Effects of inhaled cannabis high in Δ9-THC or CBD on the aging brain: A translational MRI and behavioral study
Aymen H. Sadaka, Justin Canuel, Marcelo Febo, Clare T. Johnson, Heather B. Bradshaw, Richard J. Ortiz, Federica Ciumo, Praveen P Kulkarni, Michael A. Gitcho, Craig F. Ferris
Frontiers in Aging Neuroscience February 1, 2023 DOI: 10.3389/fnagi.2023.1055433 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | 19-20 month old mice |
| Interventions | Vaporized cannabis high in Δ9-THC placebo |
| Dose | ~10% Δ9-THC, ~10% CBD |
| Duration | 30 min daily for 28 days, followed by a two-week washout period |
| Measures | Voxel based morphometry, diffusion weighted imaging, resting state functional connectivity, tail-flick test, open field test, novel object preference test |
| Topics | Cannabis CBD |
| Citations | 29 |
| Key findings | Chronic vaporized Δ9-THC produced antinociceptive effects without tolerance in aged mice, while its anxiolytic and cognitive effects waned; CBD had no behavioral effects. Δ9-THC decreased midbrain dopaminergic volume and fractional anisotropy, with volume increasing after washout. High-CBD cannabis increased network strength and efficiency, persisting after washout. The authors indicate THC-dominant cannabis may be an effective analgesic but not for anxiety or cognitive decline. |
Abstract
With the recent legalization of inhaled cannabis for medicinal and recreational use, the elderly represents one of the newest, rapidly growing cohorts of cannabis users. To understand the neurobiological effects of cannabis on the aging brain, 19-20 months old mice were divided into three groups exposed to vaporized cannabis containing ~10% Δ9-THC, ~10% CBD, or placebo for 30 min each day. Voxel based morphometry, diffusion weighted imaging, and resting state functional connectivity data were gathered after 28 days of exposure and following a two-week washout period. Tail-flick, open field, and novel object preference tests were conducted to explore analgesic, anxiolytic, and cognitive effects of cannabis, respectively. Vaporized cannabis high in Δ9-THC and CBD achieved blood levels reported in human users. Mice showed antinociceptive effects to chronic Δ9-THC without tolerance while the anxiolytic and cognitive effects of Δ9-THC waned with treatment. CBD had no effect on any of the behavioral measures. Voxel based morphometry showed a decrease in midbrain dopaminergic volume to chronic Δ9-THC followed but an increase after a two-week washout. Fractional anisotropy values were reduced in the same area by chronic Δ9-THC, suggesting a reduction in gray matter volume. Cannabis high in CBD but not THC increased network strength and efficiency, an effect that persisted after washout. These data would indicate chronic use of inhaled cannabis high in Δ9-THC can be an effective analgesic but not for treatment of anxiety or cognitive decline. The dopaminergic midbrain system was sensitive to chronic Δ9-THC but not CBD showing robust plasticity in volume and water diffusivity prior to and following drug cessation an effect possibly related to the abuse liability of Δ9-THC. Chronic inhaled CBD resulted in enhanced global network connectivity that persisted after drug cessation. The behavioral consequences of this sustained change in brain connectivity remain to be determined.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
Citations in the library
Cited by 8
- Developmental changes in brain structure and function following exposure to oral LSD during adolescence. Scientific Reports August 11, 2024
- Sex-dependent developmental changes in behavior, brain structure, functional connectivity, and sensory perception following exposure to psilocybin during adolescence Neuropsychopharmacology February 18, 2026
- Cannabis smoke and oral Δ9THC enhance working memory in aged but not young adult subjects bioRxiv (Cold Spring Harbor Laboratory) September 29, 2024
- Effects of cannabis smoke and oral Δ9THC on cognition in young adult and aged rats Psychopharmacology February 7, 2025
- Acute and Extended Anxiolytic Effects of Cannabidiol in Cannabis Flower: A Quasi-Experimental ad libitum Use Study Cannabis and Cannabinoid Research January 22, 2024
and 3 more in the library
Cites 12
- Increased global integration in the brain after psilocybin therapy for depression. Nature Medicine April 11, 2022
- The neuropsychopharmacology of cannabis: A review of human imaging studies Pharmacology & Therapeutics October 20, 2018
- Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties Journal of Translational Medicine October 2, 2020
- Functional brain connectomes reflect acute and chronic cannabis use Scientific Reports February 14, 2022
- Cannabis and synaptic reprogramming of the developing brain. Nature Reviews Neuroscience July 2021
and 7 more in the library