Draft: An Open-Label Pilot Study #

Introduction #

Meditation is a cornerstone practice for many contemplative traditions. Practitioners sit, settle, and turn attention inward—often in the morning before the rest of life intrudes. It’s a quiet practice, and the proposal that follows is intended in that spirit.

Many meditators already use a mild stimulant—tea or coffee—to support their morning sitting. This is so common it barely registers as pharmacological assistance. It’s worth asking whether other substances might also help. We propose investigating tetrahydroharmine (THH).

THH is a naturally occurring beta-carboline alkaloid found in Banisteriopsis caapi, one of the principal ingredients in ayahuasca.¹ Taken alone in small doses, its subjective effects are subtle—some optimism, a sense of well-being, increased alertness. We hypothesize that daily low-dose THH before meditation will be associated with self-reported improvements in the ability to observe mental content without reactivity.

Method #

Design #

Open-label pilot intervention study.

Participants #

Adults (18+) who have a pre-established daily meditation practice of at least 1 year.

Power #

This section is a work in progress.

We aim to recruit at least 200 participants, which provides adequate power (0.80) to detect small effects (d=0.2) on individual Likert items without correction for multiple comparisons.

Recruitment #

Recruiting daily meditators willing to purchase and self-administer an obscure alkaloid is the study’s most significant practical challenge. The intersection of these populations is small, and we do not yet have a concrete recruitment strategy. Outreach through meditation communities, psychedelic harm-reduction forums, and contemplative practitioner networks are plausible channels, but whether they can deliver the target sample size remains an open question.

Inclusion Criteria #

• 18 years or older
• Daily meditation practice of at least 1 year
• Resident of the United States
• Willing to self-administer THH before morning meditation for 7 consecutive days

Exclusion Criteria #

• Current use of MAO inhibitors, serotonin reuptake inhibitors, or lithium²
• History of epilepsy or seizure disorder³
• Pregnancy or breastfeeding⁴

Substance #

THH is a legal, unscheduled substance available from commercial sources such as Bounty Botanicals (listed for reference, not as an endorsement). Participants source their own THH.

Shulgin reportedly took 300mg of THH on a single occasion.⁵ For this study’s purposes, that is far more than necessary. We recommend 5–15mg, which amounts to a small pinch of powder—well under ⅛ teaspoon. Precision is not critical. One or two small pinches between thumb and forefinger is sufficient.

Take THH at least 30 minutes prior to meditation. Start small and increase gradually until you can discern a psychoactive effect from THH. The study observation period is 7 days; participants who have not discerned a psychoactive effect by the end of that period are still welcome to complete the survey.

Timeline #

7-day observation period + post survey.

Measures #

Structure #

Administered after the 7-day observation period via an anonymous Google Form. No identifying information is collected.

Demographics:

1. Age (years, numeric)
2. Gender (multiple choice: male, female, non-binary, prefer not to say)
3. Meditation tradition (free text): “What type of meditation do you practice? (e.g., Vipassana, Zen, TM, mindfulness, IFS, other)”
4. Meditation experience (numeric): “How many years have you maintained a regular meditation practice?”
5. Meditation duration (numeric): “How long is your typical morning meditation in minutes?”
6. Customary substance use (free text): “What substances, if any, do you customarily use before meditation? (e.g., tea, coffee, other)”
7. Prior THH experience (multiple choice: none, 1–5 times, 6–20 times, more than 20 times): “How many times have you used THH before this study?”
8. Prior ayahuasca experience (multiple choice: none, 1–5 times, 6–20 times, more than 20 times): “How many times have you used ayahuasca before this study?”
9. THH source (free text): “Where did you obtain your THH?”

Data Quality:

1. Adherence (numeric): “On how many of the 7 days did you take THH before meditation?”
2. Attention check (5-point Likert): “Please select ‘Agree’ for this item.”
3. Substance use changes (free text): “Did your substance use before meditation change in any way during the study period besides THH? (e.g., started, stopped, or changed dose of anything)”
4. Life changes (free text): “Did anything else change in your life during the study period that may have affected your meditation? (e.g., stress, schedule, travel, illness, major life events)”
5. Seriousness (5-point Likert): “I answered the questions in this survey thoughtfully and honestly.”

Retrospective:

1. Psychoactive effect (multiple choice: yes clearly, possibly, no): “Did you notice a psychoactive effect from THH during the study period?” (If no, skip the rest)
2. Side effects (free text): nausea, headache, appetite changes, mood changes, sleep disturbance,⁶ other (free text)
3. Unblending capacity (5-point Likert): “Compared to your usual practice before the study, when difficult thoughts or emotions arose during meditation, how easily could you observe them without getting caught up in them?”
4. THH and meditation (5-point Likert): “Compared to your usual practice, do you think THH improved your meditation?”
5. Continuation intent (5-point Likert): “How likely are you to continue using THH after the study concludes?”
6. Practice changes (free text): “Did your meditation practice change in any way during the study period (duration, technique, frequency)?”
7. Open-ended (free text): “Is there anything else you’d like to share about your experience?”

Ethics #

We are exploring IRB options. Academics interested in collaboration are encouraged to contact jpritikin (at) pobox (dot) com.

Informed consent. The first screen of the survey presents a consent form describing the study’s purpose, procedures, risks, voluntary nature, and anonymity of data collection. Participants must affirm consent before proceeding to the survey questions.

Rationale for expedited review. Because the study provides dosing guidance and a sourcing link, it constitutes a research intervention rather than passive observation. However, the study almost certainly qualifies for expedited review under Category 7 of the Common Rule (45 CFR 46.110). Several features of the study support the expedited pathway:

• Minimal risk. THH is a legal, unscheduled substance. The recommended dose (5–15mg) is well below doses of the closely related beta-carboline harmine that healthy volunteers tolerated in a Phase 1 trial,⁷ and within the range of beta-carboline exposure from ceremonial ayahuasca use, which a safety review found free of serious adverse effects.⁸ No clinical trial of isolated oral THH exists; the safety case rests on analogy to harmine and on THH’s long history of ingestion as a component of ayahuasca. Notably, the analogy is conservative: harmine is a substantially more potent MAO-A inhibitor than THH, so the safety margin for THH at equivalent doses is likely wider than the harmine data alone suggest.
• Anonymous data collection. No identifying information is recorded. Disclosure of responses would not place participants at risk.
• No vulnerable populations. Participants are adults with established meditation practices.
• Self-administration. Investigators do not supply or distribute THH. Participants source and administer the substance themselves.

Adverse event reporting. The current design collects side effects only retrospectively in the post-survey. A real-time reporting mechanism during the 7-day observation period may be warranted. We defer to IRB guidance on whether and how to implement this.

Limitations #

• No control group. Expectancy effects and placebo response cannot be ruled out.
• This is a convenience sample of self-selected enthusiasts—people who have already decided to try THH.
• Investigators do not control dosing or administration. Variability across participants is expected.
• Retrospective self-report over a 7-day period is subject to recall bias.
• The observation window may be too short to capture changes in meditation practice that develop gradually.
• Dosing by “a small pinch” is imprecise. It is possible that dosage matters more than the investigators expect.
• Participants are not asked to report their dose. Dose-response patterns cannot be examined.
• Participants source THH from an unregulated market. Product purity, identity, and freedom from adulterants are not verified.
• Participants are not asked to abstain from other substances. We rely on the assumption that participants genuinely interested in evaluating THH will avoid masking its effects with other psychoactives—but this is uncontrolled.
• Meditation experience likely moderates the effect of THH on unblending, but this pilot is not powered to detect interaction effects across experience levels.

The study is designed to generate preliminary data and identify patterns worth investigating in a controlled trial.

Target Journal #

The Journal of Psychoactive Drugs is a likely fit. It publishes empirical work on psychoactive substances including pilot studies, has a history of publishing ayahuasca and harmala alkaloid research, and is receptive to studies involving novel use contexts.

Notes #