Trial reportAddiction biology2021
Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users.
Trial report in Addiction biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- The effects of standardized cannabis products in healthy volunteers and patients: a systematic literature review.Frontiers in pharmacology · 2024Pooled it
- Is resting-state functional connectivity altered in regular cannabis users? A systematic review of the literature.Psychopharmacology · 2022Pooled it
- ΔBiological psychiatry. Cognitive neuroscience and neuroimaging · 2026Trial
- Evaluating possible 'next day' impairment in insomnia patients administered an oral medicinal cannabis product by night: a pilot randomized controlled trial.Psychopharmacology · 2024Trial
- Intoxication due to Δ9-tetrahydrocannabinol is characterized by disrupted prefrontal cortex activity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Trial
- A Semi-Naturalistic, Open-Label Trial Examining the Effect of Prescribed Medical Cannabis on Neurocognitive Performance.CNS drugs · 2023Trial
- Spontaneous and deliberate creative cognition during and after psilocybin exposure.Translational psychiatry · 2021Trial
- Effect of Δ9-Tetrahydrocannabinol on frontostriatal resting state functional connectivity and subjective euphoric response in healthy young adults.Drug and alcohol dependence · 2021Trial
- Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users.Addiction biology · 2021Trial
- EEG-based network dynamics in cannabis and polydrug use: a directed transfer function approach.Psychopharmacology · 2026Article
- What Do Thirty Years of Neuroimaging Research Tell Us About Recreational Cannabis Use and Brain Integrity? A Narrative Review of the Multimodal Neuroimaging Evidence to Date.Substance abuse and rehabilitation · 2026Review
- Assessment of the associative determinants of tolerance to the effects of cannabis extract on exploratory behavior in rats.Drug and alcohol dependence reports · 2025Article
- Metabolomic profiling of cannabis use and cannabis intoxication in humans.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Effect of cannabinoids on glutamate levels in the human brain: a systematic review and meta-analysis.Journal of cannabis research · 2025Review
- A constrained disorder principle-based second-generation artificial intelligence digital medical cannabis system: A real-world data analysis.Journal of public health research · 2025Article
- Cannabis tolerance reduces symptom relief.Frontiers in pharmacology · 2025Article
- Year-Long Cannabis Use for Medical Symptoms and Brain Activation During Cognitive Processes.JAMA network open · 2024Article
- Imaging neuroinflammation in individuals with substance use disorders.The Journal of clinical investigation · 2024Review
- Impact of year-long cannabis use for medical symptoms on brain activation during cognitive processes.medRxiv : the preprint server for health sciences · 2024Article
- Expectancies of the Effects of Cannabis Use in Individuals with Social Anxiety Disorder (SAD).Brain sciences · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cannabis is the most commonly used illicit drug in the world. However, because of a changing legal landscape and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly cannabis impairment. Importantly, a growing body of evidence suggests that regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug. However, the neuroadaptations that may underlie cannabis tolerance remain unclear. Therefore, this double-blind, randomized, placebo-controlled, cross-over study assessed the acute influence of cannabis on the brain and behavioral outcomes in two distinct cannabis user groups. Twelve occasional and 12 chronic cannabis users received acute doses of cannabis (300-μg/kg delta-9-tetrahydrocannabinol) and placebo and underwent ultrahigh field functional magnetic resonance imaging and magnetic resonance spectroscopy. In occasional users, cannabis induced significant neurometabolic alterations in reward circuitry, namely, decrements in functional connectivity and increments in striatal glutamate concentrations, which were associated with increases in subjective high and decreases in performance on a sustained attention task. Such changes were absent in chronic users. The finding that cannabis altered circuitry and distorted behavior in occasional, but not chronic users, suggests reduced responsiveness of the reward circuitry to cannabis intoxication in chronic users. Taken together, the results suggest a pharmacodynamic mechanism for the development of tolerance to cannabis impairment, of which is important to understand in the context of the long-term therapeutic use of cannabis-based medications, as well as in the context of public health and safety of cannabis use when performing day-to-day operations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.