Cannabis, and specifically one of its active compounds delta-9-tetrahydrocannabinol in recreational doses, has a variety of effects on cognitive processes. Most studies employ resting state functional magnetic resonance imaging techniques to assess the stationary effects of cannabis and to-date one report addressed the impact of delta-9-tetrahydrocannabinol on the dynamics of whole-brain functional connectivity.
Methods:
Using a repeated-measures, within-subjects design, 19 healthy occasional cannabis users (smoking cannabis ⩽2 per week) underwent resting state functional magnetic resonance imaging scans. Each subject underwent two scans: in the intoxicated condition, shortly after smoking a cannabis cigarette, and in the non-intoxicated condition, with the subject being free from cannabinoids for at least one week before. All sessions were randomized and performed in a four-week interval. Data were analysed employing a standard independent component analysis approach with subsequent tracking of the functional connectivity dynamics, which allowed six connectivity clusters (states) to be individuated.
Results:
Using standard independent component analysis in resting state functional connectivity, a group effect was found in the precuneus connectivity. With a dynamic independent component analysis approach, we identified one transient connectivity state, characterized by high connectivity within and between auditory and somato-motor cortices and anti-correlation with subcortical structures and the cerebellum that was only found during the intoxicated condition. Behavioural measures of the subjective experiences of changed perceptions and tetrahydrocannabinol plasma levels during intoxication were associated with this state.
Conclusions:
With the help of the dynamic connectivity approach we could elucidate neural correlates of the transitory perceptual changes induced by delta-9-tetrahydrocannabinol in cannabis users, and possibly identify a biomarker of cannabis intoxication.
AllenEADamarajuEPlisSMet al. (2014) Tracking whole-brain connectivity dynamics in the resting state. Cereb Cortex24: 663–676.
2.
AllenEAErhardtEBWeiYet al. (2012) Capturing inter-subject variability with group independent component analysis of fMRI data: A simulation study. Neuroimage59: 4141–4159.
3.
AndrovicovaRHoracekJTinteraJet al. (2017) Individual prolactin reactivity modulates response of nucleus accumbens to erotic stimuli during acute cannabis intoxication: An fMRI pilot study. Psychopharmacology (Berl)234: 1933–1943.
4.
AnticevicAColeMWRapovsGet al. (2014) Characterizing thalamo-cortical disturbances in schizophrenia and bipolar disorder. Cereb Cortex24: 3116–3130.
5.
AshtonCH (2001) Pharmacology and effects of cannabis: A brief review. Br J Psychiatry178: 101–106.
6.
AtakanZBhattacharyyaSAllenPet al. (2013) Cannabis affects people differently: Inter-subject variation in psychogenic effects of delta-9-tetrahydrocannabinol: A functional magnetic resonance imaging study with healthy volunteers. Psychol Med43: 1255–1267.
7.
BhattacharyyaSAtakanZMartin-SantosRet al. (2012a) Neural mechanisms for the cannabinoid modulation of cognition and affect in man: A critical review of neuroimaging studies. Curr Pharm Des18: 5045–5054.
8.
BhattacharyyaSCrippaJAAllenPet al. (2012b) Induction of psychosis by Δ9-tetrahydrocannabinol reflects modulation of prefrontal and striatal function during attentional salience processing. Arch Gen Psychiatry69: 27–36.
9.
BhattacharyyaSFalkenbergIMartin-SantosRet al. (2015) Cannabinoid modulation of functional connectivity within regions processing attentional salience. Neuropsychopharmacology40: 1343–1352.
10.
BossongMJansmaJMvan HellHHet al. (2013) Default mode network in the effects of delta9-Tetrahydrocannabinol (THC) on human executive function. PLoS One8: e70074.
11.
BravermanovaAViktorinovaMTylsFet al. (2018) Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing- study on P300 and mismatch negativity in healthy volunteers. Psychopharmacology (Berl)2: 491–503.
12.
CalhounVDAdaliTPearlsonGDet al. (2001) A method for making group inferences from functional MRI data using independent component analysis. Hum Brain Mapp14: 140–151.
13.
CalhounVDEicheleTAdaliTet al. (2002) Decomposing the brain: Components and modes, networks and nodes. Trends Cogn Sci16: 255–265.
14.
ChangCGloverGH (2010) Time-frequency dynamics of resting-state brain connectivity measured with fMRI. NeuroImage50: 81–98.
15.
ChengHSkosnikPDPruceBJet al. (2014) Resting state functional magnetic resonance imaging reveals distinct brain activity in heavy cannabis users - a multi-voxel pattern analysis. J Psychopharmacol28: 1030–1040.
16.
CreanRDCraneNAMasonBJ (2011) An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions. J Addict Med5: 1–8.
17.
de BruijnSEMde GraafCWitkampRFet al. (2017) Explorative placebo-controlled double-blind intervention study with low doses of inhaled Δ9-tetrahydrocannabinol and cannabidiol reveals no effect on sweet taste intensity perception and liking in humans. Cannabis Cannabinoid Res2: 114–122.
18.
DamarajuEAllenEABelgerAet al. (2014) Dymanic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia. Neuroimage Clin5: 298–308.
19.
DamoiseauxJSRomboutsSABarkhofFet al. (2006) Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci U S A103: 13848–13853.
20.
DittrichA (1998) The standardized psychometric assessment of altered states of consciousness (ASCs) in humans. Pharmacopsychiatry31: 80–84.
FilbeyFMAsianSLuHet al. (2018a) Residual effects of THC via novel measures of brain perfusion and metabolism in a large group of chronic cannabis users. Neuropsychopharmacology43: 700–707.
23.
FilbeyFMGohelSPrashadSet al. (2018b) Differential associations of combined vs. isolated cannabis and nicotine on brain resting state networks. Brain Struct Funct223: 3317–3326.
24.
FisherASWhitfield-GabrielliSRothRMet al. (2014) Impaired functional connectivity of brain reward circuitry in patients with schizophrenia and cannabis use disorder: Effects of cannabis and THC. Schizophr Res158: 176–182.
25.
GreiciusMDKrasnowBReissALet al. (2003) Functional connectivity in the resting brain: A network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A100: 253–258.
26.
GrimmOLöfflerMKampingSet al. (2018) Probing the endocannabinoid system in healthy volunteers: Cannabidiol alters fronto-striatal resting-state connectivity. Eur Neuropsychopharmacol. Epub ahead of print 7 June 2018. DOI: 10.1016/j.euroneuro.2018.04.004.
27.
HandwerkerDARoopchansinghVGonzalez-CastilloJet al. (2012) Periodic changes in fMRI connectivity. Neuroimage63: 1712–1719.
28.
HartmanDHlinkaJPalusMet al. (2011) The role of nonlinearity in computing graph-theoretical properties of resting-state functional magnetic resonance imaging brain networks. Chaos21: 013119.
29.
HerreroMTBarciaCNavarroJM (2002) Functional anatomy of thalamus and basal ganglia. Childs Nerv Syst18: 386–404.
30.
HimbergJHyvärinenA (2003) ICASSO software for investigating the reliability of ICA estimates by clustering and visualization. In: Proceedings of the 13th Workshop on Neural Networks for Signal Processing, NNSP’03, Toulouse, France, 2003, Espoo: IEEE, pp. 259–268.
31.
HlinkaJAlexakisCHardmanJGet al. (2010) Is sedation-induced BOLD fMRI low-frequency fluctuation increase mediated by increased motion?Magn Reson Mater Phy23: 367–374.
32.
HlinkaJPalusMVejmelkaMet al. (2011) Functional connectivity in resting-state fMRI: Is linear correlation sufficient?Neuroimage54: 2218–2225.
33.
HlinkaJHadravaM (2015) On the danger of detecting network states in white noise. Front Comput Neurosci6: 74.
34.
HouckJMBryanADFeldstein EwingSW (2013) Functional connectivity and cannabis use in hih-risk adolescents. Am J Dru Alcochol Abuse39: 414–423.
35.
IsbellHGorodetzskyCWJasinskiDet al. (1967) Effects of delta-9-tetrahydrocannabinol in man. Psychopharmacologia11: 184–188.
36.
IversenI (2003) Cannabis and the brain. Brain126: 1252–1270.
37.
JonesDTVemuriPMurphyMCet al. (2012) Non-stationarity in the ‘resting brain’s’ modular architecture. PLoS One7: e39731.
38.
KiviniemiVStarckTRemesJet al. (2009) Functional segmentation of the brain cortex using high model order group PICA. Hum Brain Mapp30: 3865–3886.
39.
KiviniemiVVireTRemesJet al. (2011) A sliding time-window ICA reveals spatial variability of the default mode network in time. Brain Connect1: 339–347.
40.
KlumpersLEColeDMKhalili-MahaniNet al. (2012) Manipulating brain connectivity with delta-9-tetrahydrocannabinol: A pharmacological resting state fMRI study. Neuroimage63: 1701–1711.
41.
LangloisDSylvanCGosselinD (2010) An introduction to independent component analysis: InfoMax and FastICA algorithms. Tutor Quant Methods Psychol6: 31–38.
42.
LeeDSchroederJRKarschnerELet al (2014) Cannabis withdrawal in chronic, frequent cannabis smokers during sustained abstinence within a closed residential environment. Am J Addict23: 234–242.
43.
LoydS (1982) Least squares quantization in PCM. IEEE Trans Inf Theory28: 129–137.
44.
Martin-SantosRFagundoABCrippaJAet al. (2010) Neuroimaging in cannabis use: A systematic review of the literature. Psychol Med40: 383–398.
45.
MeszlényiRJHermannPBuzaKet al. (2017) Resting State fMRI functional connectivity analysis using dynamic time warping. Front Neurosci11: 75.
46.
MitraASnyderAZBlazeyTet al. (2015) Lag threads organize the brain’s intrinsic activity. Proc Natl Acad Sci U S A112: e7307.
47.
MustyREReggioPConsroeP (1995) A review of recent advances in cannabinoid research and the 1994 international symposium on cannabis and the cannabinoids. Life Sci56: 1933–1940.
48.
NorthoffGHeinzelAde GreckMet al. (2006) Self-referential processing in our brain – a meta-analysis of imaging studies on the self. Neuroimage31: 440–57.
49.
O’HanlonENewellFNMitchellKJ (2013) Combined structural and functional imaging reveals cortical deviations in grapheme-color synaesthesia. Front Psychol4: 755.
50.
OrrCMoriokaRBehanBet al. (2013) Altered resting-state connectivity in adolescent cannabis users. Am J Drug Alcohol Abuse39: 372–381.
51.
PowerJDSchlaggarBLPetersenSE (2015) Recent progress and outstanding issues in motion correction in resting state fMRI. Neuroimage105: 536–551.
52.
PujolJBlanco-HinojoLBatallaAet al. (2014) Functional connectivity alterations in brain networks relevant to self-awareness in chronic cannabis users. J Psychiatr Res51: 68–78.
53.
RamaekersJGvan WelJHSpronkDet al. (2016) Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes. Brain Imaging Behav10: 1254–1263.
54.
SakoğluUPearlsonGDKiehlKAet al. (2010) A method for evaluating dynamic functional network connectivity and task-modulation: Application to schizophrenia. Magn Reson Mater Phy23: 351–366.
55.
SayinU (2012) A comparative review of the neuropsychopharmacology of hallucinogen-induced altered states of consciousness: The uniqueness of some hallucinogens. Neuroquantology10: 316–340.
56.
ShaoYWangLYeEet al. (2013) Decreased thalamocortical functional connectivity after 36 hours of total sleep deprivation: Evidence from resting state fMRI. PloS One8: e78830.
57.
SmithSMFoxPTMillerKLet al. (2009) Correspondence of the brain’s functional architecture during activation and rest. Proc Natl Acad Sci USA106: 13040–13045.
58.
SmithSM (2012) The future of FMRI connectivity. Neuroimage62: 1257–1266.
59.
SchlienzNJLeeDC (2018) Co-use of cannabis, tobacco, and alcohol in adolescence: Policy and regulátory implications. Int Rev Psychiatry30: 226–237.
60.
StuderusEGammaEVollenweiderFX (2010) Psychometric evaluation of the altered states of consciousness rating scale (OAV). PloS One5: e12412.
61.
TartC (1990) Altered States of Consciousness. 3rd ed.New York: Harpercollins.
62.
ThijssenSRashidBGopalSMet al. (2017) Regular cannabis and alcohol use is associated with resting-state time course spectra in incarcerated adolescents. Drug Alcohol Depend1: 492–500.
63.
van HellHHVinkMOssewaardeLet al. (2010) Chronic effects of cannabis use on the human reward system an fMRI study. Eur Neuropsychopharmacol20: 153–163.
64.
van HellHHBossongMGJagerGet al. (2011) Evidence for involvement of the insula in the psychotropic effects of THC in humans: A double-blind, randomized pharmacological MRI study. Int J Neuropsychopharmacol14: 1377–1388.
65.
VergaraVMWeilandBJHutchisonKEet al. (2018) The impact of combinations of alcohol, nicotine, and cannabis on dynamic brain connectivity. Neuropsychopharmacology43: 877–890.
66.
VingerhoetsWAKoendersLvan den BrinkWet al. (2016) Cue-induced striatal activity in frequent cannabis users independently predicts cannabis problem severity three years later. J Psychopharmacol30: 152–158.
67.
ViverosMPMarcoEMFileSE (2006) Nicotine and cannabinoids: Parallels, contrasts and interactions. Neurosci Biobehav Rev30: 1161–1181.
68.
VollenweiderFX (2001) Brain mechanisms of hallucinogens and entactogens. Dialogues Clin Neurosci3: 365–279.
69.
WangHLRauCLLiYMet al. (2015) Disrupted thalamic resting state functional networks in schizophrenia. Front Behav Neurosci9: 45.
70.
WetherillRRFangZJagannathanKet al. (2015) Cannabis, cigarettes, and their co-occurring use: Disentangling differences in default mode network functional connectivity. Drug Alcohol Depend153: 116–123.
71.
ZhangJChenYCFengXet al. (2015) Impairments of thalamic resting-state functional connectivity in patients with chronic tinnitus. Euro J Radiol84: 1277–1284.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
