Psychomotor performance, subjective and physiological effects and whole blood Δ⁹-tetrahydrocannabinol concentrations in heavy, chronic cannabis smokers following acute smoked cannabis.

Δ⁹-Tetrahydrocannabinol (THC) is the illicit drug most frequently observed in accident and driving under the influence of drugs investigations. Whole blood is often the only available specimen collected during such investigations, yet few studies have examined relationships between cannabis effects and whole blood concentrations following cannabis smoking. Nine male and one female heavy, chronic cannabis smokers resided on a closed research unit and smoked ad libitum one 6.8% THC cannabis cigarette. THC, 11-hydroxy-THC and 11-nor-9-carboxy-THC were quantified in whole blood and plasma. Assessments were performed before and up to 6 h after smoking, including subjective [visual analog scales (VAS) and Likert scales], physiological (heart rate, blood pressure and respirations) and psychomotor (critical-tracking and divided-attention tasks) measures. THC significantly increased VAS responses and heart rate, with concentration-effect curves demonstrating counter-clockwise hysteresis. No significant differences were observed for critical-tracking or divided-attention task performance in this cohort of heavy, chronic cannabis smokers. The cannabis influence factor was not suitable for quantifying psychomotor impairment following cannabis consumption and was not precise enough to determine recent cannabis use with accuracy. These data inform our understanding of impairment and subjective effects following acute smoked cannabis and interpretation of whole blood cannabinoid concentrations in forensic investigations.

[1]  M. Huestis,et al.  Identification of recent cannabis use: whole-blood and plasma free and glucuronidated cannabinoid pharmacokinetics following controlled smoked cannabis administration. , 2011, Clinical chemistry.

[2]  E. Cone,et al.  Detection of marijuana use by oral fluid and urine analysis following single-dose administration of smoked and oral marijuana. , 2001, Journal of analytical toxicology.

[3]  S. M. Owens,et al.  Kinetic study of smoking marijuana , 1982, Journal of Pharmacokinetics and Biopharmaceutics.

[4]  Mahmoud A. ElSohly,et al.  Potency Trends of Δ9‐THC and Other Cannabinoids in Confiscated Cannabis Preparations from 1993 to 2008 * , 2010, Journal of forensic sciences.

[5]  D. Cocchetto,et al.  Relationship between plasma delta-9-tetrahydrocannabinol concentration and pharmacologic effects in man , 2004, Psychopharmacology.

[6]  N. Benowitz,et al.  Cardiovascular effects of intravenous delta‐9‐tetrahydrocannabinol: Autonomic nervous mechanisms , 1979, Clinical pharmacology and therapeutics.

[7]  Herbert Moskowitz,et al.  Laboratory studies of the effects of alcohol on some variables related to driving. , 1973 .

[8]  M. Huestis,et al.  Characterization of the absorption phase of marijuana smoking , 1992, Clinical pharmacology and therapeutics.

[9]  V. Sébille,et al.  Methodological Issues in Pharmacokinetic-Pharmacodynamic Modelling , 1998, Clinical pharmacokinetics.

[10]  D. Kelly,et al.  Delta9-tetrahydrocannabinol (THC), 11-hydroxy-THC, and 11-nor-9-carboxy-THC plasma pharmacokinetics during and after continuous high-dose oral THC. , 2009, Clinical chemistry.

[11]  S. Heishman,et al.  Alcohol and marijuana: Comparative dose effect profiles in humans , 1988, Pharmacology Biochemistry and Behavior.

[12]  M. Huestis,et al.  Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. , 1992, Journal of analytical toxicology.

[13]  M. Huestis,et al.  Direct quantification of cannabinoids and cannabinoid glucuronides in whole blood by liquid chromatography–tandem mass spectrometry , 2011, Analytical and bioanalytical chemistry.

[14]  J. Ramaekers,et al.  Visual search and urban driving under the influence of marijuana and alcohol , 2001, Human psychopharmacology.

[15]  Kathryn Wochinger,et al.  Results of the 2013–2014 National Roadside Survey of Alcohol and Drug Use by Drivers , 2009 .

[16]  M. Huestis,et al.  Relating Blood Concentrations of Tetrahydrocannabinol and Metabolites to Pharmacologic Effects and Time of Marijuana Usage , 1993, Therapeutic drug monitoring.

[17]  Wayne Hall,et al.  Adverse effects of cannabis , 1998, The Lancet.

[18]  J. Ramaekers,et al.  Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users , 2009, Journal of psychopharmacology.

[19]  J. Ramaekers,et al.  Dose related risk of motor vehicle crashes after cannabis use. , 2004, Drug and alcohol dependence.

[20]  J. Ramaekers,et al.  High-Potency Marijuana Impairs Executive Function and Inhibitory Motor Control , 2006, Neuropsychopharmacology.

[21]  M. Thevis,et al.  Temporal indication of cannabis use by means of THC glucuronide determination. , 2009, Drug testing and analysis.

[22]  I. Yamamoto,et al.  Metabolism of delta 9-tetrahydrocannabinol by cytochrome P450 isozymes purified from hepatic microsomes of monkeys. , 1995, Life sciences.

[23]  G. Berghaus,et al.  Cannabis im Strassenverkehr , 1998 .

[24]  L B Sheiner,et al.  Relationship between the pharmacokinetics and pharmacodynamics of procainamide , 1976, Clinical pharmacology and therapeutics.

[25]  Jan Meulenbelt,et al.  Cognitive and psychomotor effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg delta-9-tetrahydrocannabinol (THC) , 2009, Psychopharmacology.

[26]  D. Kelly,et al.  Disposition of cannabinoids in oral fluid after controlled around-the-clock oral THC administration. , 2010, Clinical chemistry.

[27]  M R Moeller,et al.  Cognition and motor control as a function of Delta9-THC concentration in serum and oral fluid: limits of impairment. , 2006, Drug and alcohol dependence.

[28]  G. Barnett,et al.  Marijuana effect and delta‐9‐tetrahydrocannabinol plasma level , 1984, Clinical pharmacology and therapeutics.

[29]  C. Brignell,et al.  Cognitive and subjective dose-response effects of acute oral Δ9-tetrahydrocannabinol (THC) in infrequent cannabis users , 2002, Psychopharmacology.

[30]  D. Dietrich,et al.  The Effects of Tetrahydrocannabinol on the Recognition of Emotionally Charged Words: An Analysis Using Event-Related Brain Potentials , 1998, Neuropsychobiology.

[31]  Reese T. Jones,et al.  Metabolism of tetrahydrocannabinol in frequent and infrequent marijuana users. , 1992, Journal of analytical toxicology.

[32]  C. Stough,et al.  The relationship between performance on the standardised field sobriety tests, driving performance and the level of Delta9-tetrahydrocannabinol (THC) in blood. , 2005, Forensic science international.

[33]  J. Ramaekers,et al.  Pharmacokinetic properties of delta9-tetrahydrocannabinol in serum and oral fluid. , 2007, Journal of analytical toxicology.

[34]  H. R. Jex,et al.  A ``Critical'' Tracking Task for Manual Control Research , 1966 .

[35]  S. Yamaori,et al.  Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. , 2007, Life sciences.

[36]  L. Hollister,et al.  Plasma delta‐9‐tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking , 1980, Clinical pharmacology and therapeutics.

[37]  J. Zacny,et al.  Reinforcing and subjective effects of oral delta 9-THC and smoked marijuana in humans. , 1992, Psychopharmacology.

[38]  J. Meulenbelt,et al.  Delta-9-tetrahydrocannabinol (THC) serum concentrations and pharmacological effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg THC , 2008, Psychopharmacology.

[39]  C. Hart,et al.  Effects of Acute Smoked Marijuana on Complex Cognitive Performance , 2001, Neuropsychopharmacology.

[40]  Patrice Mangin,et al.  Assessment of driving capability through the use of clinical and psychomotor tests in relation to blood cannabinoids levels following oral administration of 20 mg dronabinol or of a cannabis decoction made with 20 or 60 mg Delta9-THC. , 2005, Journal of analytical toxicology.

[41]  R. Beninger,et al.  Selective D1 and D2 dopamine agonists produce opposing effects in place conditioning but not in conditioned taste aversion learning , 1988, Pharmacology Biochemistry and Behavior.