Trial Outcomes & Findings for Using Imaging to Assess Effects of THC on Brain Activity (NCT NCT03655717)

Last Updated: 2022-07-28

Results Overview

Subjects completed the N-back task before and after receiving a combination of active dronabinol or placebo dronabinol and active ethanol or placebo ethanol. During the task, the fNIRS device was used to capture change in concentration of oxygenated hemoglobin to assess prefrontal brain activity. Outcomes reflect average change from baseline in HbO concentration over pre-dose scan and average change from baseline in HbO concentration over post-dose scan (expected peak intoxication).

Recruitment status

COMPLETED

Study phase

Target enrollment

316 participants

Primary outcome timeframe

The first Nback scan session was run before dosing (t ≈ -35min). Drug was administered (t = 0min). The second Nback scan session was run at the time of expected peak pharmacokinetic effect (t ≈ 100min). Each scan session was six minutes in duration.

Results posted on

2022-07-28

Participant Flow

Participants were recruited by study staff at the MGH Center for Addiction Medicine through advertising by email, web and bulletin board announcements posted within the local site network community.

A screening visit took place before randomization. After randomization, phase 2A completed two visits and phase 2B completed four visits. Washout achieved with at least one week between visits. Participant dropout affected by the COVID-19 pandemic. Due to character limit, sequences coded as follows: A: Placebo Dronabinol B: Dronabinol C: Placebo Dronabinol \& Placebo Ethanol D: Dronabinol \& Placebo Ethanol E: Placebo Dronabinol \& Ethanol F: Dronabinol \& Ethanol

Participant milestones

Participant milestones
Measure	Phase 2A: AB Placebo then Dronabinol Over two visits, Phase 2A participants were assigned in a random order to a single dose of either dronabinol and placebo. Visits were approximately one week apart.	Phase 2A: BA Dronabinol then Placebo	Phase 2B: CDEF Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol, then Dronabinol and Ethanol Phase 2B was a randomized, double-blind, 4-treatment, 4-period, crossover study with THC or placebo administration and ethanol or placebo administration. Over four visits participants were assigned in a random order to each of dronabinol and ethanol, dronabinol and placebo ethanol, placebo dronabinol and ethanol, or placebo dronabinol and placebo ethanol. Visits were approximately one week apart.	Phase 2B: CDFE Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Ethanol	Phase 2B: CEFD Placebo Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol, then Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol	Phase 2B: CFDE Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol	Phase 2B: CFED Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol	Phase 2B: DCEF Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol, then Dronabinol and Ethanol	Phase 2B: DCFE Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Ethanol	Phase 2B: DECF Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol	Phase 2B: DEFC Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol	Phase 2B: DFCE Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol	Phase 2B: DFEC Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol	Phase 2B: ECDF Placebo Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol	Phase 2B: ECFD Placebo Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol	Phase 2B: EDCF Placebo Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol	Phase 2B: EDFC Placebo Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol	Phase 2B: EFCD Placebo Dronabinol and Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Placebo Ethanol	Phase 2B: EFDC Placebo Dronabinol and Ethanol, then Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Placebo Ethanol	Phase 2B: FCDE Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol	Phase 2B: FCED Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol	Phase 2B: FDCE Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol	Phase 2B: FDEC Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol	Phase 2B: FECD Dronabinol and Ethanol, then Placebo Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Placebo Ethanol	Phase 2B: FEDC Dronabinol and Ethanol, then Placebo Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Placebo Ethanol
Overall Study STARTED	70	68	2	1	3	3	3	2	1	1	3	2	3	2	2	2	2	3	3	2	3	2	4	1	2
Overall Study COMPLETED	60	56	1	0	1	0	2	0	0	1	1	2	0	2	1	2	2	2	2	2	2	0	2	0	2
Overall Study NOT COMPLETED	10	12	1	1	2	3	1	2	1	0	2	0	3	0	1	0	0	1	1	0	1	2	2	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 2A: AB Placebo then Dronabinol Over two visits, Phase 2A participants were assigned in a random order to a single dose of either dronabinol and placebo. Visits were approximately one week apart.	Phase 2A: BA Dronabinol then Placebo	Phase 2B: CDEF Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol, then Dronabinol and Ethanol Phase 2B was a randomized, double-blind, 4-treatment, 4-period, crossover study with THC or placebo administration and ethanol or placebo administration. Over four visits participants were assigned in a random order to each of dronabinol and ethanol, dronabinol and placebo ethanol, placebo dronabinol and ethanol, or placebo dronabinol and placebo ethanol. Visits were approximately one week apart.	Phase 2B: CDFE Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Ethanol	Phase 2B: CEFD Placebo Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol, then Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol	Phase 2B: CFDE Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol	Phase 2B: CFED Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol	Phase 2B: DCEF Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol, then Dronabinol and Ethanol	Phase 2B: DCFE Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Ethanol	Phase 2B: DEFC Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol	Phase 2B: DFEC Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol	Phase 2B: ECFD Placebo Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol	Phase 2B: EFCD Placebo Dronabinol and Ethanol, then Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Placebo Ethanol	Phase 2B: EFDC Placebo Dronabinol and Ethanol, then Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Placebo Ethanol	Phase 2B: FCED Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol	Phase 2B: FDCE Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol	Phase 2B: FDEC Dronabinol and Ethanol, then Dronabinol and Placebo Ethanol, then Placebo Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol	Phase 2B: FECD Dronabinol and Ethanol, then Placebo Dronabinol and Ethanol, then Placebo Dronabinol and Placebo Ethanol, then Dronabinol and Placebo Ethanol
Overall Study Withdrawal by Subject	4	8	1	0	1	3	1	2	0	1	3	1	1	0	1	2	1	1
Overall Study Physician Decision	3	3	0	0	0	0	0	0	1	0	0	0	0	1	0	0	1	0
Overall Study Lost to Follow-up	3	1	0	1	1	0	0	0	0	1	0	0	0	0	0	0	0	0

Baseline Characteristics

Using Imaging to Assess Effects of THC on Brain Activity

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 2A - Total Sample n=138 Participants In a double-blind placebo-controlled, random order cross-over study of single dose dronabinol, participants received dronabinol or identical placebo on two separate study visits in randomized order.	Phase 2B - Total Sample n=52 Participants In a randomized, double-blind, 4-treatment, 4-period, crossover study with THC or placebo administration and ethanol or placebo administration, participants were randomly assigned to 1 of 4 sequences and received each of the following treatments: placebo dronabinol + placebo ethanol, placebo dronabinol + ethanol, dronabinol + placebo ethanol, \& dronabinol + ethanol.	Total n=190 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	138 Participants n=5 Participants	52 Participants n=7 Participants	190 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	24.9 years STANDARD_DEVIATION 6.49 • n=5 Participants	25.6 years STANDARD_DEVIATION 5.16 • n=7 Participants	25.1 years STANDARD_DEVIATION 6.15 • n=5 Participants
Sex: Female, Male Female	67 Participants n=5 Participants	27 Participants n=7 Participants	94 Participants n=5 Participants
Sex: Female, Male Male	71 Participants n=5 Participants	25 Participants n=7 Participants	96 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	28 Participants n=5 Participants	10 Participants n=7 Participants	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	107 Participants n=5 Participants	41 Participants n=7 Participants	148 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	11 Participants n=5 Participants	2 Participants n=7 Participants	13 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	16 Participants n=5 Participants	6 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) White	93 Participants n=5 Participants	36 Participants n=7 Participants	129 Participants n=5 Participants
Race (NIH/OMB) More than one race	12 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment United States	138 participants n=5 Participants	52 participants n=7 Participants	190 participants n=5 Participants

PRIMARY outcome

Timeframe: The first Nback scan session was run before dosing (t ≈ -35min). Drug was administered (t = 0min). The second Nback scan session was run at the time of expected peak pharmacokinetic effect (t ≈ 100min). Each scan session was six minutes in duration.

Population: Note: The Participant Flow lists Phase 2A by randomization sequence (recommended for crossover studies). Phase 2A: Includes participants that completed scans after receiving dronabinol (119 subjects) and after placebo (115 subjects) Phase 2B: Incudes participants that completed scans after receiving dronabinol + ethanol (30 subjects), dronabinol + placebo ethanol (31 subjects), placebo dronabinol + ethanol (28 subjects) and placebo dronabinol + placebo ethanol (34 subjects)

Outcome measures

Outcome measures
Measure	Phase 2A: Dronabinol Only n=119 Participants This group includes the Phase 2A visit at which dronabinol was administered. Phase 2A was a double-blind placebo-controlled, random order cross-over study in which participants received dronabinol or identical placebo on two separate study visits, one week apart.	Phase 2A: Placebo Dronabinol Only n=115 Participants This group includes the Phase 2A visit at which placebo dronabinol was administered. Phase 2A was a double-blind placebo-controlled, random order cross-over study in which participants received dronabinol or identical placebo on two separate study visits, one week apart.	Phase 2B: Dronabinol and Ethanol n=30 Participants Phase 2B was a randomized, double-blind, 4-treatment, 4-period, crossover study with THC or placebo administration and ethanol or placebo administration. Over four visits participants were assigned in a random order to each of dronabinol and ethanol, dronabinol and placebo ethanol, placebo dronabinol and ethanol, or placebo dronabinol and placebo ethanol. Visits were approximately one week apart. At this visit, participants received dronabinol and ethanol.	Phase 2B: Dronabinol and Placebo Ethanol n=31 Participants Phase 2B was a randomized, double-blind, 4-treatment, 4-period, crossover study with THC or placebo administration and ethanol or placebo administration. Over four visits participants were assigned in a random order to each of dronabinol and ethanol, dronabinol and placebo ethanol, placebo dronabinol and ethanol, or placebo dronabinol and placebo ethanol. Visits were approximately one week apart. At this visit, participants received dronabinol and placebo ethanol.	Phase 2B: Placebo Dronabinol and Ethanol n=28 Participants Phase 2B was a randomized, double-blind, 4-treatment, 4-period, crossover study with THC or placebo administration and ethanol or placebo administration. Over four visits participants were assigned in a random order to each of dronabinol and ethanol, dronabinol and placebo ethanol, placebo dronabinol and ethanol, or placebo dronabinol and placebo ethanol. Visits were approximately one week apart. At this visit, participants received placebo dronabinol and ethanol.	Phase 2B: Placebo Dronabinol and Placebo Ethanol n=34 Participants Phase 2B was a randomized, double-blind, 4-treatment, 4-period, crossover study with THC or placebo administration and ethanol or placebo administration. Over four visits participants were assigned in a random order to each of dronabinol and ethanol, dronabinol and placebo ethanol, placebo dronabinol and ethanol, or placebo dronabinol and placebo ethanol. Visits were approximately one week apart. At this visit, participants received placebo dronabinol and placebo ethanol.
Change in Concentration of Oxygenated Hemoglobin Between Pre-drug and Post-drug Scans of Patients Completing the N-back Task. Predose	0.00000000042 Δ mol/L Standard Deviation 0.00000011109	-0.00000000126 Δ mol/L Standard Deviation 0.00000012928	-0.00000000271 Δ mol/L Standard Deviation 0.00000015932	-0.00000000114 Δ mol/L Standard Deviation 0.00000015048	-0.00000000151 Δ mol/L Standard Deviation 0.00000009318	-0.00000000219 Δ mol/L Standard Deviation 0.00000012507
Change in Concentration of Oxygenated Hemoglobin Between Pre-drug and Post-drug Scans of Patients Completing the N-back Task. Peak	0.00000000013 Δ mol/L Standard Deviation 0.00000010190	0.00000000029 Δ mol/L Standard Deviation 0.00000012394	-0.00000000041 Δ mol/L Standard Deviation 0.00000010552	-0.00000000020 Δ mol/L Standard Deviation 0.00000012457	-0.00000000018 Δ mol/L Standard Deviation 0.00000009089	0.00000000070 Δ mol/L Standard Deviation 0.00000011546

OTHER_PRE_SPECIFIED outcome

Timeframe: The first resting-state scan session was run before dosing (t ≈ -45min). Drug was administered (t = 0min). The second resting-state scan session was run at the time of expected peak high (t ≈ 90min). Each scan session was six minutes in duration.

Subjects completed resting-state fNIRS scans before and after receiving a combination of active dronabinol or placebo dronabinol and active ethanol or placebo ethanol. During the task, the fNIRS device was used to capture concentration of oxygenated hemoglobin to assess prefrontal brain activity. Outcomes reflect average change from baseline in HbO concentration over pre-dose scan and average change from baseline in HbO concentration over post-dose scan (expected peak intoxication).