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Principal Investigator: Anahita Bassir Nia
Organization: YALE UNIVERSITY
Fiscal Year: 2024
Award: $155,444
Funding agency: National Institute on Alcohol Abuse and Alcoholism
ABSTRACT
There is an urgent need to develop novel pharmacological treatment for alcohol use disorder (AUD). Recently,
psychedelic compounds have attracted great attention in treatment of different psychiatric disorders following
their reported fast-acting and long-lasting effects. Preliminary evidence from observational studies, supported
by animal studies, is promising for the potential therapeutic effects of psychedelic N,N-dimethyltryptamine
(DMT) for AUD. Here, we propose to investigate the therapeutic potential of a single dose of intravenous DMT
plus a brief course of psychotherapy (including Motivational Enhancement Therapy (MET)) on alcohol
consumption in non-treatment seeking individuals with AUD, in a proof-of-concept, randomized (1:1), placebo-
controlled, double-blind, parallel group, laboratory study and clinical trial.
Methods: Otherwise healthy individuals with diagnosis of moderate to severe AUD (based on DSM5) will be
randomized to receive a single dose of intravenous DMT or active placebo (diphenhydramine). Vitals will be
closely monitored, tolerability will be measured using a Visual Analogue Scale (VAS), and DMT acute
psychedelic effects will be assessed using the Mystical Experience Questionnaire (MEQ), at the end of the
dosing day. Adverse events will be assessed using the Systematic Assessment for Treatment Emergent
Effects (SAFTEE) interview on the dosing day and weekly follow up sessions (4 weeks). One day following
drug administration, participants will attend an experimental session using Alcohol Drinking Paradigm (ADP).
All participants will consume a priming dose of alcohol at the beginning of the experimental session, which will
be followed by two 1-hour self-administration drinking sessions, over which participants will have a choice of
consuming a total of 8 drinks or receiving $5 for each drink that is not consumed. The total number of
consumed drinks is the main primary outcome. All participants will receive a brief course of psychotherapy
(including MET). We will explore the effects of DMT (plus brief psychotherapy) on participants' natural alcohol
consumption weekly for 4 weeks, using Timeline follow-back (TLFB), to measure the percentage of heavy
drinking days, abstinent days, and total amount of alcohol consumption and categorical outcomes of
abstinence, no heavy drinking and a 2-level reduction in WHO drinking risk will be compared.
Hypotheses: Relative to control (diphenhydramine, IV, 25 mg plus MET), a single psychedelic dose of
intravenous (IV) DMT (0.3 mg/kg) plus brief psychotherapy (including MET) in individuals with AUD will 1) be
safe and well-tolerated, 2) reduce alcohol consumption measured in the laboratory using Alcohol Drinking
Paradigm, the day after, and 3) reduce alcohol drinking over the following 4 weeks.
Terms: <5-HT-2A Gene><5-HT2A><5-Hydroxytryptamine (Serotonin) Receptor 2A Gene><5-Hydroxytryptamine Receptor 2A><5-Hydroxytryptamine Receptor 2A Gene><Absolute ethanol><Abstinence><Active Follow-up><Acute><Adverse Experience><Adverse event><Alcohol Chemical Class><Alcohol Drinking><Alcohol consumption><Alcohols><Animals><Anxiety><Attention><Ayahuasca><Back><Banisteriopsis><Benadryl><Bendylate><Benhydramin><Benzhydramine><Binding><Brief Psychotherapy><Cause of Death><Clinical><Clinical Trials><Consumption><Cross-Product Ratio><DSM-5><DSM-V><DSM5><Development><Diagnosis><Diagnostic and Statistical Manual of Mental Disorders, 5th edition><Diagnostic and Statistical Manual of Mental Disorders-V><Dimethyltryptamine><Diphenhydramine><Diphenylhydramin><Diphenylhydramine><Dorsum><Dose><Double-Blind Method><Double-Blind Study><Double-Blinded><Double-Masked Method><Double-Masked Study><Drugs><ETOH><ETOH level><Eldadryl><Emotional Depression><EtOH drinking><EtOH use><Ethanol><Ethyl Alcohol><FDA approved><Grain Alcohol><HTR2><HTR2 Gene><HTR2A><HTR2A gene><Hallucinogenic Agents><Hallucinogenic Drugs><Hallucinogenic Substances><Hallucinogens><Heavy Drinking><Hospitals><Hour><Human><Indigenous><Individual><Interview><Intravenous><LSD-25><Laboratories><Laboratory Study><Literature><Long-Term Effects><Longterm Effects><Lysergic Acid Diethylamide><Lysergide><Measures><Medical><Medication><Medicine><Mental Depression><Mental disorders><Mental health disorders><Meta-Analysis><Methodology><Methods><Methylcarbinol><Mice><Mice Mammals><Modern Man><Molecular Interaction><Monitor><Murine><Mus><N,N-Dimethyltryptamine><N,N-dimethyl-1H-indole-3-ethanamine><Observation research><Observation study><Observational Study><Observational research><Odds Ratio><Oral Administration><Oral Drug Administration><Out-patients><Outcome><Outpatients><Participant><Patient Self-Report><Pharmaceutical Preparations><Pharmacological Treatment><Phase><Placebo Control><Placebos><Psilocibin><Psilocybin><Psychedelic Agents><Psychedelics><Psychiatric Disease><Psychiatric Disorder><Psychotherapy><Psychotomimetic Agents><Questionnaires><Randomized><Randomized Controlled Clinical Trials><Relative Odds><Reporting><Risk><Risk Ratio><Safety><Sample Size><Self Administered><Self Administration><Self-Report><Serotonin 5-HT-2 Receptor Gene><Serotonin 5-HT-2A Receptor><Sham Treatment><Short-Term Psychotherapy><South American><Substance Use Disorder><Tea><Therapeutic><Therapeutic Effect><Tribes><United States><Visual><Woman><active followup><alcohol abuse therapy><alcohol abuse treatment><alcohol ingestion><alcohol intake><alcohol level><alcohol measurement><alcohol product use><alcohol treatment><alcohol use><alcohol use disorder><alcoholic beverage consumption><alcoholic drink intake><analog><anxiety reduction><anxiety symptoms><anxious symptom><behavioral sensitization><compare to control><comparison control><conditioned place preference><consumption measures><depression><depression symptom><depressive><depressive symptoms><determine efficacy><developmental><drink heavily><drinking><drug/agent><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><ethanol consumption><ethanol drinking><ethanol ingestion><ethanol intake><ethanol measurement><ethanol product use><ethanol use><ethanol use disorder><ethyl alcohol measurements><evaluate efficacy><examine efficacy><excessive alcohol consumption><excessive alcohol ingestion><excessive alcohol intake><excessive drinking><excessive ethanol ingestion><experience><extreme drinking><follow up><follow-up><followed up><followup><heavy alcohol use><improved><interest><intraoral drug delivery><intravenous administration><men><mental illness><motivational enhancement therapy><motivational interview><novel><place conditioning><placebo controlled><pre-clinical study><preclinical study><primary outcome><psychedelic drug><psychiatric illness><psychoeducation><psychological disorder><psychotomimetic drug><randomisation><randomization><randomized control clinical trial><randomly assigned><sham therapy><substance use and disorder><timeline>