Hi all after a bit of digging around the forum, to my surprise I noticed there is little information on cyproheptadine (AKA periactin). A simple over the counter first generation antihistamine. It is usually used as a first line treatment in serotonin syndrome in emergency settings.

However, it has good potential use for damping bad trips. LSD/psilocin/DMT/ Mescaline act as agonist and have high binding affinities to 5-HT1A, 5-HT2A, 5-HT2C receptors (just to name a few). These are thought to be some of the main receptors involved in their effects.

Cyproheptadine has a high affinity for 5-HT receptors however it acts as an antagonist and blocks these receptors, so agonist like LSD etc can't bind to it. At 4mg (3 times a day) cyproheptadine blocks 85% of 5-HT2 receptors, at 6mg 95% are blocked. Obviously there are other receptors that come into play. Cyproheptadine also has binding affinities for some dopamine receptors and other serotonin sites (and obviously histamine sites) however so do some of the aforementioned pyschedlics. Regardless this drug stands out as a safer alternative and often more easily available medication for 'aborting' trips compared to benzos.

12mg is usually a standard dose for suspected serotonin syndrome.

It takes 1-3 hours to peak in the blood stream, 8hr half life and has a LD50 in rats of 295mg/kg making it a very safe drug. Bare in mind as a first generation antihistamine it also has sedative effects.

It however could interact with MAOI's particularly pharmaceutical MAOI's as it also has anticholinergic effects so adverse effects like: blurred vision, constipation, dry mouth, urine retention, tachycardia, nasal congestion or dry throat could ensue.

All in all there is good potential use for helping dampen bad trips worthy of further discussion.

Well done on the research! Nice to know that there is something safer than benzos. It's hard to find information on how much Alprazolam you would need per 100 microrgrams of LSD or milligrams of mescaline or grams of mushrooms, so something safer like this could be manageable.

Thanks for doing some research into this, Trip. Do you have any papers or journals with further information?

This is all I could find in relation to LSD and cyproheptadine.

Thanks

There's almost nothing in the literature on cyproheptadine and psychedelics.

I attached the full study below. It's quite interesting.


There's some good articles on it's effectiveness for serotonin syndrome and its pathophysiology. However, there are also other reviews suggesting it needs more evidence. Regardless there are a number case studies and reviews stating its effectiveness and it is still used as a first line treatment.
For a drug that has antagonist effects on particular serotonin receptors it would theoretically have a decent effect on blocking LSD/ psilocin/ etc on some sites.

I've only ever heard anecdotal reports of people using it and stating it indeed has a dampening effect. I can't confirm this myself and as stated there is no studies on it.

There will likely never be one compound to completely abort all aspects of a trip, but there are medications that can/ may ease certain aspects. I think its worth discussing the safest and most available medications from a safety POV.

I had a friend who had a terrible experience on 5g of mushrooms while we were at a music festival. There were 3 reasons for this.

1) Without consulting us, he ate what was in a bag he had on his person without measuring it, thinking it was "1 helping" of mushrooms.

2) It was his first time on any psychedelic aside from cannabis.

3) A defective firework went off in close proximity.

TL;DR: He ended up at the hospital and they pumped him full of benzos, he doesn't remember anything and never tripped again.

---

Full story,

We were sitting in lawn chairs in a circle, about 8 of us, and we had each consumed anywhere between 1.75g and 3.5g of mushrooms. Except for our friend who I will call Drew. He proclaimed that he ate the contents of a bag that had 5g written on it. We wanted to panic and explain to him what he had just done, but we decided to keep our cool and let it ride out as to not to scare him.

About 20-30 minutes in he kept standing up and then sitting back down muttering to himself "it's all good." We were at All Good music festival. He was worried about where another one of our friends was and we assured him they were fine and that he should enjoy himself. Then he got up out his chair one last time and raised his hands up in the air and it exclaimed "IT'S ALL GOOD!" in a surrendering, confident kind of way.

Problem was a gigantic firework exploded not 10 ft away from us that only made it maybe 15ft into the air before exploding RIGHT as our friend screamed "IT'S ALL GOOD!" and it made him snap.

He ran off at full speed. Myself and another buddy caught up to him but we couldn't contain him, he was the biggest of all of us and he was strong. All we heard him say before we lost sight of him was that he "needed to save everyone from the impending meteor shower".

We never saw him again after that, but I spoke with him on the phone the next day while he was at the hospital with no memory of what had happened. However, another friend of mine who was a volunteer security guard/staff member who ALSO knew Drew told me what had unfolded.

Drew jumped into someones convertible with 2 people in it who were just arriving to the festival just then and proceeded to attack the people like a zombie. Security was called and it took 4 people to restrain him while they waited for an on site ambulance to take him to the hospital.

I'm guessing that in the ambulance they gave him a bunch of benzos because he doesn't remember anything. Fortunately, he doesn't have any permanent psychological damage and is the same as always.

That's why I'm all about trip killers, because had they not "killed his trip" he could very well have permanent damage to his psyche.

All in all, it was his errant decision to consume a drug without having proper knowledge of dosage that led him to that awful experience.

Thanks for the reply. The fact that is readily available OTC is quite an appealing aspect. I have also read reports of people taking antihistamines and not experiencing any softening of the effects. As we know, there are lots of factors to consider, so a proper study would indeed be helpful.

I agree, remember other antihistamines target very different receptors (with exception of H1/H2). So in cases where pyschedlics and antihistamines are used together they will likely not have a softening effect as you have read, it's very dependant on the drug molecule and the corresponding receptors it affects. Keeping in mind second generation antihistamines don't cross the blood brain barrier and therefore would be useless in damping trips (this is why first generation antihistamines have sedative effects they do cross the blood brain barrier). But in theory periactin (a first gen) shows promise and I think it's worth asking if anyone has used this combination purposely or by accident.

Different antihistamines have some noteworth effects than just allergy control, clemastine has shown promise in remylination on neuron connections for people suffering neurological diseses like MS.

Ah yes, good point and great knowledge, Trip. I appreciate the feedback. I'm going to ask my psychiatrist friend, who works in psychedelics, what he thinks about all this.

Would be great to get his opinion!