SV2A Density Cannabis Use Disorder

Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorYale University

About this trial

The main purpose of this study is to determine whether hippocampal synaptic vesicle density estimated by hippocampal \[11C\]APP-311/\[11C\]UCB-J binding in individuals diagnosed with cannabis use disorder (CUDs) improves with at least 4 weeks of confirmed abstinence from cannabis, in comparison to healthy controls (HCs). Furthermore, any change in synaptic vesicle density will be placed in functional context by measuring verbal memory, which is sensitive to hippocampal function, before and after at least 4 weeks of confirmed abstinence. Finally, the relationship between hippocampal \[11C\]UCB-J binding in CUDs with measures of cannabis exposure (e.g., age of initiation, cumulative lifetime dose) will be explored.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Able to provide informed consent

Male and female 18-75 years old

Daily cannabis use

Positive urine screen for cannabinoids and negative for all other drugs on

Disqualifiers

Laboratory tests with clinically significant abnormalities or positive urine toxicology screen with exception of cannabinoids.

Women with a positive pregnancy test or women who are lactating.

Have implanted or embedded metal objects or fragments in the head or body that would present a risk during the MRI scanning procedure, or have worked with ferrous metals either as a vocation or hobby (for example, as a sheet metal worker, welder, or machinist) in such a way that might have led to unknown, indwelling metal fragments that could cause injury if they moved in response to placement in the magnetic field

Have had exposure to ionizing radiation that in combination with the study tracer would result in a cumulative exposure that exceeds recommended exposure limits.

Trial design

Design model

Parallel

Treatments tested in this trial

  • [11C]APP311

    Drug

    For each \[11C\]APP311 (UCB-J) PET scan, up to 20 mCi of \[11C\]APP311 (UCB-J) will be administered by infusion pump. All participants will receive at least two \[11C\]APP311 (UCB-J) PET scans approx. 4 weeks days apart. Approximately 8 CUD participants will be asked to return for a third \[11C\]APP311 (UCB-J) PET scan after an additional 4 weeks following their second scan.

Treatment groups

51 Participants
are divided into 2 treatment groups
Group A: CUD GroupActive comparator 1 intervention
Group B: Healthy ControlsActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Hippocampal SV2A synaptic density

Hippocampal SV2A synaptic density will be measured using \[11C\]APP311 (UCB-J).

Time frame
All participants will receive at least two [11C]APP311 (UCB-J) PET scans approx. 4 weeks days apart.

Secondary outcomes

1

Hippocampal binding and Hippocampal Verbal Memory Task

To determine the relationship between hippocampal \[11C\]APP311 (UCB-J) binding and performance on the hippocampal verbal memory task (Auditory Verbal Learning Task \[AVLT\]), a cognitive task that measures total immediate recall, before and after 4 weeks of confirmed cannabis abstinence.

Time frame
The Auditory Verbal Learning Task (AVLT) will be administered before and after the 4 week abstinence period.
2

Hippocampal binding and Groton Maze Learning in CUDs

To determine the relationship between hippocampal \[11C\]APP311 (UCB-J) binding and performance on the Groton Maze Learning task, a cognitive task that measures total number of errors, in CUDs before and after 4 weeks of confirmed cannabis abstinence.

Time frame
The Groton Maze Learning Task will be administered before and after the 4 week abstinence period.

Other outcomes

1

Hippocampal synaptic density and first age of cannabis exposure

To determine the relationship between hippocampal synaptic density (n=26+12 historical data) and indices of cannabis exposure such as first age of cannabis exposure, as measured by self-report data.

Time frame
Before and after the 4 week abstinence period.
2

Hippocampal synaptic density and cumulative lifetime cannabis exposure.

To determine the relationship between hippocampal synaptic density (n=26+12 historical data) and indices of cannabis exposure such as cumulative lifetime cannabis exposure, as measured by self-report data.

Time frame
Before and after the 4 week abstinence period.
3

Hippocampal SV2A synaptic density after 8 weeks

To explore whether hippocampal synaptic density and function continues to improve with 8 weeks of abstinence in a subset of CUD participants using \[11C\]APP311 (UCB-J).

Time frame
Approximately 8 CUD participants will be asked to return for a third [11C]APP311 (UCB-J) PET scan after an additional 4 weeks following their second scan. (8 weeks in total).

Sponsors and contacts

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Yale University

Lead sponsor

National Institute on Drug Abuse (NIDA)

Collaborator