None listed
Conditions
Brief summary
EMMAC is a randomised controlled trial studying the effects of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer patients. Standard dose MDMA (120mg + optional 60mg) will be compared to a psychoactive placebo (Methylphenidate 20mg + optional 10mg) with both being given as a single dose. On the basis of MDMA pharmacology and recent research showing promising results with the use of psilocybin to reduce anxiety and depression in patients with advanced-stage cancer (Grob et al., 2011, Griffiths et al., 2016, Ross et al., 2016) we hypothesise that MDMA may have the potential to achieve similar positive mental health outcomes with reduced psychological risk given the differences in psychopharmacological effects.
Interventions
Single dose 3, 4-Methylenedioxymethamphetamine (MDMA) in the context of MDMA-assisted therapy.
Participants will undergo a single session of MDMA assisted-therapy. Participants will receive a 120mg oral dose. If meeting criteria, an optional supplemental 60mg oral dose will be offered after 2 hours to control for inter-participant differences in dose-response. Blood pressure and pulse rate will be measured at 2 hours, if the BP is <160 and HR <110 and/or stabilising/trending down after re-ass
Single dose 3, 4-Methylenedioxymethamphetamine (MDMA) in the context of MDMA-assisted therapy. Participants will undergo a single session of MDMA assisted-therapy. Participants will receive a 120mg oral dose. If meeting criteria, an optional supplemental 60mg oral dose will be offered after 2 hours to control for inter-participant differences in dose-response. Blood pressure and pulse rate will be measured at 2 hours, if the BP is <160 and HR <110 and/or stabilising/trending down after re-assessing at 5min intervals and both therapists are in agreement, then the supplemental dose will be made available to the participant. Participants will have the option to accept or decline the supplemental dose based on whether they feel there has been a subjective adequate effect. This choice can be discussed with the therapists. Participants will undergo 8 hours of supervised medication-assisted therapy in a comfortable non-clinical environment, with a therapeutic approach guided by the Aotearoa/New Zealand Manual for MDMA-assisted therapy treatment of depression and anxiety in the context of advanced-stage cancer. For each medication-assisted therapy session, participants will undergo 2 x 90-minute therapeutic support sessions in the week preceding (e.g. to prepare for dosing, cover psychoeducational topics, explore important issues that may arise during the dosing session). Participants will also undergo 1 x 90-minute therapeutic support session the day after dosing (eg. for debrief, integration of experience, explore spiritual/other changes experienced after dosing). The MAPS model for MDMA-assisted therapy will be followed - two therapists will be present with the participant for all pre and post MDMA-assisted therapy sessions and will both be present for 8 hours on the dosing day. All psychotherapists will have a professional qualification in either counselling, social work, psychotherapy, psychology, nursing or medicine, or equivalent experience and have formal training and supervision with MAPS. Sessions will be audio and video recorded for qualitative analysis and to assess therapist adherence to the therapy manual.
Sponsors
University of Otago
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosed with advanced-stage cancer (stage 3 or 4). 2. Prognosis of at least 3 months life expectancy from the time of screening 3. DSM-5 diagnosis of a depressive disorder, an anxiety disorder, and/or an adjustment disorder/stress reaction. 4. MADRS score > 15 and HAM-A score > 12 5. Are at least 18 years old 6. Are able to swallow pills 7. The participant agrees to have study visits recorded 8. Must agree to inform the investigators within 48 hours of any medical conditions and procedures 9. Must be willing for the investigators to communicate directly with their medical team (oncologist, GP, palliative care physician, etc). 10. Agree to refrain from starting any new psychiatric medication and/or psychotherapy during the study period. 11. Willing to follow restrictions and guidelines concerning consumption of food, beverages, including caffeine and nicotine the night before and just prior to medication dosing. 12. Agree to have transportation other than driving themselves to where they are staying on the day of medication dosing. 13. Are able and willing to be contacted via telephone for all necessary telephone contacts. 14. Must have a negative pregnancy test if able to become pregnant, and agree to use an effective form of contraception for 10 days following the last experimental session if of child-bearing potential (Effective forms of contraception include: IUD, injected, implanted, intravaginal, or transdermal hormonal methods, abstinence, oral hormones plus barrier contraception, vasectomized sole partner, or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones. Not of childbearing potential is defined as permanent sterilization, postmenopausal, or assigned male at birth.). 15. Must provide a contact/support person in the event of the participant being unreachable by study staff or in the event of severe emergent distress or suicidality. 16. Are proficient in speaking and reading English. 17. Agree to not use any medications on the prohibited medications list during the study. 18. Agree to the lifestyle modifications illustrated below, comply with requirements for fasting, refrain from certain medications prior to Experimental Sessions, not participate in any other interventional clinical trials during the duration of the study, remain at the study site after each Experimental Session until cleared to be driven home after, and commit to medication dosing, therapy, and study procedures. All participants must agree to the following lifestyle modifications at enrollment and throughout the duration of the study. Participants are eligible to enroll in the study if they: • Are willing to commit to medication dosing, therapy sessions, follow-up sessions, completing evaluation instruments, and all necessary telephone contact. • Agree to not participate in any other interventional clinical trials during the duration of this study. Leading up to Experimental Sessions • Agree to take nothing by mouth except alcohol-free liquids after 12:00 A.M. (midnight) the evening before each Experimental Session. • Refrain from the use of any psychoactive medication not approved by the research team from Baseline through Study Termination. • Agree not to use caffeine or nicotine for 2 hours before and at least 6 hours after the initial dose during each Experimental Session. • Are willing to comply with medication requirements per protocol. Medications will only be discontinued after enrollment per clinical judgment of the site physician in consultation with the prescribing physician. • Are on a stable dose of allowable opiates for 2 weeks leading up to the Experimental Session as determined by the study physician.. During this period and throughout the study, the participant will be allowed to take their usual pain medication if needed for breakthough pain. • Agree that, for 1 week preceding each Experimental Session to refrain from: o Taking any herbal supplement (except with prior approval of the research team). o Taking any nonprescription medications (with the exception of non-steroidal anti-inflammatory medications or acetaminophen/paracetamol unless with prior approval of the research team). o Taking any prescription medications (with the exception of birth control, thyroid hormones, or other medications approved by the research team).
Exclusion criteria
1. Pregnancy or lactation 2. BMI < 15 3. Recent or current use of illicit drugs including methamphetamine, heroin, and synthetic cannabinoids. Other non-prescribed drugs will prompt exclusion at the discretion of the study physician 4. Unable to give adequate informed consent 5. Upon review of past and current drugs/medication must not be taking a medication that is exclusionary (see Study Reference Manual), or has stopped taking an exclusionary drug for less than the requisite washout period (see Study Reference Manual) 6. Liver function test >3 times the upper limit of normal or creatinine clearance <30 mL/min 7. Upon review of medical or psychiatric history must not have any current or past diagnosis that would be considered a risk for participation in the study. Any participant presenting current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS, and clinical judgement of the investigator will be excluded; however, history of suicide attempts is not, in itself, exclusionary. Any participant who is likely to require hospitalization related to suicidal ideation and behaviour, in the judgement of the Study physician will not be enrolled. Any participant presenting with the following on the Baseline C-SSRS will be excluded: - Suicidal ideation score of >4 within the last month, at a frequency of once a week or more - Suicidal ideation score of 5 within the last 6 months - Any suicidal behaviour, including suicide attempts or preparatory acts, within the last 6 months. Participants with non-suicidal self-injurious behaviour may be included if approved by the Study physician 8. Have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of increases in blood pressure and heart rate. This includes, but is not limited to, a history of myocardial infarction, cerebrovascular accident, or aneurysm. Participants with other mild, stable chronic medical problems may be enrolled if the site physician, CI, and Study physician agree the condition would not significantly increase the risk of MDMA administration or be likely to produce significant symptoms during the study that could interfere with study participation or be confused with side effects of the IMP. Examples of stable medical conditions that could be allowed include, but are not limited to diabetes mellitus (Type 2), human immunodeficiency virus (HIV) infection, gastroesophageal reflux disease (GERD), etc. Any medical disorder judged by the investigator to significantly increase the risk of MDMA administration by any mechanism would require exclusion. 9. Have uncontrolled essential hypertension using the standard criteria of the American Heart Association (values of 140/90 milligrams of mercury [mmHg] or higher assessed on three separate occasions). 10. Have a history of ventricular arrhythmia at any time, other than occasional premature atrial contractions (PACs) or premature ventricular contractions (PVCs) in the absence of ischemic heart disease. 11. Have Wolff-Parkinson-White syndrome or any other accessory pathway that has not been successfully eliminated by ablation. 12. Have a history of arrhythmia, other than occasional PACs or PVCs in the absence of ischemic heart disease, within 12 months of screening. Participants with a history of atrial fibrillation, atrial tachycardia, atrial flutter or paroxysmal supraventricular tachycardia or any other arrhythmia associated with a bypass tract may be enrolled only if they have been successfully treated with ablation and have not had recurrent arrhythmia for at least one year off all antiarrhythmic drugs, and confirmed by a cardiologist. 13. Have a marked Baseline prolongation of QT/QTc interval e.g., repeated demonstration of a QTc interval >450 milliseconds (ms) in males and >460 ms in females. For transgender or non-binary participants, QTc interval will be evaluated based on sex assigned at birth, unless the participant has been on hormonal treatment for 5 or more years. Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome). 14. Require use of concomitant medications that prolong the QT/QTc interval during Experimental Sessions. Refer to Section 8.2 15. Have any current problem which, in the opinion of the investigator or Study physician, might interfere with participation
Outcome results
None listed