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Is it Safe to Mix Psychedelics With Syrian Rue (an MAOI)?

As psychedelics continue to become more mainstream, growing their presence in our at-home pharmacopeia, some companies are beginning to claim the benefits of mixing psilocybin mushrooms with effect-enhancing supplements like adaptogenic mushrooms and Syrian rue. 

Today we’ll go over research studies that examine the active ingredients of Syrian rue to better understand how they extend the duration of a psilocybin or DMT experience, but can cause potentially fatal medical contraindications when taken with certain psychedelics and antidepressants

We’ll also be discussing safety practices for journeyers to properly manage expectations when using Syrian rue with psilocybin mushrooms and other psychedelic substances. Later, we’ll hear accounts from Psychedelic Passage survey respondents who have used Syrian rue in conjunction with psychedelics. 

As always, we note that we are not medical professionals. All of the information provided today is strictly for educational purposes and you should always consult your doctor before making any changes to your prescription medications, nutritional supplements, and diet.

What is Syrian Rue?

Native to Asia, Africa, Europe, and the western United States, Syrian rue (Peganum harmala) is a plant known for producing mild sedative and hallucinogenic effects in humans. The plant has a rich presence in folk medicine, having been used for its fruits, roots, and bark over many centuries.

Some in vitro studies have found P.harmala seed extracts to be useful in fighting against certain bacteria including Staphylococcus aureus (staph infections pathogen) and Salmonella spp (salmonella infection pathogen) (Moloudizargari et al., 2013). 

Its antimicrobial, cardiovascular, and cytotoxic effects have been fairly well studied. For the purposes of our discussion, it’s important that we trace this drug’s mechanisms back to its chemical structure. 

P.harmala contains a number of alkaloids that function as monoamine oxidase inhibitors (MAOIs). Some of these alkaloids include harmine, harmaline, and hamalol. 

Today, MAOIs are a class of medications used to treat depression and are often considered as a last resort due to their extensive medical contraindications and hypertentive side effects. First introduced in the 1950s, these drugs work to ease depression by inhibiting monoamine oxidase.

People with depression commonly experience low levels of dopamine, serotonin, and norepinephrine. Collectively, these neurotransmitters are called monoamines. Our bodies naturally produce a chemical called monoamine oxidase which removes these neurotransmitters from the brain. 

Thus, by inhibiting their removal, MAOIs permit these neurotransmitters to remain in circulation, which results in an elevated mood and more functional emotional regulation. This is also why some choose to employ Syrian rue supplements for their antidepressant and analgesic effects.

The Effects of Mixing Psychedelics With Syrian Rue

More recently, Syrian rue has garnered the sights of psychedelic enthusiasts who seek to magnify the effects of psilocybin mushrooms. Though we do not negate the anecdotal reports that implicate Syrian rue in the potency increase experienced by psilocybin mushroom journeyers, we do aim to reduce harm caused by their combination. 

Those who combine P.harmala with psilocybin and with other psychedelics like DMT, do so to increase the length and intensity of the experience. P.harmala is reported to increase the duration of psilocybin and DMT drug experiences, sometimes by twice the length. 

A normal psilocybin experience typically lasts anywhere from 6 to 8 hours. What’s important to note here is that for many people, 6 to 8 hours is already more than enough time spent in such an altered state of consciousness.

Therefore, if you plan to use additive supplements for increasing the amount of time spent in a psilocybin or DMT experience, understand that such prolongation and intensification of effects may not be conducive to your mental wellness. 

Especially for those who have never journeyed with these psychedelics or have only done so a handful of times, it’s important that you establish a relationship with the raw psychedelic medicine before deciding if the amplification of its effects is something you’d truly desire to do.

The same goes for Syrian rue. If you’re planning on combining it with psilocybin or DMT, you should become familiar with its raw effects before deciding if you’d like to employ it on your next journey.

A quick internet search uncovers a plethora of discussions on the effects of this drug combination. The most common downfalls reported in online forums are using too much of the psychedelic drug, too much Syrian rue, or both.

Though we do not advocate for this drug combination, for harm reduction purposes we advise that you never take your regular psilocybin or DMT dose in combination with Syrian rue. Because Syrian rue significantly increases effect intensity, you may use half your regular psychedelic dose.

If you aim to have a macrodose psilocybin experience, it’s also imperative that you start at the least viable dose of Syrian rue and then work your way up (within reason) until desired effects are reached. On discussion forums, most longtime journeyers report a “sweet spot” with a psilocybin to Syrian rue ratio of 2:1.

Otherwise, you might find yourself experiencing very unpleasant side effects such as nausea, vomiting, diarrhea, and sometimes a sensitivity to light.

Users describe this Syrian rue ‘overdose’ experience as motion sickness that’s accompanied by accelerated heart rhythm. Some reports indicate that high-dose Syrian rue use causes difficulty walking, a perceptual acceleration of sound, and visual trails following somatic movement. 

Though we’ll discuss this at further length in the next section, it’s important that you understand the consequences of mixing Syrian rue with SSRIs and antidepressants. 

This combination has a high potential for causing serotonin syndrome, a fatal condition caused by toxic levels of serotonin in the brain. Never combine or attempt to combine Syrian rue with SSRIs and antidepressants. 

The Science Behind Mixing Psychedelics With MAOIs

In a separate article on the psilocybin-blunting effects of SSRIs and antidepressants, we discussed the potential hazards of mixing psychedelics with antidepressants. This section will focus specifically on mixing psychedelics with antidepressants and r-MAOIs, like Syrian Rue.

Serotonergic psychedelics are psychedelic drugs that bind to 5-HT2A (serotonin) receptors in order to produce their hallucinogenic effects on the brain. This class of psychedelic drugs include LSD, psilocybin, MDMA, and DMT.

In binding to these receptor sites, serotonergic psychedelics stimulate the production of serotonin. As we know, MAOIs inhibit the removal of serotonin. Here, we find the contraindication for their combined use. 

Taking a drug that increases serotonin levels, as psychedelics do, in conjunction with a drug that inhibits their removal, as Syrian rue does, increases the chances of experiencing serotonin syndrome. 

Serotonin syndrome is a potentially fatal drug reaction that results from an overaccumulation of serotonin in the brain. Symptoms of serotonin syndrome include vomiting, diarrhea, muscle spasms, sweating, shivering, and confusion.

Antidepressants & Syrian Rue

The same reigns true for mixing SSRIs and other antidepressants with Syrian rue. If you’re taking a prescription medication that increases serotonin levels by inhibiting their removal or reuptake, such as pharmaceutical MAOIs, SSRIs, or SNRIs, you run a very high risk of inducing serotonin syndrome. 

MDMA & Syrian Rue

Though mixing any serotonergic psychedelic with an MAOI is not advised, we should note that mixing Syrian rue with MDMA is guaranteed to be the most catastrophic of all. 

MDMA’s serotonin releasing properties are many times greater than other psychedelic drugs. Thus, MDMA-Syrian rue combination is the most potentially fatal, making cardiac arrest from hypertensive crisis extremely likely. MDMA should never be combined with an MAOI.

A 2016 literary review conducted by PK Gilmman came to the same conclusion. Gillman states “Some (illicit drugs) interact potently with MAOIs, because many of them are transporter inhibitors, or releasors of serotonin and or noradrenaline: e.g. the interaction of moclobemide and MDMA is predictably toxic (causing fatal ST) and has caused a number of tragedies”.

Ketamine & Syrian Rue

Though ketamine is not a traditional psychedelic, some have begun to use it for its therapeutic and hallucinogenic properties. Ketamine is a serotonin–norepinephrine reuptake inhibitor (SNRI). 

Thus, combining a drug (ketamine) that inhibits these neurotransmitters from being taken back into the receptors that release them, with a drug (Syrian rue) that inhibits their removal, could almost guarantee serotonin syndrome. 

This combination would leave no option for expelling excess serotonin. Ketamine should never be combined with an MAOI, like Syrian rue.

LSD & Syrian Rue

Research has found that combining an MAOI, like Syrian rue, with LSD (Lysergic acid diethylamide), can greatly diminish LSD’s hallucinogenic effects. 

A 1996 study conducted by RL Carhart-Harris and DJ Nutt found strong anecdotal evidence of a correlation between MAOI use and blunted or greatly reduced LSD effects.

A 1995 study by Katherine R. Bonson and Dennis L. Murphy recruited subjects who used LSD during chronic antidepressant use. The subjects who had used MAOIs experienced a significant reduction of subjective LSD effects, where those who used tricyclic antidepressants experienced an increase. 

Psilocybin Mushrooms & Syrian Rue

The combination of psilocybin and Syrian rue is a bit different because psilocybin mushrooms already contain MAOIs like harmane and harmine (Felix Blei et al., 2020). 

Though there seem to be no studies on the effects of Syrian Rue with psilocybin mushrooms, we should note the difference between pharmaceutical MAOIs and the MAOIs found in Syrian rue.

Pharmaceutical MAOI antidepressants should never be used with psilocybin mushrooms because they irreversibly bind to neurotransmitter receptors. This makes it very probable for serotonin syndrome to be induced as the brain cannot metabolize their release. The MAOIs in Syrian rue are reversible which suggest less of a risk in their combination with psilocybin. 

Though there are proper dosage guidelines for psychedelics, there is no research indicating proper dosage for Syrian rue and psilocybin in combination. Because of this, many who use this combination experience side effects such as prolonged vomiting and unpleasantly intense psilocybin trips.

Such potentiation of the MAOIs already present in psilocybin could cause psychedelic experiences that heighten effects of depersonalization, which may increase psychological discomfort. 

Being that these are two MAOI-containing drugs being used in combination, the potential for serotonin syndrome is still present, though at a much reduced risk. However, a reduced risk by comparison is not sufficient information to indicate the safety of combining these two drugs. 

DMT & Syrian Rue

Ayahuasca is a hallucinogenic brew that contains DMT and β-carboline alkaloids. Combining DMT with the beta-carbolines in Syrian rue causes a very potent effect. The potentiation and elongation of DMT effects with Syrian rue are so intense, that journeyers often report having ayahuasca-like experiences with this combination.

Anecdotal Reports

To offer some first-hand accounts of people who have used psychedelics in combination with Syrian rue, we asked survey respondents to submit their personal accounts. Here’s what some of them had to say.

“Had a bad experience and really had trouble breathing. I had to exert massive effort to keep breathing. I honestly think I could have died that day if I took a little bit more.” 

Anonymous Survey Respondent

“Hi, I had taken Syrian rue seed tea combined with smoked DMT. (The) trip was prolonged 1 hour compared to 10-15 mins without rue and there were qualitative differences too. It was too intense.

I don’t even remember much. Side effects are hard to describe. I was feeling nausea, headache and unpleasant body load, decreased pain threshold, anxiety. 

After DMT was ingested, well, none of the serious side effects were noticed other than tremendous anxiety and after the trip I was unable to sleep that night due to stimulation from harmalas.

Syrian rue has its own distinct psychedelic and stimulant effects. Visual trails, loud buzzing sound (like a tattoo machine) in every noise outside and inside, dreamy state, dissociation, uplifted mood/euphoria. 

I used to drink just harmala tea and have fun listening to music and watching videos, enjoying that altered state. It’s a decent psychedelic, but only if seeds are fresh. I remember trying to brew tea from 3-4 year old seeds and all I got was some nausea and an overall intoxicated feeling.” 

-Anonymous Survey Respondent

“When I was new to DMT and Changa and had been working my way up with dosage in increments getting a feel for it, one night I thought I would throw caution to the wind a bit and try for my first mystical breakthrough.

I consumed 3.5g of Syrian rue tea and then an hour later I loaded 125mg of 40% Changa with a bonus 25mg of FB DMT sandwiched within the changa. I only remember parts of maybe the first minute of the experience.

My sitter said I looked like I was in the downhill skiing position while laying down repeating wow over and again until from that point I just remember the experience taking a dark twist and for the next 75 – 90 mins only really remembering pure anxiety mixed with some fear…

…while picturing myself as a bear in a cave and getting relief and a sense of safety by performing very deep long growling sounds that seemed to be keeping whatever felt threatening at bay. My wife who was my sitter said I remained in the fetal position for this whole time grunting and growling…

…like an animal in a mantra-like fashion until I came out of it a bit disorientated and sweating profusely before needing to vomit once and then everything calming down. Not sure if this was an overdose of DMT or a reaction caused by the combo… Haven’t tried the combo again since then…” 

Anonymous Survey Respondent

Closing Off

As we’ve reviewed today, MDMA and ketamine should never, under any circumstance be combined with Syrian rue due to a high likelihood of inducing serotonin syndrome. Combination of Syrian rue with LSD demonstrates potential risk for diminished effects. 

Combining Syrian rue with DMT or psilocybin shows a reduced risk of serotonin syndrome, but your dosage should be appropriately adjusted so as to reduce the risk of discomfort due to overly intense effects. 

If you’re considering taking a psilocybin-Syrian rue dose, take serious consideration of the true potency of these combinations. Hallucinogenic effects can always be amplified by increasing your psychedelic dosage appropriately, but once a psychedelic experience begins, its potency cannot be reversed. 

Always abide by safety measures when consuming any psychedelic substance. Be aware of the effects that result from combining psychedelics with SSRIs and consult a qualified psychedelic facilitator to receive proper screening before embarking on a journey.

Note that people who are pregnant, have low blood pressure, and kidney or liver problems, should never take Syrian rue as it could cause uterine contractions, miscarriage, kidney and liver damage, and lowered blood pressure.

If you’d like to get in contact with our pre-vetted network of psychedelic facilitators, we empower you to book a consultation with us. Our facilitators are located around the country, ready and more than willing to assist you on your healing journey, from the comfort of your own home.

If you’re interested in learning more about all-things-psychedelic, head on over to our resource page for more informative articles like this one. Well friends, that’s all we have for you today. As always, safe and mindful journeying!

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At Psychedelic Passage, we offer professional 1-on-1 guidance and companionship on your journey of healing. We simply can't sit back and let Americans continue to sit in silent suffering trying to battle mental health issues within a broken health care system, all while knowing that effective alternatives exist. We stand for the sacred, at-home, ceremonial use of psychedelics for consciousness exploration, which we believe to be a fundamental human right.


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