Trial Outcomes & Findings for Effects of Genotype on Resting State Connectivity During Methamphetamine Administration (NCT NCT03973489)

Last Updated: 2024-11-15

Results Overview

Pearson correlation coefficient (r) was used to calculate cortico-striatal and intra-striatal functional connectivity during resting state. These r values were then converted into Fisher's Z-scores using the transformation: z = arctanh(r) = 0.5\*ln((1+r)/(1-r)). Fisher's Z-transformation linearizes Pearson correlations and allows for statistical analysis. The Z-scores represent the strength and direction of functional connectivity between brain regions. A Z-score of 0 represents the population mean for functional connectivity between brain regions. Larger Z-scores indicate stronger connectivity (potentially indicating greater activation or association), while smaller (negative) Z-scores indicate weaker connectivity, which could suggest reduced synchronization or disrupted brain function. Z-scores above or below ±1 standard deviation from the mean may indicate notable deviations from the expected connectivity patterns in the population.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

69 participants

Primary outcome timeframe

1 hour prior to and 1.5 hours post study drug administration on visits 2 and visit 3 (randomized to placebo or methamphetamine; washout period between visit 2 and 3 was at least 3 days)

Results posted on

2024-11-15

Participant Flow

Participant milestones

Participant milestones
Measure	Wild Type (WT) MUD Group: Methamphetamine First, Then Placebo Wild Type (WT) Group: individuals who are WT for the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Wild Type (WT) MUD Group: Placebo First, Then Methamphetamine Wild Type (WT) Group: individuals who are WT for the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Common Variant (CV) MUD Group: Methamphetamine First, Then Placebo Common Variant (CV) Group: individuals who are hetero-or homozygous for the valine codon occurring at amino acid position 288 (V288V) single nucleotide polymorphism (SNP) on the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Common Variant (CV) MUD Group: Placebo First, Then Methamphetamine Common Variant (CV) Group: individuals who are hetero-or homozygous for the valine codon occurring at amino acid position 288 (V288V) single nucleotide polymorphism (SNP) on the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Wild Type (WT) Healthy Control Group: Methamphetamine First, Then Placebo Wild Type (WT) Group: individuals who are WT for the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Wild Type (WT) Healthy Control Group: Placebo First, Then Methamphetamine Wild Type (WT) Group: individuals who are WT for the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Common Variant (CV) Healthy Control Group: Methamphetamine First, Then Placebo Common Variant (CV) Group: individuals who are hetero-or homozygous for the V288V SNP on the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Common Variant (CV) Healthy Control Group: Placebo First, Then Methamphetamine Common Variant (CV) Group: individuals who are hetero-or homozygous for the V288V SNP on the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.
First Intervention (1 Day) STARTED	4	3	2	5	4	4	2	2
First Intervention (1 Day) COMPLETED	4	3	2	5	4	4	2	2
First Intervention (1 Day) NOT COMPLETED	0	0	0	0	0	0	0	0
Washout Period (at Least 3 Days) STARTED	4	3	2	5	4	4	2	2
Washout Period (at Least 3 Days) COMPLETED	2	3	2	3	1	4	1	2
Washout Period (at Least 3 Days) NOT COMPLETED	2	0	0	2	3	0	1	0
Second Intervention (1 Day) STARTED	2	3	2	3	1	4	1	2
Second Intervention (1 Day) COMPLETED	2	3	2	2	1	4	1	2
Second Intervention (1 Day) NOT COMPLETED	0	0	0	1	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Wild Type (WT) MUD Group: Methamphetamine First, Then Placebo Wild Type (WT) Group: individuals who are WT for the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Common Variant (CV) MUD Group: Placebo First, Then Methamphetamine Common Variant (CV) Group: individuals who are hetero-or homozygous for the valine codon occurring at amino acid position 288 (V288V) single nucleotide polymorphism (SNP) on the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Wild Type (WT) Healthy Control Group: Methamphetamine First, Then Placebo Wild Type (WT) Group: individuals who are WT for the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Common Variant (CV) Healthy Control Group: Methamphetamine First, Then Placebo Common Variant (CV) Group: individuals who are hetero-or homozygous for the V288V SNP on the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.
Washout Period (at Least 3 Days) Lost to Follow-up	1	0	1	0
Washout Period (at Least 3 Days) Withdrawal by Subject	0	1	1	0
Washout Period (at Least 3 Days) Physician Decision	0	0	1	1
Washout Period (at Least 3 Days) Too much motion in scanner	1	1	0	0
Second Intervention (1 Day) Adverse Event	0	1	0	0

Baseline Characteristics

Effects of Genotype on Resting State Connectivity During Methamphetamine Administration

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Wild Type (WT) MUD Group n=7 Participants Wild Type (WT) Group: individuals who are WT for the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Common Variant (CV) MUD Group n=7 Participants Common Variant (CV) Group: individuals who are hetero-or homozygous for the V288V SNP on the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Wild Type (WT) Healthy Control Group n=8 Participants Wild Type (WT) Group: individuals who are WT for the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Common Variant (CV) Healthy Control Group n=4 Participants Common Variant (CV) Group: individuals who are hetero-or homozygous for the V288V SNP on the TAAR1 gene Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	Total n=26 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	4 Participants n=4 Participants	26 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	11 Participants n=21 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	15 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants	4 Participants n=4 Participants	23 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	4 Participants n=4 Participants	21 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: 1 hour prior to and 1.5 hours post study drug administration on visits 2 and visit 3 (randomized to placebo or methamphetamine; washout period between visit 2 and 3 was at least 3 days)

Population: Participants were excluded from further analyses if they did not complete pre and post imaging outcome measures during visit. Placebo and methamphetamine administration include individuals who completed the respective visit at either the first or second intervention.

Outcome measures

Outcome measures
Measure	MUD Group, CV Genotype, Pre Placebo Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Post Placebo Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Pre Placebo Administration n=5 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Post Placebo Administration n=5 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Pre Methamphetamine Administration n=4 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Post Methamphetamine Administration n=4 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Pre Methamphetamine Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Post Methamphetamine Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Pre Placebo Administration n=3 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Post Placebo Administration n=3 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Pre Placebo Administration n=5 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Post Placebo Administration n=5 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Pre Methamphetamine Administration n=4 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Post Methamphetamine Administration n=4 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Pre Methamphetamine Administration n=8 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Post Methamphetamine Administration n=8 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.
Functional Connectivity During Resting State Magnetic Resonance Imaging (MRI) Cortico striatal	0.91 Fisher's Z-score Standard Deviation 0.96	0.52 Fisher's Z-score Standard Deviation 0.29	0.54 Fisher's Z-score Standard Deviation 0.5	0.32 Fisher's Z-score Standard Deviation 0.14	0.34 Fisher's Z-score Standard Deviation 0.22	0.49 Fisher's Z-score Standard Deviation 0.29	0.21 Fisher's Z-score Standard Deviation 0.33	0.58 Fisher's Z-score Standard Deviation 0.36	0.09 Fisher's Z-score Standard Deviation 0.04	0.14 Fisher's Z-score Standard Deviation 0.15	0.18 Fisher's Z-score Standard Deviation 0.09	0.15 Fisher's Z-score Standard Deviation 0.1	0.142 Fisher's Z-score Standard Deviation 0.09	0.101 Fisher's Z-score Standard Deviation 0.56	0.010 Fisher's Z-score Standard Deviation 0.10	0.164 Fisher's Z-score Standard Deviation 0.09
Functional Connectivity During Resting State Magnetic Resonance Imaging (MRI) Intra-striatal	0.36 Fisher's Z-score Standard Deviation 0.06	0.3 Fisher's Z-score Standard Deviation 0.09	0.25 Fisher's Z-score Standard Deviation 0.15	0.20 Fisher's Z-score Standard Deviation 0.14	0.19 Fisher's Z-score Standard Deviation 0.11	0.25 Fisher's Z-score Standard Deviation 0.10	0.23 Fisher's Z-score Standard Deviation 0.84	0.10 Fisher's Z-score Standard Deviation 0.08	0.25 Fisher's Z-score Standard Deviation 0.81	0.24 Fisher's Z-score Standard Deviation 0.18	0.35 Fisher's Z-score Standard Deviation 0.14	0.31 Fisher's Z-score Standard Deviation 0.09	0.192 Fisher's Z-score Standard Deviation 0.09	0.19 Fisher's Z-score Standard Deviation 0.32	0.26 Fisher's Z-score Standard Deviation 0.16	0.17 Fisher's Z-score Standard Deviation 0.21

PRIMARY outcome

Timeframe: 2.5 hours prior to and between 1-4 hours post study drug administration on visits 2 and visit 3 (randomized to placebo or methamphetamine; washout period between visit 2 and 3 was at least 3 days)

Population: Participants were excluded from further analyses if they did not complete all pre and post imaging measures during visit. Placebo and methamphetamine administration include individuals who completed the respective visit at either the first or second intervention.

The Morphine Benzedrine group (MBG) scale is a subscale of the Addiction Research Center Inventory (ARCI-49), a 49 item questionnaire consisting of true/false items, which measures the euphoric effects of the study drug. The MBG scale ranges from 0-16 with higher numbers indicating more euphoria. The questionnaire was administered every hour for four hours following study drug administration and the highest score during this time is considered the post drug administration score.

Outcome measures

Outcome measures
Measure	MUD Group, CV Genotype, Pre Placebo Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Post Placebo Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Pre Placebo Administration n=5 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Post Placebo Administration n=5 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Pre Methamphetamine Administration n=4 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Post Methamphetamine Administration n=4 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Pre Methamphetamine Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Post Methamphetamine Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Pre Placebo Administration n=3 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Post Placebo Administration n=3 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Pre Placebo Administration n=5 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Post Placebo Administration n=5 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Pre Methamphetamine Administration n=4 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Post Methamphetamine Administration n=4 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Pre Methamphetamine Administration n=8 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Post Methamphetamine Administration n=8 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.
Euphoria Effects of Study Drug	2.9 score on a scale Standard Deviation 2.0	6.0 score on a scale Standard Deviation 3.6	3.0 score on a scale Standard Deviation 2.2	5.2 score on a scale Standard Deviation 3.7	1.3 score on a scale Standard Deviation 1.5	4.8 score on a scale Standard Deviation 1.5	3.3 score on a scale Standard Deviation 2.5	6.0 score on a scale Standard Deviation 3.5	1.7 score on a scale Standard Deviation 0.6	3.0 score on a scale Standard Deviation 2.0	4.6 score on a scale Standard Deviation 3.4	5.8 score on a scale Standard Deviation 4.0	2.3 score on a scale Standard Deviation 2.5	8.8 score on a scale Standard Deviation 4.9	3.0 score on a scale Standard Deviation 1.7	10.9 score on a scale Standard Deviation 4.1

PRIMARY outcome

Timeframe: 2 hours prior to and 3 hours post study drug administration on visits 2 and visit 3 (randomized to placebo or methamphetamine; washout period between visit 2 and 3 was at least 3 days)

Current craving for methamphetamine was assessed using the Stimulant Craving Questionnaire (STCQ), which is a 10-item self-report measure that uses a seven-point scale, with answers ranging from 0 ("strongly disagree") to 6 ("strongly agree"). A composite score was computed by averaging the responses for all 10 items after reverse scoring items 4 and 7. Scores range from 0 to 6 with higher scores representing higher craving for methamphetamine.

Outcome measures

Outcome measures
Measure	MUD Group, CV Genotype, Pre Placebo Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Post Placebo Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Pre Placebo Administration n=5 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Post Placebo Administration n=5 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Pre Methamphetamine Administration n=4 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Post Methamphetamine Administration n=4 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Pre Methamphetamine Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Post Methamphetamine Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Pre Placebo Administration n=3 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Post Placebo Administration n=3 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Pre Placebo Administration n=5 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Post Placebo Administration n=5 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Pre Methamphetamine Administration n=4 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Post Methamphetamine Administration n=4 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Pre Methamphetamine Administration n=8 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Post Methamphetamine Administration n=8 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.
Craving Assessed With the Stimulant Craving Questionnaire (STCQ)	3.9 units on a scale Standard Deviation 1.4	3.2 units on a scale Standard Deviation 1.4	2.7 units on a scale Standard Deviation 1.3	2.3 units on a scale Standard Deviation 1.2	4.3 units on a scale Standard Deviation 1.2	4.3 units on a scale Standard Deviation 1.3	1.7 units on a scale Standard Deviation 1.5	2.1 units on a scale Standard Deviation 1.2	0 units on a scale Standard Deviation 0	0.2 units on a scale Standard Deviation 0.3	0.3 units on a scale Standard Deviation 0.4	0.2 units on a scale Standard Deviation 0.4	0.2 units on a scale Standard Deviation 0.3	0.4 units on a scale Standard Deviation 0.6	0.1 units on a scale Standard Deviation 0.2	0.2 units on a scale Standard Deviation 0.3

PRIMARY outcome

Timeframe: 2 hours prior to and 3 hours post study drug administration on visits 2 and visit 3 (randomized to placebo or methamphetamine; washout period between visit 2 and 3 was at least 3 days)

Population: Participants were excluded from further analyses if they did not complete pre and post imaging measures during visit. Placebo and methamphetamine administration include individuals who completed the respective visit at either the first or second intervention. One participant (MUD, CV, post placebo administration) did not complete the final set of data but did complete both imaging measures.

Two computer tests were administered to measure how each medication intervention effects cognitive functioning. The tests administered included the Rapid Visual Information Processing Task (RVIPT), a 6 minute test of sustained attention in which participants are requested to detect target sequences of digits and the Digit Symbol Substitution Task (DSST), a 2 minute test of psychomotor speed and sustained attention consisting of digit-symbol pairs followed by a list of digits where the subject identifies the symbol that corresponds to each digit as fast as possible. The number of correct responses within the allowed time is measured. Higher scores on both tasks indicate better performance.

Outcome measures

Outcome measures
Measure	MUD Group, CV Genotype, Pre Placebo Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Post Placebo Administration n=6 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Pre Placebo Administration n=5 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Post Placebo Administration n=5 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Pre Methamphetamine Administration n=4 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Post Methamphetamine Administration n=4 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Pre Methamphetamine Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Post Methamphetamine Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Pre Placebo Administration n=3 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Post Placebo Administration n=3 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Pre Placebo Administration n=5 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Post Placebo Administration n=5 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Pre Methamphetamine Administration n=4 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Post Methamphetamine Administration n=4 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Pre Methamphetamine Administration n=8 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Post Methamphetamine Administration n=8 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.
Cognitive Function DSST	42.3 number of correct answers Standard Deviation 11.1	44.3 number of correct answers Standard Deviation 23.3	50.8 number of correct answers Standard Deviation 3.7	53.2 number of correct answers Standard Deviation 6.1	42.8 number of correct answers Standard Deviation 17.2	42.5 number of correct answers Standard Deviation 9.8	42.9 number of correct answers Standard Deviation 9.3	44.7 number of correct answers Standard Deviation 8.8	63.7 number of correct answers Standard Deviation 8.1	57.0 number of correct answers Standard Deviation 1.0	47.8 number of correct answers Standard Deviation 9.1	60.4 number of correct answers Standard Deviation 15.4	75.8 number of correct answers Standard Deviation 16.7	68.3 number of correct answers Standard Deviation 10.0	61.0 number of correct answers Standard Deviation 9.7	59.9 number of correct answers Standard Deviation 13.1
Cognitive Function RVIP	24.0 number of correct answers Standard Deviation 4.4	29.7 number of correct answers Standard Deviation 8.4	29.8 number of correct answers Standard Deviation 5.7	34.8 number of correct answers Standard Deviation 11.5	27.5 number of correct answers Standard Deviation 13.2	33.8 number of correct answers Standard Deviation 9.5	31.9 number of correct answers Standard Deviation 10.0	34.3 number of correct answers Standard Deviation 7.5	28.3 number of correct answers Standard Deviation 4.2	31.7 number of correct answers Standard Deviation 8.1	37.8 number of correct answers Standard Deviation 9.3	39.6 number of correct answers Standard Deviation 11.4	27.3 number of correct answers Standard Deviation 7.8	38.3 number of correct answers Standard Deviation 5.7	35.5 number of correct answers Standard Deviation 14.1	42.6 number of correct answers Standard Deviation 12.3

SECONDARY outcome

Timeframe: 2.5 hours prior to and 3 hours post study drug administration on visits 2 and visit 3 (randomized to placebo or methamphetamine; washout period between visit 2 and 3 was at least 3 days)

Population: Participants were excluded from further analyses if they did not complete all pre and post outcome measures during visit. Placebo and methamphetamine administration include individuals who completed the respective visit at either the first or second intervention. One participant (MUD, CV, post placebo administration) did not complete the final set of data but did complete both imaging measures.

Saliva samples were acquired to test concentration of methamphetamine levels

Outcome measures

Outcome measures
Measure	MUD Group, CV Genotype, Pre Placebo Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Post Placebo Administration n=6 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Pre Placebo Administration n=5 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Post Placebo Administration n=5 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Pre Methamphetamine Administration n=4 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, CV Genotype, Post Methamphetamine Administration n=4 Participants Individuals with Methamphetamine Use Disorder (MUD) and Common Variant (CV) of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Pre Methamphetamine Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	MUD Group, WT Genotype, Post Methamphetamine Administration n=7 Participants Individuals with Methamphetamine Use Disorder (MUD) and Wild Type (WT) variant of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Pre Placebo Administration n=3 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Post Placebo Administration n=3 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Pre Placebo Administration n=5 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype prior to receiving placebo during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Post Placebo Administration n=5 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype after placebo administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Pre Methamphetamine Administration n=4 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, CV Genotype, Post Methamphetamine Administration n=4 Participants Healthy Controls (HC) with no substance use disorders and Common Variant (CV) of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Pre Methamphetamine Administration n=8 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype prior to receiving methamphetamine during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.	HC Group, WT Genotype, Post Methamphetamine Administration n=8 Participants Healthy Controls (HC) with no substance use disorders and Wild Type (WT) variant of the TAAR1 genotype after methamphetamine administration during visit. Magnetic resonance imaging (MRI): On visits 2 and 3, subjects will undergo a baseline MRI scan approximately 1 hour after the start of each visit followed by drug administration (placebo or MA) and a second scan 1.5 hours after that. Methamphetamine Hydrochloride Tablets: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits. Participants will receive the following doses of methamphetamine hydrochloride in accordance with their weight: if weight is between 50-60 kg, 15 mg dose of methamphetamine hydrochloride will be administered. Similarly, for 60-80 kg, 20 mg dose; 80-100 kg, 25 mg dose; and 100+ kg, 30 mg dose. Placebo oral tablet: Study participants will receive an oral dose of methamphetamine hydrochloride on one of two scan days and an identical looking placebo in tablet form on the other scan day. Drug type will be randomized between the two visits.
Methamphetamine Concentration in Saliva (ng/ml)	5320 ng/ml Standard Deviation 4794	3750 ng/ml Standard Deviation 3408	3328 ng/ml Standard Deviation 3327	1827 ng/ml Standard Deviation 1032	2828 ng/ml Standard Deviation 1539	3140 ng/ml Standard Deviation 3289	6067 ng/ml Standard Deviation 8015	3984 ng/ml Standard Deviation 3994	0 ng/ml Standard Deviation 0	0 ng/ml Standard Deviation 0	0 ng/ml Standard Deviation 0	0 ng/ml Standard Deviation 0	0 ng/ml Standard Deviation 0	467 ng/ml Standard Deviation 296	0 ng/ml Standard Deviation 0	253 ng/ml Standard Deviation 101

Adverse Events

Methamphetamine

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Methamphetamine n=24 participants at risk Adverse events related to methamphetamine administration	Placebo n=20 participants at risk Adverse events related to placebo administration.
General disorders Headache	8.3% 2/24 • 24 hours	10.0% 2/20 • 24 hours
General disorders Dizziness	8.3% 2/24 • 24 hours	10.0% 2/20 • 24 hours
General disorders Psychomotor slowing	0.00% 0/24 • 24 hours	5.0% 1/20 • 24 hours
General disorders Parasthesia	20.8% 5/24 • 24 hours	5.0% 1/20 • 24 hours
General disorders Confusion/Memory Impairment	4.2% 1/24 • 24 hours	0.00% 0/20 • 24 hours
General disorders Fatigue/Somnolence	12.5% 3/24 • 24 hours	5.0% 1/20 • 24 hours
General disorders Taste abnormality	0.00% 0/24 • 24 hours	5.0% 1/20 • 24 hours
General disorders Dry mouth	25.0% 6/24 • 24 hours	5.0% 1/20 • 24 hours
General disorders Heart Palpitations	16.7% 4/24 • 24 hours	0.00% 0/20 • 24 hours
General disorders Other	12.5% 3/24 • 24 hours	10.0% 2/20 • 24 hours

Additional Information

William Hoffman

VA Portland Health Care System

Phone: 503-220-8262

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place