Acute effects of different types of cannabis on young adult and adolescent resting-state brain networks
Natalie Ertl, Tom P. Freeman, Claire Mokrysz, Shelan Ofori, Anna Borissova, Kat Petrilli, Helen Valerie Curran, Will Lawn, Matthew B. Wall
Neuropsychopharmacology May 28, 2024 DOI: 10.1038/s41386-024-01891-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 46 |
| Population | Semi-regular cannabis users (usage frequency between 0.5 and 3 days/week) aged 16–17 years (adolescents) and 26–29 years (young adults) |
| Interventions | Vaporized cannabis THC CBD |
| Dose | THC: 8 mg/75 kg, THC + CBD: 8 mg/75 kg THC & 24 mg/75 kg CBD |
| Topics | Cannabis CBD |
| Keywords | Placebo Resting State FMRI Hippocampal formation Endocannabinoid system Delta-9-tetrahydrocannabinol Dronabinol |
| Citations | 19 |
| Key findings | Cannabis caused reductions in within-network connectivity in the default mode, executive control, salience, hippocampal, and limbic striatal networks compared to placebo, and CBD did not attenuate these effects. |
Abstract
Adolescence is a time of rapid neurodevelopment and the endocannabinoid system is particularly prone to change during this time. Cannabis is a commonly used drug with a particularly high prevalence of use among adolescents. The two predominant phytocannabinoids are Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which affect the endocannabinoid system. It is unknown whether this period of rapid development makes adolescents more or less vulnerable to the effects of cannabis on brain-network connectivity, and whether CBD may attenuate the effects of THC. Using fMRI, we explored the impact of vaporized cannabis (placebo, THC: 8 mg/75 kg, THC + CBD: 8 mg/75 kg THC & 24 mg/75 kg CBD) on resting-state networks in groups of semi-regular cannabis users (usage frequency between 0.5 and 3 days/week), consisting of 22 adolescents (16-17 years) and 24 young adults (26-29 years) matched for cannabis use frequency. Cannabis caused reductions in within-network connectivity in the default mode (F[2,88] = 3.97, P = 0.022, η² = 0.018), executive control (F[2,88] = 18.62, P < 0.001, η² = 0.123), salience (F[2,88] = 12.12, P < 0.001, η² = 0.076), hippocampal (F[2,88] = 14.65, P < 0.001, η² = 0.087), and limbic striatal (F[2,88] = 16.19, P < 0.001, η² = 0.102) networks compared to placebo. Whole-brain analysis showed cannabis significantly disrupted functional connectivity with cortical regions and the executive control, salience, hippocampal, and limbic striatal networks compared to placebo. CBD did not counteract THC's effects and further reduced connectivity both within networks and the whole brain. While age-related differences were observed, there were no interactions between age group and cannabis treatment in any brain network. Overall, these results challenge the assumption that CBD can make cannabis safer, as CBD did not attenuate THC effects (and in some cases potentiated them); furthermore, they show that cannabis causes similar disruption to resting-state connectivity in the adolescent and adult brain.
Comparable studies
Other randomized controlled trials on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants | 2012 | Randomized controlled trial | n = 48 |
| Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... | 2009 | Double-blind, randomized, placebo-controlled crossover trial | n = 15 |
| Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects | 2012 | Randomized controlled trial | n = 16 |
| Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... | 2009 | Randomized controlled trial | n = 15 |
| Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use | 2019 | Randomized, double-blind, within-subjects crossover | n = 14 |
Citations in the library
Cited by 6
- Dissociable effects of LSD and MDMA on striato-cortical connectivity in healthy subjects. Neuropsychopharmacology October 31, 2025
- Receptor-enriched analysis of functional connectivity (REACT) for understanding cannabinoid neuropsychopharmacology bioRxiv (Cold Spring Harbor Laboratory) June 5, 2025
- Adverse outcomes following psychedelic use in adolescents and adults: associations with age and personality traits. Child and Adolescent Psychiatry and Mental Health February 24, 2026
- Brain Network Convergence of Abnormal Gray Matter and Functional Activity of Pathological Dissociative Symptoms. Psychiatry and Clinical Neurosciences August 29, 2026
- Plasma cannabinoid pharmacokinetics following the inhalation of vaporised cannabis with and without cannabidiol. Drug and Alcohol Dependence July 1, 2026
and 1 more in the library
Cites 27
- The Brain's Default Mode Network Annual Review of Neuroscience May 4, 2015
- The salience network is responsible for switching between the default mode network and the central executive network: Replication from DCM Neuroimage May 24, 2014
- Homological scaffolds of brain functional networks Journal of the Royal Society, Interface October 29, 2014
- Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Archives of General Psychiatry 2009
- Increased global integration in the brain after psilocybin therapy for depression. Nature Medicine April 11, 2022
and 22 more in the library