Cannabis and tolerance: acute drug impairment as a function of cannabis use history

Abstract Cannabis use history as predictor of neurocognitive response to cannabis intoxication remains subject to scientific and policy debates. The present study assessed the influence of cannabis on neurocognition in cannabis users whose cannabis use history ranged from infrequent to daily use. Drug users (N = 122) received acute doses of cannabis (300 μg/kg THC), cocaine HCl (300 mg) and placebo. Cocaine served as active control for demonstrating neurocognitive test sensitivity. Executive function, impulse control, attention, psychomotor function and subjective intoxication were significantly worse after cannabis administration relative to placebo. Cocaine improved psychomotor function and attention, impaired impulse control and increased feelings of intoxication. Acute effects of cannabis and cocaine on neurocognitive performance were similar across cannabis users irrespective of their cannabis use history. Absence of tolerance implies that that frequent cannabis use and intoxication can be expected to interfere with neurocognitive performance in many daily environments such as school, work or traffic.

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Does variation in trait schizotypy and frequency of cannabis use influence the acute subjective, cognitive and psychotomimetic effects of delta-9-tetrahydrocannabinol? A mega-analysis

Journal of Psychopharmacology ◽

10.1177/0269881120959601 ◽

2021 ◽

pp. 026988112095960

Author(s):

Abigail M Freeman ◽

Claire Mokrysz ◽

Chandni Hindocha ◽

Will Lawn ◽

Celia JA Morgan ◽

...

Keyword(s):

Personality Traits ◽

Memory Impairment ◽

Linear Models ◽

Cannabis Use ◽

Acute Effects ◽

Double Blind ◽

Schizotypal Personality ◽

Domain Specific ◽

Individual Participant ◽

Psychotomimetic Effects

Background: While the acute effects of cannabis are relatively benign for most users, some individuals experience significant adverse effects. This study aimed to identify whether variation in schizotypal personality traits and frequency of cannabis use influence the acute effects of delta-9-tetrahydrocannabinol (THC). Methods: Individual participant data from four double-blind, randomised, placebo-controlled, acute crossover studies involving 128 cannabis users were combined for a mega-analysis. Using multilevel linear models and moderation analyses, frequency of cannabis use and schizotypal personality traits were investigated as potential moderators of the subjective, cognitive and psychotomimetic effects of acute THC. Results: There was evidence of a moderating effect where increased frequency of cannabis use was associated with reduced intensity of subjective (changes in alertness and feeling stoned) and psychosis-like effects following THC when compared with placebo. Moderating effects of cannabis use frequency on acute memory impairment were weak. Trait schizotypy did not moderate the acute psychosis-like effects of THC compared with placebo. Conclusions: Our results suggest that a pattern of domain-specific tolerance develops to the acute effects of THC. Tolerance to the alertness-reducing effects occurred more readily than tolerance to psychotomimetic effects. Only partial tolerance to feeling stoned was found, and there was weak evidence for tolerance to memory impairment. Trait schizotypy did not moderate THC’s effects on psychotomimetic symptoms.

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Cannabis Use, Age of Initiation, and Neurocognitive Performance: Findings from a Large Sample of Heavy Drinking Emerging Adults

Journal of the International Neuropsychological Society ◽

10.1017/s1355617721000618 ◽

2021 ◽

Vol 27 (6) ◽

pp. 533-545

Author(s):

Melissa Parlar ◽

Emily MacKillop ◽

Tashia Petker ◽

James Murphy ◽

James MacKillop

Keyword(s):

Working Memory ◽

Emerging Adults ◽

Memory Performance ◽

Heavy Drinking ◽

Cannabis Use ◽

Neurocognitive Functioning ◽

Adhd Symptoms ◽

Neurocognitive Performance ◽

Cross Sectional ◽

Large Sample

AbstractObjective:To evaluate the associations between cannabis use and neurocognitive functioning, including self-reported attention deficit hyperactivity disorder (ADHD) symptoms, in a large sample of emerging adults (ages 21–25) using a cross-sectional design. A secondary objective was to examine age of cannabis initiation as a moderator.Methods:Participants were high-risk drinking emerging adults (n = 598) reporting past-month cannabis use in the following categories: 1) non-users (i.e., never or not in the past month; n = 276), 2) occasional users (i.e., monthly or weekly users; n = 201), and 3) daily users (n = 121). Categorical comparisons were conducted on working memory, attention, behavioral inhibition, delay and probability discounting, verbal intelligence, and ADHD symptoms. Complementary dimensional analyses examined cannabis severity in relation to neurocognition using regressions. Covariates were age, race, sex, income, years of education, tobacco use, and alcohol use.Results:Frequency of cannabis use was significantly associated with poorer working memory performance, more impulsive delay discounting, and greater endorsement of ADHD symptoms, but not other domains. Effect sizes were small and poorer performance was selectively present among daily, not occasional, cannabis users. Earlier age of initiation was not independently or interactively associated with neurocognitive performance.Conclusions:Daily cannabis use was selectively adversely associated with aspects of memory, impulsivity, and subjective attentional functioning, but most cognitive indicators were not implicated, and evidence of amplification by earlier age of initiation was not observed. Ascertaining causal versus consequential roles of cannabis in neurocognitive functioning is an important priority.

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Characteristics of pregnant illicit drug users and associations between cannabis use and perinatal outcome in a population-based study☆

Drug and Alcohol Dependence ◽

10.1016/j.drugalcdep.2010.01.007 ◽

2010 ◽

Vol 109 (1-3) ◽

pp. 243-247 ◽

Cited By ~ 66

Author(s):

Marleen M.H.J. van Gelder ◽

Jennita Reefhuis ◽

Alissa R. Caton ◽

Martha M. Werler ◽

Charlotte M. Druschel ◽

...

Keyword(s):

Perinatal Outcome ◽

Drug Users ◽

Illicit Drug ◽

Population Based ◽

Cannabis Use ◽

Population Based Study ◽

Illicit Drug Users

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Contribution of alcohol and drug co-use to substance use problems: Data from a nationally-representative sample of US adults who have never been to treatment

Nordic Studies on Alcohol and Drugs ◽

10.1177/1455072518806122 ◽

2018 ◽

Vol 35 (6) ◽

pp. 428-442 ◽

Cited By ~ 9

Author(s):

Katherine J. Karriker-Jaffe ◽

Meenakshi S. Subbaraman ◽

Thomas K. Greenfield ◽

William C. Kerr

Keyword(s):

Drug Users ◽

Healthcare Providers ◽

Heavy Drinking ◽

Alcohol Problems ◽

Cannabis Use ◽

Increased Risk ◽

Physical Health Problems ◽

Nationally Representative ◽

Abuse Treatment ◽

Drug And Alcohol

Aims: Combined use of alcohol with drugs elevates risk for problems including injury and driving while intoxicated. We assessed contributions of heavy drinking (5+ drinks for men/4+ for women), drug use (cannabis and other drugs) and simultaneous co-use to DSM-5 alcohol use disorder (AUD) and drug abuse (DA). We expected co-use to increase risk for AUD and DA. Methods: Using population-weighted data from adults in the 2014–2015 National Alcohol Survey who had never been to treatment ( N = 3386 drinkers, 50% male, 13% Hispanic, 11% Black, mean age 45 years; N = 439 drug users, 56% male, 20% Hispanic, 15% Black, mean age 36), we tested hypotheses using logistic regression adjusting for demographics, family history of alcohol problems and impulsivity. Results: Ten percent of drinkers and 26% of drug users met criteria for mild AUD; <1% of drinkers and 4% of drug users met criteria for DA. Heavy drinking significantly increased risk for AUD, as did monthly or weekly use of cannabis. When simultaneous co-use was added, increased risk associated with cannabis use was reduced to non-significance. Weekly cannabis use, weekly use of other drugs and simultaneous drug and alcohol co-use were associated with significantly elevated risk of DA. In bivariate analyses, simultaneous co-use was associated with significantly greater endorsement of each of the separate AUD and DA symptom domains, including alcohol craving, tolerance and withdrawal, as well as drug and alcohol social and physical health problems. Conclusion: Healthcare providers should screen for simultaneous co-use of alcohol and drugs to help identify patients who may benefit from substance abuse treatment.

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Preliminary Evidence for a Sex-Specific Relationship between Amount of Cannabis Use and Neurocognitive Performance in Young Adult Cannabis Users

Journal of the International Neuropsychological Society ◽

10.1017/s135561771300088x ◽

2013 ◽

Vol 19 (9) ◽

pp. 1009-1015 ◽

Cited By ~ 33

Author(s):

Natania A. Crane ◽

Randi Melissa Schuster ◽

Raul Gonzalez

Keyword(s):

Decision Making ◽

Sex Differences ◽

Young Adult ◽

Episodic Memory ◽

Memory Performance ◽

Cannabis Use ◽

Neurocognitive Deficits ◽

Neurocognitive Performance ◽

Preclinical Research ◽

The Impact

AbstractAccumulating evidence suggests neuropsychological deficits from cannabis use, with a burgeoning area of preclinical research indicating possible sex-differences. However, few studies have examined how cannabis use may differentially impact neurocognition in male and female cannabis users. As such, we examined potential sex-differences in associations between amount of cannabis use (across several time frames) and neurocognitive performance among young adult regular cannabis users. Consistent with previous studies, more cannabis use was generally associated with poorer episodic memory and decision-making, but not other measures of inhibitory control. However, patterns of results suggested sex-specific dissociations. In particular, more cannabis use was more consistently associated with poorer episodic memory performance in females than males. Conversely, more cannabis use was associated with poorer decision-making performance for males, but not females. These results provide further evidence for residual cannabis-associated neurocognitive deficits and suggest the importance of examining the impact of cannabis on neurocognition separately for males and females. (JINS, 2013, 19, 1–7)

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Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes

Brain Imaging and Behavior ◽

10.1007/s11682-015-9488-z ◽

2015 ◽

Vol 10 (4) ◽

pp. 1254-1263 ◽

Cited By ~ 26

Author(s):

J. G. Ramaekers ◽

J. H. van Wel ◽

D. Spronk ◽

B. Franke ◽

G. Kenis ◽

...

Keyword(s):

Impulse Control ◽

Drug Users ◽

Low Activity

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Acute effects of cocaine on the neurobiology of cognitive control

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2008.0106 ◽

2008 ◽

Vol 363 (1507) ◽

pp. 3267-3276 ◽

Cited By ~ 91

Author(s):

Hugh Garavan ◽

Jacqueline N Kaufman ◽

Robert Hester

Keyword(s):

Cognitive Control ◽

Cognitive Processes ◽

Impulse Control ◽

Control Function ◽

Brain Regions ◽

Acute Effects ◽

Neurocognitive Dysfunction ◽

Action Monitoring ◽

Motor Response Inhibition ◽

Drug Naïve

Compromised ability to exert control over drug urges and drug-seeking behaviour is a characteristic of addiction. One specific cognitive control function, impulse control, has been shown to be a risk factor for the development of substance problems and has been linked in animal models to increased drug administration and relapse. We present evidence of a direct effect of cocaine on the neurobiology underlying impulse control. In a laboratory test of motor response inhibition, an intravenous cocaine administration improved task performance in 13 cocaine users. This improvement was accompanied by increased activation in right dorsolateral and inferior frontal cortex, regions considered critical for this cognitive function. Similarly, for both inhibitory control and action monitoring processes, cocaine normalized activation levels in lateral and medial prefrontal regions previously reported to be hypoactive in users relative to drug-naive controls. The acute amelioration of neurocognitive dysfunction may reflect a chronic dysregulation of those brain regions and the cognitive processes they subserve. Furthermore, the effects of cocaine on midline function suggest a dopaminergically mediated intersection between cocaine's acute reinforcing effects and its effects on cognitive control.

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Comparative study of acute effects of single doses of fexofenadine, olopatadine,d-chlorpheniramine and placebo on psychomotor function in healthy volunteers

Human Psychopharmacology Clinical and Experimental ◽

10.1002/hup.538 ◽

2003 ◽

Vol 18 (8) ◽

pp. 611-618 ◽

Cited By ~ 18

Author(s):

Hiroyuki Kamei ◽

Yukihiro Noda ◽

Kazuhiro Ishikawa ◽

Koji Senzaki ◽

Isao Muraoka ◽

...

Keyword(s):

Comparative Study ◽

Healthy Volunteers ◽

Psychomotor Function ◽

Acute Effects

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Risks of Young Age for Selected Neurocognitive Deficits in Medulloblastoma Are Associated With White Matter Loss

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.2.472 ◽

2001 ◽

Vol 19 (2) ◽

pp. 472-479 ◽

Cited By ~ 211

Author(s):

Raymond K. Mulhern ◽

Shawna L. Palmer ◽

Wilburn E. Reddick ◽

John O. Glass ◽

Larry E. Kun ◽

...

Keyword(s):

White Matter ◽

Sustained Attention ◽

Verbal Memory ◽

Young Age ◽

Factual Knowledge ◽

Test Results ◽

Neurocognitive Deficits ◽

Neurocognitive Performance ◽

Neurocognitive Tests ◽

Neurocognitive Test

PURPOSE: To test the hypothesis that inadequate development of normal-appearing white matter (NAWM) is associated with the relationship between young age at the time of craniospinal irradiation (CRT) and deficient neurocognitive performance in survivors of childhood medulloblastoma. PATIENTS AND METHODS: Forty-two patients treated since 1985 participated in this cross-sectional study. All had been treated with CRT with or without chemotherapy and had survived 1 or more years after treatment. Neurocognitive evaluations were conducted with tests of intellect (intelligent quotient; IQ), verbal memory, and sustained attention. Quantitative magnetic resonance imaging, using a hybrid neural network, assessed the volume of NAWM. RESULTS: Neurocognitive test results were below normal expectations for age at the time of testing. A young age at CRT was significantly associated with worse performance on all neurocognitive tests except that of verbal memory. An increased time from completion of CRT was significantly associated with worse performance on all neurocognitive tests except that of sustained attention. After statistically controlling for the effects of time from CRT, we examined the association of NAWM with neurocognitive test results. These analyses revealed that NAWM accounted for a significant amount of the association between age at CRT and IQ, factual knowledge, and verbal and nonverbal thinking, but not sustained attention or verbal memory. CONCLUSION: The present results suggest that, at least for some cognitive functions, deficient development and/or loss of NAWM after CRT may provide a neuroanatomical substrate for the adverse impact of a young age at the time of CRT.

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Epidemiology of substance use among secondary school learners in Atteridgeville, Gauteng

South African Journal of Psychiatry ◽

10.4102/sajpsychiatry.v18i1.320 ◽

2012 ◽

Vol 18 (1) ◽

pp. 6 ◽

Cited By ~ 4

Author(s):

S V Moodley ◽

M J Matjila ◽

M Y H Moosa

Keyword(s):

Substance Use ◽

Secondary Schools ◽

Drug Users ◽

Illicit Drug ◽

Intervention Strategy ◽

Sampling Technique ◽

Cannabis Use ◽

Cluster Sampling ◽

Prevalence Rates ◽

Cross Sectional

Introduction. Adolescent substance use has a number of adverse consequences for both the individual and society. Anecdotal evidence suggested the existence of a serious substance use problem among learners in Atteridgeville, part of the City of Tshwane Metropolitan Municipality in Gauteng, South Africa. Objectives. The objectives of the study were to determine the prevalence rates and age of initiation of substance use among learners attending secondary schools in Atteridgeville, and the factors, if any, associated with cannabis use.Methods. This was a cross-sectional study. A cluster sampling technique was employed. Twenty-two of the total of 191 grade 8 - 11 classes in the nine Atteridgeville secondary schools were randomly selected, with all 895 learners in the selected classes being invited to participate. Self-administered questionnaires were used to collect data. Statistical analysis was conducted using the survey estimation commands in STATA 10.0. Results. The lifetime prevalence rates for the three most commonly used substances were 51.4% (95% confidence interval (CI) 41.5 - 61.5%) for alcohol, 25.2% (95% CI 17.1 - 33.3%) for cigarettes and 13.2% (95% CI 8.3 - 18.2%) for cannabis. Alcohol was also found to have the lowest mean age of initiation at 14.6 years (standard deviation 2.0). Based on CRAFFT screening scores, 30.3% (95% CI 24.5 - 36.1%) of learners met the criteria for possible problem substance use. Following multivariate analysis, the factors found to be significantly associated with lifetime cannabis use were age, gender, lifetime cigarette use, lifetime alcohol use, the number of illicit drug users among the learners’ five closest friends, and an older sibling with a history of illicit drug use.Conclusion. The results of the study suggest that substance use among learners in Atteridgeville is widespread and that a comprehensive intervention strategy is required.

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