Effects of Hemp-Derived Cannabinoids on Menopause Symptoms

This study implements a randomized, double-blind, placebo-controlled, observational field experiment design to examine the impact of hemp-derived cannabinoids on symptoms of menopause/perimenopause. The study will require 3 months to complete.

Healthy adult women (between the ages of 40-60) experiencing psychological and physical symptoms of menopause or perimenopause will be recruited via advertisements on social media, physicians' offices, in the community, at menopause conferences/conventions, and on internet forums. Prospective participants will complete a brief online screening survey to determine whether they meet eligibility requirements. Eligible participants will be asked to provide their first name and phone number if they want to be contacted via text message to participate.

Initial Zoom Session: Eligible participants who agree to participate will be asked to schedule an initial Zoom session, during which they will provide informed consent, review the study requirements, and complete cognitive tests including tests of memory and verbal fluency. Tests include the Rey Auditory Verbal Learning Test (RAVLT), FAS Verbal Fluency Test, Digit Span Forward and Backward (DSF, DSB), Corsi Forward and Backward, and Prospective Memory (PM) Tasks. They will also be given the contact information for a company that manufactures and distributes hemp-derived cannabinoids. Participants will be asked to contact the company and request that they directly ship the product to them (the participant). The product will be provided at no cost to the participant (or to the PI or their lab). The PI will randomize each participant to the active or placebo condition and will subsequently contact the distributor to inform them of which product to ship (active or placebo). Participants will be given a link to an online Qualtrics survey that will be used to assess demographic characteristics, medications, and menopause/perimenopause symptoms, including depression, anxiety, perceived stress, physical and emotional health, insomnia, and everyday memory problems (Center for Epidemiologic Studies Depression Scale \[CES-D\], Beck Anxiety Inventory \[BAI\], Perceived Stress Scale \[PSS\], Short Form Health Survey \[SF-36\], Insomnia Severity Index \[ISI\], and Everyday Memory Questionnaire \[EMQ\], respectively).

Baseline: Participants will then complete four weeks of baseline assessments via ecological momentary assessment (EMA). Specifically, twice a day: shortly after they eat breakfast, and shortly after they eat dinner participants will complete a brief survey on their phone. For each EMA survey, they will be asked to indicate whether they experienced various emotional/psychological symptoms of menopause as well as whether they experienced various physical symptoms of menopause since their last EMA assessment. For each endorsed symptom, they will be asked to rate its severity as well as how much it interfered with their life using a 0 to 10 visual analog scale. In the morning survey, they will also be asked to indicate how well they slept the night before. Once a week, participants will also complete a series of EMA cognitive tests, including tests of verbal memory, spatial memory, working memory, inhibition, psychomotor speed, and attention (assessed using NeuroUX's Memory List, CopyKat, 2-Back, Digit Symbol Substitution, Color Names, Quick Tap Level 1and 2, and Trail Making A and B). Participants will be sent text messages with a link to the tests and will be instructed to complete them on their smartphone. At the end of the month, participants will meet a researcher over Zoom where they will complete additional cognitive tests (RAVLT, FAS, DSF/DSB, Corsi, PM). Cognitive tests involving word lists or letter sets (i.e., RAVLT, FAS) will be counterbalanced using a Latin Square design. At the end of the session, they will be sent a link to complete an online survey that will be used to assess menopause/perimenopause symptoms, including depression, anxiety, perceived stress, physical and emotional health, insomnia, and everyday memory problems (CES-D BAI, PSS, SF-36, ISI, EMQ, respectively). This period of time constitutes the baseline assessment period.

Phase 1: Phase 1 will begin after 4 weeks of baseline assessments and will continue for 4 weeks. During this phase, participants will be asked to take the active or placebo version of the product (in a double-blind manner) three times a day (once after breakfast, lunch and dinner) and to complete EMA survey assessments twice a day (after orally ingesting the morning and evening doses). There will be a brief dose escalation procedure for the first week so they can slowly adjust to the product. Participants will be sent reminders and links via text message. For each EMA survey, they will be asked to indicate whether they took the study product, and if so what time they took the product. If they indicate they have not taken the product yet they will instructed to do so or provide a reason why they cannot do so. Next, they will be asked to indicate whether they experienced various emotional symptoms of menopause/perimenopause as well as whether they experienced various physical symptoms of menopause/perimenopause since their last EMA survey assessment. For each endorsed symptom, they will be asked to rate its severity as well as how much it interfered with their life using a 0 to 10 visual analog scale. In the morning survey, they will also be asked to indicate how well they slept the night before. Participants will also report on whether they experienced any side effects. Once a week, participants will also complete a series of EMA cognitive tests, including tests of verbal memory, spatial memory, inhibition, psychomotor speed, and attention (assessed using NeuroUX's Memory List, CopyKat, 2-Back, Digit Symbol Substitution, Color Names, Quick Tap Level 1and 2, and Trail Making A and B). Participants will be sent text messages with a link to the tests and will be instructed to complete them on their smartphone. At the end of the four weeks, participants will meet a researcher over Zoom where they will complete additional cognitive tests (RAVLT, FAS, DSF/DSB, Corsi, PM). At the end of the session, they will be sent a link to complete an online survey that will be used to assess menopause/perimenopause symptoms, including depression, anxiety, perceived stress, physical and emotional health, insomnia, and everyday memory problems (CES-D, BAI, PSS, SF-36, ISI, EMQ, respectively).

Phase 2: Phase 2 will begin after 4 weeks of phase 1 assessments and will continue for 4 weeks. During this phase, participants will be asked to take the active or placebo version of the product (in a double-blind manner) three times a day (once after breakfast, lunch, and dinner). They will complete the same EMA survey assessments twice a day (after orally ingesting the morning and evening doses). Participants will be sent reminders and links via text message. For each EMA survey they will be asked to indicate whether they took the study product, and if so what time they took the product. If they indicate they have not taken the product yet they will instructed to do so or provide a reason why they cannot do so. Next, they will be asked to indicate whether they experienced various emotional symptoms of menopause/perimenopause as well as whether they experienced various physical symptoms of menopause/perimenopause since their last EMA survey assessment. For each endorsed symptom, they will be asked to rate its severity as well as how much it interfered with their life using a 0 to 10 visual analog scale. In the morning survey, they will also be asked to indicate how well they slept the night before. Participants will also report on whether they experienced any side effects. Once a week, participants will also complete a series of cognitive tests using EMA, including tests of verbal memory, spatial memory, inhibition, psychomotor speed, and attention (assessed using NeuroUX's Memory List, CopyKat, 2-Back, Digit Symbol Substitution, Color Names, Quick Tap Level 1and 2, and Trail Making A and B). Participants will be sent text messages with a link to the tests and will be instructed to complete them on their smartphone. At the end of the four weeks, participants will meet a researcher over Zoom where they will complete additional cognitive tests (RAVLT, FAS, DSF/DSB, Corsi, PM). At the end of the session, they will be sent a link to complete the online survey (including the CES-D, BAI, PSS, SF-36, ISI, and EMQ). The study ends after phase 2.

• Physical Symptoms Daily Assessment [Time frame: Physical symptoms will be assessed during each session (morning and night) of the daily EMA assessments, for the 3 month duration of the study]
• Side Effects Daily Assessment [Time frame: Side effects will be assessed during each session (morning and night) of the daily EMA assessments, for the 3 month duration of the study.]
• Verbal Memory Monthly Assessment: RAVLT [Time frame: The RAVLT will be administered during monthly Zoom sessions, during four different sessions. They will occur at approximately week 1, 5, 9, and 13.]
• Verbal Fluency Monthly Assessment: FAS [Time frame: The FAS verbal fluency test will be administered during monthly Zoom sessions, during four different sessions. They will occur at approximately week 1, 5, 9, and 13.]
• Short-Term/Working Memory Monthly Assessment: Digit Span Forward and Backwards [Time frame: The digit span tests will be administered during monthly Zoom sessions, during four different sessions. They will occur at approximately week 1, 5, 9, and 13.]
• Short-Term/Working Spatial Memory Monthly Assessment: Corsi Forward and Backward [Time frame: The Corsi tests will be administered during monthly Zoom sessions, during four different sessions. They will occur at approximately week 1, 5, 9, and 13.]
• Prospective Memory Monthly Assessment: Difficulty Ratings [Time frame: The prospective memory tests will be administered during monthly Zoom sessions, during four different sessions. They will occur at approximately week 1, 5, 9, and 13.]
• Brain Fog Monthly Assessment: Everyday Memory Questionnaire [Time frame: The survey will be completed shortly after the monthly Zoom sessions, during four different sessions. They will occur at approximately week 1, 5, 9, and 13.]
• Stress Monthly Assessment: Perceived Stress Scale [Time frame: The survey will be completed shortly after the monthly Zoom sessions, during four different sessions. They will occur at approximately week 1, 5, 9, and 13.]
• Health Monthly Assessment: SF-36 Health Survey Questionnaire [Time frame: The survey will be completed shortly after the monthly Zoom sessions, during four different sessions. They will occur at approximately week 1, 5, 9, and 13.]
• Sleep Monthly Assessment: Insomnia Severity Index [Time frame: The survey will be completed shortly after the monthly Zoom sessions, during four different sessions. They will occur at approximately week 1, 5, 9, and 13.]
• Sleep Daily Assessment [Time frame: Sleep quality will be assessed during each morning session of the daily EMA assessments, for the 3 month duration of the study.]