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Neuroscientists "Trippin" on Magic Mushroom

paracelsius

paracelsius

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Joined
Mar 11, 2020
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197
In case you missed it. A big battle is raging right now in psychedelic neuroscience research, I’d call it the Battle of Mushroom with two sides firing shots at each other: the “Tripping” School led by Roland Griffiths and Matt Johnson at Johns Hopskins and others, and the “Non-Tripping’ School led by Dave Olsen at UC-Davis, Scott Thompson at UMaryland and others.

Here is the issue: the first School believe for psychedelics (especially mushroom psilocybin) to have therapeutic effect, in particular fast and long lasting anti-depressant, you’d have to trip during the experience. The deeper (mystical) the Trip the better therapeutic outcome. Else you are wasting your time and $$:

The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects​

David B Yaden, Roland R Griffiths

Free PMC article https://pubmed.ncbi.nlm.nih.gov/33861219/

Abstract​

Classic psychedelics produce altered states of consciousness that individuals often interpret as meaningful experiences. Across a number of human studies, when the participant-rated intensity of the overall drug effects are statistically controlled for, certain subjective effects predict therapeutic and other desirable outcomes. Underlying neurobiological mechanisms are likely necessary but not sufficient to confer full and enduring beneficial effects. We propose that the subjective effects of psychedelics are necessary for their enduring beneficial effects and that these subjective effects account for the majority of their benefit.
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"Subjective Effects" = scientific euphemism for "Trippin"

On the other hand, the other side believes Tripping is not necessary for psyhedelics to have therapeutic benefit. So you can microdose (doses that wont make you trip say like 50 mg dried cubensis) and still have therapeutic effect.

The Subjective Effects of Psychedelics May Not Be Necessary for Their Enduring Therapeutic Effects​

David E Olson

Free PMC article https://pubmed.ncbi.nlm.nih.gov/33861218/

Abstract​

Psychedelics represent one of the most promising classes of experimental medicines for the treatment of neuropsychiatric disorders due to their ability to promote neural plasticity and produce both rapid and sustained therapeutic effects following a single administration. Conventional wisdom holds that peak mystical experiences induced by psychedelics are a critical component of their therapeutic mechanisms of action, though evidence supporting that claim is largely correlational. Here, I present data suggesting that the subjective effects induced by psychedelics may not be necessary to produce long-lasting changes in mood and behavior. Understanding the role of subjective effects in the therapeutic mechanisms of psychedelics will have important implications for both basic neuroscience and for increasing patient access to the next generation of medicines developed as a result of psychedelic research.
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Both sides agree this much:

1. magic mushroom (psilocybin) has a fast and long lasting (up to a year) antidepressant effect in humans after a single dose. Faster, longer and better than most antidepressant pharmaceuticals. Also true for other psychedelics like 5MeO...etc

2. the target of psychedelics in the brain is a type of serotonin receptor called 5HT2AR located deep in layer 7 of cortical neurons. Its activation by psychedelics is required to Trip. So far so good: both sides agree.

Where they disagree is whether: “Tripping” is required to see antidepressant effect? I mean say at least 25 mg pure psilocybin for avg human (~2 to 4 g dried mushroom depending on strains). Now, yesterday the California Non-Tripping School fired a big shot in this paper here:

5-HT2ARs Mediate Therapeutic Behavioral Effects of Psychedelic Tryptamines​

Lindsay P Cameron, Seona D Patel, Maxemiliano V Vargas, Eden V Barragan , Hannah N Saeger, Hunter T Warren, Winston L Chow, John A Gray, David E Olson

Abstract​

Psychedelic compounds have displayed antidepressant potential in both humans and rodents. Despite their promise, psychedelics can induce undesired effects that pose safety concerns and limit their clinical scalability. The rational development of optimized psychedelic-related medicines will require a full mechanistic understanding of how these molecules produce therapeutic effects. While the hallucinogenic properties of psychedelics are generally attributed to activation of serotonin 2A receptors (5-HT2ARs), it is currently unclear if these receptors also mediate their antidepressant effects as several nonhallucinogenic analogues of psychedelics with antidepressant-like properties have been developed. Moreover, many psychedelics exhibit promiscuous pharmacology, making it challenging to identify their primary therapeutic target(s). Here, we use a combination of pharmacological and genetic tools to demonstrate that activation of 5-HT2A receptors is essential for tryptamine-based psychedelics to produce antidepressant-like effects in rodents. Our results suggest that psychedelic tryptamines can induce hallucinogenic and therapeutic effects through activation of the same receptor.
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So there you have it: The California School shooting itself in the foot (or almost). Sorry for a long post. Hope you enjoy reading. I find very very fascinating. and thought BLers more than most ppl are well placed to chip in with their own experience of either full trip or microdose or anything in-between

edit: In case you wondering how researchers know the mouse is actually Tripping (well if you activate 5HT2aR in mice/rats say with LSD or tryptamines, they will rotate their head side-to-side in very characteristic manner called Head-Twitch Response, google it if you interested). similar thing to measure antidepressant effects in rodents: forced swim test (google is your friend if interested")... Have a Safe and Happy Weekend.
 
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Opi_Kid_Rock said:
bump
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Stuff is spot on right here. I find this stuff fascinating as well. I love mushrooms. I’ve used high dosing therapeutically and I’ve micro dosed. I understand both parties but it all goes against the nature of the fruit in the first place imo. It’s about each other’s experiences. Everyone is different…. different in many ways.
Great post!
 
Subjective effects are needed to experience some benefits from psychedelics while even without “tripping” psychedelics do have some beneficial effects.
 
I don’t know about microdosing and can imagine it can be contraproductive but I think that big enough dose, even with hallucinogenic effects blocked/minimized would produce some benefits.
 
someguyontheinternet said:
I tried microdosing and felt it didn't help anything even with multiple different dosing schedules. There are also studies showing it isn't any better than placebo
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Absolute same experience.
The experiences and breakthroughs I’ve had above 3.5 grams that turned my life around. More than any type of rehabilitation or therapeutic setting. More than any of what the doctors could provide (SSRIs are a tough pill to swallow, and it was intended) Too many positives to list right now because I’d miss some and sell them short.
6 grams on July 2nd is still providing me with clarity. Most definitely cleared my mind and allowed me to truly do some more work on it for the time being.
 
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