Microdosing LSD in Women With Premenstrual Disorders

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.

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.

• 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.
• 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)