Trial Outcomes & Findings for Cannabidiol in Youth Alcohol Use Disorder (NCT NCT05317546)

Last Updated: 2025-08-14

Results Overview

Using magnetic resonance spectroscopy and a within-subjects design, we measured Concentrations of Glx (i.e., glutamate + glutamine) levels in the anterior cingulate cortex in adolescents during cannabidiol (600mg) or placebo administration. Values provided are absolute values (mmol/kg) measured 3 hours after medication administration. Due to complexities of this method, "normal" levels of Glx are not known; thus, we cannot make conclusions about the meaning of "higher" or "lower" glutamate levels when comparing cannabidiol to placebo.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Changes 3 hours after administration of 600mg CBD vs. placebo

Results posted on

2025-08-14

Participant Flow

Participants were recruited from September 2022 to April 2024, and data collection was completed in June 2024. Participants were recruited using a mix of approaches, including social media campaigns and in-person events. All participants completed a centralized intake process for youth substance use studies at the Medical University of South Carolina to determine eligibility before consenting for this specific study.

All participants that were eligible and enrolled in the study (N= 36) completed randomized to a group.

Participant milestones

Participant milestones
Measure	Cannabidiol, Then Placebo In counterbalanced order, 19 youth (ages 17-22) were randomized to receive 600mg of cannabidiol before placebo three hours before a neuroimaging and behavioral assessment paradigm, separated by an approximate 18-day washout period.	Placebo, Then Cannabidiol In counterbalanced order, 17 youth (ages 17-22) were randomized to receive 600mg of placebo before cannabidiol three hours before a neuroimaging and behavioral assessment paradigm, separated by an approximate 18-day washout period.
First Allocation STARTED	19	17
First Allocation COMPLETED	19	17
First Allocation NOT COMPLETED	0	0
First Wash-Out Period STARTED	19	17
First Wash-Out Period COMPLETED	18	15
First Wash-Out Period NOT COMPLETED	1	2
Second Allocation STARTED	18	15
Second Allocation COMPLETED	18	15
Second Allocation NOT COMPLETED	0	0
Second Wash-out Period STARTED	18	15
Second Wash-out Period COMPLETED	18	14
Second Wash-out Period NOT COMPLETED	0	1
Follow-Up STARTED	18	14
Follow-Up COMPLETED	18	14
Follow-Up NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cannabidiol, Then Placebo In counterbalanced order, 19 youth (ages 17-22) were randomized to receive 600mg of cannabidiol before placebo three hours before a neuroimaging and behavioral assessment paradigm, separated by an approximate 18-day washout period.	Placebo, Then Cannabidiol In counterbalanced order, 17 youth (ages 17-22) were randomized to receive 600mg of placebo before cannabidiol three hours before a neuroimaging and behavioral assessment paradigm, separated by an approximate 18-day washout period.
First Wash-Out Period Withdrawal by Subject	1	2

Baseline Characteristics

Cannabidiol in Youth Alcohol Use Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cannabidiol, Then Placebo n=19 Participants In counterbalanced order, 19 youth (ages 17-22) were randomized to receive 600mg of cannabidiol before placebo three hours before a neuroimaging and behavioral assessment paradigm, separated by an approximate 18-day washout period.	Placebo, Then Cannabidiol n=17 Participants In counterbalanced order, 17 youth (ages 17-22) were randomized to receive 600mg of placebo before cannabidiol three hours before a neuroimaging and behavioral assessment paradigm, separated by an approximate 18-day washout period.	Total n=36 Participants Total of all reporting groups
Age, Continuous	20.4 years STANDARD_DEVIATION 1.5 • n=5 Participants	20.5 years STANDARD_DEVIATION 1.8 • n=7 Participants	20.5 years STANDARD_DEVIATION 1.5 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	16 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants	14 Participants n=7 Participants	31 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants	17 participants n=7 Participants	36 participants n=5 Participants

PRIMARY outcome

Timeframe: Changes 3 hours after administration of 600mg CBD vs. placebo

Outcome measures

Outcome measures
Measure	Cannabidiol (600mg) n=34 Participants Outcomes when participants were given cannabidiol (600mg)	Placebo n=35 Participants Outcomes when participants were given matched placebo
Concentrations of Glx (i.e., Glutamate + Glutamine)	18.76 mmol/kg Standard Deviation 0.98	18.57 mmol/kg Standard Deviation 1.15

PRIMARY outcome

Timeframe: Changes 3 hours after administration of 600mg CBD vs. placebo

Using magnetic resonance spectroscopy and a within-subjects design, we measured GABA+ (GABA plus macromolecules) levels in the anterior cingulate cortex in adolescents during cannabidiol (600mg) or placebo administration. Values provided are absolute values (mmol/kg) measured 3 hours after medication administration. Due to complexities of this method, "normal" levels of GABA are not known; thus, we cannot make conclusions about the meaning of "higher" or "lower" GABA levels when comparing cannabidiol to placebo.

Outcome measures

Outcome measures
Measure	Cannabidiol (600mg) n=34 Participants Outcomes when participants were given cannabidiol (600mg)	Placebo n=35 Participants Outcomes when participants were given matched placebo
GABA+	4.25 mmol/kg Standard Deviation 0.26	4.22 mmol/kg Standard Deviation 0.34

PRIMARY outcome

Timeframe: Changes 3 hours after administration of 600mg CBD vs. placebo

Population: 33 participants had complete, usable data (n=3 dropped out before visit 2; n=1 without MRI data at visit 2; n= 1 with head motion at visit 1).

Assessing the change in neural reactivity to alcohol cues after each round of medication: Cannabidiol vs. placebo. Cue reactivity is a type of learned response which is observed in individuals who use substances (e.g., alcohol) and involves significant physiological reactions to presentations of substance-related stimuli (i.e., alcohol images) in comparison to neutral images (e.g., non-alcoholic beverages ) measured by BOLD (Blood Oxygen Level-Dependent response). ROIs were (left and right hemisphere): amygdala, caudate, insula, nucleus accumbens, and putamen. The mean Z-statistic within each ROI mask is reported. A Z-score of 0 represents the population mean (e.g., no activation), where higher absolute Z-scores indicate greater evidence of activation (positive or negative) in the ROI compared to baseline. Z-scores do not have inherent clinical thresholds. Higher Z-scores generally reflect stronger task-related BOLD signal changes.

Outcome measures

Outcome measures
Measure	Cannabidiol (600mg) n=33 Participants Outcomes when participants were given cannabidiol (600mg)	Placebo n=33 Participants Outcomes when participants were given matched placebo
Alcohol Cue Reactivity Neural Activation Anterior Cingulate Cortex	1.02 Z-score Standard Deviation 1.58	0.87 Z-score Standard Deviation 1.37
Alcohol Cue Reactivity Neural Activation Nucleus Accumbens (L)	0.62 Z-score Standard Deviation 0.85	0.35 Z-score Standard Deviation 1.28
Alcohol Cue Reactivity Neural Activation Nucleus Accumbens (R)	0.53 Z-score Standard Deviation 0.91	0.56 Z-score Standard Deviation 1.26
Alcohol Cue Reactivity Neural Activation Amygdala (L)	0.66 Z-score Standard Deviation 1.23	0.55 Z-score Standard Deviation 0.92
Alcohol Cue Reactivity Neural Activation Amygdala (R)	0.68 Z-score Standard Deviation 1.10	0.47 Z-score Standard Deviation 1.09
Alcohol Cue Reactivity Neural Activation Caudate (L)	0.29 Z-score Standard Deviation 1.00	0.24 Z-score Standard Deviation 0.84
Alcohol Cue Reactivity Neural Activation Caudate (R)	0.51 Z-score Standard Deviation 1.00	0.35 Z-score Standard Deviation 1.11
Alcohol Cue Reactivity Neural Activation Insula (L)	0.10 Z-score Standard Deviation 1.37	0.33 Z-score Standard Deviation 1.24
Alcohol Cue Reactivity Neural Activation Insula (R)	0.12 Z-score Standard Deviation 1.23	0.30 Z-score Standard Deviation 1.24
Alcohol Cue Reactivity Neural Activation Putamen (L)	0.40 Z-score Standard Deviation 1.16	0.42 Z-score Standard Deviation 1.12
Alcohol Cue Reactivity Neural Activation Putamen (R)	0.42 Z-score Standard Deviation 1.14	0.37 Z-score Standard Deviation 1.16

PRIMARY outcome

Timeframe: Changes 2 hours after administration of 600mg CBD vs. placebo

Population: Some participants did not have usable data based on data quality markers.

All participants underwent an in vivo, olfactory alcohol cue exposure procedure. Participants smelled water followed by the participant's preferred beverage containing alcohol and apple juice in a counterbalanced order for three minutes each, with a three-minute rest period in between each liquid. The contents were poured into a cup in the participant's presence. During the task, electrocardiogram data were collected and used to create the heart rate variability (HRV) outcome related to the Sympathetic: Vagal ratio, which is the ratio of low-frequency to high-frequency power, derived from spectral HRV analysis. Higher values suggest increased sympathetic activity or reduced vagal activity.

Outcome measures

Outcome measures
Measure	Cannabidiol (600mg) n=32 Participants Outcomes when participants were given cannabidiol (600mg)	Placebo n=32 Participants Outcomes when participants were given matched placebo
Heart Rate Variability	0.84 frequency ratio Standard Deviation 0.37	0.81 frequency ratio Standard Deviation 0.41

PRIMARY outcome

Timeframe: Changes 2 hours after administration of 600mg CBD vs. placebo

All participants underwent an in vivo, olfactory alcohol cue exposure procedure. Participants smelled water followed by the participant's preferred beverage containing alcohol and apple juice in a counterbalanced order for three minutes each, with a three-minute rest period in between each liquid. The contents were poured into a cup in the participant's presence. After each beverage exposure, self-reported alcohol craving was collected via the PhenX Toolkit Alcohol Urges Questionnaire (AUQ). The AUQ consists of eight statements about the participant's feelings and thoughts about drinking as they are completing the questionnaire (i.e., right now). The participant was asked to respond to each statement about alcohol craving via a 7-item Likert scale ranging from "strongly disagree" to "strongly agree" with a scare range of 8 to 56 where higher scores represent higher alcohol craving.

Outcome measures

Outcome measures
Measure	Cannabidiol (600mg) n=34 Participants Outcomes when participants were given cannabidiol (600mg)	Placebo n=35 Participants Outcomes when participants were given matched placebo
PhenX Toolkit Alcohol Urges Questionnaire Alcohol Cue	23.18 score on a scale Standard Deviation 11.73	21.40 score on a scale Standard Deviation 11.22
PhenX Toolkit Alcohol Urges Questionnaire Apple Juice Cue	18.56 score on a scale Standard Deviation 9.65	17.63 score on a scale Standard Deviation 10.26
PhenX Toolkit Alcohol Urges Questionnaire Water Cue	16.47 score on a scale Standard Deviation 7.64	15.50 score on a scale Standard Deviation 7.14
PhenX Toolkit Alcohol Urges Questionnaire Baseline	16.18 score on a scale Standard Deviation 7.30	14.94 score on a scale Standard Deviation 6.80

Adverse Events

Cannabidiol (600mg)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Cannabidiol (600mg) n=34 participants at risk Adverse events assessed after the acute Cannabidiol (600mg) administration and washout period (\~18 days).	Placebo n=35 participants at risk Adverse events assessed after the acute placebo administration and washout period (\~18 days).
Eye disorders Conjunctivitis	2.9% 1/34 • Number of events 1 • At least 36 days (18-days for the first wash-out period and 18-days for the second wash-out period before follow-up) Participants were asked about adverse events at every visit. Medication allocation visits (visit 1 and visit 2) adverse events were assessed by a medical clinician. At the follow-up visit (visit 3), they were assessed by study staff.	0.00% 0/35 • At least 36 days (18-days for the first wash-out period and 18-days for the second wash-out period before follow-up) Participants were asked about adverse events at every visit. Medication allocation visits (visit 1 and visit 2) adverse events were assessed by a medical clinician. At the follow-up visit (visit 3), they were assessed by study staff.
Gastrointestinal disorders Gastroenteritis	0.00% 0/34 • At least 36 days (18-days for the first wash-out period and 18-days for the second wash-out period before follow-up) Participants were asked about adverse events at every visit. Medication allocation visits (visit 1 and visit 2) adverse events were assessed by a medical clinician. At the follow-up visit (visit 3), they were assessed by study staff.	2.9% 1/35 • Number of events 1 • At least 36 days (18-days for the first wash-out period and 18-days for the second wash-out period before follow-up) Participants were asked about adverse events at every visit. Medication allocation visits (visit 1 and visit 2) adverse events were assessed by a medical clinician. At the follow-up visit (visit 3), they were assessed by study staff.
General disorders Dry Mouth	2.9% 1/34 • Number of events 1 • At least 36 days (18-days for the first wash-out period and 18-days for the second wash-out period before follow-up) Participants were asked about adverse events at every visit. Medication allocation visits (visit 1 and visit 2) adverse events were assessed by a medical clinician. At the follow-up visit (visit 3), they were assessed by study staff.	0.00% 0/35 • At least 36 days (18-days for the first wash-out period and 18-days for the second wash-out period before follow-up) Participants were asked about adverse events at every visit. Medication allocation visits (visit 1 and visit 2) adverse events were assessed by a medical clinician. At the follow-up visit (visit 3), they were assessed by study staff.
Respiratory, thoracic and mediastinal disorders Pharyngitis	0.00% 0/34 • At least 36 days (18-days for the first wash-out period and 18-days for the second wash-out period before follow-up) Participants were asked about adverse events at every visit. Medication allocation visits (visit 1 and visit 2) adverse events were assessed by a medical clinician. At the follow-up visit (visit 3), they were assessed by study staff.	2.9% 1/35 • Number of events 1 • At least 36 days (18-days for the first wash-out period and 18-days for the second wash-out period before follow-up) Participants were asked about adverse events at every visit. Medication allocation visits (visit 1 and visit 2) adverse events were assessed by a medical clinician. At the follow-up visit (visit 3), they were assessed by study staff.

Additional Information

Dr. Lindsay Squeglia

Medical University of South Carolina

Phone: 843-792-5454

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place