Evidence map›Paper›PMID 31187152›Full record

Trial reportPsychopharmacology2019

Highs and lows of cannabinoid-dopamine interactions: effects of genetic variability and pharmacological modulation of catechol-O-methyl transferase on the acute response to delta-9-tetrahydrocannabinol in humans.

Mohini Ranganathan, Joao P De Aquino, Jose A Cortes-Briones, Rajiv Radhakrishnan, Brian Pittman, Savita Bhakta, Deepak C D'Souza

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Psychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00678730 (Pharmacogenetics of Cannabinoid Response), which is not on this map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 29% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT00678730 early_phase1completednot on this map

Pharmacogenetics of Cannabinoid Response

TypeinterventionalSponsorYale UniversityRan2007 to 2014Enrolled72ConditionsCOMT Gene PolymorphismArmsdelta 9 tetrahydrocannabinol
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Cannabis Pharmacogenomics: A Path to Personalized Medicine.Current issues in molecular biology · 2023
    Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Mohini Ranganathan *Department of Psychiatry, Yale University School of Medicine, 300 George St, Suite 901, New Haven, CT, 06510, USA. mohini.ranganathan@yale.edu.
Joao P De Aquino *Department of Psychiatry, Yale University School of Medicine, 300 George St, Suite 901, New Haven, CT, 06510, USA.
Jose A Cortes-BrionesDepartment of Psychiatry, Yale University School of Medicine, 300 George St, Suite 901, New Haven, CT, 06510, USA.
Rajiv RadhakrishnanDepartment of Psychiatry, Yale University School of Medicine, 300 George St, Suite 901, New Haven, CT, 06510, USA.
Brian PittmanDepartment of Psychiatry, Yale University School of Medicine, 300 George St, Suite 901, New Haven, CT, 06510, USA.
Savita BhaktaDepartment of Psychiatry, University of California San Diego School of Medicine, San Diego, 9500 Gilman Dr, La Jolla, CA, 92094, USA.
Deepak C D'SouzaDepartment of Psychiatry, Yale University School of Medicine, 300 George St, Suite 901, New Haven, CT, 06510, USA.
Yale University · USConnecticut Mental Health Center · USUniversity of California, San Diego · USVA Connecticut Healthcare System · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Schizophrenia Research FellowshipR25MH071584 · NIMH · YALE UNIVERSITY · PI Christopher John Pittenger · 2005 to 2026
$4.4M
NCATS NIH HHS UL1 TR001863NIH HHS R01 DA12382NIH HHS R25 MH071584
6 · The paper itself

Abstract

rationaleThe catechol-O-methyl transferase (COMT) enzyme has been implicated in determining dopaminergic tone and the effects of delta-9-tetrahydrocannabinol (THC) in the human brain.

objectiveThis study was designed to evaluate the effect of (1) a functional polymorphism and (2) acute pharmacological inhibition of COMT on the acute response to THC in humans.

methodsSub-study I: The effect of intravenous (IV) THC (0.05 mg/kg) was investigated in 74 healthy subjects genotyped for the COMT rs4680 (Val/Met) polymorphism in a 2-test-day double-blind, randomized, placebo-controlled study. Sub-study II: COMT rs4680 homozygous subjects (Val/Val and Met/Met) from sub-study I received the COMT enzyme inhibitor tolcapone (200 mg) followed by IV THC or placebo on two additional test days. Subjective, behavioral, and cognitive data were obtained periodically on each test day.

resultsSub-study I: Val/Val individuals were most sensitive to THC-induced attention and working memory deficits. In contrast, the psychotomimetic and subjective effects of THC were not influenced by COMT genotype. Sub-study II: Tolcapone reduced THC-induced working memory deficits, but not THC's psychotomimetic effects. Tolcapone and COMT genotype (met/met) were associated with an increased report of feeling "mellow."

conclusionsThe interaction between COMT rs4680 polymorphisms and tolcapone on the cognitive, but not on the psychotomimetic and overall subjective effects of THC, suggests that modulation of dopaminergic signaling may selectively influence specific cannabinoid effects in healthy individuals. The role of dopaminergic signaling in the cognitive effects of cannabinoids should be considered in drug development efforts targeting these effects. CLINICALTRIALS.GOV REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00678730?term=NCT00678730&rank=1 ClinicalTrials.gov Identifier: NCT00678730.

Indexed as

Administration, IntravenousAdolescentAdultAttentionBrainCannabinoid Receptor AgonistsCatechol O-MethyltransferaseCatechol O-Methyltransferase InhibitorsDopamineDouble-Blind MethodDronabinolFemaleGenetic VariationHumansMaleMemory, Short-TermCannabinoid Receptor AgonistsCatechol O-MethyltransferaseCatechol O-Methyltransferase InhibitorsCOMT protein, humanDopamineDronabinolCannabinoidCannabisCOMTDopamineTHCTolcapone

Identifiers

PMID31187152
OpenAlexW2950243730

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.