Nabilone produces marked impairments to cognitive function and changes in subjective state in healthy volunteers

Wesnes, Keith; Annas, Peter; Edgar, Chris J.; Deeprose, Catherine; Karlsten, Rolf; Philipp, Andrew; Kalliomäki, Jarkko; Segerdahl, Märta

doi:10.1177/0269881109105900

Cited by 29 publications

(35 citation statements)

References 33 publications

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“…Evidence of behavioral effects in healthy volunteers was very limited, with conflicting effects on derived memory parameters in the 100 mg cohorts, and weak endorsement of sedative‐like effects by women of nonchild‐bearing potential receiving 100 mg. Modulation of neuronal activity by the endocannabinoid system may be strongly activity‐dependent,15 and effects may differ in pathological states in which increased excitation of neuronal circuitry might occur. In contrast, single clinical doses of the cannabinoid agonist nabilone (which would be less dependent on activity state for effects) are associated with notable impairment on cognitive performance and strong endorsement of several of the ARCI‐53 scales in healthy volunteers 16. Older volunteers and women of nonchild‐bearing potential were included to provide information on safety and tolerability prior to conducting proof‐of‐concept studies.…”

Section: Discussionmentioning

confidence: 99%

Fatty Acid Amide Hydrolase Inhibition by JNJ‐42165279: A Multiple‐Ascending Dose and a Positron Emission Tomography Study in Healthy Volunteers

Postnov

Schmidt

Pemberton

et al. 2018

Clinical Translational Sci

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Inhibition of fatty acid amide hydrolase (FAAH) potentiates endocannabinoid activity and is hypothesized to have therapeutic potential for mood and anxiety disorders and pain. The clinical profile of JNJ‐42165279, an oral selective FAAH inhibitor, was assessed by investigating the pharmacokinetics, pharmacodynamics, safety, and binding to FAAH in the brain of healthy human volunteers. Concentrations of JNJ‐42165279 (plasma, cerebrospinal fluid (CSF), urine) and fatty acid amides (FAA; plasma, CSF), and FAAH activity in leukocytes was determined in a phase I multiple ascending dose study. A positron emission tomography study with the FAAH tracer [11C]MK3168 was conducted to determine brain FAAH occupancy after single and multiple doses of JNJ‐42165279. JNJ‐42165279 administration resulted in an increase in plasma and CSF FAA. Significant blocking of brain FAAH binding of [11C]MK3168 was observed after pretreatment with JNJ‐42165279. JNJ‐42165279 produces potent central and peripheral FAAH inhibition. Saturation of brain FAAH occupancy occurred with doses ≥10 mg of JNJ‐42165279. No safety concerns were identified.

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Section: Discussionmentioning

confidence: 99%

Fatty Acid Amide Hydrolase Inhibition by JNJ‐42165279: A Multiple‐Ascending Dose and a Positron Emission Tomography Study in Healthy Volunteers

Postnov

Schmidt

Pemberton

et al. 2018

Clinical Translational Sci

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“…Whether working memory is impaired by cannabis is less clear, possibly because of the wide range of different working memory tasks employed. Acute administration of THC, dronabinol, or nabilone affected working memory inconsistently across Sternberg, delayed matching to sample, spatial or numeric working memory, n-back, digit recall, and digit span tasks (36)(37)(38)(39)(40)42,43,(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78). Similarly, chronic cannabis use was shown to impair working memory in young adults on immediate recall (79), verbal reasoning (80), and verbal n-back (81) working memory tasks, but not on spatial working memory (48,82) or digit span (52,53), whereas spatial working memory was impaired in adolescent users (46), suggestive of differential effects in the developing brain.…”

Section: Acute and Chronic Effects Of Cannabinoids On Cognitionmentioning

confidence: 99%

Acute and Chronic Effects of Cannabinoids on Human Cognition—A Systematic Review

Broyd

Hell

Beale

et al. 2016

Biological Psychiatry

538

395

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Cannabis use has been associated with impaired cognition during acute intoxication as well as in the unintoxicated state in long-term users. However, the evidence has been mixed and contested, and no systematic reviews of the literature on neuropsychological task-based measures of cognition have been conducted in an attempt to synthesize the findings. We systematically review the empirical research published in the past decade (from January 2004 to February 2015) on acute and chronic effects of cannabis and cannabinoids and on persistence or recovery after abstinence. We summarize the findings into the major categories of the cognitive domains investigated, considering sample characteristics and associations with various cannabis use parameters. Verbal learning and memory and attention are most consistently impaired by acute and chronic exposure to cannabis. Psychomotor function is most affected during acute intoxication, with some evidence for persistence in chronic users and after cessation of use. Impaired verbal memory, attention, and some executive functions may persist after prolonged abstinence, but persistence or recovery across all cognitive domains remains underresearched. Associations between poorer performance and a range of cannabis use parameters, including a younger age of onset, are frequently reported. Little further evidence has emerged for the development of tolerance to the acutely impairing effects of cannabis. Evidence for potential protection from harmful effects by cannabidiol continues to increase but is not definitive. In light of increasing trends toward legalization of cannabis, the knowledge gained from this body of research needs to be incorporated into strategies to minimize harm. Review Acute and Chronic Effects of Cannabinoids on Human Cognition-A Systematic ReviewSamantha J. Broyd, Hendrika H. van Hell, Camilla Beale, Murat Yücel, and Nadia Solowij ABSTRACT Cannabis use has been associated with impaired cognition during acute intoxication as well as in the unintoxicated state in long-term users. However, the evidence has been mixed and contested, and no systematic reviews of the literature on neuropsychological task-based measures of cognition have been conducted in an attempt to synthesize the findings. We systematically review the empirical research published in the past decade (from January 2004 to February 2015) on acute and chronic effects of cannabis and cannabinoids and on persistence or recovery after abstinence. We summarize the findings into the major categories of the cognitive domains investigated, considering sample characteristics and associations with various cannabis use parameters. Verbal learning and memory and attention are most consistently impaired by acute and chronic exposure to cannabis. Psychomotor function is most affected during acute intoxication, with some evidence for persistence in chronic users and after cessation of use. Impaired verbal memory, attention, and some executive functions may persist after prolonged abstinence, but persistenc...

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“…There are many studies which could be considered as providing a background to the present findings, since they have shown that basic cognitive variables (attention and memory) can predict performance (Echevarry, Godoy & Olaz, 2007;Wesnes et al, 2009;Wesnes, Pincock, Richardson, Helm & Halis, 2003;Wesnes, Ward, McGinty & Petrini, 2000). However, there is very little research relating psychological and psychophysiological stress to school performance (Lupien & Maheu, 2007;Sandberg, 2007;Steptoe, 2007).…”

Section: Discussionmentioning

confidence: 83%

“…Participants" basic cognitive function (attention and memory) was evaluated by means of the Cognitive Drug Research (CDR) battery (Wesnes, Pincock, Richardson, Helm & Halis, 2003;Wesnes, Ward, McGinty & Petrini, 2000), a specialized system that provides a computerized assessment of cognitive function (Haskell, Kennedy, Wesnes & Scholey, 2005;Kennedy, Haskell, Wesnes & Scholey, 2004;Wesnes et al, 2000). This battery has previously been used in research with children and has shown excellent reliability (Wesnes et al, 2003) when measuring variables such as attention and episodic working memory (Wesnes et al, 2009). The version of the CDR battery used here consists of 11 tasks administered in the following order: word presentation, immediate word recall, picture presentation, simple reaction time, digit vigilance, choice reaction time, spatial working memory, numerical working memory, delayed word recall, word recognition and picture recognition (Wesnes, Ward, McGinty & Petrini, 2000).…”

Section: Psychological Assessment Instrumentsmentioning

confidence: 99%

“…The relationship between basic cognitive function, composed of attention and memory variables, and children"s basic learning in primary school has been well documented (Echevarry, Godoy & Olaz, 2007;Wesnes et al, 2009;Wesnes, Pincock, Richardson, Helm & Halis, 2003;Wesnes, Ward, McGinty & Petrini, 2000). However, although the direct relationship between cognition and performance is now widely accepted, research has yet to elucidate fully the variables that affect this relationship and which mediate or modify the effect of cognitive skills on school performance.…”

Section: Introductionmentioning

confidence: 99%

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Psychological and psychobiological stress in the relationship between basic cognitive function and school performance. [El estrés psicológico y psicobiológico en la relación entre funcionamiento cognitivo básico y rendimiento académico]

Martín

Trianes-Torres²,

Maldonado-Montero³

et al. 2015

analesps

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Título: El estrés psicológico y psicobiológico en la relación entre funcionamiento cognitivo básico y rendimiento académico. Resumen: Este estudio analiza el papel desempeñado por el estrés cotidiano, evaluado a través de auto-informe y de los niveles psicobiológicos, en relación con la función cognitiva básica a la hora de predecir el rendimiento académico. La muestra está compuesta por 100 alumnos (55 niñas y niños de 45, con un rango de edad de 8 a 11 años) de una escuela pública de Málaga capital (España). El estrés diario se evaluó mediante el Inventario de estresores cotidianos en niños (IIEC; Trianes et al, 2009). El estrés psicobiológico se midió a través de la ratio cortisol / DHEA, derivado de varias muestras de saliva tomadas por la mañana en dos días consecutivos. Las habilidades cognitivas básicas se evaluaron por medio del sistema de evaluación cognitiva computarizada (batería CDR; Wesnes et al, 2003Wesnes et al, , 2000. Por último, el rendimiento académico se evaluó a través del valor medio de las calificaciones finales registradas en el informe de la escuela del niño. Además de los análisis estadísticos descriptivos y correlacionales, se realizaron análisis de regresión múltiple con el fin de evaluar el modelo. Los resultados muestran que el estrés diario autopercibido por los niños, actúa pronosticando el rendimiento académico con mayor peso que el funcionamiento cognitivo básico. Por lo tanto, a fin de lograr el buen rendimiento escolar, un alumno no sólo requiere una buena función cognitiva básica, sino que también debe presentar bajos niveles de estrés cotidiano autopercibido. Estos hallazgos sugieren una nueva forma de explicar y predecir el fracaso escolar. Palabras clave: Funcionamiento cognitivo básico; rendimiento académico; estrés cotidiano; ratio cortisol/dheas; infancia.Abstract: This study analyses the role played by daily stress, assessed through self-report and at the psychobiological level, in relation to basic cognitive function when predicting school performance. The sample comprised 100 schoolchildren (55 girls and 45 boys, age range 8 to 11 years) from a state school in the city of Malaga (Spain). Daily stress was assessed through the Children"s Daily Stress Inventory (IIEC in Spanish; Trianes et al., 2009). Psychobiological stress was measured through the cortisol/DHEAS ratio, derived from saliva samples taken in the morning on two consecutive days. Basic cognitive skills were assessed by means of the Computerized Cognitive Assessment System (CDR battery; Wesnes et al., 2003Wesnes et al., , 2000. Finally, the measure of school performance was the mean value of the final grades recorded in the child"s school report. In addition to descriptive and correlational statistical analyses, multiple regression analyses were conducted in order to assess the model. The results show that children"s daily stress self-reported contributes to predict school performance, and has proven to be more influential than basic cognitive function when it comes to predict school performance. Therefore...

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Nabilone produces marked impairments to cognitive function and changes in subjective state in healthy volunteers

Cited by 29 publications

References 33 publications

Fatty Acid Amide Hydrolase Inhibition by JNJ‐42165279: A Multiple‐Ascending Dose and a Positron Emission Tomography Study in Healthy Volunteers

Fatty Acid Amide Hydrolase Inhibition by JNJ‐42165279: A Multiple‐Ascending Dose and a Positron Emission Tomography Study in Healthy Volunteers

Acute and Chronic Effects of Cannabinoids on Human Cognition—A Systematic Review

Psychological and psychobiological stress in the relationship between basic cognitive function and school performance. [El estrés psicológico y psicobiológico en la relación entre funcionamiento cognitivo básico y rendimiento académico]

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