Testing 3,4-Methylenedioxymethamphetamine with Methylphenidate against a placebo for chronic neuropathic pain

Exclusion

• −Known hypersensitivity to study drugs or any study drug excipients
• −Past or current history of a psychotic disorder, mania, hypomania, bipolarity, current suicidal ideation, stimulant use disorder (i.e., cocaine, amphetamine, methamphetamine, MDMA, methylphenidate (Ritalin), etc , and any other substance use disorder within the past 12 months assessed by history and confirmed the Mini-International Neuropsychiatric Interview \[MINI\]. Other secondary psychiatric comorbidities (e.g., anxiety disorders, trauma related disorders, other personality disorders. etc.) will not be excluded
• −Participants with a history of suicide attempts are not excluded unless a significant risk of suicidal behavior is present at the time of screeningScreeningThe checks done before joining, to see whether a study fits.Read more → as determined by the CRSS (Columbia suicide rating scale)
• −History of prior MDMA use (excluded to maintain blinding integrity)
• −Long QT syndrome, measured by an ECG with a QTc more than 450 ms for males, and 470 ms for females.
• −Presence of a relative or absolute contraindication to MDMA or Methylphenidate:
• −Cerebrovascular conditions: acute stroke or recent history of intracerebral hemorrhage (ischemic or hemorrhagic stroke occurring within the past 6 months)
• −Conditions at risk of elevation of blood pressure and increase heart rate, such as glaucoma, tension, agitation, thyrotoxicosis, pheochromocytoma
• −Motor tics and/or family history or diagnosis of Tourette's syndrome
• −Moderate to severe chronic kidney disease or kidney failure, such as requiring dialysis, significant treatment adjustments for kidney function, or regular nephrologist follow-upFollow-upContinued check-ins after the treatment part is finished.Read more →)
• −Moderate to severe liver disease, such as cirrhosis, a history of significant jaundice unrelated to temporary illness, or any liver condition requiring regular monitoring by a specialist).
• −Current treatment with selective serotonin reuptake inhibitors (SSRI's) and serotonin-norepinephrine reuptake inhibitors (SNRI's), tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans) and 5-HT3 receptor antagonist antiemetics (risk of Serotonin Syndrome)
• −Hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (methylphenidate contains lactose)
• −Seizure disorders
• −Medications that interact with study drugs including:
• −Any lifetime history use of any stimulant medication (e.g., Adderall, Vyvanse, Ritalin)
• −Caffeine intake within 24 hours
• −Monoamine oxidase inhibitors (MAOI) within 14 days (e.g. phenelzine, moclobemide, isoniazid, linezolid, phenelzine, harmine) due to risk of hypertensive crisis
• −CYP2D6 substrates and modifiers (such as: buproprion, fluoxetine, paroxetine, duloxetine, mirabegron).
• −Adrenergic agents (e.g. clonidine) risk of sudden death
• −Vasopressor agents (ephedrine pseudoephedrine)
• −Coumarin anticoagulants (e.g., warfarin),
• −Anticonvulsants (e.g., phenobarbital, diphenylhydantoin, primidone)
• −Anti-psychotics and inhibitors of dopamine uptake (e.g. haloperidol, DOPA, tricyclic antidepressants)
• −Concomitant medication that could prolong ECG QT interval (e.g. ondansetron, risperidone, methadone)
• −Selective Serotonin Reuptake Inhibitors (citalopram, sertraline, fluvoxamine, escitalopram)
• −Selective Norepinephrine Uptake Inhibitors (e.g. venlafaxine, duloxetine); Serotonergic Drugs (e.g. dextromethorphan, fentanyl, St. John's Wort, tramadol, 5-hydroxytryptophan); serotonin 5-HT1 receptor agonists (triptans) and 5-HT3 receptor antagonist antiemetics due risk of Serotonin Syndrome which is a potentially life- threatening condition
• −Currently engaged in psychotherapy for CNP (other psychotherapy for non-CNP is allowed).
• −Any other clinically significant medical illness that, in the opinion of the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study.
• −Pregnancy, or breastfeeding
• −Pre-existing cardiovascular disorders evidenced in clinical records or disclosed on patient self-report, such as: uncontrolled hypertension (sustained blood pressure ≥160/100 mmHg), angina (ongoing angina at rest, recent hospitalization for acute coronary syndrome within the past 3 months, or a history of revascularization (e.g., stenting or bypass surgery) within the past 6 months), arterial occlusive disease; heart failure, hemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction (within the past 6 months), potentially life-threatening arrhythmias (new-onset within the last 3 months), arrhythmias causing hemodynamic instability (SBP \< 90 mm Hg), or requiring urgent intervention (e.g., atrial fibrillation with rapid ventricular response or ventricular tachycardia), channelopathies, aneurysmal vascular disease (e.g., thoracic and/or abdominal aorta, intracranial, and peripheral arterial vessels), advanced arteriosclerosis