Repeated Δ9-tetrahydrocannabinol exposure in adolescent monkeys: persistent effects selective for spatial working memory.
Christopher D. Verrico, Hong Gu, Melanie L Peterson, Allan R Sampson, David A Lewis
American Journal of Psychiatry April 2014 DOI: 10.1176/appi.ajp.2013.13030335 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 14 |
| Population | Adolescent male rhesus monkeys |
| Intervention | THC |
| Duration | 6-month exposure, with assessments 23 or 71 hours after drug administration |
| Topics | Cannabis |
| Key findings | Repeated THC exposure blunted the trajectory of accuracy improvements on the spatial working memory task in a delay-dependent manner, while object working memory improvements did not differ from controls. Acute THC effects on working memory showed neither sensitivity nor tolerance after six months. |
Abstract
Epidemiological findings suggest that, relative to adults, adolescents are more vulnerable to the adverse persistent effects of cannabis on working memory. However, the potential confounds inherent in human studies preclude direct determination of a cause-and-effect relationship between adolescent cannabis use and heightened susceptibility to persistent working memory impairments. Consequently, the authors examined the effects of repeated exposure to Δ9-tetrahydrocannabinol (THC) on performance of spatial and object working memory tasks in adolescent monkeys. Seven pairs of male adolescent rhesus monkeys, matched for baseline cognitive performance, received vehicle or THC intravenously 5 days/week for 6 months. Performance on spatial and object memory tasks was assessed 23 or 71 hours after drug administration throughout the study. In addition, acute effects on working memory were also assessed at the beginning and end of the 6-month period. Relative to the vehicle-exposed control animals, those with repeated THC exposure had a blunted trajectory of accuracy improvements on the spatial working memory task in a delay-dependent manner. Accuracy improvements on the object working memory task did not differ between groups. Relative to the acute effects of THC on working memory at the beginning of the study, neither sensitivity nor tolerance was evident after 6 months of THC exposure. Because maturation of performance is later for spatial than for object working memory, these findings suggest that persistent effects of THC on cognitive abilities are more evident when exposure coincides with the developmental stage during which the underlying neural circuits are actively maturing.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 11
- Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males Translational Psychiatry November 29, 2016
- The Bridge Between Classical and “Synthetic”/Chemical Psychoses: Towards a Clinical, Psychopathological, and Therapeutic Perspective Frontiers in Psychiatry November 20, 2019
- The CannTeen study: verbal episodic memory, spatial working memory, and response inhibition in adolescent and adult cannabis users and age-matched controls Psychopharmacology April 29, 2022
- Investigating the "two-hit hypothesis": Effects of prenatal maternal immune activation and adolescent cannabis use on neurodevelopment in mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2023
- Alterations in rat prefrontal cortex kynurenic acid levels are involved in the enduring cognitive dysfunctions induced by tetrahydrocannabinol exposure during the adolescence. Frontiers in Psychiatry 2022
and 6 more in the library
Cites 12
- Cannabis Use during Adolescent Development: Susceptibility to Psychiatric Illness Frontiers in Psychiatry 2013
- Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users Psychopharmacology October 30, 2010
- Delay- and dose-dependent effects of Δ⁹-tetrahydrocannabinol administration on spatial and object working memory tasks in adolescent rhesus monkeys. Neuropsychopharmacology May 2012
- Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study: naturalistic study [corrected]. The British Journal of Psychiatry October 2010
- The influence of recency of use on fMRI response during spatial working memory in adolescent marijuana users. Journal of Psychoactive Drugs September 2010
and 7 more in the library