Psychedelic Properties of Peganum Harmala: Macrodose and Microdose Reports.

Michael Doty, MA, PhD(c), LMFTA, KAP

Peganum harmala has been used for millennia in traditional medicine and religious

rites. Recent phytopharmaceutical research has given credence to its traditional uses,

demonstrating a wide range of potential therapeutic uses, including its use as antidepressant and

anxiolytic agent. Entheogenic at high doses, P. harmala can create profound psychedelic

experiences with lasting positive effects that echo those seen in research on other psychedelics.

Anecdotal evidence from online forums suggests P. harmala may be able to provide results

similar to microdosing other psychedelics, though no research exists on this potential. This paper

presents the first evidence of P. harmala’s effects when used in a daily microdosing protocol.

Keywords—Peganum harmala, Syrian rue, macrodose, microdose, EEG, psychedelic,

entheogen, affect, burnout, extraction.

The following is a personal account of the author’s self-experimentation with Peganum

harmala. While P. harmala has been extensively studied as a traditional medicine, its inclusion

in psychedelic scientific literature is virtually nonexistent and preliminary data on its use as a

psychedelic in its own right is sparse. What does exist casts an uncertainty toward whether or not

it can provide a psychedelic experience on its own or if its value is limited to being used for its

ability to inhibit monoamine oxidase. The author determined that the best way to begin to fill the

gap in scientific literature was to document a series of bioassays using a range of doses and

simple extraction techniques. Please be aware that while the author attempts to be as objective as

possible, the following paper is a culmination of his individual subjective experiences with P.

harmala and the indicated results may not be generalizable. The author advises the reader to

keep this in mind and to be aware of the potential risks inherent in this form of research. The

author notes that while P. harmala and its alkaloids are legal and unscheduled where he resides,

this is not the case everywhere and the author encourages readers to respect their local laws and

regulations.

Peganum harmala, commonly known as Syrian rue, has a long history of use as a folk

medicine (Aziz, Khan, Adnan, & Izatullah, 2017), with over 30 uses in traditional medicine

(Niroumand, Farzaei, & Amin, 2015). Current research has demonstrated antibacterial (Bibi,

2017), antiviral (Moradi, Karimi, Rafieian-Kopaei, & Fotouhi, 2017), antifungal (Soliman et al.,

2017), and anticancer (Li et al., 2017) effects. Research suggests its primary phytochemical

constituents, a group of 5 β-carboline alkaloids collectively known as the harmala alkaloids, may

produce antidepressant effects through their action as reversible inhibitors of monoamine oxidase

(RIMA) and ability to increase brain-derived neurotrophic factor (BDNF; Fortunato et al., 2010).

The harmala alkaloids are also present in the ayahuasca vine, Banisteriopsis caapi, used in the

South American medicinal brew Ayahuasca, where the harmalas aid in the activation of

dimethyltryptamine found in other plants (McKenna, Towers, & Abbott, 1984). Some scholars

believe Syrian rue’s uses extended beyond traditional medicine and was combined with acacia

trees to create a sort of Ayahuasca analogue used for religious purposes (Shanon, 2008).

Today, while traditional uses for P. harmala continue, modern use in research and

entheogenic applications use a variety of extracts, from simple aqueous extracts to the use of

various solvents (Shulgin & Shulgin, 1997). Outside of pharmacological research and traditional

medicine, P. harmala’s use is primarily as a substitute for B. caapi in analogs of Ayahuasca

(Sayin, 2014). As its common psychoactive use is as an admixture with DMT containing plants

for Ayahuasca analogues, little documentation of full-dose experiences exists, as many user

reports focus found on www.erowid.org and www.dmt-nexus.me on its action as a RIMA and

higher doses are known to cause adverse effects (Shulgin & Shulgin, 1997). Anecdotal evidence

from experience reports retrieved from a search of the www.dmt-nexus.me forum suggests that

small, sub-perceptual doses of Syrian rue, also known as a microdose (Fadiman, 2011),

consumed as a tea or extract, can have positive effects on depression and anxiety.

Peganum harmala and other harmala alkaloid containing plants are unscheduled, legal,

and readily available in the United States and one, Passiflora incarnata (passion flower), is

commonly sold as a mood support supplement. Recent research suggests microdosing other

substances such as psilocybin and LSD can result in effects such as elevated mood and decreased

anxiety, along with increases factors associated with wellbeing (e.g., Fadiman & Korb, 2017). If

shown to be effective, P. harmala and other harmala-containing plants may provide legal

microdosing alternatives. This project aims to discover if P. harmala as an effect on affective

states and emotional well-being.

The aim of present study was twofold: First, to document a full-dose psychedelic

experience with P. harmala, and to address the action of microdoses of P. harmala extract on

affect and well-being. A secondary aim of this study is to identify potential neurological activity,

as assessed by encephalography (EEG). Because of its use as an Ayahuasca analog, potential

EEG results will be compared with existing literature on Ayahuasca’s effects on EEG activity

(Don et al., 1998; Riba et al., 2002).

Experimentation

The author conducted a series of four experiments using P. harmala seeds obtained from

a single source, https://www.shamansgarden.com/. During the course of experimentation, the

author abstained from all other psychoactive drugs with the exception of caffeine or where

otherwise noted. The first 3 experiments utilized timestamps in the following format: 24-hour

time (T + M) where T represents the time the dose was taken and M represents the elapsed time

in minutes.

Experiment 1: Whole Seed

Dose Preparation

Nine grams of seeds were chewed and swallowed along with water slightly acidified with

lime juice.

Study Design and Procedure

The study consisted of a single bioassay. Seeds were consumed after fasting for 18 hours.

The author recorded subjective effects during the experiment to the best of his ability. Additional

subjective effects were recorded the next morning.

Experience Report

12:53 (T=0): Finished swallowing 9g Syrian Rue seeds with water and lime juice.

13:20 (T+27): Pretty sure I am starting to feel something.

13:53 (T+60): Warm core; sweating even though its 72F and I am only wearing shorts.

Effects seem minimal, although there has been some time dilation.

14:08 (T+75): Took 0.57g phenethylamine PEA to test monoamine oxidase effect.

14:36 (T+101): I feel on the verge of an experience. Noticeable diuretic effect; urination

every 20-30 minutes.

14:53 (T+118): Pupils are slightly dilated. I feel something best described as something a

little more than stoned.

18:45 (T+352): Back to baseline, or pretty much so. Only noticeable effects were a

sensation of warmth, slight time dilation, dilated pupils, and the stoned feeling.

20:41 (T+468): While I thought I was back to baseline two hours ago, I feel very relaxed.

While concentrating on a documentary, I notice a slight pastel color overlay to my visual field,

particularly peripherally, that has fluid movement.

Experiment 2: Reduced Extract

Dose Preparation

Ten grams of seeds were boiled in a 60/40 solution of vinegar and distilled water for 30

minutes. Resultant liquid was poured off and set aside. Solids were boiled and strained two

additional times for 30 minutes each in distilled water. The aqueous extract was then reduced

under low heat until a tar-like residue weighing 2.35g remained.

Study Design and Procedure

The study consisted of a single bioassay. Extract was consumed approximately 3 hours

following a meal. The participant recorded subjective effects during the experiment to the best of

his ability. Additional subjective effects were recorded the next morning.

Experience Report

19:15 (T=0): 2.35g extract was rolled into small spheres and swallowed.

19:20 (T=5): Put on music and relaxed.

20:00 (T=45): Got up to use the restroom. Sensation of warmth throughout my body.

20:40 (T=85): Music ended; put on movie.

21:45 (T=150): Experiencing significant time dilation. I am halfway through the movie

but feel as though it should be over. Some haloing around light sources.

22:30 (T=195): Finished the movie and put on a documentary.

22:45 (T=210): I decided silence was better and turned off all media.

Following morning: After turning off media and lying in silence, I swam around my

thoughts for a while and enjoyed some simple linear close-eyed visuals (CEVs) before finally

drifting off. Sleep was restful.

Experiment 3: High-Dose Aqueous Extract

Dose Preparation

An aqueous extract was prepared by boiling 24g P. harmala seeds in distilled water

acidified with 6oz of lemon juice for 1.5 hours. Solids were filtered and the remaining liquid was

set aside. Solids were reboiled for 30 minutes in distilled water acidified with 2oz of lemon juice,

before being filtered again. Solids were boiled for a third time using only distilled water for an

additional 30 minutes. After filtering, the liquids were combined and reduced to a total volume

of 8oz.

Study Design and Procedure

The study consisted of a single bioassay. The extract was consumed approximately 5

hours after a small meal. The author recorded subjective effects during the experiment to the best

of his ability. Additional subjective effects were recorded the next morning.

Experience Report

16:56 (T=0): Quickly drank 4oz of P. harmala extract, equivalent to 12g seeds. The

immediate thought was that the taste was wretched; extremely bitter and acidic. A small amount

of tart cherry juice was used as a chaser.

17:19 (T+23): Clearly intoxicated. I can think clearly but have trouble maintaining focus.

As I am writing this, I feel a wave of extreme intensity.

17:25 (T+29): I had to lie down. Experiencing a sense of whole-body vibration, and a

sensation of spinning rapidly. Close-eyed visuals (CEV) of geometric forms. Writing is difficult.

At this point, it became extremely difficult to document the experience. The following

was written the next morning:

Around that time, my body was vibrating and I felt like I was spinning. It was like being

on a merry-go-round that was vibrating left and right, up and down. Any physical movement

resulted in almost immediate motion sickness. There was also a tone heard predominantly on the

right side that turned out to be pulses of sound that seemed to match the frequency of the

vibration. CEV geometry slowly transformed into a humanoid figure that encompassed all of

what I could see. Sometimes it was the vague outline of a face, other times it was a bust or

mostly full figure. From these views, the entity appeared bipedal entity with an elongated head.

When it would appear solid, I would ask questions, such as “who are you” or “what do you have

to tell me” but the only replies I received were smiles.

Then, near 17:45 (T+49), nausea set in. The impending purge felt greater than what I had

prepared for, so I made my way to the restroom. Movement was difficult to say the least. My

open-eyed visual field was dominated by neon outlines protruding 2-3 inches away from objects.

As I was raising the lid to the toilet, I vomited, covering the toilet and the wall behind it. I was

experiencing extreme time dilation and it seemed like it took forever to clean the mess, as it was

complicated by visual distortion, translucent and opaque tracers, and afterimages that appeared

glitch-like, as if perceptual framerates were distorted. Furthermore, the aforementioned neon

outlines were present around the interior of the toilet bowl, forming semicircles within the larger

circle created by the exterior of the toilet bowl. The semicircles rotated 45 degrees in one

direction before going back the other way.

When I finally returned to my room, I found it nearly impossible to regulate my body

temperature. Sitting up to take my shirt off almost made me vomit. As I settled back in to the

vibrations and spinning sensation, which was much less intense than earlier, I entered into a

period of internal hallucinations that were all encompassing and simultaneously indistinguishable

from reality while possessing a surreal dream-like hypnogogic quality. The prominent visions

were of a former psychotherapy client who had passed away a year earlier, a woman, a 4-5 year

old girl, and a lot of houses.

The houses happened first and most frequently, and the view was always from above.

Early on, the client appeared, sitting in a chair. In a telepathic manner, he told me he was gifting

me with a message that I wouldn’t be able to perceive until the time was right. He faded into

darkness and I was flying above houses before quickly circling down to a grassy field, where the

woman appeared. I embraced her and the scene changed to a young girl who was spinning

around in the sun. I got the impression they were my future partner and child.

After that encounter, I transitioned in and out of mostly all-encompassing fuzzy,

dreamlike hallucinations, but I could still clearly hear the music that was playing. For most of the

night, I couldn’t tell if I was sleeping. I awoke at 05:45am, wide awake and feeling fine other

than a sense of dehydration.

Experiment 4: Microdosing

Dose Preparation

P. harmala seeds were obtained from https://www.shamansgarden.com/. An aqueous

extract was prepared by simmering 20g P. harmala seeds in distilled water for 6 hours, allowing

it to sit for 40 hours, and simmering again for 2 hours. The resultant liquid was strained and

filtered, reduced to approximately 100ml, and filtered again. Distilled water was added to bring

the volume to 200ml, creating a concentration of approximately 1g/10ml. This concentration

provides an equivalent dose of 0.5g/5ml, approximately 1/10 the reported MAOI dose and 1/28

the mean of the range reported for psychoactive effects described by Ott and Shulgin (Erowid,

2020), failing into the suggested range of a microdose (Fadiman, 2011). The extract was stored

in the refrigerator and mixed well before measuring daily doses.

Study Design and Procedure

The study consisted of 18 consecutive days of data collection, the first 6 being control

days and the remaining 12 as microdose days. On all 18 days, approximately 10 minutes of EEG

resting state data was collected. EEG data collection occurred one hour after waking. The

participant was instructed to recline on a couch and relax while listening to a piece of music,

alternating between Shpongle's "How the Jellyfish Jumped up the Mountain" (Posford &

Rothfield, 2013) and "Ineffable Mysteries” (Posford & Rothfield, 2009). Two pieces were

chosen to provide variety and these were used because of their identical length, 10 minutes 24

seconds, and similar tempo. Survey data was collected via online form nightly before bed for all

18 study days.

Beginning on day 7 and continuing daily for the remainder of the study, doses of

0.5g/5ml P. harmala extract were administered immediately upon awakening. Extract was

removed from refrigeration, mixed well, measured with an oral syringe, and consumed directly

via injection into the back of the mouth.

Measurements

EEG data was collected using Muse headset, recording through 4 electrodes in locations

a_TP10, TP9, AF7, and Af8, and recorded with the MuseMonitor app. Data collection occurred

approximately +60 min from drug administration. Data was imported into EEGLAB, channel

means were removed and data was filtered through the Basic FIR filter to a range of 1 – 50 Hz.

Artifacts were processed visually. Statistical analysis of EEG recordings was performed using

EEGLAB’s STUDY function. An alpha level of 5%, was used and all P values lower than 0.05

are clearly distinguished in spectral plots. Power spectra for all channels were analyzed for

significance.

After preliminary analyses showed remaining artifacts, datasets underwent further visual

processing. Following a second analysis of power spectra, datasets from sessions 1, 2, and 3

were rejected due to large amounts of noise, presumably from a poorly fitting headset.

The author completed an online questionnaire nightly via the Google Forms platform

(www.google.com/forms) and took approximately 3 minutes to complete. The questionnaire

consisted of 5 items addressing burnout and The Positive and Negative Affect Schedule

(PANAS-X), a 60-item survey (Watson & Clark, 1994). The PANAS-X contains 13 subscales:

Negative Affect, Positive Affect, Fear, Hostility, Guilt, Sadness, Joviality, Self-Assurance,

Attentiveness, Shyness, Fatigue, Serenity, and Surprise. Survey data was analyzed in Statistica

using multivariate analysis of variance (MANOVA) with repeated measures, with treatment

groups (control, microdose) as factors, and linear regression. Differences were considered

statistically significant for P<0.05.

Results

EEG Recordings. Between-session analyses shows significant differences in control and

microdose EEG recordings on the between 42-44 Hz on the TP9 channel (Fig. 1) and at 11 Hz on

the AF7 channel (Fig. 2).

Subjective Ratings

With the exception of three PANAS-X subscales, Positive Affect,

Attentiveness, and Surprise, and two burnout items, physical exhaustion and somatic distress, all

between-group differences (Table 1) were significant, with the greatest effect seen as reductions

in Negative Affect and Hostility. Within-group analyses (Table 2) and linear regression (Fig. 3,

Table 2) show and show significant changes over the course of the study. No significant

differences were found when preforming an ANOVA with repeated measures using music choice

as a factor.

Microdosing Discussion

Results indicate that daily administration of subperceptual doses of P. harmala produce

significant changes in affect and neurological activity. While a significant difference was not

present between the control and microdose groups in the Positive Affect subscale, significant

reductions in negative emotion subscales and increases in positive emotion subscales lend

validity to the overall subjective experience of an overall better mood and reduction in symptoms

of stress and anxiety. This supports animal research showing that harmala alkaloids exhibit

antidepressant-like effects (Fortunato et al., 2010) and is in step with observed effects in a

number of microdosing studies (e.g., Fadiman & Korb, 2017, Passe, 2019; Polito & Stevenson,

2019).

EEG research on the effects of full doses of Ayahuasca, also rich in harmala alkaloids, is

limited and it is likely that the presence of DMT in Ayahuasca has an effect on EEG results.

However, the presence of harmala alkaloids allows for some comparison. Early research showed

significance increases in power in the 32-44 Hz frequency band, as well as nonsignificant

increase in beta band and decreases in both alpha and theta bands (Don et al., 1998). While the

gamma band was not investigated in subsequent research, showed significant effects across all

frequency bands, although the researchers did not find significance at the alpha-2 sub-band

(10.5-13 Hz; Riba et al., 2002).

Interestingly, the present study found significant effects between 11-12 Hz, a novel

finding in regards to Ayahuasca research, while also serving to confirm previous findings

relating to gamma band activity (Don et al., 1998).

The results of the survey data, indicating a cumulative effect across a number of affective

qualities, match the author’s qualitative reflection on the experience. While subjectivity

suggested an improvement in positive affect, this is not indicated by the results. The subjective

perception of improved positive affect may in part be due to a reduction in negative affect and

other negatively valenced measures. Additionally, the author experienced fewer intrusive

thoughts related to PTSD. The overall qualitative impression is that while stressors were still

present and in awareness, there was a sense of not feeling as bothered by stressors.

This study has several limitations. As a single-participant study, control for confounding

variables is lacking and it is impossible to rule out other potential factors contributing to the

effect. One such confounding variable may be the simple act of relaxing for 10 minutes per day.

The extraction technique also presents limitations. Like all plants, variance in phytochemical

concentration is expected and without a refined extraction of alkaloids, exact dosing is

impossible. As an aqueous extract, brewing time, temperature, and source material all play a role

in the variability of alkaloid content. Finally, this researcher was previously inexperienced with

EEG data collection and processing. Inexperience in fitting the EEG hardware may be a factor in

only finding significant differences in left-hemisphere channels. An additional consideration that

may be a limitation is questionnaire design; by positioning burnout questions before the PANAS-

X, there could be a priming effect.

Further research is necessary to establish significant results that are able to be generalized

to the population at large. By using a larger sample size and standardized extracts, statistical

power and inference of results would be of greater significance. Accessibility of P. harmala, its

low price (approximately $0.03 per 0.5g dose) and ease of extraction create an opportunity for

much larger participant pools, although collecting EEG data still creates constraints. A large-

scale survey study combined with a smaller scale EEG study could yield significant results that

verify P. harmala’s efficacy for microdosing.

The next step in this line of inquiry is to perform a small-scale pilot study to expand the

data pool in a similar way to other microdosing studies, with participants self-reporting data.

Extending data collection after the cessation of microdosing can be used to determine potential

prolonged effects. This phase could focus on survey data, making EEG data collection optional

or excluded from the phase. Following this the abovementioned large-scale studies could

proceed.

This study helps to confirm reports of P. harmala’s effects on decreasing negative affect

when used in a daily microdosing protocol, providing evidence that it may prove to be a low

cost, legal alternative for other psychedelic medicines.

Conclusion

This series of experiments serves to further establish the pscyhoactivity of P. harmala, as

well as its potential as a legal and cost-effective substance for microdosing protocols. Observable

effects varied, however the most consistently noticeable effects across doses, with the exception

of microdoses, were a sense of warmth and time dilation. Higher doses led to CEVs. At the

highest studied dose, effects also included open-eyed visuals (OEVs), auditory hallucinations, a

sense of somatic vibration, vertigo, nausea, and vomiting. Observed content at the highest dose

included an apparent nonhuman entity encounter, whose presence seemed to guide the entire

experience by showing the author a number of different scenarios that seemed unrelated in the

moment. After a long period of integration, the author has determined that much of the content

shown related to a sense of identity, interconnectedness, and community.

The apparent entity encounter had a significant quality, as it was the first time the author

had an experience of that nature. Of note, the author felt as though he was confronted with the

what felt to be same entity during an ayahuasca experience three months later. During both

experiences, the author felt as though the entity had imparted wisdom and guidance. Entity

encounters are common phenomena, particularly with dimethyltryptamine (DMT) and ayahuasca

(Luke, 2011; Meyer, 1994; Strassman, Wojtowicz, Luna, & Frecska, 2008). Meyer’s (n.d.)

review of 340 DMT experience reports showed that 226 reports, or 66.47%, contained

descriptions of entities. A pharmacological of DMT study conducted at the University of New

Mexico discovered that approximately half of the trials resulted in entity experiences. Although

beyond the scope of this paper, researching psychedelic entity encounters could offer valuable

insight into the nature of consciousness and warrants further investigation.

During the course of experimentation, no adverse effects were noticed aside from nausea

and vomiting at the highest studied dose. Those effects subsided during the peak effects and the

author experienced no negative residual effects the following day. While further research is

necessary to address limitations, cofounding variables, and biases, these experiments suggest that

P. harmala can reliably induce a psychedelic state similar to classic serotonergic psychedelics

and shows potential antidepressant and anxiolytic effects when microdosed.