or perhaps attributable to confounding variables (19,24).Although studies have demonstrated that heavy marijuana use may impact IQ test performance even a month after cessation (16,25), deficits seem to be more related to recent use rather than reflecting a permanent insult to cognition (22,26,27). Indeed, some studies find no long-term association of marijuana use and IQ (22,28) or, if so, only on measures of verbal ability (19).…”

mentioning

confidence: 99%

“…There is evidence to suggest that the adolescent brain may be particularly vulnerable, especially with regard to neurocognitive functioning (10,11). Marijuana use in adolescence, when the brain is still undergoing major developmental changes, has been associated with decreased intelligence (12,13), reduced memory (13)(14)(15), poorer attention (16)(17)(18), and lower verbal ability (19)(20)(21). However, these findings come from cross-sectional studies, where the temporal ordering of cause and effect is uncertain.…”

mentioning

confidence: 99%

Impact of adolescent marijuana use on intelligence: Results from two longitudinal twin studies

Jackson

Isen

Khoddam

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

163

131

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Marijuana is one of the most commonly used drugs in the United States, and use during adolescence-when the brain is still developing-has been proposed as a cause of poorer neurocognitive outcome. Nonetheless, research on this topic is scarce and often shows conflicting results, with some studies showing detrimental effects of marijuana use on cognitive functioning and others showing no significant long-term effects. The purpose of the present study was to examine the associations of marijuana use with changes in intellectual performance in two longitudinal studies of adolescent twins (n = 789 and n = 2,277). We used a quasiexperimental approach to adjust for participants' family background characteristics and genetic propensities, helping us to assess the causal nature of any potential associations. Standardized measures of intelligence were administered at ages 9-12 y, before marijuana involvement, and again at ages 17-20 y. Marijuana use was self-reported at the time of each cognitive assessment as well as during the intervening period. Marijuana users had lower test scores relative to nonusers and showed a significant decline in crystallized intelligence between preadolescence and late adolescence. However, there was no evidence of a dose-response relationship between frequency of use and intelligence quotient (IQ) change. Furthermore, marijuana-using twins failed to show significantly greater IQ decline relative to their abstinent siblings. Evidence from these two samples suggests that observed declines in measured IQ may not be a direct result of marijuana exposure but rather attributable to familial factors that underlie both marijuana initiation and low intellectual attainment.M arijuana is one of the most commonly used drugs in the United States, with a lifetime use prevalence of 50% (1, 2). Despite this, research on the long-term effects of marijuana use is scarce compared with that of other illicit substances. Changing cultural attitudes toward marijuana have recently led to social and legal acceptance of recreational use (3, 4), making research on the potential consequences particularly salient.Previous research has shown that marijuana use can have a high societal cost through increased unemployment, absenteeism, decreased productivity, and increased rates of crime and incarceration (5-8). Given that about 19% of youth and young adults (ages 18-25 y) in the United States have used marijuana in the past month (9), the potential impact is nontrivial. There is evidence to suggest that the adolescent brain may be particularly vulnerable, especially with regard to neurocognitive functioning (10, 11). Marijuana use in adolescence, when the brain is still undergoing major developmental changes, has been associated with decreased intelligence (12, 13), reduced memory (13-15), poorer attention (16-18), and lower verbal ability (19-21). However, these findings come from cross-sectional studies, where the temporal ordering of cause and effect is uncertain. For longitudinal studies examining marijuana use and ch...

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Neuropsychological functioning in adolescent marijuana users: Subtle deficits detectable after a month of abstinence

Cited by 260 publications

References 102 publications

A Cannabinoid CB1 Receptor Antagonist Ameliorates Impairment of Recognition Memory on Withdrawal from MDMA (Ecstasy)

A Cannabinoid CB1 Receptor Antagonist Ameliorates Impairment of Recognition Memory on Withdrawal from MDMA (Ecstasy)

Chronic exposure to cannabinoids during adolescence causes long‐lasting behavioral deficits in adult mice

Impact of adolescent marijuana use on intelligence: Results from two longitudinal twin studies

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