Lysergic Acid Diethylamide (LSD)-Assisted Psychotherapy in People With Illness-related Anxiety

Sponsor
Multidisciplinary Association for Psychedelic Studies (Other)
Overall Status
Completed
CT.gov ID
NCT00920387
Collaborator
(none)
12
Enrollment
1
Location
2
Arms
55
Duration (Months)
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will find out whether psychotherapy combined with lysergic acid diethylamide (LSD) is safe and is helpful in people who are anxious because they have a potentially fatal disease. The study will measure anxiety and quality of life before and after people have two sessions with either full or active placebo dose of LSD. They expect LSD-assisted psychotherapy to reduce anxiety and improve quality of life.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: 200 mcg LSD
  • Drug: 20 mcg LSD
  • Behavioral: Therapy
Phase 2

Detailed Description

Diagnosis with a potentially fatal illness is distressing and can provoke anxiety that further reduces quality of life, and a treatment that reduces anxiety when facing deteriorating health and mortality will improve quality of life for people with such illnesses. Forty to fifty years ago, researchers investigated lysergic acid diethylamide (LSD) in combination with psychotherapy to treat anxiety when facing advanced stage cancer. This psychedelic (hallucinogenic) drug can produce transformative or mystical experiences and insights that can help in anxiety reduction. This study will be a randomized, active placebo controlled,double-blind pilot study of the safety and efficacy of LSD-assisted psychotherapy as a way of reducing anxiety in people with potentially fatal illnesses. This study will examine whether two sessions of LSD-assisted psychotherapy scheduled two to four weeks apart will reduce anxiety and improve quality of life for people experiencing anxiety as a result of a potentially fatal illness.

Study subjects will receive either 200 or 20 mcg (micrograms) LSD during two day-long psychotherapy sessions scheduled two to four weeks apart. Subjects in this study will have a 66% of receiving the full dose of 200 mcg LSD, and they have a 33% chance of getting the active placebo dose of 20 mcg LSD. Neither the researchers nor the subject will know whether he got 200 or 20 mcg LSD. Upon participant agreement, all psychotherapy sessions will be recorded to audio and video.

The randomized part of the study will last three and a half months (14 weeks).

People who learn they got the active placebo dose of LSD during the randomized phase can go on to to take part in an "open label" study phase, where they will get the full dose of LSD during two day-long psychotherapy sessions scheduled two to four weeks apart. "Open label" means that they and the researchers will both be aware that they are getting the full dose of LSD.

Participants who received the full dose of LSD and took part in all study visits will be assessed for symptoms of anxiety and depression and quality of life 12 months after their final experimental session.

Study Design

Study Type:
Interventional
Actual Enrollment :
12 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
LSD-assisted Psychotherapy in Persons Suffering From Anxiety Associated With Advanced-stage Life Threatening Diseases. A Phase-II, Double-blind, Placebo-controlled Dose-response Pilot Study
Study Start Date :
Feb 1, 2008
Actual Primary Completion Date :
Jul 1, 2012
Actual Study Completion Date :
Sep 1, 2012

Arms and Interventions

ArmIntervention/Treatment
Experimental: Full Dose LSD (200 mcg)

200 mcg LSD administered once during each of two LSD-assisted therapy sessions, scheduled two to four weeks apart.

Drug: 200 mcg LSD
Administering 200 mcg LSD orally once at the start of each of two day-long psychotherapy session
Other Names:
  • Lysergic acid diethylamide
  • Behavioral: Therapy
    Therapy provided by male and female co-therapists

    Active Comparator: Active Placebo LSD (20 mcg)

    20 mcg LSD administered once during each of two LSD-assisted therapy sessions, scheduled two to four weeks apart.

    Drug: 20 mcg LSD
    Administer 20 mcg LSD orally once at the start of each of two day-long psychotherapy session
    Other Names:
  • Lysergic acid diethylamide
  • Behavioral: Therapy
    Therapy provided by male and female co-therapists

    Outcome Measures

    Primary Outcome Measures

    1. Baseline State-Trait Anxiety Inventory (STAI) [Baseline (Visit 4)]

      The STAI differentiates between State Anxiety, defined as "anxiety experienced in reaction to a specific environmental circumstance," and Trait Anxiety, defined as "long-standing nervous affect or anxiety disorder." The STAI-state subscale is a 20-item self-reported scale which assesses subjects' levels of transient, situationally oriented, anxiety. Participants respond to each item by selecting a response from a 4-point Likert scale ranging from 4 ("Not at all") to 1 ("Very much so"). STAI-state scores are summed for a total score that range from 20 to 80, with higher scores indicating greater state anxiety. The STAI-trait subscale also consists of 20-items and is scored the same way, with total scores ranging from 20 to 80, with higher scores indicating greater trait anxiety.

    2. Primary Endpoint State-Trait Anxiety Inventory (STAI) [2 months after second experimental session]

      The STAI differentiates between State Anxiety, defined as "anxiety experienced in reaction to a specific environmental circumstance," and Trait Anxiety, defined as "long-standing nervous affect or anxiety disorder." The STAI-state subscale is a 20-item self-reported scale which assesses subjects' levels of transient, situationally oriented, anxiety. Participants respond to each item by selecting a response from a 4-point Likert scale ranging from 4 ("Not at all") to 1 ("Very much so"). STAI-state scores are summed for a total score that range from 20 to 80, with higher scores indicating greater state anxiety. The STAI-trait subscale also consists of 20-items and is scored the same way, with total scores ranging from 20 to 80, with higher scores indicating greater trait anxiety.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Have a diagnosis of advanced-stage potentially fatal illness. As well as metastatic cancer this may include autoimmune, neurological, infectious or rheumatoid diseases as well. The participant must have a probability of survival of more than six months. The estimated life expectancy in relation to the study must be documented.

    • The participant makes the decision to participate in the study by his or her own will and that there is no inhibition to his or her will or ability of deciding due to the primary disease.

    • Meet DSM-IV criteria for Anxiety Disorder as indicated by the SCID or have a score of at least 40 on each part of the STAI.

    • Have failed to respond adequately or at all to medication or psychotherapy intended to reduce anxiety, or have refused to take anxiolytic medication.

    • May be diagnosed with another affective disorder other than anxiety disorder, except bipolar-I disorder.

    • Are at least 18 years of age.

    • Are willing to commit to medication dosing, experimental sessions, follow-up sessions, and to complete evaluation instruments (although they may withdraw from the study at any time without cause).

    • Are willing to withdraw from taking any psychiatric medications during the experimental session period. Drugs must be discontinued long enough before the first LSD treatment session to avoid the possibility of a drug-drug interaction (the interval will be at least 5 times the particular drug's half-life).

    • If in ongoing psychotherapy, those recruited into the study may continue to see their outside therapist, provided they sign a release for the investigators to communicate directly with their therapist. Participants should not change therapists, increase or decrease the frequency of therapy or commence any new type of therapy until after the evaluation session 2 months after the second LSD treatment session.

    • Participants must agree that, for one week preceding each LSD treatment session:

      1. Clinical judgment will be used to determine permissible herbal supplements.
      1. They will not initiate any new prescription medications (except with prior approval of the research team).
      1. Clinical judgment will be used to determine permissible nonprescription medications.
    • Participants must be willing to follow restrictions and guidelines concerning consumption of food, beverages and nicotine the night before and just prior to each LSD session.

    Exclusion Criteria:
    • Women who are pregnant or nursing, or of child bearing potential and are not practicing an effective means of birth control.

    • Anyone with past or present diagnosis with a primary psychotic disorder.

    • Meeting DSM-IV criteria for Dissociative Disorder or Bipolar-I Affective Disorder.

    • Meeting DSM-IV criteria for abuse of or dependence on any substance (other than caffeine or nicotine) in the past 60 days.

    • Diagnosed with significant somatic problems, that in the clinical judgment of the investigators poses too great a potential for side effects.

    • No sufficient liver function at the baseline examination or the day before the experimental sessions.

    • Having evidence of CNS affection from the primary disease (e.g. brain metastasis), shown by neurocognitive impairment.

    • Weighing less than 45 kg.

    • Reasonably judged to present a serious suicide risk or who are likely to require psychiatric hospitalization during the course of the study.

    • Unable to fully understand the potential risks and benefits of the study and give informed consent.

    • Requiring ongoing concomitant therapy with a psychotropic drug (other than as needed, anxiety medications, and pain control medications) and are unable or unwilling to comply with the washout period.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Private Practices of Peter Gasser MDSolothurnSwitzerland

    Sponsors and Collaborators

    • Multidisciplinary Association for Psychedelic Studies

    Investigators

    • Principal Investigator: Peter Gasser, MD, Private practices of Peter Gasser; Swiss Medical Association for Psycholytic Therapy (SAPT)

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Multidisciplinary Association for Psychedelic Studies
    ClinicalTrials.gov Identifier:
    NCT00920387
    Other Study ID Numbers:
    • LDA1
    First Posted:
    Jun 15, 2009
    Last Update Posted:
    Mar 14, 2022
    Last Verified:
    Feb 1, 2022
    Keywords provided by Multidisciplinary Association for Psychedelic Studies
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsParticipants were recruited through general information about the study reported in media, by flyers, presentations in hospitals or cancer support groups, or referral from other physicians.
    Pre-assignment Detail
    Arm/Group TitleFull Dose LSD (200 mcg) Blinded Stage 1Active Placebo LSD (20 mcg) Stage 1Full Dose LSD (200 mcg) Open-Label Stage 2
    Arm/Group Description200 mcg LSD administered once during each of two blinded LSD-assisted therapy sessions, scheduled two to four weeks apart during Stage 1 200 mcg LSD: Administering 200 mcg LSD orally once at the start of each of two day-long psychotherapy session Therapy: Therapy provided by male and female co-therapists20 mcg LSD administered once during each of two blinded LSD-assisted therapy sessions, scheduled two to four weeks apart during Stage 1. 20 mcg LSD: Administer 20 mcg LSD orally once at the start of each of two day-long psychotherapy session Therapy: Therapy provided by male and female co-therapists200 mcg LSD administered open-label once during two experimental sessions, scheduled two to eight weeks apart during Stage 2
    Period Title: Stage 1
    STARTED840
    COMPLETED740
    NOT COMPLETED100
    Period Title: Stage 1
    STARTED003
    COMPLETED003
    NOT COMPLETED000

    Baseline Characteristics

    Arm/Group TitleFull Dose LSD (200 mcg)Active Placebo LSD (20 mcg)Total
    Arm/Group Description200 mcg LSD administered once during each of two LSD-assisted therapy sessions, scheduled two to four weeks apart. 200 mcg LSD: Administering 200 mcg LSD orally once at the start of each of two day-long psychotherapy session Therapy: Therapy provided by male and female co-therapists20 mcg LSD administered once during each of two LSD-assisted therapy sessions, scheduled two to four weeks apart. 20 mcg LSD: Administer 20 mcg LSD orally once at the start of each of two day-long psychotherapy session Therapy: Therapy provided by male and female co-therapistsTotal of all reporting groups
    Overall Participants8311
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    49.6
    (8.4)
    57.4
    (9.9)
    51.7
    (9.1)
    Sex: Female, Male (Count of Participants)
    Female
    3
    37.5%
    1
    33.3%
    4
    36.4%
    Male
    5
    62.5%
    2
    66.7%
    7
    63.6%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    History of suicidal tendencies (Count of Participants)
    None
    8
    100%
    1
    33.3%
    9
    81.8%
    Mild
    0
    0%
    2
    66.7%
    2
    18.2%
    Type of life-threatening illness (Count of Participants)
    Metastatic breast carcinoma
    3
    37.5%
    1
    33.3%
    4
    36.4%
    Metastatic gastric carcinoma
    2
    25%
    0
    0%
    2
    18.2%
    Plasmocytoma
    1
    12.5%
    0
    0%
    1
    9.1%
    Non-Hodgkin's Lymphoma
    0
    0%
    1
    33.3%
    1
    9.1%
    Celiac Disease
    0
    0%
    1
    33.3%
    1
    9.1%
    Parkinson's Disease
    1
    12.5%
    0
    0%
    1
    9.1%
    Bechterew's Disease
    1
    12.5%
    0
    0%
    1
    9.1%

    Outcome Measures

    1. Primary Outcome
    TitleBaseline State-Trait Anxiety Inventory (STAI)
    DescriptionThe STAI differentiates between State Anxiety, defined as "anxiety experienced in reaction to a specific environmental circumstance," and Trait Anxiety, defined as "long-standing nervous affect or anxiety disorder." The STAI-state subscale is a 20-item self-reported scale which assesses subjects' levels of transient, situationally oriented, anxiety. Participants respond to each item by selecting a response from a 4-point Likert scale ranging from 4 ("Not at all") to 1 ("Very much so"). STAI-state scores are summed for a total score that range from 20 to 80, with higher scores indicating greater state anxiety. The STAI-trait subscale also consists of 20-items and is scored the same way, with total scores ranging from 20 to 80, with higher scores indicating greater trait anxiety.
    Time FrameBaseline (Visit 4)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleFull Dose LSD (200 mcg)Active Placebo LSD (20 mcg)
    Arm/Group Description200 mcg LSD administered once during each of two LSD-assisted therapy sessions, scheduled two to four weeks apart. 200 mcg LSD: Administering 200 mcg LSD orally once at the start of each of two day-long psychotherapy session Therapy: Therapy provided by male and female co-therapists20 mcg LSD administered once during each of two LSD-assisted therapy sessions, scheduled two to four weeks apart. 20 mcg LSD: Administer 20 mcg LSD orally once at the start of each of two day-long psychotherapy session Therapy: Therapy provided by male and female co-therapists
    Measure Participants83
    STAI-state
    53.1
    (4.7)
    47.7
    (7.7)
    STAI-trait
    53.2
    (4.3)
    43.3
    (7.0)
    2. Primary Outcome
    TitlePrimary Endpoint State-Trait Anxiety Inventory (STAI)
    DescriptionThe STAI differentiates between State Anxiety, defined as "anxiety experienced in reaction to a specific environmental circumstance," and Trait Anxiety, defined as "long-standing nervous affect or anxiety disorder." The STAI-state subscale is a 20-item self-reported scale which assesses subjects' levels of transient, situationally oriented, anxiety. Participants respond to each item by selecting a response from a 4-point Likert scale ranging from 4 ("Not at all") to 1 ("Very much so"). STAI-state scores are summed for a total score that range from 20 to 80, with higher scores indicating greater state anxiety. The STAI-trait subscale also consists of 20-items and is scored the same way, with total scores ranging from 20 to 80, with higher scores indicating greater trait anxiety.
    Time Frame2 months after second experimental session

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleFull Dose LSD (200 mcg)Active Placebo LSD (20 mcg)
    Arm/Group Description200 mcg LSD administered once during each of two LSD-assisted therapy sessions, scheduled two to four weeks apart. 200 mcg LSD: Administering 200 mcg LSD orally once at the start of each of two day-long psychotherapy session Therapy: Therapy provided by male and female co-therapists20 mcg LSD administered once during each of two LSD-assisted therapy sessions, scheduled two to four weeks apart. 20 mcg LSD: Administer 20 mcg LSD orally once at the start of each of two day-long psychotherapy session Therapy: Therapy provided by male and female co-therapists
    Measure Participants83
    STAI-state
    41.5
    (3.2)
    51.7
    (5.3)
    STAI-trait
    45.2
    (3.7)
    49.0
    (6.1)

    Adverse Events

    Time FrameFrom enrollment to end of Stage 2 (approximately 11 months)
    Adverse Event Reporting Description
    Arm/Group TitleFull Dose LSD (200 mcg Stage 1)Active Placebo LSD (20 mcg Stage 1)Full Dose LSD (200 mcg Stage 2)
    Arm/Group Description200 mcg LSD administered once during each of two LSD-assisted therapy sessions, scheduled two to four weeks apart. 200 mcg LSD: Administering 200 mcg LSD orally once at the start of each of two day-long psychotherapy session Therapy: Therapy provided by male and female co-therapists20 mcg LSD administered once during each of two LSD-assisted therapy sessions, scheduled two to four weeks apart. 20 mcg LSD: Administer 20 mcg LSD orally once at the start of each of two day-long psychotherapy session Therapy: Therapy provided by male and female co-therapists200 mcg LSD administered once during each of two LSD-assisted therapy sessions, scheduled two to eight weeks apart. 200 mcg LSD: Administering 200 mcg LSD orally once at the start of each of two day-long psychotherapy session Therapy: Therapy provided by male and female co-therapists
    All Cause Mortality
    Full Dose LSD (200 mcg Stage 1)Active Placebo LSD (20 mcg Stage 1)Full Dose LSD (200 mcg Stage 2)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/8 (12.5%) 0/4 (0%) 0/3 (0%)
    Serious Adverse Events
    Full Dose LSD (200 mcg Stage 1)Active Placebo LSD (20 mcg Stage 1)Full Dose LSD (200 mcg Stage 2)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/8 (12.5%) 1/4 (25%) 0/3 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastic Esophageal Cancer1/8 (12.5%) 0/4 (0%) 0/3 (0%)
    Renal and urinary disorders
    Pyelonephritis0/8 (0%) 1/4 (25%) 0/3 (0%)
    Other (Not Including Serious) Adverse Events
    Full Dose LSD (200 mcg Stage 1)Active Placebo LSD (20 mcg Stage 1)Full Dose LSD (200 mcg Stage 2)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total8/8 (100%) 4/4 (100%) 3/3 (100%)
    Blood and lymphatic system disorders
    Anemia1/8 (12.5%) 0/4 (0%) 0/3 (0%)
    Eye disorders
    Mydriasis3/8 (37.5%) 0/4 (0%) 0/3 (0%)
    General disorders
    Feeling Cold6/8 (75%) 0/4 (0%) 1/3 (33.3%)
    Impaired Gait2/8 (25%) 0/4 (0%) 2/3 (66.7%)
    Feeling of Relaxation0/8 (0%) 1/4 (25%) 0/3 (0%)
    Asthenia0/8 (0%) 1/4 (25%) 0/3 (0%)
    Infections and infestations
    Pneumonia1/8 (12.5%) 0/4 (0%) 0/3 (0%)
    Injury, poisoning and procedural complications
    Femur Fracture1/8 (12.5%) 0/4 (0%) 0/3 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm progression1/8 (12.5%) 0/4 (0%) 0/3 (0%)
    Nervous system disorders
    Headache1/8 (12.5%) 0/4 (0%) 0/3 (0%)
    Disturbance in Attention0/8 (0%) 1/4 (25%) 0/3 (0%)
    Psychiatric disorders
    Anxiety2/8 (25%) 2/4 (50%) 1/3 (33.3%)
    Anger1/8 (12.5%) 2/4 (50%) 0/3 (0%)
    Affect Liability1/8 (12.5%) 1/4 (25%) 1/3 (33.3%)
    Emotional Distress5/8 (62.5%) 1/4 (25%) 0/3 (0%)
    Time Perception Altered4/8 (50%) 0/4 (0%) 2/3 (66.7%)
    Thinking Abnormal1/8 (12.5%) 1/4 (25%) 0/3 (0%)
    Perseveration0/8 (0%) 0/4 (0%) 1/3 (33.3%)
    Tachyphrenia0/8 (0%) 1/4 (25%) 0/3 (0%)
    Feeling Abnormal5/8 (62.5%) 2/4 (50%) 1/3 (33.3%)
    Derealization1/8 (12.5%) 0/4 (0%) 1/3 (33.3%)
    Bradyphrenia1/8 (12.5%) 0/4 (0%) 0/3 (0%)
    Hallucination1/8 (12.5%) 0/4 (0%) 0/3 (0%)
    Illusions6/8 (75%) 1/4 (25%) 2/3 (66.7%)
    Depersonalization0/8 (0%) 0/4 (0%) 1/3 (33.3%)
    Altered Perception of Music0/8 (0%) 1/4 (25%) 0/3 (0%)
    Reproductive system and breast disorders
    Menorrhagia1/8 (12.5%) 0/4 (0%) 0/3 (0%)
    Skin and subcutaneous tissue disorders
    Palmar-plantar Erythrody Saesthesia Syndrome1/8 (12.5%) 0/4 (0%) 0/3 (0%)
    Skin Lesion0/8 (0%) 1/4 (25%) 0/3 (0%)
    Perspiration2/8 (25%) 0/4 (0%) 0/3 (0%)
    Pruritus0/8 (0%) 1/4 (25%) 0/3 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleJulie B. Wang, MPH, PhD/ Senior Clinical Data Scientist
    OrganizationMultidisciplinary Association for Psychedelic Studies (MAPS) Public Benefit Corp.
    Phone(831) 429-6362
    Emailjuliewang@mapsbcorp.com
    Responsible Party:
    Multidisciplinary Association for Psychedelic Studies
    ClinicalTrials.gov Identifier:
    NCT00920387
    Other Study ID Numbers:
    • LDA1
    First Posted:
    Jun 15, 2009
    Last Update Posted:
    Mar 14, 2022
    Last Verified:
    Feb 1, 2022