Treatment Engagement in Families With Substance Use and Psychosis: A Pilot Study
Phase: NA
Conditions: Psychosis, Substance Use, Substance Use Disorders, Family, Cannabis, Marijuana, Alcohol, Schizophrenia, Schizoaffective Disorder, Bipolar Disorder, Mental Disorder
Sponsor: Mclean Hospital

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
1 
STUDY PROTOCOL 
 
Official Title: Treatment Engagement in Families with Substance Use and Psychosis: A Pilot Study 
 
NCT #: NCT05380583 
 
Date: 03/28/2024 (IRB approval date 04/02/2024) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
2 
Detailed Protocol 
 
Protocol Title and Date: 
Treatment Engagement in Families with Substance Use and Psychosis: A Pilot Study 
March 28, 2024 
 
Principal Investigator: 
Julie M. McCarthy, Ph.D., McLean Imaging Center, McLean Hospital, 115 Mill St., Belmont, 
MA 02478, 617-855-3521 (office), jmccarthy@mclean.harvard.edu (email). 
 
Study Performance Site:  Admissions Building and McLean Imaging Center, McLean 
Hospital, 115 Mill St., Belmont, MA 02478 
 
I.  Background and Significance  
Treatment Engagement Challenges: Psychosis and Substance Use Disorders. Co-
occurring substance use disorders significantly increase the likelihood of treatment dropout 
for people with first episode psychosis (FEP) (Conus et al., 2010). This is a critical concern, 
because approximately 50-70% of people with FEP have a lifetime history of substance use 
disorder (Cather et al., 2018; Shinn et al., 2015), endorse recent tobacco, alcohol, and 
cannabis use (Oluwoye et al., 2019), and approximately 30% of people with FEP disengage 
from treatment (Dixon et al., 2016; Doyle et al., 2014). Though evidence-based treatments 
are available for FEP and substance use (e.g., Kane et al., 2016), they cannot be effective 
if clients are not engaged in treatment. Insufficient readiness to engage in substance use 
treatment likely contributes to poor outcomes among clients with co-occurring substance 
use disorders and FEP. These results call for novel strategies to increase substance use 
disorder treatment engagement, which has the potential to make a significant impact on 
reducing substance use in this population.  
Treatment Engagement Intervention. Community Reinforcement Approach and Family 
Training (CRAFT) is an evidence-based intervention that increases treatment engagement 
for substance use disorders regardless of diagnosis (Meyers et al., 1999). CRAFT 
acknowledges that people with substance use disorders may not be ready to change their 
substance use, and it capitalizes on the motivation of concerned significant others (CSOs 
e.g., family members) as agents of change. Such families often seek additional support, as 
they experience elevated family distress associated with the identified patient’s (IP) 
addiction and psychosis (Orford et al., 2013). CRAFT has not been studied with CSOs of 
individuals with co-occurring substance use and psychosis to date. Targeting CSOs may 
decrease family distress and facilitate greater substance use treatment engagement in FEP 
IPs. In this context, the CSOs are the subjects of intervention.  
Many individuals with FEP have frequent contact or live with family (Drapalski et al., 
2018), but time, transportation, finances, and childcare are barriers to family members 
accessing additional services. Utilizing telemedicine (e.g., video conferencing) mitigates 
these barriers, and such technology typically achieves similar results to in-person therapy 
(Hulsbosch et al., 2017; Tse et al., 2015). å 
Phase 1: We will first develop a CRAFT for FEP delivered via telemedicine (CRAFT-
FT) manual/training protocol by conducting an open-label cross-over feasibility pilot test in 
families with substance use and FEP with subjects (N=14) completing the first half of 
sessions in-person and the second half via telemedicine in counterbalanced order; we will 
also recruit corresponding FEP clients (N=14). Second, we will collect interview/focus group 
feedback on feasibility/delivery preferences to refine the manual. Third, we will further test 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
3 
the manual feasibility and collect feedback in a second two-arm pilot (CRAFT-F N=7; CRAFT-
FT N=7); we will also recruit corresponding FEP clients in each condition (CRAFT-F N=7; 
CRAFT-FT N=7). FEP clients will complete assessments only, as the study intervention is 
targeted toward family members.  
In light of COVID-19 guidelines and subject/staff safety concerns, we may forego the 
cross-over and randomized designs involving in-person visits to have family subjects 
participate in the CRAFT-FT via virtual visits only.  
Phase 2: After developing the above intervention, we will take the adapted CRAFT-FT 
protocol, now termed CRAFT for early psychosis (CRAFT-EP), and conduct a small pilot 
randomized controlled trial comparing CRAFT-EP plus treatment as usual (TAU) to TAU 
alone. Family members (N=40) will be randomized to CRAFT-EP + TAU (N=20) or TAU 
alone (N=20). The CRAFT-EP intervention nis targeted toward family members, but given 
participant feedback from the development stage of the study, FEP clients will now have 
the option for limited intervention participation if their family member is randomized to 
CRAFT-EP + TAU. We will also recruit FEP clients (up to N=40) for assessment purposes 
for CRAFT-EP + TAU (N=20) and TAU alone (N=20). If a FEP client subject does not have 
a family member participating in the study, the FEP client will be automatically be 
assigned to the TAU alone group. Total target enrollment is N=80 (N=40 family members 
and up to N=40 FEP clients). To account for potential attrition, an additional N=12 
participants (N=6 family member and N=6 FEP clients) may be recruited, and the overall 
total enrollment would be up to N=92 (N=46 family members and N=46 FEP clients).  
 
II.  Specific Aims 
 
Phase 1: 
Develop a feasible telemedicine and in-person Community Reinforcement Approach and 
Family Training (CRAFT) protocol to improve treatment engagement for families with 
substance use and psychosis.  
 
Hypothesis 1A: The adapted CRAFT protocol will be feasible as measured by session 
completion rate (%) and participant satisfaction questionnaire/interview assessments.  
 
Phase 2: 
Test preliminary efficacy of CRAFT-EP plus TAU compared to TAU alone.  
 
Hypothesis 2A: CRAFT-EP will improve IP substance use treatment engagement compared 
to TAU as measured by FEP client readiness to change substance use and past 30-day 
sessions attended %. 
 
Hypothesis 2B: CRAFT-EP will reduce FEP client substance use more than TAU as 
measured by self-report past 30-day use, and biological verification of use (e.g., urine) 
when available.  
 
Hypothesis 2C: CRAFT-EP will result in greater improvements in family wellbeing 
compared to TAU, as measured by self-report mood, anxiety, happiness, and family 
relationship measures.  
 
 
 
 
 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
4 
III.  Subject Selection 
 
Family members: 
 
Phase 1 Inclusion: 
1) Ages 18-70. 
2) Having a relative who: 
a. Is a patient with early course psychosis (DSM-5 schizophrenia, schizoaffective 
disorder, schizophreniform, psychosis NOS, delusional disorder, brief psychotic 
disorder, major depression with psychosis, and bipolar disorder with psychosis) 
with first onset in the past 6 years, and 
b. Used tobacco, alcohol, or cannabis in the past 90 days and/or has no apparent 
immediate interest in abstinence (responding “No” to “Do you think they want 
to quit right now?” in reference to overall substance use). 
3) The person(s) who can best describe the client with first episode psychosis (FEP). 
4) At least 4 days per month contact with the client. 
5) Access to a computer with internet or mobile phone with video conferencing 
capabilities. 
6) Ability to provide written informed consent. 
7) Speak and read English. 
 
Phase 1 Exclusion: 
 
1) DSM-5 moderate or severe substance use disorder in the past year 
2) Lifetime psychotic disorder 
3) History of domestic violence with the IP  
Psychiatric, cognitive, or medical impairments that would interfere with the ability to follow 
through with the treatment plan. 
 
Phase 2 Inclusion:  
 
1) Ages 18-70. 
2) Having a relative who: 
a. Is a patient with early course psychosis (schizophrenia, schizoaffective 
disorder, schizophreniform, psychosis NOS, delusional disorder, brief psychotic 
disorder, major depression with psychosis, and bipolar disorder with psychosis 
(as reported by family member, clinician, or chart review)) with first onset in 
the past 6 years, and 
b. Used alcohol or cannabis in the past 30 days and/or has no apparent immediate 
interest in abstinence (responding “No” to “Do you think they want to quit right 
now?” in reference to overall substance use). 
c. Family member has concerns about the relative’s substance use. 
d. Is 18-35 years of age 
3) The person(s) who can best describe the client with first episode psychosis (FEP). 
4) At least 4 days per month contact with the client. 
5) Access to a computer with internet or mobile phone with video conferencing 
capabilities. 
6) Ability to provide written informed consent. 
7) Speak and read English. 
 
Phase 2 Exclusion:  

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
5 
 
1) DSM-5 moderate or severe substance use disorder in the past year. 
2) Lifetime psychotic disorder. 
3) History of domestic violence with the IP that would interfere with the ability to safely 
follow through with the intervention plan.  
4) Psychiatric, cognitive, or medical impairments that would interfere with the ability to 
follow through with the intervention plan. 
5) Prior participation of a family member of the FEP client in the study 
6) Significant prior experience with CRAFT (e.g., having completed a CRAFT course prior 
to study enrollment) 
 
FEP clients: 
 
Phase 1 Inclusion: 
 
1) Ages 18-35. 
2) FEP in the past 6 years with a Diagnostic and Statistical Manual (DSM)-5 diagnosis 
of affective (bipolar disorder or major depressive disorder with psychotic features) or 
non-affective psychosis (schizophrenia spectrum disorder) as assessed by the 
Structured Clinical Interview for DSM-5, Research Version (SCID-5; First et al., 
2015). 
3) Used tobacco, alcohol, or cannabis within the past 90 days and/or no apparent 
immediate interest in abstinence (Responding “No” to “Do you want to quit right 
now?” in reference to overall substance use). 
4) Ability to provide informed consent (or assent with their legal guardian providing 
informed consent). 
5) Speak/read English. 
 
Phase 2 Inclusion:  
 
1) Ages 18-35. 
2) FEP onset in the past 6 years with a Diagnostic and Statistical Manual (DSM)-5 
diagnosis of affective (bipolar disorder or major depressive disorder with psychotic 
features) or non-affective psychosis (schizophrenia spectrum disorder) as assessed 
by the Structured Clinical Interview for DSM-5, Research Version (SCID-5; First et 
al., 2015) 
3) Used alcohol or cannabis within the past 30 days and/or no apparent immediate 
interest in abstinence (Responding “No” to “Do you want to quit right now?” in 
reference to overall substance use). 
4) They or others have concerns about the client’s substance use. 
5) Ability to provide written informed consent (or assent with their legal guardian 
providing informed consent). 
6) Speak/read English 
 
In Phase 1, Participants (N = 56) Participants will be recruited from families in the McLean 
OnTrack or similar first episode psychosis clinics or inpatient units using clinician referral, 
flyers, groups, medical record pre-screening (e.g., EPIC), and participants who completed 
SBDP research studies and agreed to be contacted about future research opportunities. 
Prior to consenting inpatient participants, the physician in charge would complete the 
Clinical Capacity form. Eligibility screening will be completed prior to recruitment. 
Participants will be screened and recruited through McLean Hospital’s Schizophrenia and 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
6 
Bipolar Disorder Research Program (Dost Öngür, MD, PhD, Director). The PI, Julie McCarthy, 
clinic, and/or research staff will identify appropriate early psychosis families and supervise 
a research assistant who will assist with screening, recruitment, and scheduling.  
 
In Phase 2, Participants (N = 92) will be recruited from families in the McLean OnTrack or 
similar first episode psychosis or general outpatient clinics, clinical evaluation centers, 
inpatient units using clinician referral, assertive community treatment, partial hospital, 
and residential programs. Participants will also be recruited from the community, 
newsletters, list serves, flyers, groups, medical record pre-screening (e.g., EPIC), and 
participants who completed SBDP research studies and agreed to be contacted about 
future research opportunities. This study is also included in protocol 2022P002927, the 
Registry of Research Participants for the Psychotic Disorder Division. We will access the 
registry to identify participants that might be eligible for the study. We will also invite 
participants and potential participants that we screen to consent to the registry if they are 
interested. Clinicians from any of the above settings may notify their patients and families 
about the research study and refer them to the study team to obtain information about 
the study. Referrals can be done in person, by phone, email, video conferencing, or in the 
course of routine medical care or by providing a flyer, brochure, other IRB-approved 
written or electronic recruitment materials/links, or name and contact information of 
research staff to patients and family members. When making referrals, clinicians may 
share the name and contact information of potential participants with the research staff 
for those individuals who want the research staff to contact them directly. Further 
recruitment will occur online (e.g., via Rally, MAPNet, Facebook, Instagram, and Reddit) 
and a REDCAP CRAFT-FT Eligibility Survey (Prescreen) link with preliminary eligibility 
questions to facilitate subsequent phone screening. Phone screens may be conducted by 
telephone and/or video conferencing To facilitate recruitment of family dyads, if a 
potential participant requests that research staff contact their family member who may be 
interested, research staff may contact that family member directly. Prior to consenting 
inpatient participants, the physician in charge would complete the Clinical Capacity form 
either on paper or digitally via REDCap. Eligibility screening will be completed prior to 
recruitment. The Discussion of Clinical Appropriateness form will be used to obtain 
permission to contact inpatients after discharge if they would prefer to be enrolled after 
their hospitalization. Participants will be screened and recruited through McLean Hospital’s 
Schizophrenia and Bipolar Disorder Research Program (Dost Öngür, MD, PhD, Director). 
The PI, Julie McCarthy, clinic, and/or research staff will identify appropriate early 
psychosis families and supervise a research assistant who will assist with screening, 
recruitment, and scheduling.  
For Phases 1 and 2, adults will be recruited. For this study all subjects meeting criteria 
for participation (as detailed in the protocol) will be offered participation in this research 
study. We welcome all subjects whose data would be relevant to the study regardless of 
race, sex, ethnicity, religious beliefs, or sexual orientation. 
IV.  Subject Enrollment  
 
The PI or trained research staff will conduct the informed consent procedures. The informed 
consent interview may take place in person and/or via virtual visit to minimize participant 
burden and time on campus. Virtual visits refer to videoconferencing, telephone, and/or 
online questionnaires. Whenever possible, virtual visits will be conducted using the Partners 
HIPAA-compliant Zoom platform. For subjects unable to use Zoom, virtual visits will be 
conducted by telephone. If conducted in person it will take place in a quiet, private room 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
7 
where the subject will be given another opportunity for questions or concerns. The 
purposes, procedures, risks of the study, and that subject’s right to withdraw from any 
procedures at any time will be explained by research staff verbally and with a written 
document to be read by subjects. Subjects will be encouraged to read through and consider 
the informed consent form; we will give subjects all the time they need to do so. The PI and 
research staff will be available to subjects to answer any questions related to the study. 
Consent will be documented by the subject’s signature (witnessed) on the written 
document. Individuals under legal guardianship will need their legal guardian provide 
consent and the individual will need to provide their assent to participate in the study. 
 
When digital consent will be used remotely or in-person, we will use REDCap or Adobe Sign 
and return the signed consent in-person or electronically with the REDCap survey Login 
feature or SEND SECURE. REDCap and Adobe Sign are validated password-protected and 
Partners-approved signature platforms. Though it is not always possible to validate the 
identity of the individual “on the other end of the computer” or for remote consent by mail, 
the present protocol is considered minimal risk, and in-person and remote digital signatures 
are generally approved for low risk research, according to the PHRC consent policy. 
 
As with all consent procedures, the consent form will be reviewed and the subject will 
complete the Informed Consent Survey to ensure that they understand the consent form 
and can have any questions answered. The research staff member conducting the consent 
will also sign and date the version of the consent form reviewed with the subject. 
Documentation of remote consent will be entered into the subject file.  
 
Written consent will be obtained in all cases using forms approved by the Partners IRB, 
except participants who choose to enroll in only the medical records portion of the study or 
joining a family member’s coaching session* will complete verbal/implied consent 
documented in the Medical Records Fact Sheet or Session Fact Sheet* with Documentation 
of Verbal Consent completed, as appropriate. Any subject who does not agree to participate 
(or who the PI deems is not able to provide informed consent) will not be enrolled. 
*Consent procedures involving joining a coaching session and Session Fact Sheet apply to 
Phase 2 only. 
 
V.  Study Procedures 
 
Phase 1 Study Procedures:  
 
The study may consist of 3 in-person assessments, 6-8 therapy sessions (in-person or 
virtual visit), and 1 follow-up assessment (follow-up). Assessments may completed in 
person and/or during a virtual visit. Virtual visits refer to videoconferencing, telephone, 
and/or online questionnaires. Whenever possible, virtual visits will be conducted using the 
Partners/MGB HIPAA-compliant Zoom platform. For subjects unable to use Zoom, virtual 
visits will be conducted by telephone. We may ask subjects to complete the procedures 
detailed below, including activities/questionnaires using a computer, tablet, or pencil and 
paper, interviews, audio/video recording, an intervention, and urine and breath measures. 
If subjects have completed certain interviews, questionnaires, or tasks in the past month 
(or year for SCID-5) as part of another Schizophrenia and Bipolar Disorder Program study, 
they may not have to repeat them again for this study to reduce subject burden. 
 
a) Consent procedures 
b) Substance use screening (FEP clients only) 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
8 
c) Clinical interview 
d) Self-report questionnaires asking about preferences, daily life experiences (e.g., drug 
use), and symptoms (e.g., depression) 
e) Intervention (family members only) 
f) Focus group (family member only) 
 
FEP clients who have been pre-screened for eligibility will also have the option to participate 
by granting access to medical record data including psychiatric diagnosis, symptoms, and 
use of treatment services by agreeing to participate by completing the Medical Records Fact 
Sheet (and Contact Sheet if opting for payment in the form of a gift card) in lieu of the full 
set of research procedures.  
 
Substance Use Screening 
FEP subjects may complete breath samples** to detect recent alcohol use (Alco-Sensor IV, 
Intoximeters, Inc.) and recent smoking (Micro Smokerlyzer, Bedfont). FEP subjects may 
also provide a urine sample** to screen for recent drug use). FEP subjects will complete 
substance use screening in person whenever possible. In the event that in person screening 
is not possible (e.g., to minimize in person contact during the COVID-19 pandemic), a drug 
and/or nicotine test, as appropriate, may be mailed to subjects. The principal investigator 
or trained research staff would be in communication with subjects about administration and 
results of the tests. The results of the test would be presented to study staff, either during 
a virtual visit or sent as a photo via email, so the results are clearly visualized by staff. 
 
Clinical Interview 
Subjects may complete the following measures in person and/or via virtual visit, and the 
interview may be audio/video recorded:  
 
Structured Clinical Interview for DSM-5 (SCID-5-RV) 
Positive and Negative Syndrome Scale (PANSS) 
Montgomery-Asberg Depression Rating Scale (MADRS) 
Young Mania Rating Scale (YMRS) 
Fagerstrom Test for Nicotine Dependence (FTND) 
Substance Use Questionnaire – Family (SUQ-Family)*  
Substance Use Questionnaire – Client (SUQ–Client)** 
Timeline Followback (TLFB)** 
Treatment Satisfaction Interview* 
 
Questionnaires  
Subjects may complete questionnaires about demographic/medical information, menstrual 
(for women), and substance use history, as well as several questionnaires about symptom 
severity, mood, family distress, and feedback about the intervention throughout the study. 
Subjects may complete questionnaires in person and/or remotely via REDCap. 
These include: 
 
Demographic Form 
Beck Depression Inventory – II (BDI-II) 
State-Trait Anxiety Inventory-Short Form (STAI-SF) 
Happiness Scale 
Relationship Happiness Scale (RHS-Family)*  
Relationship Happiness Scale – (RHS-Client)** 
Readiness Scale – Family* 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
9 
Readiness Scale – Client** 
Readiness to Change Questionnaire – Family (RCQ-Family)* 
Readiness to Change Questionnaire – Client (RCQ-Client)** 
Treatment Engagement Survey – Family (TES-Family)* 
Treatment Engagement Survey – Client (TES-Client)** 
Credibility/Expectancy Questionnaire (CEQ)* 
Session Survey* 
Working Alliance Inventory – Short Revised (WAI-SR) 
Motivation and Pleasure Scale – Self-Report (MAP-SR) 
Drinking Motives Questionnaire – Revised (DMQ-R)** 
Marijuana Motives Measure (MMM)** 
Motives for Smoking Scale (MSS)** 
Five Facet Mindfulness Questionnaire (FFMQ) 
Perceived Stress Scale (PSS) 
 
*Measures for family members only. 
** Measures for FEP clients only. 
 
Intervention (only family members) 
We will tailor CRAFT for FEP with in-person (CRAFT-F) and telemedicine delivery (CRAFT-
FT) in 6-8 sessions of approximately 45 minute therapy. Topics include building motivation, 
self-care, communication, and understanding family interactions. The sessions will be in 
person and/or virtual visits (video conferencing) and audio/video recorded. The audio/video 
recording will include identifiable information (e.g., face and potentially first names), but 
we will label the recordings with codes instead of names. We will store the recordings 
indefinitely, and they will not be erased. The audio recording will be sent securely to trained 
coders who will review sessions for therapist quality assurance and training purposes. At 
any time, subjects may request (verbally or in writing) to have their audio/video recordings 
erased. Session notes will be documented with: 
 
Notes Template 
Functional Analysis Worksheet (when conducting functional analysis exercise) 
 
Focus group (only family members) 
We may conduct 1-2 in person or virtual focus groups with subjects who are available at a 
mutual time following each Part 1 and Part 2 of the pilot to validate proposed changes to 
the manual and collect feedback to inform further manual improvements. The Focus Group 
Questions and responses from the treatment Satisfaction Survey and Session Surveys will 
be used to guide the semi-structured interview. The group may be audio/video recorded. 
Regarding confidentiality, subjects will be asked to not take screenshots, photographs, or 
recordings of any kind with any electronic equipment, refrain from using last names, and to 
keep information shared during the group confidential. The audio recordings may be sent 
securely to a MGB-approved transcription service in order to obtain research grade 
transcriptions for analysis. 
 
Timing of Measures 
Study assessment procedures will take approximately the following durations to complete: 
Visit 1: 3 hours 
Visit 2: 1 hour 
Visit 3: 1 hour  
Follow-up: 30 minutes 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
10 
Focus Group: 30-60 minutes 
If virtual visit assessments are used, number of visits may vary to reduce participant burden 
and time on campus. If subjects have completed certain study procedures as part of another 
Schizophrenia and Bipolar Disorder Program study within the past 30 days (e.g., clinical 
interview,) or past year for the SCID-5, they may not be repeated to reduce participant 
burden. FREQUENCY: The Informed Consent Survey Family/Client, Demographic Form, 
SCID-5, DMQ-R**, MMM**, and MSS** may be assessed at baseline, the Treatment 
Satisfaction Interview* may be assessed at the final session or post-treatment, the Focus 
Group Questions* may be assessed once any time after post-treatment for each subject, 
and the Functional Analysis* will be assessed once during treatment. The CEQ* may be 
assessed at baseline and post-treatment, the WAI may be assessed once at mid-treatment 
for Clients and session 2 and post-treatment for Families. The PANSS, MAP-SR, MADRS, 
YMRS, and substance use screening** may be assessed at baseline, mid-treatment, and 
post-treatment. The PSS and FFMQ may be assessed at baseline and post-treatment (and 
at follow-up for Families). The Session Survey may be assessed following each intervention 
session. Remaining measures may be collected at baseline and repeated mid-treatment 
(approximately week 3), and post-treatment (approximately week 6-8), and measures may 
be assessed via online survey or phone/virtually at 3-month follow-up. 
 
Study intervention procedures will take approximately 45 minutes weekly for a total of 6-8 
sessions in person and/or via virtual visits.  
 
Phase 2 Study Procedures: 
 
The study may consist of 3 in-person assessments, 8 coaching sessions (in-person or virtual 
visit), and 1 follow-up assessment (follow-up). Assessments may be completed in person 
and/or during a virtual visit. Virtual visits refer to videoconferencing, telephone, and/or 
online questionnaires. Whenever possible, virtual visits will be conducted using the 
Partners/MGB HIPAA-compliant Zoom platform. For subjects unable to use Zoom, virtual 
visits will be conducted by telephone. We may ask subjects to complete the procedures 
detailed below, including activities/questionnaires using a computer, tablet, or pencil and 
paper, interviews, audio/video recording, an intervention, and urine and breath measures. 
If subjects have completed certain interviews, questionnaires, or tasks in the past month 
(or year for SCID-5) as part of another Schizophrenia and Bipolar Disorder Program study, 
they may not have to repeat them again for this study to reduce subject burden. 
 
g) Consent procedures 
h) Substance use screening (FEP clients only) 
i) Clinical interview 
j) Self-report questionnaires asking about preferences, daily life experiences (e.g., drug 
use), symptoms (e.g., depression), and debriefing 
k) Intervention (family members, option for client-relative participation) 
l) Focus group (family member only) 
 
FEP clients who have been pre-screened for eligibility will also have the option to participate 
by granting access to medical record data including psychiatric diagnosis, symptoms, and 
use of treatment services by agreeing to participate by completing the Medical Records Fact 
Sheet (and Contact Sheet if opting for payment in the form of a gift card) in lieu of the full 
set of research procedures.  
 
Substance Use Screening 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
11 
FEP subjects may complete breath samples** to detect recent alcohol use (Alco-Sensor IV, 
Intoximeters, Inc.) and recent smoking (Micro Smokerlyzer, Bedfont). FEP subjects may 
also provide a urine sample** to screen for recent drug use). FEP subjects will complete 
substance use screening in person whenever possible. In the event that in person screening 
is not possible (e.g., to minimize in person contact during the COVID-19 pandemic), a drug 
and/or nicotine test, as appropriate, may be mailed to subjects. The principal investigator 
or trained research staff would be in communication with subjects about administration and 
results of the tests. The results of the test would be presented to study staff, either during 
a virtual visit or sent as a photo via email, so the results are clearly visualized by staff. 
 
Clinical Interview 
Subjects may complete the following measures in person and/or via virtual visit, and the 
interview may be audio/video recorded:  
 
Structured Clinical Interview for DSM-5 (SCID-5-RV) 
Positive and Negative Syndrome Scale (PANSS)** 
Montgomery-Asberg Depression Rating Scale (MADRS) 
Young Mania Rating Scale (YMRS)** 
Fagerstrom Test for Nicotine Dependence (FTND) 
Substance Use Questionnaire – Family (SUQ-Family)*  
Substance Use Questionnaire – Client (SUQ–Client)** 
Timeline Followback (TLFB)** 
Satisfaction Interview* 
 
The audio recordings from this study may also be used for training purposes, i.e., to train 
research staff (e.g., research assistants, postdoctoral fellows, etc.) and students on SCID 
and scales administration. Trainees may include research staff and students who are not 
directly involved in this study (i.e., members of the lab who are not study staff.) Any audio 
recordings used for training purposes will be stored in a Partners Dropbox folder that is 
shared only with the specific individuals who are undergoing the training. Trainees will be 
given view-only access (vs. edit access) and will be instructed that they are not 
permitted to download any of the audio files. 
 
Questionnaires  
Subjects may complete questionnaires about demographic/medical information, menstrual 
(for women), and substance use history, as well as several questionnaires about symptom 
severity, mood, family distress, and feedback about the intervention throughout the study. 
Subjects may complete questionnaires in person and/or remotely via REDCap. 
These include: 
 
Demographic Form 
Beck Depression Inventory – II (BDI-II) 
State-Trait Anxiety Inventory-Short Form (STAI-SF) 
Happiness Scale 
Relationship Happiness Scale (RHS-Family)*  
Relationship Happiness Scale – (RHS-Client)** 
Readiness Scale – Family* 
Readiness Scale – Client** 
Readiness to Change Questionnaire – Family (RCQ-Family)* 
Readiness to Change Questionnaire – Client (RCQ-Client)** 
Treatment Engagement Survey – Family (TES-Family)* 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
12 
Treatment Engagement Survey – Client (TES-Client)** 
Credibility/Expectancy Questionnaire (CEQ)* 
Session Survey* 
Working Alliance Inventory – Short Revised (WAI-SR) 
Motivation and Pleasure Scale – Self-Report (MAP-SR) 
Drinking Motives Questionnaire – Revised (DMQ-R)** 
Marijuana Motives Measure (MMM)** 
Motives for Smoking Scale (MSS)** 
Stigma Resistance Scale – Family (SRS-Family) 
Stigma Resistance Scale – Client (SRS-Client) 
Perceived Stress Scale (PSS) 
Patient Health Questionnaire 9 (PHQ-9) 
Generalized Anxiety Disorder 7 (GAD-7) 
Family Questionnaire 
World Health Organization Quality of Life - BREF (WHOQOL-BREF) 
Generalized Self-Efficacy Scale 
Debriefing Interview 
 
*Measures for family members only. 
** Measures for FEP clients only. 
 
 
Intervention (family members, optional client participation)  
We will tailor CRAFT for FEP with telemedicine delivery (CRAFT-FT) in 8 sessions of 
approximately 60-minute coaching. Topics include building motivation, self-care, 
communication, and understanding family interactions. 
 
CRAFT-FT is now termed CRAFT for early psychosis (CRAFT-EP). Participants will be 
randomized to treatment as usual or treatment as usual + CRAFT-EP to assess preliminary 
efficacy of the intervention. Given focus group feedback, we will have eight standard 
coaching sessions offered, with the option for one in-person visit when hospital policies 
allow for in-person care without masks. FEP clients will have the option to participate in one 
coaching session to communicate their needs or provide feedback to their family member if 
both parties are interested in a joint session. If the FEP client chooses to participate in a 
session without full participation in the larger study, they will be asked to complete a verbal 
consent after reviewing the Session Fact Sheet with research staff, who would document 
the verbal consent. 
 
The sessions will be in person and/or virtual visits (video conferencing) and audio/video 
recorded. The audio/video recording will include identifiable information (e.g., face and 
potentially first names), but we will label the recordings with codes instead of names. We 
will store the recordings indefinitely, and they will not be erased. The audio recording will 
be sent securely to trained coders who will review sessions for therapist quality assurance 
and training purposes. At any time, subjects may request (verbally or in writing) to have 
their audio/video recordings erased.  
 
Session notes may be documented as needed with: 
 
Notes Template 
CRAFT-EP Session Checklists: 
 
Session 1 Introduction and Self-Care 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
13 
 
Session 2 Communication  
 
Session 3 Functional Analysis 
 
Session 4 Positive Reinforcement 
 
Session 5 Treatment Engagement 
 
Session 6 Natural Consequences 
 
Session 7 Problem Solving 
 
Session 8 Final Session 
CRAFT-EP Worksheets that to be shared and potentially completed with subjects: 
 
Happiness Scale 
Communication Worksheet 
Functional Analysis Worksheet (when conducting functional analysis exercise) 
Positive Reinforcement Worksheet 
Natural Consequences Worksheet 
Problem Solving Worksheet 
Next Steps Worksheet 
 
CRAFT-EP informational handouts to be shared with subjects also include: 
 
Program Outline 
 
Milestone Conversations 
 
Psychosis and Substance Use 
 
Goal Setting Guidelines 
 
Communication Guidelines 
 
Communication Examples 
 
Treatment Engagement 
 
Problem Solving Guidelines 
 
CRAFT-EP Resources** 
 
Email Template 
** CRAFT-EP Resources will also be offered to family members in the control condition and 
to interested client relatives at the conclusion of their study participation. Relevant 
resources from the CRAFT-EP Resources sheet may also be offered to potential participants 
who were deemed ineligible on the phone screen and/or the REDCAP eligibility prescreen 
survey. 
 
Focus group (only family members) 
We may conduct 1-2 in person or virtual focus groups with subjects who are available at a 
mutual time following each Part 1 and Part 2 of the pilot to validate proposed changes to 
the manual and collect feedback to inform further manual improvements. The Focus Group 
Questions and responses from the Satisfaction Survey and Session Surveys will be used to 
guide the semi-structured interview. The group may be audio/video recorded. Regarding 
confidentiality, subjects will be asked to not take screenshots, photographs, or recordings 
of any kind with any electronic equipment, refrain from using last names, and to keep 
information shared during the group confidential. The audio recordings may be sent securely 
to a MGB-approved transcription service in order to obtain research grade transcriptions for 
analysis. 
 
Timing of Measures 
Study assessment procedures will take approximately the following durations to complete: 
Visit 1: 3 hours (4 hours for FEP clients) 
Visit 2: 1 hour 
Visit 3: 1 hour  
Follow-up: 30 minutes 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
14 
Focus Group: 30-60 minutes 
If virtual visit assessments are used, number of visits may vary to reduce participant burden 
and time on campus. If subjects have completed certain study procedures as part of another 
Schizophrenia and Bipolar Disorder Program study within the past 30 days (e.g., clinical 
interview,) or past year for the SCID-5, they may not be repeated to reduce participant 
burden. FREQUENCY: The Informed Consent Survey Family/Client, Demographic Form, 
SCID-5, DMQ-R**, MMM**, and MSS** may be assessed at baseline, the Debriefing 
Interview and Satisfaction Interview* may be assessed at the final session or post-
intervention, the Focus Group Questions* may be assessed once any time after post-
intervention for each subject, and the Functional Analysis* will be assessed once during 
intervention. The CEQ* may be assessed at baseline and post-intervention, the WAI may 
be assessed once at mid- intervention for Clients and session 2 and post- intervention for 
Families. The PANSS, MAP-SR, MADRS, YMRS, and substance use screening** may be 
assessed at baseline, mid-, and post-intervention. The PSS and the SRS may be assessed 
at baseline and post-intervention (and at follow-up for Families). The Session Survey may 
be assessed following each intervention session. Remaining measures may be collected at 
baseline and repeated mid-intervention (approximately week 4), and post-intervention 
(approximately week 8), and measures may be assessed via online survey or 
phone/virtually at 3-month follow-up. 
 
Study intervention procedures will take approximately 60-90 minutes weekly for a total of 
8 sessions in person and/or via virtual visits.  
 
 
 
VI.  Biostatistical Analysis 
 
Interviews and questionnaires mentioned above are all variables that will be analyzed.   
 
The study will be considered complete when 20 family member subjects and up to 20 FEP 
clients have completed the tasks outlined above for the development phase 1, and 40 
family member subjects and up to 40 FEP clients have completed the tasks outlined above 
for the randomized controlled trial phase 2 (we will enroll up to 148 total participants across 
phases 1 and 2 (74 family members and 74 FEP clients to account for potential attrition). 
 
Phase 1 outcome measures for statistical analysis will include: 
Primary 
1. Title: Percentage of Sessions Completed 
Description: Percentage of sessions completed during the intervention  
Time Frame: Post-intervention, approximately Week 6-8 
Secondary 
2. Title: Mean Session Satisfaction Rating 
Description: Participants will report weekly satisfaction ratings following each 
session on the Session Survey. Ratings will range from 1 (poor) to 5 (excellent) for 
overall experience and convenience.  
Time Frame: Up to 8 weeks 
3. Title: Percentage of Participant Preference for In-person, Telemedicine, or Both 
Session Formats 
Description: Percentage of participant preference for in-person, telemedicine, or 
both sessions formats as assessed categorically during the Treatment Satisfaction 
Interview.  

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
15 
Time Frame: Up to 8 weeks 
 
Descriptive statistics will assess the preliminary feasibility with respect to participant 
satisfaction with the initial version of the CRAFT-F/FT protocol and session completion % at 
post-intervention. We will also review recorded interview/focus group data as qualitative 
feedback to inform a feasible revised protocol tailored to the unique needs of families with 
co-occurring substance use disorders and FEP. Following iterative feasibility testing of the 
revised protocol, we will again conduct descriptive statistics and collect feedback to confirm 
its feasibility. GLM and correlational analyses will be used to explore preliminary efficacy of 
the intervention and its relationship with sample characteristics.  
 
Phase 2 Outcome measures for statistical analysis include: 
Primary 
Outcome 1 
Title: Mean readiness to change substance use 
Description: Mean readiness to cutdown/quit using [most problematic substance] for 
the client with psychosis using importance-confidence-readiness rulers (0 = not at all to 
10 = extremely). 
Time Frame: Baseline, mid-intervention (week 4), post-intervention (week 8) 
Secondary  
Outcome 2 
Title: Percentage of Session Attendance  
Description: Percentage of treatment sessions attended by the client with psychosis 
in past 30 days. 
Time Frame: Baseline, mid-intervention (week 4), post-intervention (week 8) 
Outcome 3 
Title: Substance Use  
Description: Client Timeline Follow Back (TLFB) past 30 day substance use, urine 
toxicology screen for drugs of abuse. 
Time Frame: Baseline, mid-intervention (week 4), post-intervention (week 8) 
Outcome 4 
Title: Family Wellbeing: Depression 
Description: Beck Depression Inventory-II total; scores range from 0 to 63 with higher 
scores representing more severe depressive symptoms.  
Time Frame: Baseline, mid-intervention (week 4), post-intervention (week 8) 
Outcome 5 
Title: Family Wellbeing: Anxiety 
Description: State-Trait Anxiety Inventory-Short Form; total scores range from 6 to 24 
with higher scores representing more severe anxiety symptoms. 
Time Frame: Baseline, mid-intervention (week 4), post-intervention (week 8) 
Outcome 6 
Title: Family Wellbeing: Relationship  
Description: General Happiness item on Relationship Happiness Scale; scores range 
from 1 to 10 with higher scores representing greater relationship happiness. 
Time Frame: Baseline, mid-intervention (week 4), post-intervention (week 8) 
 
For the randomized controlled trial phase, repeated measures random regression analyses 
comparing the rate of change between groups (CRAFT-EP + TAU vs. TAU alone) for the 
primary analyses (treatment engagement: FEP client readiness to change substance use), 
as well as secondary analyses (treatment engagement % session attendance, substance 
use outcomes, and family wellbeing measures). We will use a model for the mean of the 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
16 
outcome variable that includes terms for intervention, time, and the intervention-by-time 
interaction, and we will use generalized estimating equations to adjust standard errors for 
the correlation of observations within individuals. The coefficient for the intervention-by-
time interaction term at after session 8 quantifies the difference between groups at session 
8, adjusted for baseline. In separate analyses, we will use linear regression to explore the 
association between baseline predictor variables with treatment engagement, substance 
use, and family wellbeing outcomes. We will perform exploratory analyses of the 3-month 
follow-up time point and potential moderating effects of sex to inform the design of future 
studies.  
 
Power. N/A 
 
VII.  Risks and Discomforts 
 
One potential risk is a breach of confidentiality. This could lead a subject’s employer, 
insurance company, or others to learn about their participation in the research study.  
 
It is possible that some of the questions in the medical, personality or psychiatric 
assessments and tasks may cause subjects to become fatigued or emotionally upset and 
distressed, but this is unlikely and would be expected to be very mild should it occur. 
Subjects will be informed that they may take a break at any time or refuse to answer any 
questions that they wish. Study personnel will be trained to manage any distress that arises. 
 
 
 
VIII.  Potential Benefits 
 
There are no known direct benefits to subjects. For participants assigned to the CRAFT-EP 
intervention, possible benefits may include gaining additional support and coping skills. 
Families with a history of psychosis and/or substance use may benefit in the future from 
what we learn in this study.  
 
IX.  Monitoring and Quality Assurance 
 
The PI will have responsibility for continuous monitoring of data and safety of subjects in 
the study. Data and safety monitoring will take place continuously throughout the study 
during weekly study meetings, and we will review deviations and adverse events in monthly 
meetings. We will report both adverse events and all serious adverse events that occur 
during the study to the Partners IRB. We will provide the Partners IRB with a summary of 
any unexpected and related adverse events as well as any other unanticipated problems 
that occurred at the time during the annual continuing review. 
 
Suicidality: If participants spontaneously report suicidality during the phone screen or 
study visit or if they endorse suicidality on an instrument (MADRS response 4 or 6 on item 
10; SCID-5 response of 2 or 3 on A17 or affirmative response on OP9-OP12 and OP14; 
BDI-II response 2 or greater on item 9), research staff will implement the study suicidality 
standard operating procedures. 
Domestic Violence: If participants spontaneously report a history of domestic violence with 
a member of their current household or if they endorse such a history on an instrument 
(phone screen domestic violence question affirmative response involving a member of their 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
17 
current household, SCID-5 response L1-8 affirmative response with respect to domestic 
violence involving a member of their current household), research staff will implement the 
study domestic violence standard operating procedures.  
 
All adverse events and unanticipated problems involving risks to subjects or others will be 
investigated by the PI and reported to the PHRC in accordance with the PHRC adverse event 
and unanticipated problems reporting guidelines.  
 
The PI will ensure that the study adheres to the IRB-approved protocol and will frequently 
monitor the overall progress of the study. 
 
 
X.  References 
Cather et al. (2017). Improved depressive symptoms in adults with schizophrenia during a 
smoking cessation attempt with varenicline and behavioral therapy. J. Dual Diagn. 13, 168-
178. 
 
Conus et al. (2010). Rate and predictors of service disengagement in an epidemiological 
first-episode psychosis cohort. Schizophrenia Research, 118, 256–263. 
 
Dixon et al. (2016). Treatment engagement of individuals experiencing mental illness: 
review and update. World Psychiatry, 15, 13–20. 
 
Doyle et al. (2014). First-episode psychosis and disengagement from treatment: a 
systematic review. Psychiatric Services, 65(5), 603–611.  
 
Drapalski et al. (2018). Family involvement in the clinical care of clients with first-episode 
psychosis in the RAISE Connection Program. Psychiatric Services, 69(3), 358–361.  
 
Hulsbosch et al. (2017). Videoconferencing in a mental health service in The Netherlands: 
A randomized controlled trial on patient satisfaction and clinical outcomes for outpatients 
with severe mental illness. Journal of Telemedicine and Telecare, 23(5), 513-520.  
 
Kane et al. (2016). Comprehensive Versus Usual Community Care for First-Episode 
Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program.American 
Journal of Psychiatry, 173(4), 362–372.  
 
Meyers et al. (1999). Community reinforcement and family training (CRAFT): Engaging 
unmotivated drug users in treatment. Journal of Substance Abuse, 10(3), 291–308.  
 
Oluwoye et al. (2019). Impact of tobacco, alcohol and cannabis use on treatment outcomes 
among patients experiencing first episode psychosis: Data from the national RAISE-ETP 
study. Early Intervention in Psychiatry, 13(1), 142–146. 
 
Orford et al. (2013). Addiction in the family is a major but neglected contributor to the 
global burden of adult ill-health. Social Science & Medicine, 78, 70-77.  
 
Shinn et al., (2015). McLean OnTrack: A transdiagnostic program for early intervention in 
first-episode psychosis. Early Interv. Psych. 11, 83-90.  
 
Tse et al. (2015). Teletherapy delivery of caregiver behavior training for children with 
attention-deficit hyperactivity disorder. Telemedicine and e-Health,21(6), 451-458. 

 
Substance Use and Psychosis 
 
Version Date: March 28, 2024 
18