Functional consequences of marijuana use in adolescents

Nearly half of 12th graders have tried marijuana, and 6% use daily. This paper reviews studies on neuropsychological functioning, brain structure, brain function, and subjective and objective measures of sleep in relation to adolescent marijuana use. Adolescents who use marijuana heavily tend to show disadvantaged attention, learning, and processing speed; subtle abnormalities in brain structure; increased activation during cognitive tasks despite intact performance; and compromised objective indicators of sleep quality. Some abnormalities appear to persist beyond a month of abstinence, but may resolve within three months if cessation is maintained. Recommendations for future studies include characterizing these indices in youth prior to the onset of marijuana use then examining change after chronic use has started, and using large samples of youth with varying degrees of involvement with marijuana as well as alcohol, nicotine, and other drugs to characterize the interactive influences on neurocognition and neural health.     

Functional MRI study of working memory in MDMA users

Rationale Methylene-dioxymethamphetamine (MDMA) is known to cause degeneration of serotonin nerve terminals after acute doses in animals. Similarly, behavioral studies in human MDMA users regularly find abnormalities in memory, mood, and impulse control. However, studies of brain function using brain imaging in MDMA users have been less consistent.Objectives The purpose of this study was to determine, using functional magnetic resonance imaging (fMRI), whether individuals with a self-reported history of MDMA use would differ from non-MDMA using controls on activation while performing a working memory task.Methods Fifteen MDMA using subjects and 19 non-MDMA using controls underwent fMRI scanning while performing the immediate and delayed memory task (IMT/DMT). The study was based on a block design in which the delayed memory task (DMT) alternated with the immediate memory task (IMT), which served as a control condition. FMRI scans were acquired on a 1.5 T scanner, using a gradient echo echoplanar pulse sequence.Results Random effects SPM99 analysis showed significantly greater activation (whole volume corrected cluster P<0.05) during the DMT relative to the IMT in the MDMA subjects compared with the control subjects in the medial superior frontal gyrus, in the thalamus extending into putamen, and in the hippocampus.Conclusions Although these effects could be due to other drugs used by MDMA users, these results are consistent with behavioral problems that are associated with MDMA use, and with animal studies on the effects of MDMA on brain function.     

Sleep architecture in adolescent marijuana and alcohol users during acute and extended abstinence

This study examined sleep changes following cessation of marijuana and alcohol use during late adolescence. Twenty-nine heavy marijuana and alcohol users and 20 matched controls were studied during a 28-day monitored abstinence period. Sleep was examined as a function of prior substance use during Nights 1–2 and Nights 27–28. On Night 2, percent rapid eye movement sleep was predicted by past month alcohol use, whereas percent slow wave sleep was predicted by marijuana intake. By Night 28, neither alcohol nor marijuana use predicted any sleep architecture measure. However, on Night 28, indices of period limb movements (PLMs) in sleep were predicted by marijuana and alcohol intake. Results indicate that in adolescents: (1) cessation of heavy marijuana and alcohol use may influence sleep; (2) most sleep abnormalities abate within several weeks of abstinence; and (3) PLMs may increase following abstinence.     

Characteristics of clinically anxious versus non-anxious regular, heavy marijuana users

Both the key mechanism of action for marijuana (the endocannabinoid system) and the symptoms associated with marijuana withdrawal suggest an important link to anxiety. Despite this link, there is a dearth of research on the characteristics of heavy marijuana users with clinical-level anxiety compared to those with heavy marijuana use alone. Over 10,000 participants (friends or affiliates of the National Organization for the Reform of Marijuana Laws) provided data via online survey. After careful, conservative screening, anxiety, other psychopathology, other drug use, and marijuana-related problems were examined in 2567 heavy marijuana users. Subsequently, 275 heavy users with clinical-level anxiety were compared to demographically-equivalent non-anxious heavy users on psychopathology, drug use, and cannabis-related problems. Among several psychological variables (including anxiety, depression, schizotypy, and impulsivity), anxiety was most strongly predictive of amount of marijuana used and marijuana-related problems. Group comparison (n=550 total) revealed that clinically anxious heavy users exhibited more use, more non-anxiety psychopathological symptoms, and a greater number and severity of marijuana-related problems than their non-anxious peers. The findings reveal that anxiety shows an important relation to marijuana use and related problems among regular, heavy users. Further examinations of common and unique factors predisposing individuals for anxiety and marijuana abuse appear warranted.     

Longitudinal study of cognition among adolescent marijuana users over three weeks of abstinence

Background

Cognitive deficits that persist up to a month have been detected among adult marijuana users, but decrements and their pattern of recovery are less known in adolescent users. Previously, we reported cognitive deficits among adolescent marijuana users after one month of abstinence (Medina, Hanson, Schweinsburg, Cohen-Zion, Nagel, & Tapert, 2007). In this longitudinal study, we characterized neurocognitive changes among marijuana-using adolescents across the first three weeks of abstinence.

Method

Participants were adolescent marijuana users with limited alcohol and other drug use (n = 19) and demographically similar non-using controls (n = 21) ages 15–19. Participants completed a brief neuropsychological battery on three occasions, after 3 days, 2 weeks, and 3 weeks of stopping substance use. Abstinence was ascertained by decreasing tetrahydrocannabinol metabolite values on serial urine drug screens. Verbal learning, verbal working memory, attention and vigilance, and time estimation were evaluated.

Results

Marijuana users demonstrated poorer verbal learning (p < .01), verbal working memory (p < .05), and attention accuracy (p < .01) compared to controls. Improvements in users were seen on word list learning after 2 weeks of abstinence and on verbal working memory after 3 weeks. While attention processing speed was similar between groups, attention accuracy remained deficient in users throughout the 3-week abstinence period.

Conclusions

This preliminary study detected poorer verbal learning and verbal working memory among adolescent marijuana users that improved during three weeks of abstinence, while attention deficits persisted. These results implicate possible hippocampal, subcortical, and prefrontal cortex abnormalities.     

Changes in brain gray matter in abstinent heroin addicts

Background

Previous neuroimaging studies have documented changes in the brain of heroin addicts. However, few researches have detailed whether such changes can be amended after short-term abstinence.

Methods

We used magnetic resonance imaging (MRI) to investigate gray matter volume in 20 heroin-dependent patients at 3 days and at 1 month after heroin abstinence; 20 normal subjects were also included as controls.

Results

Decreased gray matter density in frontal cortex, cingulate and the occipital regions were found in heroin users after three days of abstinence. In contrast, after 1-month abstinence, no significant difference was found in superior frontal gyrus between heroin addicts and controls, but changes in other brain regions, including right middle frontal gyrus, left cingulate gyrus and left inferior occipital gyrus, still remained.

Conclusion

Our findings illustrate that abnormal gray matter in some brain regions of heroin addicts can return to normal after one-month abstinence.     

Neurophysiological and cognitive effects of smoked marijuana in frequent users

Rationale

Previously, we reported that acute marijuana intoxication minimally affected complex cognitive performance of daily marijuana smokers. It is possible that the cognitive tests used were insensitive to marijuana-related cognitive effects.

Objectives

In the current study, electroencephalographic (EEG) signals were recorded as daily marijuana users performed additional tests of immediate working memory and delayed episodic memory, before and after smoking marijuana.

Methods

Research volunteers (N = 24), who reported smoking ∼ 24 marijuana cigarettes/week, completed this study. Participants completed baseline computerized cognitive tasks, smoked a single marijuana cigarette (0%, 1.8%, or 3.9% ?⁹-THC w/w), and completed additional cognitive tasks; sessions were separated by at least 72-hours. Cardiovascular and subjective effects were also assessed throughout sessions.

Results

Overall performance accuracy was not significantly altered by marijuana, although the drug increased response times during task performance and induced a response bias towards labeling “new” words as having been previously seen in the verbal episodic memory task. Marijuana reduced slow wave evoked potential amplitude in the episodic memory task and decreased P300 amplitude and EEG power in the alpha band in the spatial working memory task. Heart rate and “positive” subjective-effect ratings were increased in a ?⁹-THC concentration-dependent manner.

Conclusions

Relative to previous findings with infrequent marijuana users, the frequent users in the current study exhibited similar neurophysiological effects but more subtle performance effects. These data emphasize the importance of taking into account the drug-use histories of research participants and examining multiple measures when investigating marijuana-related effects on cognitive functioning.     

Effects of research setting on observed depressive symptoms in marijuana users

A post hoc analysis examined depressive symptoms in regular marijuana smokers interested in nontreatment, laboratory studies, and marijuana-dependent treatment-seekers considering clinical trial participation. Among marijuana-dependent treatment-seeking patients screened for a clinical trial, the mean Beck Depression Inventory Score (BDI) was significantly higher than for marijuana-using volunteers screened for nontreatment laboratory studies. Mean self-reported baseline marijuana use was not significantly different between groups, and BDI score was not correlated with use. Although the methods by which the two groups were selected influenced their characteristics (i.e., treatment-seekers are more likely to be experiencing some degree of clinical distress), it is notable that treatment-seeking, and not marijuana use per se, is associated with significantly higher rates of depression.     

Childhood predictors of adolescent marijuana use: early sensation-seeking, deviant peer affiliation, and social images

This study examined psychosocial mechanisms by which children's early sensation-seeking may influence their later marijuana use. In a longitudinal study, 4th and 5th grade elementary school children (N=420) were followed until they were in 11th and 12th grades in high school with annual or biennial assessments. Sensation-seeking (assessed over the first 4 assessments) predicted affiliating with deviant peers and level of favorable social images of kids who use marijuana (both assessed over the subsequent 3 assessments). Affiliation with deviant peers and the growth in social images predicted marijuana use in 11th and 12th grades. Affiliation with deviant peers mediated the effect of early sensation-seeking on subsequent marijuana use. The theoretical and applied significance of this influence of early sensation-seeking is discussed.     

Psychological studies of marijuana and alcohol in man

Regular users of marijuana (cannabis sativa) were given smoked and orally administered marijuana, a placebo, or alcohol. They were unable to distinguish between smoked marijuana and the tetrahydrocannabinol-free placebo. The oral administration of tincture of cannabis produced primarily dysphoric symptoms and was similar to alcohol in this respect. The smoked marijuana altered pulse rate, time estimation, and EEG, but had no effect on a measure of field dependence or on a digit symbol substitution task. Both drugs appeared to be mild intoxicants in a laboratory setting. Consideration of the dose, prior experience with drugs, setting, and possible cross tolerance of marijuana and alcohol are important in evaluating the significance of the clinical effects.Based on a paper presented at the 125th Annual Meeting of the American Psychiatric Association, Bal Harbour, Florida, May 1969.This work was supported by National Institute of Mental Health grants K-1-MH-32904 and MH-15842, and by State of California Department of Mental Hygiene grant # 1–50.This paper does not reflect the views or policies of the California Department of Mental Hygiene.Staff Psychiatrist, and Assistant Professor of Psychiatry in Residence.Research Psychologist, and Associate Professor of Medial Psychology in Residence.     

fMRI脑功能成像技术用于网络游戏成瘾诊断测评

目的运用蹦RI脑功能成像技术,总结网络游戏成瘾青少年的神经影像学改变,为其诊断和治疗提供客观依据。方法选择12名网络游戏成瘾青少年（IAD组）和12名正常青少年（对照组）参与本研究,两组被试者分别观看网络游戏相关图片和中性图片,同时采用fMRI技术扫描,获取被试者的大脑活动信号,使用SPM5软件分析处理。结果与观看中性图片时比较,IAD组观看游戏图片时双侧背外侧前额叶、扣带回前部、顶下小叶、颞下回、小脑、右侧岛叶及右侧角回激活增多。IAD组观看游戏图片时以下区域激活增多：双侧背外侧前额叶、双侧颞叶、小脑、右侧顶下小叶、右侧楔叶、左侧海马、海马旁回、左侧尾状核;对照组观看游戏图片时全脑未见激活增多。结论网络游戏成瘾的青少年脑功能成像影像改变与正常青少年存在差异,为网络成瘾的诊断测评标准提供了新的客观依据。     

Short-term effects of marijuana smoking on cognitive behavior in experienced male users

The effects of smoking marijuana on the ability to use abstract concepts was tested in 12 experienced marijuana users. Each subject was tested three times, after smoking prepared 300 mg cigarettes containing either 0, 1.5 or 2.9% ⁹-THC in different sessions according to a Latin Square design. The same number of whole and/or partial cigarettes was smoked by each subject in each of the three sessions. This was determined for individual subjects by the number of 2.9% ⁹-THC marijuana cigarettes that the subject had been willing to smoke in a pre-experimental session up to a maximum of 1200 mg. The following tests of concept formation and usage were used: 1. a letter series test; 2. a word grouping test; 3. a conceptual clustering memory test; 4. a closure speed test; 5. Witkin's Embedded Figures Test; 6. a size weight illusion test; 7. Luchin's Water Jar Test; 8. Luchin's Hidden Word Test; and 9. an anagram test. Marijuana smoking led to a dose-related impairment on the letter series, word grouping, closure speed, and Embedded Figures test. Performance on the size-weight illusion, Luchin's Water Jar, Luchin's Hidden Word, and the anagram tests were unaffected. Conceptual clustering decreased after marijuana smoking. In most cases only the differences between 0 and 2.9% ⁹-THC marijuana were statistically significant.This study is a partial report of a Ph. D. dissertation of J. H. P. submitted to the University of Michigan while on a USPHS predoctoral traineeship, NIMH, USPHS 5TOI MH-0667-13. Also supported in part by grant USPHS MH-11846.     

Tolerability and effects of oral Delta9-tetrahydrocannabinol in older adolescents with marijuana use disorders

OBJECTIVE: The tolerability and effects of oral Delta(9)-tetrahydrocannabinol (THC) have been previously investigated in adult marijuana abusers. However, no studies have included adolescent participants. This double-blind laboratory study investigated the tolerability and effects of oral THC in a group of older adolescents with marijuana use disorders. METHODS: Eight participants (ages 16-21 years), smoking an average of 5.2 days/week and 2.5 "joints"/day, completed this four-session study, during which they received one of four oral THC doses (0, 2.5, 5, 10 mg) each session. Administration of oral THC doses was counterbalanced across participants. During each session, participants completed the Digit-Symbol Substitution Task (DSST) and subjective-effect ratings at baseline and 1, 2, and 3 h after oral THC administration. RESULTS: Oral THC (5 mg and 10 mg) increased several "positive" subjective-effect ratings (e.g., "Good Drug Effect"), while producing no significant effects on cardiovascular measures, DSST performance, or "negative" subjective-effect ratings. CONCLUSIONS: These results indicate that oral THC was well tolerated and suggest further study of this medication in adolescent marijuana abusers.     

Validation of the Cannabis Expectancy Questionnaire (CEQ) in adult cannabis users in treatment

Background

Outcome expectancies are a key cognitive construct in the etiology, assessment and treatment of Substance Use Disorders. There is a research and clinical need for a cannabis expectancy measure validated in a clinical sample of cannabis users.

Method

The Cannabis Expectancy Questionnaire (CEQ) was subjected to exploratory (n = 501, mean age 27.45, 78% male) and confirmatory (n = 505, mean age 27.69, 78% male) factor analysis in two separate samples of cannabis users attending an outpatient cannabis treatment program. Weekly cannabis consumption was clinically assessed and patients completed the Severity of Dependence Scale-Cannabis (SDS-C) and the General Health Questionnaire (GHQ-28).

Results

Two factors representing Negative Cannabis Expectancies and Positive Cannabis Expectancies were identified. These provided a robust statistical and conceptual fit for the data. Internal reliabilities were high. Negative expectancies were associated with greater dependence severity (as measured by the SDS) and positive expectancies with higher consumption. The interaction of positive and negative expectancies was consistently significantly associated with self-reported functioning across all four GHQ-28 scales (Somatic Concerns, Anxiety, Social Dysfunction and Depression). Specifically, within the context of high positive cannabis expectancy, higher negative expectancy was predictive of more impaired functioning. By contrast, within the context of low positive cannabis expectancy, higher negative expectancy was predictive of better functioning.

Conclusions

The CEQ is the first cannabis expectancy measure to be validated in a sample of cannabis users in treatment. Negative and positive cannabis expectancy domains were uniquely associated with consumption, dependence severity and self-reported mental health functioning.     

Development and validation of the Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ) in adult cannabis users in treatment

Background

There are few valid clinical assessment instruments for cannabis. Self-efficacy, or the ability of users to resist temptation, is a central feature of social cognitive theory. This study outlines the development and validation of the Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ), which measures the situational confidence to refuse cannabis.

Method

One thousand two hundred and forty-six patients referred for cannabis assessment completed the CRSEQ including measures of cannabis consumption and dependence severity (Severity of Dependence Scale-Cannabis, SDS-C). The CRSEQ was subject to independent exploratory (n = 621, mean age 26.88, 78.6% male) and confirmatory (n = 625, mean age 27.51, 76.8% male) factor analysis.

Results

Three factors: Emotional Relief, Opportunistic and Social Facilitation were identified. They provided a good statistical and conceptual fit for the data. Emotional Relief cannabis refusal self-efficacy was identified as most predictive of cannabis dependence, after controlling for cannabis consumption.

Conclusions

The CRSEQ is recommended as a psychometrically sound and clinically useful measure for cannabis misuse treatment planning and assessment.     

Memory-related hippocampal dysfunction in poly-drug ecstasy (3,4-methylenedioxymethamphetamine) users

Rationale 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is neurotoxic in animal studies and its use has been associated with cognitive impairments in humans. Objective To study hippocampal activation during the retrieval from episodic memory in polyvalent users of ecstasy. Methods Twelve polyvalent ecstasy users and twelve matched controls were examined by means of functional magnetic resonance imaging (fMRI) while they retrieved face-profession associations from episodic memory. Results Ecstasy users had a normal structural MRI scan without focal brain lesions or anatomical abnormalities. They exhibited equal retrieval accuracy during memory retrieval to that of the matched controls. Yet, their retrieval-related activity was lower and more spatially restricted in the left anterior hippocampus than that of the controls. Conclusions These results provide evidence for abnormal hippocampal functioning in MDMA users even at the presence of normal memory performance. This finding may be linked to MDMA-induced neurotoxicity and suggests that diminished hippocampal activation during memory retrieval might be a more sensitive or earlier index of MDMA-related neurotoxicity than neuropsychological performance.     

Consumer use and understanding of labelling information on edible marijuana products sold for recreational use in the states of Colorado and Washington

BackgroundIn 2014, the states of Colorado and Washington began allowing retail sales of marijuana for recreational use. The regulatory agencies in these states have implemented specific labelling requirements for edible marijuana products sold for recreational use to help address concerns such as delayed activation time, accidental ingestion, and proper dosing.MethodsWe conducted 12 focus groups with 94 adult consumers and nonconsumers of edibles in Denver and Seattle to collect information on their use and understanding of labelling information on edible marijuana products sold for recreational use. Specifically, we asked participants about the usefulness, attractiveness, ease of comprehension, relevancy, and acceptability of the label information.ResultsSome focus group participants look for and read specific information, such as the potency profile and serving size statement, but do not read or were unfamiliar with other labelling features. The focus groups revealed that participants have some concerns about the current labelling of edibles. In particular, participants were concerned that there is too much information on the labels so consumers may not read the label, there is no obvious indication that the product contains marijuana (e.g., a Universal Symbol), and the information on consumption advice is not clear. Participants in both locations suggested that education in a variety of formats, such as web- and video-based education, would be useful in informing consumers about the possible risks of edibles.ConclusionThe focus group findings suggest that improvements are needed in the labelling of edibles to prevent unintentional ingestion among adult nonusers and help ensure proper dosing and safe consumption among adult users. These findings, along with lessons learned from Colorado and Washington, can help inform the labelling of edibles as additional states allow the sale of edibles for recreational use.     

Functional magnetic resonance imaging studies of opioid receptor-mediated modulation of noxious-evoked BOLD contrast in rats

Rationale Functional magnetic resonance imaging (fMRI) in rats can non-invasively identify brain regions activated by physiological stimuli and the effects of pharmacological intervention on these responses. Objectives This study was conducted to investigate the effects of systemic administration of the μ-opioid receptor agonist morphine on whole brain functional signal intensity in anaesthetised rats; to investigate whether pre-treatment with the opioid receptor antagonist naloxone blocks the effects of morphine; to determine whether pre-treatment with morphine attenuates noxious-evoked changes in whole brain functional signal intensity. Methods Continuous whole brain fMRI scanning was used to study brain signal intensity prior to, and following, systemic administration of morphine (5 mg/kg, n=7), systemic administration of naloxone (1 mg/kg) and morphine (n=8). Effects of pre-treatment with saline (n=5) or morphine (5 mg/kg, n=5) on formalin (5%, intraplantar)-evoked changes in signal intensity were determined. Data were processed using SMP99 with fixed-effects analysis (p<0.05). Results Morphine produced significant positive bilateral increases in signal intensity in the cingulate cortex, amygdala, thalamus, hypothalamus and PAG (p<0.05), and these effects were blocked by naloxone. Intraplantar injection of formalin produced a significant positive increase in signal intensity in the cingulate cortex, somatosensory cortex, amygdala, thalamus, hypothalamus and PAG (p<0.05). Morphine attenuated formalin-evoked increases in signal intensity in the PAG, amygdala, hypothalamus and cingulate cortex. Conclusion Our data demonstrate that morphine modulates noxious-evoked changes in signal intensity in discrete brain regions. fMRI studies in rats are able to identify specific brain regions involved in the pharmacological modification of physiologically evoked changes in regional brain activation.     

Impaired perception of self-motion (heading) in abstinent ecstasy and marijuana users

Rationale

Illicit drug use can increase driver crash risk due to loss of control over vehicle trajectory. This study asks, does recreational use of ±3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) and tetrahydrocannabinol (THC; marijuana) impair cognitive processes that help direct our safe movement through the world?

Objective

This study assesses the residual effects of combined MDMA/THC use, and of THC use alone, upon perceived trajectory of travel.

Methods

Perception of self-motion, or heading, from optical flow patterns was assessed using stimuli comprising random dot ground planes presented at three different densities and eight heading angles (1, 2, 4 and 8° to the left or right). On each trial, subjects reported if direction of travel was to the left or the right.

Results

Results showed impairments in both drug groups, with the MDMA/THC group performing the worst.

Conclusions

The finding that these psychoactive agents adversely affect heading perception, even in recently abstinent users, raises potential concerns about MDMA use and driving ability.

     

Cannabis use and neurocognitive functioning in a non-clinical sample of users

Objective

With the recent debates over marijuana legalization and increases in use, it is critical to examine its role in cognition. While many studies generally support the adverse acute effects of cannabis on neurocognition, the non-acute effects remain less clear. The current study used a cross-sectional design to examine relationships between recent and past cannabis use on neurocognitive functioning in a non-clinical adult sample.

Method

One hundred and fifty-eight participants were recruited through fliers distributed around local college campuses and the community. All participants completed the Brief Drug Use History Form, the Structured Clinical Interview for DSM-IV Disorders, and neurocognitive assessment, and underwent urine toxicology screening. Participants consisted of recent users (n = 68), past users (n = 41), and non-users (n = 49).

Results

Recent users demonstrated significantly (p < .05) worse performance than non-users across cognitive domains of attention/working memory (M = 42.4, SD = 16.1 vs. M = 50.5, SD = 10.2), information processing speed (M = 44.3, SD = 7.3 vs. M = 52.1, SD = 11.0), and executive functioning (M = 43.6, SD = 13.4 vs. M = 48.6, SD = 7.2). There were no statistically significant differences between recent users and past users on neurocognitive performance. Frequency of cannabis use in the last 4 weeks was negatively associated with global neurocognitive performance and all individual cognitive domains. Similarly, amount of daily cannabis use was negatively associated with global neurocognitive performance and individual cognitive domains.

Conclusions

Our results support the widespread adverse effects of cannabis use on neurocognitive functioning. Although some of these adverse effects appear to attenuate with abstinence, past users' neurocognitive functioning was consistently lower than non-users.