MDMA-assisted Therapy for Adjustment Disorder (AD) in Dyads of Patients With Cancer and a Concerned Significant Other

Inclusion Criteria:

1. Are at least 18 years old

2. Are considered important to their well-being by patient participants (e.g., spouseor close family member)

3. Meet DSM-5 criteria for current AD (no criteria for another mental disorder and doesnot correspond to an exacerbation of a preexisting mental disorder. Does notrepresent a normal bereavement)

4. Satisfies diagnostic criteria for AD using the ADNM-2020 (score ≥ 47.5 on the scale)

5. Are able to swallow pills.

6. Are willing to be driven home after the experimental sessions, either by a driverarranged by the participant or by the site personnel or taxi and agree not to driveafter each Experimental Session until the therapists deem it safe to do so

7. If able to become pregnant (i.e. assigned female at birth, fertile, followingmenarche and until becoming post-menopausal unless permanently sterile), must have ahighly sensitive negative pregnancy test at study entry and prior to eachExperimental Session, and must agree to use adequate birth control through 10 daysafter the last Experimental Session. Adequate birth control methods includeintrauterine device (IUD), injected, implanted, intravaginal, or transdermalhormonal methods, abstinence, oral hormones plus a barrier contraception,vasectomized sole partner, or double barrier contraception. Two forms ofcontraception are required with any barrier method or oral hormones (i.e. condomplus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptivesplus spermicide or condom).

8. Must agree to inform the Clinical Investigators within 48 hours of any medicalconditions and procedures

9. Are proficient in speaking and reading English

10. Agree to have all clinic visit sessions recorded to audio and video

11. Agree to the following lifestyle modifications (described in more detail in Section 4.3 Lifestyle Modifications): comply with requirements for fasting and refrainingfrom certain medications prior to Experimental Sessions, not enroll in any otherinterventional clinical trials during the duration of the study, be driven homeafter each Experimental Session, and commit to medication dosing, therapy, and studyprocedures.

12. May have well-controlled hypertension that has been successfully treated withanti-hypertensive medicines, if they pass additional screening to rule outunderlying cardiovascular disease.

13. May have asymptomatic Hepatitis C virus (HCV) that has previously undergoneevaluation and treatment as needed.

14. May have alcohol or substance use disorder if participant is not in withdrawal orrequiring detox. Participants must have a plan, agreed upon by investigator, therapyteam, and study physician, to reduce use of alcohol or other substances and tomanage symptoms without self-medicating. Enrollment will require that, in thejudgment of the investigator, therapy team, and study physician, the plan fordecreasing substance use is realistic and has a good chance of succeeding in orderto prevent substance use from impacting the safety or efficacy of theinvestigational treatment.

15. May have a history of or current Diabetes Mellitus (Type 2) if additional screeningmeasures rule out underlying cardiovascular disease, if the condition is judged tobe stable on effective management, and with approval by the study physician.

16. May have hypothyroidism if taking adequate and stable thyroid replacementmedication.

17. May have a history of, or current, glaucoma if approval for study participation isreceived from an ophthalmologist.

Exclusion Criteria:

1. Concurrent or recent (less than four weeks) cytotoxic chemotherapy or radiationtherapy, that impairs general level of physical functioning (index participant)

2. Weigh less than 48 kg not correspond to an exacerbation of a preexisting mental disorder. Does not
represent a normal bereavement)
 

3. Satisfies diagnostic criteria for AD using the ADNM-2020 (score ≥ 47.5 on the scale)
 

4. Are able to swallow pills.
 

5. Are willing to be driven home after the experimental sessions, either by a driver
arranged by the participant or by the site personnel or taxi and agree not to drive
after each Experimental Session until the therapists deem it safe to do so
 

6. If able to become pregnant (i.e. assigned female at birth, fertile, following
menarche and until becoming post-menopausal unless permanently sterile), must have a
highly sensitive negative pregnancy test at study entry and prior to each
Experimental Session, and must agree to use adequate birth control through 10 days
after the last Experimental Session. Adequate birth control methods include
intrauterine device (IUD), injected, implanted, intravaginal, or transdermal
hormonal methods, abstinence, oral hormones plus a barrier contraception,
vasectomized sole partner, or double barrier contraception. Two forms of
contraception are required with any barrier method or oral hormones (i.e. condom
plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives
plus spermicide or condom).
 

7. Must agree to inform the Clinical Investigators within 48 hours of any medical
conditions and procedures
 

8. Are proficient in speaking and reading English
 

9. Agree to have all clinic visit sessions recorded to audio and video
 

10. Agree to the following lifestyle modifications (described in more detail in Section
 4.3 Lifestyle Modifications): comply with requirements for fasting and refraining
from certain medications prior to Experimental Sessions, not enroll in any other
interventional clinical trials during the duration of the study, be driven home
after each Experimental Session, and commit to medication dosing, therapy, and study
procedures.
 

11. May have well-controlled hypertension that has been successfully treated with
anti-hypertensive medicines, if they pass additional screening to rule out
underlying cardiovascular disease.
 

12. May have asymptomatic Hepatitis C virus (HCV) that has previously undergone
evaluation and treatment as needed.
 

13. May have alcohol or substance use disorder if participant is not in withdrawal or
requiring detox. Participants must have a plan, agreed upon by investigator, therapy
team, and study physician, to reduce use of alcohol or other substances and to
manage symptoms without self-medicating. Enrollment will require that, in the
judgment of the investigator, therapy team, and study physician, the plan for
decreasing substance use is realistic and has a good chance of succeeding in order
to prevent substance use from impacting the safety or efficacy of the
investigational treatment.
 

14. May have a history of or current Diabetes Mellitus (Type 2) if additional screening
measures rule out underlying cardiovascular disease, if the condition is judged to
be stable on effective management, and with approval by the study physician.
 

15. May have hypothyroidism if taking adequate and stable thyroid replacement
medication.
 

16. May have a history of, or current, glaucoma if approval for study participation is
received from an ophthalmologist.
 
 Exclusion Criteria:
 

17. Concurrent or recent (less than four weeks) cytotoxic chemotherapy or radiation
therapy, that impairs general level of physical functioning (index participant)
 

18. Weigh less than 48 kg
 

19. Condition impairing oral intake or digestive absorption

20. Are not able to give adequate informed consent

21. Significant suicide risk as defined by suicidal ideation with intend and a plan asendorsed on items 5 on the C-SSRS within the past 6 months or at V0 (see Appendix A)

22. Have any current problem which, in the opinion of the investigator or studyphysician, might interfere with participation

23. Would present a serious risk to others as established through clinical interview andcontact with treating psychiatrist.

24. Have a history of, or a current primary psychotic disorder, major depressivedisorder with psychotic features, bipolar affective disorder type 1 or history of orcurrent dissociative identity disorder

25. Require ongoing concomitant therapy with a psychiatric medication with exceptionsdescribed in Section 8.0: Concomitant Medications.

26. Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment.

27. Have used Ecstasy (material represented as containing MDMA) more than 10 timeswithin the last 10 years or at least once within 6 months of the first ExperimentalSession;

28. Have a history of ventricular arrhythmia at any time, other than occasionalpremature ventricular contractions (PVCs) in the absence of ischemic heart disease.

29. Have Wolff-Parkinson-White syndrome or any other accessory pathway that has not beensuccessfully eliminated by ablation.

30. Have a history of arrhythmia, other than premature atrial contractions (PACs) oroccasional PVCs in the absence of ischemic heart disease, within 12 months ofscreening. Participants with a history of atrial fibrillation, atrial tachycardia, atrialflutter or paroxysmal supraventricular tachycardia or any other arrhythmiaassociated with a bypass tract may be enrolled only if they have been successfullytreated with ablation and have not had recurrent arrhythmia for at least one yearoff all antiarrhythmic drugs, and confirmed by a cardiologist.

31. Have evidence or history of significant (controlled or uncontrolled) hematological,endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, renal,gastrointestinal, immunocompromising, or neurological disease, including seizuredisorder, or any other medical disorder judged by the investigator to significantlyincrease the risk of MDMA administration (participants with hypothyroidism who areon adequate and stable thyroid replacement will not be excluded). Note: ifparticipants present with a history of glaucoma, enrollment would be allowed onlywith the approval of their ophthalmologist

32. Have uncontrolled hypertension using the standard criteria of the American HeartAssociation (values of 140/90 milligrams of Mercury [mmHg] or higher assessed onthree separate occasions)

33. Have a heart rate > 100 bpm on three separate occasions

34. Have a marked Baseline prolongation of QT/QTc interval (For purposes of eligibility,this is defined as repeated demonstration of a QT interval corrected usingFridericia's formula [QTcF] >450 milliseconds [ms] and >460 ms in females. Fortransgender or non-binary participants, QTc interval will be evaluated based on sexassigned at birth, unless the participant has been on hormonal treatment for five ormore years.

35. Have a history of additional risk factors for Torsade de pointes (e.g., heartfailure, hypokalemia, family history of Long QT Syndrome)

36. Require use of concomitant medications that prolong the QT/QTc interval duringExperimental Sessions. Refer to Section 12.0 Concomitant Medications.

37. Have symptomatic liver disease

38. Have history of hyponatremia or hyperthermia

39. Are pregnant, nursing, or able to become pregnant and are not practicing aneffective means of birth control.

40. Have hypersensitivity to any ingredient of the IMP (Investigational MedicinalProduct).