Acute effects of THC on time perception in frequent and infrequent cannabis users
- 1.5k Downloads
Cannabinoids have been shown to alter time perception, but existing literature has several limitations. Few studies have included both time estimation and production tasks, few control for subvocal counting, most had small sample sizes, some did not record subjects’ cannabis use, many tested only one dose, and used either oral or inhaled administration of Δ9-tetrahydrocannabinol (THC), leading to variable pharmacokinetics, and some used whole-plant cannabis containing cannabinoids other than THC. Our study attempted to address these limitations.
This study aims to characterize the acute effects of THC and frequent cannabis use on seconds-range time perception. THC was hypothesized to produce transient, dose-related time overestimation and underproduction. Frequent cannabis smokers were hypothesized to show blunted responses to these alterations.
IV THC was administered at doses from 0.015 to 0.05 mg/kg to 44 subjects who participated in several double-blind, randomized, counterbalanced, crossover, placebo-controlled studies. Visual time estimation and production tasks in the seconds range were presented to subjects three times on each test day.
All doses induced time overestimation and underproduction. Chronic cannabis use had no effect on baseline time perception. While infrequent/nonsmokers showed temporal overestimation at medium and high doses and temporal underproduction at all doses, frequent cannabis users showed no differences. THC effects on time perception were not dose related.
A psychoactive dose of THC increases internal clock speed as indicated by time overestimation and underproduction. This effect is not dose related and is blunted in chronic cannabis smokers who did not otherwise have altered baseline time perception.
KeywordsCannabinoids Δ9-tetrahydrocannabinol Time perception Temporal processing
The authors wish to acknowledge support from the (1) Department of Veterans Affairs, (2) National Institute of Mental Health, (3) National Institute of Drug Abuse, (4) National Institute of Alcoholism and Alcohol Abuse (NIAAA) and (5) the Yale Center for Clinical Investigation (YCCI). This research project was funded in part by grants from NIH (R01 DA012382, R21 DA020750, R21 MH086769, R21 AA016311 to DCD). The authors also thank Angelina Genovese, R.N.C., M.B.A.; Michelle San Pedro, R.N.; Elizabeth O’Donnell, R.N.; Brenda Breault, R.N., B.S.N.; Sonah Yoo, R.Ph.; Rachel Galvan, R.Ph.; and Willie Ford of the Neurobiological Studies Unit at the VA Connecticut Healthcare System, West Haven Campus for their central contributions to the success of this project. The experiments comply with the current laws of the USA.
Funding and Conflict of Interest
The authors wish to acknowledge support from the (1) Department of Veterans Affairs, (2) National Institute of Mental Health, (3) National Institute of Drug Abuse, (4) National Institute of Alcoholism and Alcohol Abuse (NIAAA) and (5) the Yale Center for Clinical Investigation (YCCI). This research project was funded in part by grants from NIH (R01 DA012382, R21 DA020750, R21 MH086769, R21 AA016311 to DCD). Patrick Skosnik, Ashley Williams, Ashley Schnakenberg, Rajiv Radhakrishnan, Brian Pittman, and R. Andrew Sewell report no financial relationships with commercial interests. Mohini Ranganathan has in the past three years and currently receives research grant support administered through Yale University School of Medicine from Eli Lilly Inc. Deepak Cyril D’Souza has in the past three years and currently receives research grant support administered through Yale University School of Medicine from Astra Zeneca, Abbott Laboratories, Eli Lilly Inc., Organon, Pfizer Inc., and Sanofi; he is also a consultant for Bristol Meyers Squibb.
- Carbuto M, Sewell RA, Williams A, Forselius-Bielen K, Braley G, Elander J, Pittman B, Schnakenberg A, Bhakta S, Perry E, Ranganathan M, D’Souza DC (2012) The safety of studies with intravenous delta(9)-tetrahydrocannabinol in humans, with case histories. Psychopharmacology (Berl) 219:885–896CrossRefGoogle Scholar
- Chen JP, Paredes W, Li J, Smith D, Lowinson J, Gardner EL (1990b) Delta 9-tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis. Psychopharmacology 102:156–162PubMedCrossRefGoogle Scholar
- Cohen J (1973) Eta-squared and partial eta-squared in communication science. Hum Commun Res 28:473–490Google Scholar
- Dornbush R, Clare G, Zaks A, Crown P, Volavka J, Fink M (1971) 21-day administration of marijuana in male volunteers. In: Lewis M (ed) Current research in marijuana. Academic, New York, pp 115–128Google Scholar
- D’Souza DC, Braley G, Blaise R, Vendetti M, Oliver S, Pittman B, Ranganathan M, Bhakta S, Zimolo Z, Cooper T, Perry E (2008a) Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Delta-9-tetrahydrocannabinol in humans. Psychopharmacology (Berlin) 198:587–603CrossRefGoogle Scholar
- D’Souza DC, Fridberg DJ, Skosnik PD, Williams A, Roach B, Singh N, Carbuto M, Elander J, Schnakenberg A, Pittman B, Sewell RA, Ranganathan M, Mathalon D (2012) Dose-related modulation of event-related potentials to novel and target stimuli by intravenous delta(9)-THC in humans. Neuropsychopharmacology 37:1632–1646PubMedCrossRefGoogle Scholar
- First M, Spitzer R, Gibbon M, Williams J (2007) Structured Clinical Interview for Axis I DSM-IV Disorders, Research Version. B.R. Department, New York State Psychiatric Institute, New YorkGoogle Scholar
- Lichtman AH, Martin BR (2005) Cannabinoid tolerance and dependence. Handb Exp Pharmacol (168):691–717Google Scholar
- Morrow R (1944) Psychophysical and other functions. In: Mayor’s Committee on Marihuana (ed) The Marihuana Problem in the City of New York, City of New YorkGoogle Scholar
- Office of Applied Studies (2006) (Office of Applied Studies 2006; Office of National Drug Control Policy 2008) Results from the 2005 National Survey on Drug Use and Health: National findings. Substance Abuse and Mental Health Services Administration, Rockville, MDGoogle Scholar
- Office of National Drug Control Policy (2008) Marijuana: the greatest cause of illegal drug abuse. The marijuana factbook. ONDCP, Washington, DCGoogle Scholar
- Pistis M, Ferraro L, Pira L, Flore G, Tanganelli S, Gessa GL, Devoto P (2002) Delta(9)-tetrahydrocannabinol decreases extracellular GABA and increases extracellular glutamate and dopamine levels in the rat prefrontal cortex: an in vivo microdialysis study. Brain Res 948:155–158PubMedCrossRefGoogle Scholar
- Wall M, Brine D, Perez-Reyes M (1976) Metabolism of cannabinoids in man. In: Braude M, Szara S (eds) Pharmacology of marihuana. Raven, New York, p 536Google Scholar
- Webb P, Strube F, Leavitt J, Norris G, Fitz-Gerald M, Nixon F, Straumanis J (1993) Time distortion as a persistent sequelae of chronic THC use. In: Harris L (ed) NIDA Research Monograph 132, Problems of Drug Dependence. US Government Printing Office, Washington, DCGoogle Scholar