Microdosing LSD in Women With Premenstrual Disorders (L4Her)

Friederike Holze

Status: Not yet enrolling

Conditions: PMS; PMDD

Treatments: Drug: LSD 10 μg every Day; Drug: Placebo; Drug: LSD 10 μg every other day

Study type: Interventional

Funder types: Other

Identifiers

NCT07189299

BASEC 2025-00745

Details and patient eligibility

About

The investigators aim to investigate the role of the serotonin 2A receptor in women with premenstrual disorders. This study uses a double-blind, randomized, controlled design with 3 arms: Intervention 1: 10 micg LSD for ~10 days during the late luteal phase (for 3 cycles) Intervention 2: 10 micg LSD every other day for ~10 days during the late luteal phase (for 3 cycles) Control intervention: Placebo for ~10 days during the late luteal phase (for 3 cycles) Each participant will be treated in only one arm. The study employs a parallel design with three treatment arms and consists of a two-cycle observational phase followed by a three-cycle treatment phase.

Full description

Premenstrual disorders (premenstrual syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD)) affect many women (20 - 30% for PMS and 1.2 - 6.4% for PMDD) and are associated with affective symptoms, pain, mood impairment, insomnia, loss of well-being, and productivity making it complex disorders with combined mood, physical, and cognitive symptoms.

The serotonin 2A receptor has been shown to be potentially involved in the pathophysiology of premenstrual disorders, however the mechanism remains to be investigated. Anecdotal evidence suggests that low doses of psychedelics like LSD or psilocybin, taken during the luteal phase, may help alleviate symptoms. However, this approach lacks scientific validation and requires further research. We therefore seek to investigate if repeated and targeted administration of low doses of the serotonin 2A receptor agonist LSD modulates the symptom burden in premenstrual disorders.

The study employs a parallel design with three treatment arms and consists of a two-cycle observational phase followed by a three-cycle treatment phase. Timepoints below are based on a 28-day menstrual cycle, but will be adapted based on individual menstrual cycle durations.

Enrollment: 150 estimated patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion crtieria:

• Between 18-45 years.

• Are menstruating and have cycles with a duration between 21 - 35 days.

• Meet DSM-V criteria for PMDD or criteria for severe PMS with daily ratings over 2 cycles to confirm luteal symptoms.

  1. For PMDD, participants must have a minimal average luteal phase score of mild (≥3 on a 6-point scale) for at least 5 Symptoms on the DRSP including 1 mood symptom during the 5 most symptomatic of the final 7 luteal phase days and the first 2 days of menses onset, and the average follicular phase score must not be >2 on these same items.
  2. For severe PMS, participants must have a minimal average luteal phase score of mild (≥3 on a 6-point scale) for at least 4 Symptoms on the DRSP including 1 mood symptom, during the 5 most symptomatic of the final 7 luteal phase days and the first 2 days of menses onset, and the average follicular phase core must not be >2 on these same items.

• Have reported PMDD/PMS symptoms for the majority of menstrual cycles (>9 of 12) during the year prior to screening.

• Sufficient understanding of the German language

• 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.

• Willing not to drive or operate heavy machinery during the acute treatment phases of the study.

• Willing to refrain from more than 7 standard alcoholic drinks a week, more than 10 cigarettes a day, and any illicit substances.

• Willing to use effective contraceptive measures throughout study participation.

Exclusion Criteria:

• Known hypersensitivity to LSD
• Current treatment for PMS/PMDD
• Use of an oral hormonal contraceptive < 6 months.
• Past or present bipolar or psychotic disorder, including depressive disorder with psychotic features.
• First degree relative with a psychotic disorder.
• Significant prodromal psychotic symptoms (Prodromal Questionnaire-16 symptoms ≥ 6).
• Borderline personality disorder.
• Current post-traumatic stress disorder.
• Pregnant or breastfeeding
• Planned pregnancy.
• Current or recent history of significant suicide ideation or suicide behavior within the past 6 months.
• Current substance use disorder (< 12 months) other than tobacco smoking.
• Other illness that excludes repeated LSD administration or requires interfering medication.
• Participation in another clinical trial (currently or within the last 30 days)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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150 participants in 3 patient groups, including a placebo group

10 μg LSD every day during the acute symptom phase

Experimental group

Description:

Participants receive 10 μg LSD daily, starting at symptom onset (or latest 7 days after ovulation) until day 3 of the following cycle for 3 menstrual cycles

Treatment:

Drug: LSD 10 μg every Day

10 μg LSD every second day during acute symptom phase

Experimental group

Description:

10 μg LSD every second day during acute symptom phase starting at symptom onset (or 7 days after ovulation) until day 3 of the following cycle for 3 menstrual cycles

Treatment:

Drug: LSD 10 μg every other day

Placebo Control

Placebo Comparator group

Description:

The subjects in the control arm will receive oral placebo over 3 cycles during the luteal phase, starting at symptom onset (or latest 7 days after ovulation) until day 3 of the following cycle.

Treatment:

Drug: Placebo