Many people who have tried both ayahuasca and magic mushrooms say they feel very different, even though both are psychedelics. In this clip from Dennis McKenna’s 2015 London Real interview, Brian Rose describes what he has noticed, and the ethnopharmacologist explains both the experience and the chemistry behind it.
It’s an unusually clear explanation from someone who has studied these plants for decades.
▶ Watch the full episode: Dennis McKenna – The Screaming Abyss
Start with respect
The clip opens with Brian explaining that his first psychedelic experiences were ayahuasca ceremonies with a shaman, surrounded by respect and ritual. He brought the same approach to psilocybin: planned, dark, alone, and taken seriously.
McKenna agrees, and sets out the principle he and his brother Terence always stressed: set and setting. Setting is your environment: somewhere safe, where nobody will disturb you. Set is everything you bring with you: your mindset, your expectations and your intention. Why are you doing this, and what do you hope to get out of it?
He recalls Terence telling him, before he ever tried LSD, to read Carl Jung’s Psychology and Alchemy first. He didn’t, but later saw why: the book is a useful map of the images and ideas that arise.
Lessons versus downloads
Then Brian describes the difference he has noticed. Ayahuasca, he says, tends to leave him with a clear list of things to do: often about relationships or our connection with plants. Mushrooms usually don’t.
McKenna confirms this is common. Ayahuasca, in his description, works more like a counsellor: it gives you ideas about what you should be doing, from relationships to what he calls the wider mission of saving the planet, a theme he links to the symbiosis between plants and people.
Mushrooms are different. They don’t lay out an agenda. Instead, he says, they just “download information”: this is what it is, deal with it. Terence compared it to having a conversation with a leprechaun, mischievous and elusive, never quite answering your question directly.
The chemistry
McKenna then explains why the two feel related. Psilocybin, the active compound in magic mushrooms, is chemically very close to DMT, the main psychedelic component of ayahuasca. He describes psilocybin as effectively an orally active form of DMT: a small chemical difference lets it work when swallowed, without the MAO inhibitor that ayahuasca brews need.
So at higher doses, he says, all three take you into the same “tryptamine space”. It’s like looking at the same thing through slightly different portals.
What to take from it
McKenna’s framing is useful even if you never take a psychedelic: the substance matters, but so do intention, preparation and environment. And similar chemistry doesn’t mean identical experiences, because each “portal” shapes what you see.
This clip is for information only and is not medical advice. Psychedelics are illegal in many countries and carry real psychological risks, especially for people with a personal or family history of mental illness.
Who is Dennis McKenna?
Dennis McKenna is an American ethnopharmacologist who has researched plant hallucinogens, including ayahuasca, for more than 50 years. He is the younger brother of the late writer Terence McKenna, and his memoir The Brotherhood of the Screaming Abyss tells their story.
In the full 2015 episode, he talks with Brian Rose about his brother, the history of psychedelic research and plant medicines. You can also watch another clip from the same interview: Dennis McKenna – The Heroic Dose.
See everything Dennis McKenna has done with London Real on his guest page: Dennis McKenna on London Real.
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Transcript
Transcript: Dennis McKenna – Ayahuasca vs Mushrooms: Lessons, Downloads And The Chemistry Of DMT
0:00 Brian Rose: For me, I had my ayahuasca experiences first. I was in a ceremony with a shaman, and there was so much respect around it. That’s how I treat my psilocybin experiences: there’s an occasion, it’s planned, it’s dark, I’m alone, it’s big, and I am scared. That’s how I’ve been conditioned to approach it, and I quite like it that way.
0:19 Dennis McKenna: And that’s the other thing Terence talked about, and everybody’s talked about, and I talk about a lot: the importance of set and setting. People say, how can we use these things safely and still get a lot out of it? Pay attention to set and setting. Those are the two big variables. Plan for it, have an intention, and arrange your setting so that, number one, you’re safe. So maybe not on the freeway, maybe not even at a rock concert. Do it in a place where no one is going to bother you, at least no one you don’t want to bother you. Not the neighbours, not the local constabulary. Maybe your significant other could be close by or share it.
1:21 Dennis McKenna: But setting is important, and intention. That’s part of the whole respect thing. Why am I doing this? What do I expect to get out of it? And then the set is really everything you bring to it: who you are, what your expectation is. It’s you, your mindset, and everybody’s mindset is different.
1:52 Dennis McKenna: Terence told me once, when we were young, before I’d ever taken LSD: don’t take LSD until you’ve read Psychology and Alchemy by Jung. We were reading Jung at that time. He said you’ll get much more out of it if you do. Well, I hadn’t read it when I took LSD the first time, but later I did, and I realised what he meant. A lot of what comes up in Psychology and Alchemy is a good map for the gestalts and ideas that come up during a psychedelic experience. So setting is one variable, and set is the other, which is much trickier. But they’re both important.
2:49 Brian Rose: I find with ayahuasca I get a distinct, finite set of lessons: one, two, three, this is what I need to go and do. Sometimes it’s related to plant symbiosis, sometimes to relationships, usually with other people. It’s very deep. But with psilocybin, sometimes I don’t have any specific lessons a day or two afterwards. Is that something you hear a lot, that it’s typical to have a different kind of experience?
3:31 Dennis McKenna: Yeah, I’d say so. Ayahuasca is often much more of a counsellor in some ways. It does give you ideas about what you should be doing, about your relationships, or insights into this whole mission we’re engaged in, which is ultimately to save the planet. That plant-human symbiosis thing. It’s much more about that. Mushrooms are not that way so much. They don’t really lay out an agenda. They just download information. They say, this is what it is, this is what’s going on here. And you say, but that’s crazy. Sorry, that’s what it is. Deal with it.
4:39 Brian Rose: Terence called it having a conversation with a leprechaun. You want to engage in the conversation and they’re not answering your questions.
4:48 Dennis McKenna: They’re dodgy, they’re very tricky. They’re elfin, they’re mischievous. And this comes up again in discussions of DMT. Mushrooms are really a form of DMT. They’re really the orally active form of DMT, if you understand the chemistry. Psilocybin is one molecule away from DMT: it’s 4-hydroxy-dimethyltryptamine. That hydroxy group is just different enough that it’s orally active without an MAO inhibitor. So it really is DMT, and at higher doses you get into those areas. This is tryptamine land, the tryptamine space, and mushrooms, ayahuasca and DMT all get you into that place.
5:53 Dennis McKenna: I forgot what my thread was. I got so entranced. But they’re all in that DMT space, and they’re all a little different. You’re looking at the same thing, but through slightly different portals, if you will.
6:24 Brian Rose: Yes. The lessons versus the information.
6:28 Dennis McKenna: Right. Mushrooms download stuff, and you can take away from it what you will. With ayahuasca, you often come away with a sense that you really have to do something: change something, change your diet, talk to your loved one and get something straightened out. With mushrooms, there’s not necessarily a plan for action. This is the lesson for the day, this is what you come away with, but there’s not necessarily anything to do about it.
