Performance impairment during Δ9-tetrahydrocannabinol (THC) intoxication has been well described in occasional cannabis users. It is less clear whether tolerance develops to the impairing effects of THC in heavy users of cannabis. The aim of the present study was to assess neurocognitive performance during acute THC intoxication in occasional and heavy users. Twenty-four subjects (12 occasional cannabis users and 12 heavy cannabis users) participated in a double-blind, placebo-controlled, two-way mixed model design. Both groups received single doses of THC placebo and 500 μg/kg THC by smoking. Performance tests were conducted at regular intervals between 0 and 8 h after smoking, and included measures of perceptual motor control (critical tracking task), dual task processing (divided attention task), motor inhibition (stop signal task) and cognition (Tower of London). THC significantly impaired performance of occasional cannabis users on critical tracking, divided attention and the stop signal task. THC did not affect the performance of heavy cannabis users except in the stop signal task, i.e. stop reaction time increased, particularly at high THC concentrations. Group comparisons of overall performance in occasional and heavy users did not reveal any persistent performance differences due to residual THC in heavy users. These data indicate that cannabis use history strongly determines the behavioural response to single doses of THC.
Ameri A (1999) The effects of cannabinoids on the brain. Prog Neurobiol58: 315–348.
2.
Azorlosa JL Greenwald MK Stitzer ML (1995) Marijuana smoking: effects of varying puff volume and breathhold duration. J Pharmacol Exp Ther272: 560–569.
3.
Azorlosa JL Heishman SJ Stitzer ML Mahaffey JM (1992) Marijuana smoking: effect of varying delta 9-tetrahydrocannabinol content and number of puffs. J Pharmacol Exp Ther261: 114–122.
4.
Cappell H Pliner P (1974) Regulation of the self-administration of marihuana by psychological and pharmacological variables. Psychopharmacologia40: 65–76.
5.
Casswell S Marks D (1973) Cannabis induced impairment of performance of a divided attention task. Nature241: 60–61.
6.
Chait LD Zacny JP (1992) Reinforcing and subjective effects of oral delta 9-THC and smoked marijuana in humans. Psychopharmacology (Berl)107: 255–262.
7.
Curran HV Brignell C Fletcher S Middleton P Henry J (2002) Cognitive and subjective dose-response effects of acute oral Delta 9-tetrahydrocannabinol (THC) in infrequent cannabis users. Psychopharmacology (Berl)164: 61–70.
8.
DHHS/SAMHSA (2004) Results From the 2004 National Survey of Drug Use and Health: National Findings. pp. 1–294.
9.
Dussault C Brault M Bouchard J Lemire AM (2002) The contribution of alcohol and other drugs among fatally injured drivers in Quebec: some preliminary results. Proceedings of the 16th International Conference on Alcohol, Drugs and Traffic Safety T2002, Montreal, pp. 423–430.
10.
Eldreth DA Matochik JA Cadet JL Bolla KI (2004) Abnormal brain activity in prefrontal brain regions in abstinent marijuana users. Neuroimage23: 914–920.
11.
EMCCDA (2006) Annual report 2006: the state of the drugs problem in Europe.
12.
Fillmore MT Rush CR Hays L (2002) Acute effects of oral cocaine on inhibitory control of behavior in humans. Drug Alcohol Depend67: 157–167.
13.
Hall W Solowij N (1998) Adverse effects of cannabis. Lancet352: 1611–1616.
14.
Haney M Ward AS Comer SD Foltin RW Fischman MW (1999) Abstinence symptoms following oral THC administration to humans. Psychopharmacology (Berl)141: 385–394.
15.
Hart CL van Gorp W Haney M Foltin RW Fischman MW (2001) Effects of acute smoked marijuana on complex cognitive performance. Neuropsychopharmacology25: 757–765.
16.
Hart CL Ward AS Haney M Comer SD Foltin RW Fischman MW (2002) Comparison of smoked marijuana and oral Delta(9)-tetrahydrocannabinol in humans. Psychopharmacology (Berl)164: 407–415.
17.
Heishman SJ Huestis MA Henningfield JE Cone EJ (1990) Acute and residual effects of marijuana: profiles of plasma THC levels, physiological, subjective, and performance measures. Pharmacol Biochem Behav37: 561–565.
18.
Heishman SJ Stitzer ML Bigelow GE (1988) Alcohol and marijuana: comparative dose effect profiles in humans. Pharmacol Biochem Behav31: 649–655.
19.
Heishman SJ Stitzer ML Yingling JE (1989) Effects of tetrahydrocannabinol content on marijuana smoking behavior, subjective reports, and performance. Pharmacol Biochem Behav34: 173–179.
20.
Jentsch JD Taylor JR (1999) Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology (Berl)146: 373–390.
21.
Jex HR McDonnell JD Phatak AV (1966) A “critical” tracking task for man-machine research related to the operator's effective delay time. I. Theory and experiments with a first-order divergent controlled element. NASA CR-616. NASA Contract Rep NASA CR1–105.
22.
Jones RT Benowitz NL Herning RI (1981) Clinical relevance of cannabis tolerance and dependence. J Clin Pharmacol21: 143S–152S.
23.
Kanayama G Rogowska J Pope HG Gruber SA Yurgelun-Todd DA (2004) Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study. Psychopharmacology (Berl)176: 239–247.
24.
Kauert GF Iwersen-Bergmann S Toennes SW (2006) Assay of Delta9-tetrahydrocannabinol (THC) in oral fluid-evaluation of the OraSure oral specimen collection device. J Anal Toxicol30: 274–277.
25.
Kelly TH Foltin RW Emurian CS Fischman MW (1990) Multidimensional behavioral effects of marijuana. Prog Neuropsychopharmacol Biol Psychiatry14: 885–902.
26.
Kelly TH Foltin RW Fischman MW (1993) Effects of smoked marijuana on heart rate, drug ratings and task performance by humans. Behav Pharmacol4: 167–178.
27.
Kirk JM de Wit H (1999) Responses to oral delta9-tetrahydrocannabinol in frequent and infrequent marijuana users. Pharmacol Biochem Behav63: 137–142.
28.
Koob GF Sanna PP Bloom FE (1998) Neuroscience of addiction. Neuron21: 467–476.
29.
Kreek MJ Nielsen DA Butelman ER LaForge KS (2005) Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction. Nat Neurosci8: 1450–1457.
30.
Lamers CT Ramaekers JG (2001) Visual search and urban driving under the influence of marijuana and alcohol. Hum Psychopharmacol16: 393–401.
31.
Logan GD Cowan WB Davis KA (1984) On the ability to inhibit simple and choice reaction time responses: a model and a method. J Exp Psychol Hum Percept Perform10: 276–291.
Moskowitz H (1973) Laboratory studies of the effects of alcohol on some variables related to driving. J Safety Res5: 185–192.
34.
Movig KL Mathijssen MP Nagel PH van Egmond T de Gier JJ Leufkens HG (2004) Psychoactive substance use and the risk of motor vehicle accidents. Accid Anal Prev36: 631–636.
35.
Nordstrom BR Hart CL (2006) Assessing cognitive functioning in cannabis users: cannabis use history an important consideration.Neuropsychopharmacology 31: 2798–2799.
36.
Nowlan R Cohen S (1977) Tolerance to marijuana: heart rate and subjective “high”. Clin Pharmacol Ther22: 550–556.
37.
Pope HG Gruber AJ Hudson JI Cohane G Huestis MA Yurgelun-Todd D (2003) Early-onset cannabis use and cognitive deficits: what is the nature of the association. Drug Alcohol Depend69: 303–310.
38.
Pope HG Gruber AJ Yurgelun-Todd D (2001) Residual neuropsychologic effects of cannabis. Curr Psychiatry Rep3: 507–512.
39.
Ramaekers JG Berghaus G van Laar M Drummer OH (2004) Dose related risk of motor vehicle crashes after cannabis use. Drug Alcohol Depend73: 109–119.
40.
Ramaekers JG Kauert G Theunissen EL Moeller MR (2006a) Up in smoke: comparability of THC dosing across performance studies. Neuropsychopharmacology31: 2800–2801.
41.
Ramaekers JG Kauert G van Ruitenbeek P Theunissen EL Schneider E Moeller MR (2006b) High-Potency Marijuana Impairs Executive Function and Inhibitory Motor Control.Neuropsychopharmacology 31: 2296–2303.
42.
Ramaekers JG Kuypers KP (2006) Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on behavioral measures of impulsivity: alone and in combination with alcohol. Neuropsychopharmacology31: 1048–1055.
43.
Ramaekers JG Moeller MR van Ruitenbeek P Theunissen EL Schneider E Kauert G (2006c) Cognition and motor control as a function of Delta9-THC concentration in serum and oral fluid: limits of impairment. Drug Alcohol Depend85: 114–122.
44.
Ramaekers JG Robbe HW O'Hanlon JF (2000) Marijuana, alcohol and actual driving performance. Hum Psychopharmacol15: 551–558.
45.
Shallice T (1982) Specific Impairments of Planning.London: Phil. Trans. of the Royal Society of London; pp. 199–209.
46.
Solowij N Michie PT Fox AM (1991) Effects of long-term cannabis use on selective attention: an event-related potential study. Pharmacol Biochem Behav40: 683–688.
47.
Solowij N Michie PT Fox AM (1995) Differential impairments of selective attention due to frequency and duration of cannabis use. Biol Psychiatry37: 731–739.
48.
Solowij N Stephens RS Roffman RA Babor T Kadden R Miller M (2002) Cognitive functioning of long-term heavy cannabis users seeking treatment. JAMA287: 1123–1131.
49.
Weil AT Zinberg NE Nelsen JM (1968) Clinical and psychological effects of marihuana in man. Science162: 1234–1242.
