Clinical TrialMajor Depressive Disorder (MDD)LSDPlaceboNot yet recruiting

Shortened LSD Intervention for Major Depressive Disorder

This Phase I, open-label, single-group trial (n=10) will evaluate the safety and potential clinical effectiveness of a shortened LSD experience in adults with major depressive disorder (MDD). Participants will receive oral LSD hemi-L-tartrate 250 µg followed 45 minutes later by oral risperidone 1 mg, with the aim of assessing whether risperidone can abbreviate the subjective effects of LSD while still offering possible antidepressant benefit. The study will enrol adults aged 21 to 70 years with DSM-5 MDD and a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 28 at screening. Participants will be monitored for 10.5 hours after dosing and assessed at several time points for subjective effects and discharge readiness. The primary outcome is change in MADRS at 1 month.

Target Enrollment
10 participants
Study Type
Phase I interventional
Design
Non-randomized

Detailed Description

The purpose of this study is to determine the safety and clinical effectiveness of a shortened lysergic acid diethylamide (LSD) experience. This will be achieved by administering the drug risperidone 45-minutes after the administration of LSD.

Study Arms & Interventions

LSD + Risperidone

experimental

Interventions

  • LSD250 mcg
    via Oral• single dose, followed 45 minutes later by risperidone• 1 doses total
  • Placebo1 mg
    via Oral• single dose, given 45 minutes after LSD• 1 doses total

    Unmatched intervention: Risperidone

Participants

Ages
21 – 70
Sexes
Male & Female

Inclusion Criteria

  • Have given written informed consent
  • Meet DSM-5 criteria for MDD
  • MADRS \>= 28 at screening Can read, write, and speak English fluently
  • Be judged by study team clinicians to be at low risk for suicidality

Exclusion Criteria

  • Women who are pregnant, nursing, or not practicing an effective means of birth control
  • Cardiovascular conditions: hypertension with resting blood pressure systolic \>139 or diastolic \>89, angina, heart rate \> 99, a clinically significant ECG abnormality (e.g., atrial fibrillation, QTc \> 450), TIA in the last 6 months stroke, peripheral or pulmonary vascular disease, cardiac valvulopathy
  • Epilepsy
  • Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
  • Currently taking antipsychotics, or MAO inhibitors
  • Patients taking antidepressant medications and unable to taper
  • Moderate or strong CYP2D6 inhibitor antidepressants must undergo a washout period of 4 weeks or five half-lives prior to treatment
  • Currently taking CYP2D6 inhibitor other than an antidepressant that will be tapered
  • Currently taking efavirenz, Acetaldehyde dehydrogenase inhibitors such as disulfiram (Antabuse), Alcohol dehydrogenase inhibitors, or UGT1A9 inhibitors or UGT1A10 inhibitors such as phenytoin, regorafenib, eltrombopag
  • Have a seizure disorder, multiple sclerosis, history of significant head trauma, CNS tumor, movement disorders or any neurodegenerative condition
  • Morbidly obese (\>100 lbs. above ideal body weight, or BMI \>=40, or BMI \>=35 with high blood pressure or diabetes)
  • Be judged by a study team clinician to be at risk for moderate or severe alcohol or benzodiazepine withdrawal
  • Body weight \< 45 kg
  • Significant acute adverse reaction (e.g., dystonia) to an antipsychotic
  • Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (including substance-induced), Bipolar I or II Disorder or Major
  • Depression with psychotic features
  • Have a first degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or Bipolar I Disorder.

Study Details

Study Team

Sponsors & Collaborators

Investigators

  • SN
    Sandeep Nayak

Locations

Johns Hopkins Center for Psychedelic and Consciousness Research — Baltimore, Maryland, United States

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