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Lysergic Acid Diethylamide (LSD) as Treatment for Cluster Headache (LCH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03781128
Recruitment Status : Recruiting
First Posted : December 19, 2018
Last Update Posted : January 9, 2020
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Brief Summary:

Background: After no official research in humans in the last 40 years, research and therapeutic uses of the serotonergic psychedelic lysergic acid diethylamide (LSD) are now re-recognized and include its use in brain research, alcoholism, anxiety associated with terminal illness, and treatment of headache disorders. Specifically, LSD has been reported to abort attacks, to decrease frequency and intensity of attacks, and to induce remission in patients suffering from cluster headache (CH).

Objective: To investigate the effects of an oral LSD pulse regimen (3 x 100 µg LSD in three weeks) in patients suffering from CH compared with placebo.

Design: Double-blind, randomized, placebo-controlled two-phase cross-over study design.

Participants: 30 patients aged ≥ 25 and ≤ 75 years with chronic or episodic CH with predictable periods lasting approximately 2 months and attacks responding to oxygen.

Main outcome measures: Changes in frequency and intensity of CH attacks assessed with a standardized headache diary Significance: CH is often rated as the most painful of all primary headaches, which not only causes significant disability, but is also associated with enormous personal, economic, and psychiatric burden. At the moment, there is no specific treatment available for CH, but serotonergic compounds represent an important drug class, especially in the abortive management of cluster attacks. However, there is a need for new treatment approaches, as CH is also often insufficiently managed with available medication. This study will evaluate the potential benefit and safety of a treatment with LSD for patients with CH.


Condition or disease Intervention/treatment Phase
Cluster Headache Drug: Lysergic Acid Diethylamide Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Double-blind, randomized, placebo-controlled two-phase cross-over study design.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: double-blind
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Lysergic Acid Diethylamide (LSD) as Treatment for Cluster Headache: a Randomized, Double-blind, Placebo-controlled Phase II Study
Actual Study Start Date : January 2, 2019
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Headache

Arm Intervention/treatment
LSD, Placebo
Lysergic acid diethylamide (3 x 100 µg LSD in three weeks, per os) followed by Placebo
Drug: Lysergic Acid Diethylamide
100 µg, per os, 3 times within 3 weeks
Other Name: LSD

Drug: Placebo
placebo in an identical-looking vial as LSD, per os, 3 times within 3 weeks

Placebo, LSD
Placebo (3 x 1 vial looking like LSD in three weeks, per os) followed by Lysergic acid diethylamide
Drug: Lysergic Acid Diethylamide
100 µg, per os, 3 times within 3 weeks
Other Name: LSD

Drug: Placebo
placebo in an identical-looking vial as LSD, per os, 3 times within 3 weeks




Primary Outcome Measures :
  1. Change in frequency of the cluster headache attacks [ Time Frame: 8 weeks before and after pulse regimen ]
    assessed with a standardized headache diary, within-subjects analysis

  2. Change in intensity of the cluster headache attacks [ Time Frame: 8 weeks before and after pulse regimen ]
    assessed with a standardized headache diary, within-subjects analysis


Secondary Outcome Measures :
  1. Episode abortion [ Time Frame: through study completion, an average of 1 year ]
    assessed with a standardized headache diary

  2. Change in duration of attacks [ Time Frame: 8 weeks after pulse regimen ]
    assessed with a standardized headache diary

  3. Time to first attack after completion of pulse regimen [ Time Frame: 8 weeks after pulse regimen ]
    assessed with a standardized headache diary

  4. Cumulative time with headache [ Time Frame: 8 weeks after pulse regimen ]
    assessed with a standardized headache diary

  5. Change in cluster period duration and interval between cluster periods [ Time Frame: 8 weeks after pulse regimen ]
    assessed with a standardized headache diary

  6. Number of attacks requiring abortive medication [ Time Frame: 8 weeks after pulse regimen ]
    assessed with a standardized headache diary

  7. Number of Attack-associated autonomic symptoms [ Time Frame: 8 weeks after pulse regimen ]
    assessed with a standardized headache diary

  8. Quality of life assessed by questionnaires: 36-item short-form health survey (SF-36) [ Time Frame: through study completion, an average of 1 year ]
    assessment with the validated 36-item short-form health survey (SF-36), which measures health-related quality of life

  9. Quality of life assessed by questionnaires: 5-level EuroQoL-5D (EQ-5D-5L) [ Time Frame: through study completion, an average of 1 year ]
    assessment with the 5-level EuroQoL-5D (EQ-5D-5L), which is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life

  10. Quality of life assessed by questionnaires: Headache Impact Test (HIT-6) [ Time Frame: through study completion, an average of 1 year ]
    assessment with the Headache Impact Test (HIT-6), which measures the adverse impact of headache on social functioning, role functioning, vitality, cognitive functioning and psychological distress.

  11. Acute autonomic effects assessed by blood pressure [ Time Frame: 10 hours after drug administration ]
    systolic and diastolic blood pressure in mmHg

  12. Acute autonomic effects assessed by heart rate [ Time Frame: 10 hours after drug administration ]
    heart rate in beats per minute

  13. Acute autonomic effects assessed by body temperature [ Time Frame: 10 hours after drug administration ]
    body temperature in °Celsius

  14. Adverse Events [ Time Frame: through study completion, an average of 1 year ]
    adverse events will be recorded

  15. Acute psychological effects assessed by questionnaire Visual analogue scales (VAS) [ Time Frame: 10 hours after drug administration ]
    assessment of subjective effects using visual analogue scales

  16. Acute psychological effects assessed by SCQ [ Time Frame: 10 hours after drug administration ]
    assessed with the states of consciousness questionnaire (SCQ)

  17. Acute psychological effects assessed by questionnaire 5-dimensions of altered states of consciousness [ Time Frame: 10 hours after drug administration ]
    assessed with the 5-dimensions of altered states of consciousness questionnaire (5D-ASC)

  18. Persisting effects attributed to the LSD experience [ Time Frame: through study completion, an average of 1 year ]
    assessment of persisting effects with the persisting effects questionnaire (PEQ) which assesses changes in attitude, mood, behavior and spiritual experience. The questionnaire will be completed at the beginning, after pulse regimens, and at the end of the study.

  19. Change of attack frequency at the end of the study compared with baseline [ Time Frame: through study completion, an average of 1 year ]
    pre-post study comparison in all subjects, assessed with a standardized headache diary

  20. Change of attack intensity at the end of the study compared with baseline [ Time Frame: through study completion, an average of 1 year ]
    pre-post study comparison in all subjects, assessed with a standardized headache diary

  21. Change in attack frequency before and after pulse regimen [ Time Frame: 8 weeks after first pulse regimen ]
    between-subjects analysis before cross-over, assessed with a standardized headache diary

  22. Change in attack intensity before and after pulse regimen [ Time Frame: 8 weeks after first pulse regimen ]
    between-subjects analysis before cross-over, assessed with a standardized headache diary



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   25 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 25 and ≤ 75 years
  • Chronic cluster headache (according to the International Headache Society (IHS) criteria) OR
  • Episodic cluster headache (according to the IHS criteria) with recurrent predictable episodes lasting approximately 2 months and expected ongoing cluster period for at least one month beyond the inclusion
  • Attacks respond to oxygen
  • Sufficient understanding of the study procedures and risks associated with the study
  • Participants must be willing to adhere to the study procedures and sign the consent form
  • Participants are willing to abstain from taking preventive and abortive medication (except from oxygen) long enough before and after the LSD/placebo treatment session to avoid the possibility of a drug-drug interaction
  • Participants are willing to refrain from taking any psychiatric medications during the experimental session period. If they are being treated with antidepressants, lithium or are taking anxiolytic medications on a fixed daily regimen, such drugs must be discontinued long enough before the LSD/placebo treatment session to avoid the possibility of a drug-drug interaction.
  • Participants must also refrain from the use of any psychoactive drugs and caffeine within 24 hours of each LSD/placebo treatment session. They must agree not to use nicotine for at least 2 hours before and 6 hours after each dose of LSD. They must agree to not ingest alcohol-containing beverages for at least 1 day before each LSD treatment session. Non-routine medications for treating breakthrough pain taken in the 24 hours before the LSD treatment session may result in rescheduling the treatment session to another date, with the decision at the discretion of the investigators after discussion with the participant.
  • Participants must be willing not to drive a traffic vehicle or to operate machines within 24 hours after LSD/placebo administration.

Exclusion Criteria:

  • Other forms of headache attacks (migraine, paroxysmal hemicranias, shortlasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, sweating and rhinorrhea (SUNCT) or with cranial autonomic symptoms (SUNA))
  • Women who are pregnant, nursing or of child-bearing potential and are not practicing an effective means of birth control (double-barrier method, i.e. pill/intrauterine device and preservative/diaphragm)
  • Past or present diagnosis of a primary psychotic disorder. Subjects with a first degree relative with psychotic disorders are also excluded.
  • Past or present bipolar disorder (DSM-IV).
  • Current substance use disorder (within the last 2 months, DSM-V, except nicotine).
  • Somatic disorders including severe cardiovascular disease, untreated hypertension (systolic blood pressure > 160mmHg without treatment, systolic blood pressure > 140 mmHg with treatment), severe liver disease (liver enzymes increase by more than 5 times the upper limit of normal) or severely impaired renal function (estimated creatinine clearance <30 ml/min), or other that in the judgement of the investigators pose too great potential for side effects.
  • Weight < 45kg
  • Participation in another clinical trial (currently or within the last 30 days)
  • Participants taking higher steroid doses (>10mg/d) over a longer time period (>2 weeks), as this would require tapering
  • Use of immunomodulatory agents (i.e. azathioprine) in the past 2 weeks
  • Use of serotonergic antiemetics (i.e. ondansetron) in the past 2 weeks

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03781128


Contacts
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Contact: Matthias Liechti, Prof. 0041 61 328 68 68 matthias.liechti@usb.ch
Contact: Yasmin Schmid, Dr. med. 0041 61 328 68 66 yasmin.schmid@usb.ch

Locations
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Switzerland
Clinical Pharmacology & Toxicology, University Hospital Basel Recruiting
Basel, Switzerland, 4031
Contact: Matthias Liechti, Prof.    +41 61 328 68 68    matthias.liechti@usb.ch   
Contact: Yasmin Schmid, Dr. med.    +41 61 328 68 66    yasmin.schmid@usb.ch   
Principal Investigator: Matthias Liechti, Prof.         
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
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Principal Investigator: Matthias Liechti University Hospital, Basel, Switzerland
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Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT03781128    
Other Study ID Numbers: BASEC 2018-01082
First Posted: December 19, 2018    Key Record Dates
Last Update Posted: January 9, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Basel, Switzerland:
lysergic acid diethylamide (LSD)
serotonin
hallucinogen
cluster headache
Additional relevant MeSH terms:
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Cluster Headache
Headache
Trigeminal Autonomic Cephalalgias
Headache Disorders, Primary
Headache Disorders
Lysergic Acid Diethylamide
Pain
Neurologic Manifestations
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hallucinogens
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Receptor Agonists