Cannabis Use DisorderNCT03718520
The Influence of in Utero Cannabis Exposure on Neonatal Brain Morphology and Structural Connectivity
An observational study of Cannabis Use Disorder and PREG1, run by University of Colorado, Denver at 2 sites in United States.
Trial summary
Cannabis is the most commonly used drug by women during pregnancy with an estimated prevalence of use in Colorado of 5.7%. THC and its metabolites freely cross the placenta and blood-brain barrier to bind with cannabinoid receptors, disrupting the endogenous cannabinoid signaling system during a critical period of… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cannabis Use Disorder, PREG1, Drug Use
- How many people
- 168 participants
- Where
- 2 sitesUnited States
- Study dates
- 7 Nov 2018to 31 Mar 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Adult, Older adult
Study population: This will be an observational, pre-birth prospective pilot study of 110 mother-infant pairs (50 with prenatal cannabis exposure and 60 unexposed pairs) who deliver at two academic medical centers in the Denver Metro area of Colorado (Denver Health Medical Center and the University of Colorado Hospital at Anschutz. Unexposed controls will be frequency matched to exposed cases by maternal education level. To isolate the influence of cannabis exposure, mothers using tobacco, alcohol or other drugs during pregnancy will be excluded.
Who may be able to join
- pregnant women who are receiving prenatal care at the University of Colorado Hospital at Anschutz (UCH) or Denver Health Medical Center.
- maternal positive urine toxicology screen for cannabis at any clinical prenatal visit or self-report of cannabis during pregnancy at a clinical visit
- greater than ≥ 28 weeks gestation,
- aged ≥18 years,
- expecting a singleton birth,
- live in Colorado, and plan to deliver at UCH or Denver Health Medical Center .
- Inclusion criteria for unexposed controls will be identical to that of exposed cases with the exception that they cannot have a positive toxicology screen for cannabis or self-reported cannabis use during pregnancy.
Who cannot join
- use of tobacco, alcohol or other drugs during pregnancy,
- serious chronic diseases (cancer, psychiatric diseases, steroid-dependent asthma, pre-existent diabetes mellitus of any kind),
- mothers who subsequently experience a fetal death or deliver a premature infant (< 37 weeks of gestation).
- Postnatal exclusions will include failure to collect meconium samples at birth, infant neurological trauma, other neurological conditions in the infant (e.g., epilepsy),
- suspicion of metal in body or other MRI contraindications in either the mother or infant.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Colorado Hospital
Aurora, Colorado, 80045
Denver Health Medical Center
Denver, Colorado, 80204
About this study
Cannabis is the most commonly used drug by women during pregnancy with an estimated prevalence of use in Colorado of 5.7%. THC and its metabolites freely cross the placenta and blood-brain barrier to bind with cannabinoid receptors, disrupting the endogenous cannabinoid signaling system during a critical period of development of cortical circuitry structure and function. The density of cannabinoid receptors in the developing brain is high, especially in the limbic areas and prefrontal lobes. Research in animal models suggests synaptic plasticity in the prefrontal lobes as well the amygdala and hippocampus are impacted by the prenatal cannabis exposure; regions associated with both cognitive and emotional control, thus influencing long-term deficiencies in attention and impulsivity. This pilot study will collect preliminary data on the structural impact of in utero cannabis exposure on region-specific morphology and structural connectivity of white matter tracts that connect to the prefrontal lobes and the limbic regions shortly after birth, before confounding by the postnatal environment becomes a major influence.
Read the detailed description
Cannabis is the most commonly used psychoactive substance among pregnant women, with an estimated prevalence of use between 5 to 20% in in the United States. Little is known about the neurodevelopmental consequences for the fetus, particularly in the context of contemporary cannabis use patterns including high potency strains, cannabinoids and novel routes of administration. Colorado leads the nation in implementation of legalized medical and retail marijuana. Coupled with a growing pro-marijuana advocacy movement, marijuana may be perceived as "safe" to use during pregnancy. The local actions of endocannabinoids are in place in the placenta during fetal brain development and THC and its metabolites freely pass the placental barrier and the fetal blood-brain barrier. Furthermore, cannabinoid receptors appear to be more widespread in the fetal and neonatal prefrontal cortex (PFC) and the limbic areas (the amygdala and hippocampus) than in the adult brain, thus the in utero period may be a sensitive period of human brain development during which exogenous cannabinoids could permanently alter neurodevelopmental processes. Human epidemiologic studies across diverse populations have reported an emerging theme of deficiencies related to impulse control and executive functioning among offspring with in utero exposure to cannabis starting in adolescence. Only rudimentary aspects of executive function are present in infants, thus evidence of an impact during infancy and the toddler years is sparse, inconsistent and confounded by the postnatal environment (i.e., daycare, caregiver functioning). Research is needed to evaluate the proximal impact of in utero cannabis exposure on robust metrics of neonatal brain morphology and structural integrity of white matter tracts that connect to the PFC and the limbic regions before the influence of postnatal exposures become a major confounding influence.
To address this challenge, a pilot prospective pre-birth cohort study will be conducted to investigate the impact of chronic in utero cannabis exposure by enrolling 110 mother-infant pairs (50 exposed and 60 unexposed controls) for a neonate neuroimaging scan within 2 weeks after birth. Chronic in utero cannabis exposure will be quantified using ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS) of neonatal meconium. The associations between in utero cannabis exposure and neural morphological outcomes will be examined by structural MRI and diffusion tensor imaging (DTI). The central hypothesis is that in utero cannabis exposure will be associated with alterations in grey and white matter development in the prefrontal lobe and its connectivity to limbic regions.
Specific Aim 1: To determine the magnitude of the association between in utero exposure to cannabis and neonate brain morphology and structural connectivity.
Hypothesis: In utero exposure to cannabis (assessed by THC metabolites in meconium) will be associated with the following neonate brain structural outcomes: (1) Grey matter: reduced volume in the PFC and limbic regions (i.e. the amygdala, hippocampus); (2) White matter: reduced structural integrity (assessed by fractional anisotropy) of white matter tracts that connect to the PFC and the limbic regions including the uncinate fasciculus and the cingulum bundle. The associations will be independent of other maternal substance use (i.e. tobacco), postnatal feeding practices (i.e. breastfeeding), socio-demographic characteristics and maternal mental health.
- Conditions
- Cannabis Use Disorder, PREG1, Drug Use, Fetal Exposure During Pregnancy, Neurodevelopmental Abnormality
- Being tested
- no intervention, this is a purely observational study
- Keywords
- cannabis, fetal programming, pregnancy, infant neuroimaging
- Medical subject headings
- Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
no intervention, this is a purely observational studyOther
No intervention
| Study group | Role | What they receive |
|---|---|---|
| prenatal exposed to cannabis | 50 mother-infant pairs with self-reported maternal chronic cannabis use during pregnancy Receives: Other: no intervention, this is a purely observational study | |
| prenatal not-exposed to cannabis | 60 mother-infant pairs with no self-reported maternal cannabis use during pregnancy Receives: Other: no intervention, this is a purely observational study |
What is being measured
The primary outcome is the main question the study is designed to answer.
region specific grey matter volume (mm^2) in the PFC and limbic regions
region specific volume (mm^2)
Measured: 2 weeks postnatal age
structural integrity measured by fractional anisotrophy of white matter tracks that connect the PFC and limbic regions
mean fractional anisotrophy
Measured: 2 weeks postnatal age
Secondary outcomes (1)
Negative affectivity based on a subscale from the Infant Behavioral Questionnaire (Rothbart, 1981)
Four subscales on the IBQ-R will be combined to form a negative affectivity scale including scales of Sadness, Distress to Limitations, Fear, and Falling Reactivity/Rate of Recovery from Distress.
Measured: 1 year postpartum
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2018
- Study start7 Nov 2018
- Primary completion31 Mar 2020
- Study completion31 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cannabis Use DisorderStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Tessa Crume, PhD, MSPH, Principal investigator, University of Colorado, Colorado School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03718520
- Sponsor's protocol ID
- 18-0004
- Other IDs
- R21DA043833
- Status last verified
- Oct 2021
- First submitted
- 22 Oct 2018
- Last updated
- 27 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: A completely de-identified dataset will be created and may be shared upon PI-agreement ad development of data sharing agreements.
Publications
Crume TL, Kim P, Shen X, Iisa E, Huestis MA, Fried P, Stickrath EH, Conageski C, Phipers JE, Kinney G, Sempio C, Klawitter J, Dufford AJ. In utero chronic cannabis exposure is associated with lower total brain volume in the first month of postnatal life. Am J Drug Alcohol Abuse. 2025;51(4):458-470. doi: 10.1080/00952990.2025.2506112. Epub 2025 Jul 23.
PubMed 40700630
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of in Utero Cannabis Exposure on Neonatal Brain Morphology and Structural Connectivity
- ClinicalTrials.gov ID
- NCT03718520
- Acronym / sponsor ID
- 18-0004
- Conditions
- Cannabis Use Disorder, PREG1, Drug Use, Fetal Exposure During Pregnancy, Neurodevelopmental Abnormality
- Keywords
- cannabis, fetal programming, pregnancy, infant neuroimaging
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 168 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 7 Nov 2018 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 24 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cannabis is the most commonly used drug by women during pregnancy with an estimated prevalence of use in Colorado of 5.7%. THC and its metabolites freely cross the placenta and blood-brain barrier to bind with cannabinoid receptors, disrupting the endogenous cannabinoid signaling system during a critical period of development of cortical circuitry structure and function. The density of cannabinoid receptors in the developing brain is high, especially in the limbic areas and prefrontal lobes. Research in animal models suggests synaptic plasticity in the prefrontal lobes as well the amygdala and hippocampus are impacted by the prenatal cannabis exposure; regions associated with both cognitive and emotional control, thus influencing long-term deficiencies in attention and impulsivity. This pilot study will collect preliminary data on the structural impact of in utero cannabis exposure on region-specific morphology and structural connectivity of white matter tracts that connect to the prefrontal lobes and the limbic regions shortly after birth, before confounding by the postnatal environment becomes a major influence.
Detailed description
Cannabis is the most commonly used psychoactive substance among pregnant women, with an estimated prevalence of use between 5 to 20% in in the United States. Little is known about the neurodevelopmental consequences for the fetus, particularly in the context of contemporary cannabis use patterns including high potency strains, cannabinoids and novel routes of administration. Colorado leads the nation in implementation of legalized medical and retail marijuana. Coupled with a growing pro-marijuana advocacy movement, marijuana may be perceived as "safe" to use during pregnancy. The local actions of endocannabinoids are in place in the placenta during fetal brain development and THC and its metabolites freely pass the placental barrier and the fetal blood-brain barrier. Furthermore, cannabinoid receptors appear to be more widespread in the fetal and neonatal prefrontal cortex (PFC) and the limbic areas (the amygdala and hippocampus) than in the adult brain, thus the in utero period may be a sensitive period of human brain development during which exogenous cannabinoids could permanently alter neurodevelopmental processes. Human epidemiologic studies across diverse populations have reported an emerging theme of deficiencies related to impulse control and executive functioning among offspring with in utero exposure to cannabis starting in adolescence. Only rudimentary aspects of executive function are present in infants, thus evidence of an impact during infancy and the toddler years is sparse, inconsistent and confounded by the postnatal environment (i.e., daycare, caregiver functioning). Research is needed to evaluate the proximal impact of in utero cannabis exposure on robust metrics of neonatal brain morphology and structural integrity of white matter tracts that connect to the PFC and the limbic regions before the influence of postnatal exposures become a major confounding influence.
To address this challenge, a pilot prospective pre-birth cohort study will be conducted to investigate the impact of chronic in utero cannabis exposure by enrolling 110 mother-infant pairs (50 exposed and 60 unexposed controls) for a neonate neuroimaging scan within 2 weeks after birth. Chronic in utero cannabis exposure will be quantified using ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS) of neonatal meconium. The associations between in utero cannabis exposure and neural morphological outcomes will be examined by structural MRI and diffusion tensor imaging (DTI). The central hypothesis is that in utero cannabis exposure will be associated with alterations in grey and white matter development in the prefrontal lobe and its connectivity to limbic regions.
Specific Aim 1: To determine the magnitude of the association between in utero exposure to cannabis and neonate brain morphology and structural connectivity.
Hypothesis: In utero exposure to cannabis (assessed by THC metabolites in meconium) will be associated with the following neonate brain structural outcomes: (1) Grey matter: reduced volume in the PFC and limbic regions (i.e. the amygdala, hippocampus); (2) White matter: reduced structural integrity (assessed by fractional anisotropy) of white matter tracts that connect to the PFC and the limbic regions including the uncinate fasciculus and the cingulum bundle. The associations will be independent of other maternal substance use (i.e. tobacco), postnatal feeding practices (i.e. breastfeeding), socio-demographic characteristics and maternal mental health.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| prenatal exposed to cannabis | – | Other: no intervention, this is a purely observational study50 mother-infant pairs with self-reported maternal chronic cannabis use during pregnancy |
| prenatal not-exposed to cannabis | – | Other: no intervention, this is a purely observational study60 mother-infant pairs with no self-reported maternal cannabis use during pregnancy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Age groups
- Adult, Older adult
- Study population
- This will be an observational, pre-birth prospective pilot study of 110 mother-infant pairs (50 with prenatal cannabis exposure and 60 unexposed pairs) who deliver at two academic medical centers in the Denver Metro area of Colorado (Denver Health Medical Center and the University of Colorado Hospital at Anschutz. Unexposed controls will be frequency matched to exposed cases by maternal education level. To isolate the influence of cannabis exposure, mothers using tobacco, alcohol or other drugs during pregnancy will be excluded.
Key inclusion criteria (7 listed)
- pregnant women who are receiving prenatal care at the University of Colorado Hospital at Anschutz (UCH) or Denver Health Medical Center.
- maternal positive urine toxicology screen for cannabis at any clinical prenatal visit or self-report of cannabis during pregnancy at a clinical visit
- greater than ≥ 28 weeks gestation,
- aged ≥18 years,
- expecting a singleton birth,
Key exclusion criteria (5 listed)
- use of tobacco, alcohol or other drugs during pregnancy,
- serious chronic diseases (cancer, psychiatric diseases, steroid-dependent asthma, pre-existent diabetes mellitus of any kind),
- mothers who subsequently experience a fetal death or deliver a premature infant (< 37 weeks of gestation).
- Postnatal exclusions will include failure to collect meconium samples at birth, infant neurological trauma, other neurological conditions in the infant (e.g., epilepsy),
- suspicion of metal in body or other MRI contraindications in either the mother or infant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| no intervention, this is a purely observational studyNo intervention | Other | prenatal exposed to cannabis, prenatal not-exposed to cannabis |
Primary outcome
region specific grey matter volume (mm^2) in the PFC and limbic regions
Time frame: 2 weeks postnatal age
region specific volume (mm^2)
structural integrity measured by fractional anisotrophy of white matter tracks that connect the PFC and limbic regions
Time frame: 2 weeks postnatal age
mean fractional anisotrophy
1 secondary outcome
Negative affectivity based on a subscale from the Infant Behavioral Questionnaire (Rothbart, 1981)
Time frame: 1 year postpartum
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2021.
- Derived from this study: PubMed 40700630Crume TL, Kim P, Shen X, Iisa E, Huestis MA, Fried P, Stickrath EH, Conageski C, Phipers JE, Kinney G, Sempio C, Klawitter J, Dufford AJ. In utero chronic cannabis exposure is associated with lower total brain volume in the first month of postnatal life. Am J Drug Alcohol Abuse. 2025;51(4):458-470. doi: 10.1080/00952990.2025.2506112. Epub 2025 Jul 23.
- Individual participant dataSharing planned: No. A completely de-identified dataset will be created and may be shared upon PI-agreement ad development of data sharing agreements.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tessa Crume, PhD, MSPH principal investigator
University of Colorado, Colorado School of Public Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cannabis Use Disorder and PREG1, run by University of Colorado, Denver at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
region specific grey matter volume (mm^2) in the PFC and limbic regions (time frame: 2 weeks postnatal age). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03718520, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2021.