Subjective Effects of Ethanol, Morphine, Δ(9)-Tetrahydrocannabinol, and Ketamine Following a Pharmacological Challenge Are Related to Functional Brain Connectivity.
Daniel Kleinloog, Serge A.r.b. Rombouts, Remco Zoethout, Linda E. Klumpers, Marieke Niesters, Najmeh Khalili-Mahani, Albert Dahan, Joop van Gerven
Brain Connectivity December 2015 DOI: 10.1089/brain.2014.0314 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Repeated measures pharmacological fMRI study Peer reviewed |
|---|---|
| Sample size | 36 |
| Population | Healthy male volunteers |
| Interventions | Ethanol Morphine Δ(9)-tetrahydrocannabinol Ketamine |
| Measures | Visual analogue scales |
| Topics | Cannabis Esketamine Ketamine |
| Keywords | Connectivity FMRI Pharmacologic Resting state Subjective effects |
| Key points | Across four psychoactive drugs, drug-induced subjective perception correlated with connectivity of the posterior cingulate cortex and precentral gyrus with the sensorimotor network (p < 0.005, corrected), while relaxation and dysphoria showed no significant correlations. The authors argue that the overlap between these connectivity changes and those seen in schizophrenia supports psychomimetic drug challenges as models for psychosis. |
Abstract
This analysis examines the neuronal foundation of drug-induced psychomimetic symptoms by relating the severity of these symptoms to changes in functional connectivity for a range of different psychoactive compounds with varying degrees of psychomimetic effects. The repeated measures design included 323 resting-state functional magnetic resonance imaging time series and measures of subjective effects in 36 healthy male volunteers. Four different pharmacological challenges with ethanol, morphine, Δ(9)-tetrahydrocannabinol, and ketamine (12 subjects per drug) were applied. A set of 10 "template" resting-state networks was used to determine individual connectivity maps. Linear regression was used for each individual subject to relate these connectivity maps to three clusters of drug-induced subjective psychomimetic effects ("perception," "relaxation," and "dysphoria") as measured with visual analogue scales. Group analysis showed that the subjective effects of perception correlated significantly across drugs with the connectivity of the posterior cingulate cortex and precentral gyrus with the sensorimotor network (p < 0.005, corrected). No significant correlations were found for relaxation or dysphoria. The posterior cingulate cortex has a role in visuospatial evaluation and the precentral gyrus has been associated with auditory hallucinations. Both the posterior cingulate cortex and the precentral gyrus show changes in activation in patients with schizophrenia, which can be related to the severity of positive symptoms (i.e., hallucinations and delusions), and have previously been related to changes induced by psychoactive drugs. The similarity of functional connectivity changes for drug-induced psychomimetic effects and symptoms of psychosis provides further support for the use of pharmacological challenges with psychomimetic drugs as models for psychosis.
Comparable studies
Other experimental studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Smoked Cannabis' Psychomotor and Neurocognitive Effects in Occasional and Frequent Smokers Occasional (<2x/week) and frequent (≥4x/week) cannabis smokers | 2015 | Controlled within-subjects study | n = 25 |
| Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity Healthy volunteers experienced with cannabis but not regular users | 2019 | Within-subjects experimental design | n = 17 |
| Which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like effects? Young cannabis users | 2018 | Observational study (naturalistic, within-subject counterbalanced design) | n = 410 |
| Cannabis Essential Oil: A Preliminary Study for the Evaluation of the Brain Effects Healthy volunteers | 2018 | Experimental study | n = 5 |
| Coming off cannabis: a cognitive and magnetic resonance imaging study in patients with multiple sclerosis Patients with multiple sclerosis who began using cannabis after disease onset, used it... | 2019 | Quasi-experimental study with odd-even allocation | n = 40 |
Citations in the library
Cited by 4
- Human Laboratory Studies on Cannabinoids and Psychosis. Biological Psychiatry April 1, 2016
- Receptor-enriched analysis of functional connectivity (REACT) for understanding cannabinoid neuropsychopharmacology bioRxiv (Cold Spring Harbor Laboratory) June 5, 2025
- Resting-state connectivity studies as a marker of the acute and delayed effects of subanaesthetic ketamine administration in healthy and depressed individuals: A systematic review Brain and Neuroscience Advances 2021
- Depression in chronic ketamine users: Sex differences and neural bases. Psychiatry Research Neuroimaging November 30, 2017
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and 9 more in the library