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.

• Montgomery-Asberg-Depression-Rating Scale (MARDS) [Срок оценки: Ratings will be performed on day 3 of each menstural cycle, over the whole study period of 5 menstrual cycles, to retrospectively rate depressive symptoms during the premenstrual phase (based on an average cycle duration of 28 days)]
• Hamilton Anxiety Rating Scale (HAM-A) [Срок оценки: Ratings will be performed on day 3 of each menstural cycle , over the whole study period of 5 menstrual cycles to retrospectively rate anxiety symptoms during the premenstrual phase ((based on an average cycle duration of 28 days).]
• State-trait anxiety inventory (STAI) [Срок оценки: The STAI will be repeatedly assessed 3 times per cycle (twice during the late luteal phase (cycle day 20 and 26 based on a 28-day cycle) and on day 3 after start of mensturation) over the whole study period of 5 menstrual cycles.]
• Beck Depression Inventory (BDI) [Срок оценки: The BDI will be repeatedly assessed 3 times per cycle (twice during the late luteal phase (cycle day 20 and 26 based on a 28-day cycle) and on day 3 after start of mensturation) over the whole study period of 5 menstrual cycles.]
• Quality of Life (WHOQOL-bref) [Срок оценки: The WHOQOL-bref will be repeatedly assessed 3 times per cycle (twice during the late luteal phase (cycle day 20 and 26 based on a 28-day cycle) and on day 3 after start of me, additionally it will be assessed at screening and once during the luteal phase]
• Menstrual pain [Срок оценки: Menstrual pain will be assessed on menstruation days over 5 menstrual cycles (average cycle duration is 28 days).]
• Quality of Sleep [Срок оценки: Participants are asked to rate their sleep quality daily over 5 menstrual cycles (average cycle duration is 28 days).]
• Daily mood (AMRS) [Срок оценки: The AMRS will be administered daily over 5 menstrual cycles (average cycle duration is 28 days).]
• Female Sexual Function Index (FSFI) [Срок оценки: The outcome will be on day 3 of each menstural cycle to retrospectively rate sexual function during the premenstrual phase over 5 menstrual cycles (average cycle duration is 28 days).]
• Concomitant Medication [Срок оценки: Complete concomitant medication including on-demand medication during bleeding days (dysmenorrhea) will be assessed at screening and rescreening. The exact intake will be recorded daily over 5 menstrual cycles (average cycle duration is 28 days).]
• Subjective effects questionnaire (Visual Analog Scales, VAS) [Срок оценки: Will be assessed during the first drug administration in cycle 3, latest 7 days after ovulation (average cycle duration is 28 days). Scales will be administered at 0, 0.5, 1, 2, 3, 4, 5, and 6 hours after substance administration.]
• 5-Dimensions of Altered States of Consciousness (5D-ASC) [Срок оценки: Only once 6 hours after drug administration on the first in-house drug application (cycle 3, latest 7 days after ovulation, average cycle duration is 28 days)]