Miscellaneous Chronic tricyclic antidepressant administration was associated with subjective increases in physical, hallucinatory and psychological responses to LSD

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Chronic tricyclic antidepressant administration was associated with subjective increases in physical, hallucinatory and psychological responses to LSD. Similarly, subjects receiving lithium chronically also reported increases in their responses to LSD.

Bonson, K. R., & Murphy, D. L. (1995). Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, monoamine oxidase inhibitors or lithium. Behavioural Brain Research, 73(1), 229–233. DOI: 10.1016/0166-4328(96)00102-7


This study also found that MAOIs decreased response to LSD, but this is probably just because of the serotonin accumulation that occurs only during chronic use, i.e., one study found that people on an MAOI also had a reduced response to DMT.

The biochemical effect of MAOI to elevate serotonin and norepinephrine levels occurs rapidly. However, the therapeutic relief of depression requires several weeks of daily treatment.

Monoamine Oxidase Inhibitors (Kevin Happe) in xPharm: The Comprehensive Pharmacology Reference, 2007 (Introduction)

The limited data suggest a neurochemical effect of MAO inhibition is as DMT- and LSD-blocker - when MAOI are taken chronically, as used medicinally, so that therapeutic, high serotonin levels are achieved in the brain, both the effects of intramuscularly-injected DMT and oral LSD are inhibited.(9,12)

Jonathan Ott. Pharmahuasca: On Phenethylamines and Potentiation. MAPS newsletter, Volume 6, Number 3, Summer 1996, 32-34

I tried LSD a couple of times while on Parnate - not at low doses, mind you - and had no issues whatsoever. Well, the issue I had is that the LSD didn't have as strong an effect as I'd expect, lol.

marc2377, Jun 14 2024, reddit

In contrast, single-use of both harmalas and moclobemide have been reported to amplify the effects of LSD, as they do with mushrooms.

rtg: Yes, I've tried several times LSD and [moclobemide] combo. The doses were for LSD: from 150 to about 400ug; for moclo 300-450mg. No negative effects noted

ismene: What did you think of LSD and moclo? Did you notice much difference to a standard LSD trip?

rtg: Little more physical stimulating than normal LSD trip, the effects on psychic were rather normal, except that it was harder and longer. Moclo is an inhibitor, which in itself has no psychoactive effect, so there is no effect on experience

26-06-2011, https://bluelight.org/xf/threads/maois-reduce-the-effects-of-lsd.716792/post-12238970

My friend dosing 20 hits LSD bought me Harmala and then said four hits hit same spot intensity.

WhoManBeing, 02/21/25, https://www.shroomery.org/forums/showflat.php/Number/29133558#29133558

“I have taken harmala before with mushrooms and it was a happening not to be reckoned with...”

Solipsis, Apr 13 2014, https://www.bluelight.org/community/threads/harmaline-dmt.719208/post-12271060

Two people even said they would never take LSD again without the addition of harmala(s). More info about the combo: Using LSD as a substitute for DMT in ayahuasca I'd be curious to hear an explanation of why, exactly, chronic use of MAOIs decreases the effect of psychedelics and one-time use increases the effects.


Since lithium was mentioned in the study as an amplifier, I'll mention that someone said that someone told him/her that while on LSD and lithium everything became unbearably loud, including his/her internal monologue (also bad vasoconstriction): reddit

Contrarily...

I'm on 600 mg of lithium and I've done psilohuascha for over a year and Aya use and no issues at all. (First_manatee_614, Aug 25 2024, reddit)

Regarding the concern of combining lithium with MAOIs, there are a handful comments in r/MAOIs from people who combine the substances and MAOI expert, Ken Gillman says the combo is not life-threatening, but that doesn't necessarily mean he thinks it's safe; the drug interaction checker for MedScape lists the combo as both Serious and Monitor closely and DrugBank's lists it as MODERATE.

General physicians may note that for therapeutic drugs the only cases that have been life-threatening or fatal, as a result of serotonin toxicity, have resulted from combinations of a monoamine oxidase inhibitor (MAOI) and a serotonin reuptake inhibitor (SRI) but not from other combinations of serotonergic drugs (eg monoamine oxidase inhibitors combined with lithium or L-tryptophan or nefazodone or mirtazapine, nor from SSRIs with anything other than MAOIs).

Serotonin toxicity: Summary. Ken Gillman, MD, PsychoTropical Research, 2014, 2023

 

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Thankfully I found this thread! I was about to start a new one, but figured I'd post my question here.

Does anyone have experience with or know of the potential interactions between LSD and MAOIs as well as psilocybin and MAOIs? I've read the above mentioned sources that claim that MAOIs diminish and even abolish the subjective effects of LSD, but I've not read of any dangerous interactions between LSD + MAOIs.

However, I have read some concerning things about psilocybin + MAOIs.

Apparently, some psilocybin-containing mushrooms contain phenylethylamine (PEA), which when taken with an MAOI, can cause hypertensive emergency in a case report of someone taking tranylcypramine + Adderall XR.

We suspect phenylethylamine, found in Psilocybe cubensis and other species of psilocybin mushrooms, interacted with tranylcypromine and dextroamphetamine-amphetamine to produce this hypertensive emergency. Patients prescribed MAOIs should be warned of the potential for hypertensive emergency when consuming psilocybin mushrooms, particularly when also prescribed norepinephrine releasers such as dextroamphetamine-amphetamine.

However, I've read elsewhere (can't find source) that the PEA levels in psilocybin mushrooms aren't substantial enough to cause hypertensive emergency. Still, that's enough for me to be concerned about taking psilocybin with an MAOI.

The other concern is that psilocin is a substrate for MAO-A, so theoretically if taken with an MAOI (at a non-selective dose; e.g., Emsam >= 9 mg/24 hr), it could prolong and intensify the effects.

I recently started taking Emsam (selegiline transdermal) for maybe the 4th time now (gonna give it another go I guess). I'm two weeks in on the 6 mg/24 hr dose (which is supposedly MAO-B selective), just long enough to fully inhibit MAO enzymes. I'm on a bunch of other meds (both psych and non-psych), which for the sake of my question I suppose I should list:

Prescription psych meds:

• Vraylar (cariprazine) 1.5 mg 1 PO qam
• dextroamphetamine sulfate (Dexedrine) 10 mg 2 PO bid (40 mg/day)
• Emsam (selegiline transdermal system) 6 mg/24 hr 1 TD q24h
• lamotrigine (Lamictal) 150 mg 1 PO bid (300 mg)
• eszopiclone (Lunesta) 3 mg 1 PO qhs
• Quviviq (daridorexant) 50 mg 1 PO qhs
• lorazepam (Ativan) 1 mg 1 PO qd prn

Other prescription meds:

• levothyroxine (Synthroid) 75 mcg 1/2 PO qam (37.5 mcg/day)
• Qulipta (atogepant) 60 mg 1 PO qam
• tadalafil (Cialis) 5 mg 1 PO qam
• Mounjaro (tirzepatide) 15 mg/0.5 mL pen 15 mg SC qwk
• Nurtec ODT (rimegepant) 75 mg 1 SL/PO x1 prn
• ondansetron ODT (Zofran ODT) 8 mg 1 PO bid prn
• rizatriptan ODT (Maxalt MLT) 10 mg 1 PO x1 prn, may repeat q2h prn, max 30 mg/24 hrs
• Ventolin HFA (albuterol) 90 mcg/actuation 2 puffs q6h prn
• celecoxib (Celebrex) 100 mg 1 PO bid prn

Given that I'm on a low dose of an MAOI (Emsam 6 mg) that is supposed to be MAO-B selective, the only danger with psilocybin I could see is the potential for hypertensive emergency that I've read about. As far as LSD, I would probably just have to take a hefty dose to get effects (safe to start low and go slow though).

Any comments regarding experience or knowledge from sources would be much appreciated! Sorry if I'm hijacking this thread.

 

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However, I've read elsewhere (can't find source) that the PEA levels in psilocybin mushrooms aren't substantial enough to cause hypertensive emergency. Still, that's enough for me to be concerned about taking psilocybin with an MAOI.

I was about to say, why are they focusing on the PEA when the person consumed Adderall with a powerful MAOI!? Researchers and doctors are known to be paranoid about MAOIs, exaggerating the littlest thing.

It is, unfortunately, necessary to state clearly from the beginning that much of what is published by doctors in books and journals about MAOIs is either poorly informed, or just plain wrong. As an example, much of the information that comes with MAOIs (the PI, or product information sheet) contains inaccurate material concerning, among other things: serotonin toxicity, drug interactions generally, and dietary tyramine.

MAOIs (Parnate, Nardil): Misconceptions and Questions No. 1. Ken Gillman, MD. PsychoTropical Research. Nov. 14, 2012

Even amphetamine can be safely combined with an MAOI if the dose is kept low (sometimes the combo is prescribed).

There is now a lot of accumulated experience of the concurrent administration of MAOIs and amphetamine for therapeutic purposes in depression. It is safe when done carefully. Early concerns about frequent hypertension have not materialized and recent clinical reviews indicate judicious use is safe [354, 355].

Monoamine oxidase inhibitors: A review concerning dietary tyramine and drug interactions. Ken Gillman, MD. PsychoTropical Commentaries (2020) 1:1–71 (Releasers (indirectly acting sympatho-mimetics ISAs))

https://psychotropical.com/wp-content/uploads/2020/03/9.2-MAOI_diet_drug_interactions_2020_current_v.pdf

Comments from people who have tried the combo: https://www.shroomery.org/forums/showflat.php/Number/28919078

Oh, and I see that you, yourself, are taking Dexedrine with low dose Selegiline. I guess you're concerned that adding psilocybin or LSD to the mix would "break the camel's back". Yeah, it's always best to play it safe and either avoid or titrate your doses over the course of time, but I'm under the impression that MAO-B inhibition is quite weak, even at 100%:

MAO-A inhibition results in increases in NE, 5HT, and DA in the synaptic cleft, while selective MAO-B inhibitors increase only DA.

Therapeutic Areas I: Central Nervous System, Pain, Metabolic Syndrome, Urology, Gastrointestinal and Cardiovascular. Blackburn T, Wasley J. / Comprehensive Medicinal Chemistry II (2007) (6.03.5.2.1 Monoamine oxidase inhibitors)

And this is the reason one does not need to avoid excess tyramine on an irreversible MAO-B inhibitor:

...because 90% of MAO activity in the intestine involves the MAO-A isoform.

Effects of tyramine administration in Parkinson’s disease patients treated with selective MAO-B inhibitor rasagiline. deMarcaida JA, Schwid SR, White WB, Blindauer K, Fahn S, Kieburtz K, Stern M, Shoulson I. 2006. Movement Disorders, 21(10), 1716–1721. doi:10.1002/mds.21048 (Introduction)

Note that Selegiline is an irreversible MAO-B inhibitor in the sub-20 milligram range.

By the way, PEA is also known as beta-phenethylamine. It is almost identical to alpha-methyl-phenethylamine, which is the full name for amphetamine. PEA is similar to DMT in that it is activated by an MAOI.

Too much Phenylethylamine (PEA)?