Below is the unformatted paper. I'll attach a pdf with the figures and tables.
Microdosing Peganum harmala
Abstract—Peganum harmala has been used for thousands of years 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, microdose, EEG, psychedelic, entheogen, affect, burnout, extraction
I. INTRODUCTION (HEADING 1)
Peganum harmala, commonly known as Syrian rue, has a long history of use as a folk medicine [1], with over 30 uses in traditional medicine [2]. Current research has demonstrated antibacterial [3], antiviral [4], antifungal [5], and anticancer [6] 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) [7]. 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 [8]. 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 [9].
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 [10]. Outside of pharmacological research and traditional medicine, P. harmala’s use is primarily as a substitute for B. caapi in analogs of Ayahuasca [11]. 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 [12], consumed as a tea or extract, can have positive effects on depression and anxiety.
Peganum harmala, along with all 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 [13]. 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 wellbeing.
The aim of present study was to address the action of microdoses of P. harmala extract on affect and wellbeing. 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 [14, 15].
II. METHODS
A. Participants
Study constraints, such as potential adverse effects and accessibility to EEG hardware limited the study to two participants, the researcher and one other participant. Due to time constraints, the other participant elected to discontinue participation and dropped out on study day 3. The researcher is a 34-year old male, graduate educated, with a history of depression, anxiety, and PTSD. The participant remained abstinent from other psychoactive compounds, with the exception of caffeine, for the duration of the control and experimental phases.
B. Drug
P. harmala seeds were obtained from
Shaman's Garden Exotic Botanicals | Kratom | Kava. 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 [16], failing into the suggested range of a microdose [12]. The extract was stored in the refrigerator and mixed well before measuring daily doses.
C. Study design and procedure
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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" [17] and "Ineffable Mysteries” [18]. 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.
D. Measuresments
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 study participant 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 [19]. 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.
III. RESULTS
A. 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).
B. 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.
IV. 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 [7] and is in step with preliminary analyses of an ongoing, large-scale microdosing study [13].
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 [14]. 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) [15].
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 [14].
The results of the survey data, indicating a cumulative effect across a number of affective qualities, match the participant’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 participant 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. 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.
REFERENCES
[1] M. A. Aziz, A. H. Khan, M. Adnan and I. Izatullah, “Traditional uses of medicinal plants reported by the indigenous communities and local herbal practitioners of Bajaur Agency, Federally Administrated Tribal Areas, Pakistan,” J. Ethnopharmacol. vol. 198, pp. 268-281, Feb. 2017, doi:
Redirecting, [Online]. Available:
http://www.sciencedirect.com/science/article/pii/S0378874117301976?via=ihub
[2] M. C. Niroumand, M. H. Farzaei, G. Amin, “Medicinal properties of Peganum harmala L. in traditional Iranian medicine and modern phytotherapy: a review,” J. Tradit. Chin. Med., vol. 35, no. 1, pp. 104-109, Feb. 2015, doi:
Redirecting, [Online]. Available:
https://www.sciencedirect.com/science/article/pii/S0254627215300169
[3] F. Bibi, “Diversity of antagonistic bacteria isolated from medicinal plant Peganum harmala L.,” Saudi J. of Bio. Sci., vol. 24, no. 6, pp. 1288-1293, Sept. 2017, doi:
Redirecting, [Online]. Available:
http://www.sciencedirect.com/science/article/pii/S1319562X15002168?via=ihub
[4] M. Moradi, A. Karimi, M. Rafieian-Kopaei, and F. Fotouhi, “In vitro antiviral effects of peganum harmala seed extract and its total alkaloids against influenza virus,” Microbial Pathogenesis, vol. 110, pp. 42-49, June 2017, doi:
Redirecting, [Online]. Available:
http://www.sciencedirect.com/science/article/pii/S0882401017305843?via=ihub
[5] S. Soliman, D. Alnajdy, A. El-Keblawy, K. Mosa, G. Khoder, and A. Noreddin, “Plants' natural products as alternative promising anti-candida drugs,” Phcog Rev., vol. 11, no. 22, Sept. 2017, doi:
Plants' Natural Products as Alternative Promising Anti-candida Drugs | Pharmacognosy Reviews, [Online]. Available:
Plants' Natural Products as Alternative Promising Anti-<em>Candida</em> Drugs
[6] C. Li, Y. Wang, C. Wang, X. Yi, M. Li and X. He, "Anticancer activities of harmine by inducing a pro-death autophagy and apoptosis in human gastric cancer cells", Phytomedicine, vol. 28, pp. 10-18, 2017, doi:
Redirecting, [Online]. Available:
http://www.sciencedirect.com/science/article/pii/S0944711317300399?via=ihub
[7] J. Fortunato, G. Réus, T. Kirsch, R. Stringari, G. Fries, F. Kapczinski, J. Hallak, A. Zuardi, J. Crippa and J. Quevedo, "Chronic administration of harmine elicits antidepressant-like effects and increases BDNF levels in rat hippocampus", J. Neural. Transm., vol. 117, no. 10, pp. 1131-1137, 2010, doi:
https://dx.doi.org/10.1007/s00702-010-0451-2, [Online]. Available:
Chronic administration of harmine elicits antidepressant-like effects and increases BDNF levels in rat hippocampus - Journal of Neural Transmission
[8] D. McKenna, G. Towers and F. Abbott, "Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca", J. Ethnopharmacol., vol. 10, no. 2, pp. 195-223, April 1984, doi:
Redirecting, [Online]. Available:
https://www.sciencedirect.com/science/article/pii/0378874184900035
[9] B. Shanon, "Biblical entheogens: A speculative hypothesis", Time and Mind, vol. 1, no. 1, pp. 51-74, 2008, doi:
https://dx.doi.org/10.2752/175169608783489116, [Online]. Available:
http://www.tandfonline.com/doi/abs/10.2752/175169608783489116
[10] A. Shulgin and A. Shulgin, “Harmaline,” Tihkal: The continuation. Berkeley: Transform Press, 1997, [Online]. Available:
Erowid Online Books : "TIHKAL" - #13 HARMALINE
[11] H. Sayin, "The consumption of psychoactive plants in ancient global and Anatolian cultures during religious rituals: The roots of the eruption of mythological figures and common symbols in religions and myths", NeuroQuantology, vol. 12, no. 2, 2014, doi:
https://dx.doi.org/10.14704/nq.2014.12.2.753, [Online]. Available:
https://www.neuroquantology.com/index.php/journal/article/view/753
[12] J. Fadiman, The psychedelic explorer's guide. Rochester, Vt.: Park Street Press, 2011.
[13] J. Fadiman, and S. Korb, “Microdosing: The phenomenon, research results, and startling surprises,” Psychedelic Science 2017 conference, April 21, 2017, [Online]. Available:
http://psychedelicscience.org/confe...on,-research-results,-and-startling-surprises
[14] N. Don, B. McDonough, G. Moura, C. Warren, K. Kawanishi, H. Tomita, Y. Tachibana, M. Böhlke and N. Farnsworth, "Effects of Ayahuasca on the human EEG", Phytomedicine, vol. 5, no. 2, pp. 87-96, April 1998, doi:
https://doi.org/10.1016/S0944-7113(98)80003-2, [Online]. Available:
https://www.sciencedirect.com/science/article/pii/S0944711398800032
[15] J. Riba, P. Anderer, A. Morte, G. Urbano, F. Jané, B. Saletu and M. Barbanoj, "Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers", Br. J. of Clin. Pharmacol., vol. 53, no. 6, pp. 613-628, June 2002, doi:
https://dx.doi.org/10.1046/j.1365-2125.2002.01609.x, [Online]. Available:
https://www.iceers.org/docs/science/ayahuasca/Riba et al_2002_Topograph_pharmaco-EEG_Ayahuasca.pdf
[16] "Erowid Vault: Dosage", Erowid.org, 2017. [Online]. Available:
https://erowid.org/plants/syrian_rue/syrian_rue_dose.shtml
[17] S. Posford and R. Rothfield as Shpongle, “How the jellyfish jumped up the mountain,” Museum of Consciousness [CD], London, England: Twisted Records, 2013.
[18] S. Posford and R. Rothfield as Shpongle, “Ineffable mysteries,” Ineffable mysteries from Shpongleland [CD], London, England: Twisted Records, 2009.
[19] D. Watson and L. A. Clark, The PANAS-X: Manual for the Positive and Negative Affect Schedule – Expanded Form, The University of Iowa, 1994, [Online]. Available:
http://www2.psychology.uiowa.edu/Faculty/Clark/PANAS-X.pdf
