Dopamine challenge reveals neuroadaptive changes in marijuana abusers

Madras, Bertha K.

doi:10.1073/pnas.1412314111

Cited by 4 publications

(5 citation statements)

References 19 publications

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“…MPH could have modulated these receptors differently in HC and CUD accounting for the decreases in negative connectivity in CUD and the enhanced negative connectivity in HC. Interestingly, MPH normalized connectivity for CUD, reducing the negative connectivity to the levels in HC under placebo status, which we interpret to suggest that MPH might have alleviated the dopaminergic deficits in CUD [49][50][51]. This finding reiterates the pivotal role of NAc and the thalamus in stimulant drugs effects and in addiction [52].…”

Section: Concomitant Metabolic Changes (Mph-pl) In the Thalamic Seedssupporting

confidence: 52%

Methylphenidate’s effects on thalamic metabolism and functional connectivity in cannabis abusers and healthy controls

Demiral

Tomasi

Wiers

et al. 2018

Neuropsychopharmacol.

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Methylphenidate (MPH) is a first line treatment for ADHD and is also misused as a purported cognitive enhancer, yet its effects on brain function are still poorly understood. Recent functional magnetic resonance imaging (fMRI) studies showed that MPH altered cortico-striatal resting functional connectivity (RFC). Here we investigated the effects of MPH in thalamic connectivity since the thalamus modulates striato-cortical signaling. We hypothesized that MPH would increase thalamic connectivity and metabolism, and that this response would be blunted in cannabis abusers. For this purpose, we measured RFC in seven thalamic nuclei using fMRI and brain glucose metabolism using positron emission tomography (PET) and 18 F-fluorodeoxyglucose (FDG) in sixteen healthy controls and thirteen participants with cannabis use disorder (CUD) twice after placebo and after MPH (0.5 mg/kg, iv). MPH significantly increased thalamo-cerebellar connectivity and cerebellar metabolism to the same extent in both groups. Group comparisons revealed that in CUD compared to controls, metabolism in nucleus accumbens was lower for the placebo and MPH measures, that MPH-induced increases in thalamic metabolism were blunted, and that enhanced negative connectivity between thalamus and accumbens in CUD was normalized by MPH (reducing negative connectivity). Our findings identify the thalamus as a target of MPH, which increased its metabolism and connectivity. The reduced metabolism in nucleus accumbens and the disrupted thalamo-accumbens connectivity (enhanced negative connectivity) in CUD is consistent with impaired reactivity of the brain reward's circuit. MPH's normalization of thalamo-accumbens connectivity (reduced negative connectivity) brings forth its potential therapeutic value in CUD, which merits investigation.

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Section: Concomitant Metabolic Changes (Mph-pl) In the Thalamic Seedssupporting

confidence: 52%

Methylphenidate’s effects on thalamic metabolism and functional connectivity in cannabis abusers and healthy controls

Demiral

Tomasi

Wiers

et al. 2018

Neuropsychopharmacol.

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“…Some further matching to fentanyl (S 13,17 = 0.91) and the other two members of this family (S 13,18 = 0.82, S 13,19 = 0.81) has not been examined yet. It is worth noting that (THC) shows a high matching to both cocaine (S 13,1 = 0.85) and MDMA (S 13,5 = 0.85) that has been well depicted in a recent study on the dopamine release and the reward effect caused by cannabis [60,61].…”

Section: Euclidean Distances/similaritiesmentioning

confidence: 56%

A Metric Space Approach on the Molecular vs. Chemical Similarity of Some Analgesic and Euphoric Compounds

Xenides

Fostiropoulou²,

Vlachos³

2019

Preprint

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<p>There is a relentless effort on gaining information on the reason why some compounds could cause similar effects though they are or not structural similar. That is the chemical similarity that plays an equally important role and we approach it via metric space theory on a set of analgesic drugs and euphoric compounds. The findings of the present study are in agreement to these obtained via traditional structural indices moreover are in accord with clinical findings.</p>

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“…While the dopaminergic response to an amphetamine challenge in abstinent mild cannabis dependents was shown to be analogous to that seen in matched controls in one study [83], another investigation found significantly blunted ventral striatal methylphenidate-induced dopaminergic activity (reduced decreases in distribution volumes of [ 11 C]-raclopride) in dependent cannabis users compared to controls [84]. Taken collectively, these studies suggest that a history of chronic cannabis use may produce alterations in the brain dopamine system, an effect that may not necessarily be driven by abnormalities in D2/3 receptor levels [87]. Nonetheless, at this time, it would appear that the severity of damage caused by long-term cannabis use may be of decreased magnitude relative to other drugs of abuse [88].…”

Section: The Dopaminergic System In Cannabis Use and Dependencementioning

confidence: 94%

A review of positron emission tomography studies exploring the dopaminergic system in substance use with a focus on tobacco as a co-variate

Thiruchselvam

Malik

Foll

2016

The American Journal of Drug and Alcohol Abuse

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With the evolving sensitivity of positron emission tomography (PET) and the emergence of novel radiotracers, greater insight has been gained into the dopaminergic system as it relates to substance use. In this review, we summarize PET investigations from the last ten years that explore the dopaminergic system in tobacco, alcohol, stimulant, opiates and cannabis addiction. In light of the prevalence of substance co-use, this review will also explore tobacco and other substance abuse co-morbidity on the dopaminergic system across study samples in the reviewed literature. In non-dependence, increased DA transmission following acute stimulant administration is a robust and consistent observation, but is less detectable following acute alcohol and tobacco, where it likely represents a conditioned effect mediating reward expectation. Chronic drug exposure is generally associated with a hypo-functioning pre-synaptic dopamine system and lower D2/D3 receptor availability relative to healthy controls. Emerging evidence also shows that stimulant use disorders in particular may also be associated with greater D3 receptor availability relative to controls. A defined role for the dopaminergic system in cannabis and opiate use has yet to be elucidated. Future work is also needed to delineate the potential interactive effects of tobacco and substance co-use on the dopaminergic system.

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Dopamine challenge reveals neuroadaptive changes in marijuana abusers

Cited by 4 publications

References 19 publications

Methylphenidate’s effects on thalamic metabolism and functional connectivity in cannabis abusers and healthy controls

Methylphenidate’s effects on thalamic metabolism and functional connectivity in cannabis abusers and healthy controls

A Metric Space Approach on the Molecular vs. Chemical Similarity of Some Analgesic and Euphoric Compounds

A review of positron emission tomography studies exploring the dopaminergic system in substance use with a focus on tobacco as a co-variate

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