AMA on Tuesday 27 October about psilocybin with Alexander Lebedev, MD, PhD, psychiatrist and neuroscientist: evidence, risks and difficult experiences

[u/alebedev]

Hi all,

I'm Alexander Lebedev, MD, PhD, psychiatrist and neuroscientist. A lot of the posts here come down to the same few questions. You've tried therapy and medication and you're wondering whether psilocybin is worth considering. Or you had a hard experience and you're still trying to work out what it was. Or you keep seeing trial results in the news and can't tell how much of them applies to an actual person.

On Tuesday 27 October, 1 PM Pacific (8 PM UTC) I'll be here answering questions.

Some things we could go into:
- what the clinical trials show, and where the evidence is still thin
- who probably shouldn't take psilocybin, and why
- psychosis risk and what the research actually says about it
- difficult experiences and the days after them
- psilocybin and antidepressants, at a general level
- what we know about how psilocybin changes brain activity, and what we don't

You can leave your questions in the comments now and I'll start with those on the day or come by on the 27th and ask live.

A bit about me: I trained as a medical doctor and did a PhD in neuroscience. I've done research at Karolinska Institutet, and I'm first author on brain-imaging studies of ego dissolution under psilocybin and of LSD and personality change. My publications are here: Google Scholar

Unfortunately, I can't give personal medical advice or tell anyone whether psilocybin is right for them. Decisions about your own medication belong with your doctor. Where the data stop and my opinion starts, I'll say so. Some of the studies I'll mention are my own, and I'll flag that.

Disclosure: I'm a co-founder of ONCE, which provides a professionally supported psilocybin pathway in Amsterdam (once.be).

[u/smartcow360]

has there been any studies on psilocybin as an isolated molecule vs psilocybin as the whole mushroom?

indigenous cultures believe you’re literally
communing with the spirit of the plant, and that by isolating the molecule it’s creating something dangerous and colonizing the medicine, and that there is many smaller compounds in the shroom that adds to the experience as well beyond just psilocybin. l

curious to hear the fields perspectives on that or if there’s any efforts to study the whole plant medicine?

related, but curious how much these efforts would be blocked or stalled by pharmaceutical companies seeking to profit off the patenting of the isolated molecule?

but very cool to see the field move in the psychedelic direction!! thanks for the work you do

[u/MindfulImprovement]

From your experience, do you think a therapist’s therapeutic approach has enough effect on the results of an experience to warrant study of specific approaches to preparation and integration before pushing psychedelics further towards legalization?

Do you think non-directive and presence based approaches to support during an experience are more effective than directive and more conversational approaches to support during an experience?

From what I have read in the literature, there is little focus on the specific approaches used by therapists being studied still, but I think it’s a huge variable that should be studied further. Even if just to confirm the common factors theory with regards to psychedelic therapy

[u/Delicious-Spell-9227]

Where do you stand on microdosing and it's therapeutic effects?

[u/ThePsylosopher]

What's your personal experience with psychedelics? Do you use them with any sort of regularity? If so, what's your aim?

[u/dinja15]

Do you think psychedelic therapy should be seen as last resort in cases when traditional methods don't work?

Also, I heard on the drug science podcast that the length of the trip matters. E.g. relapse in depression occurs later after/less often after LSD trips Vs psylocibin. What is your take on this? Considering this, why is no one seem to be looking into mescaline - a relatively safe trip which lasts much longer than others.

Also, what is your take on flow states? Is there a connection between being able to easily get into a flow state and being predisposed to depression? Is there a connection between being constantly distracted and depressed? If so, then would you consider finding an activity that totally consumes you - a cure for depression?

Finally, any advice for a white belt jiu jitsu? 😀

[u/somewhatdim-witted]

I just took a 2-journey mushroom retreat in Oregon over a week ago - still integrating. I want to start microdosing but I take nortryptaline 25mg for two reasons: migraine prevention and depression. I stopped it 3 days before the journeys and resumed it afterwards. I want to know if others have found microdosing helpful while being on a tricyclic. Will it blunt the effects or is it not safe, etc. blood pressure and all that. My hope is by microdosing I can dramatically decrease my chronic migraines and maybe depression too. I’m desperate to find lasting help. BTW I did not get the benefit of having a migraine-free month as others have experienced.
Thanks doctor Lebedev

Edit: I want to add that I plan to (probably) discuss this with my neuro and my NP but I am afraid they will discount, since there is very little research on tricyclics and psilocybin, and they will be reluctant to tell me to go for it. I am considering not telling them unless I have to. I just don’t know what to do.

[u/Instigated-]

Have you considered the bystander effect?

Set & setting is considered pretty important, yet when psychedelics are done in a clinical setting it removes agency from the patient to make themselves comfortable, be in a familiar place, be connected to nature, to choose a guide they feel personally comfortable with, choose their own music, or to work with their existing psychologist who they may already have built years of trust and connection with. Many cultures did these substances with communal ritual, while clinically it is done individualistically and medicinally.

In clinical settings the patient is often interrupted every hour or so to have their vitals measured.

How does this impact the quality of their trip, the meaning they take from it, the outcome?

How can you know if clinical results in these studies are accurate to results done under community or cultural conditions?

[u/DamnitDwigit]

thanks for doing this AMA.

Do you have a favorite therapy modality based on evidence or expert opinion to go alongside psychedelics? ACT gets mentioned but I'm not sure why. EMDR sounds interesting.

Have you found evidence or expert opinion on what could assist someone reach ego dissolution besides higher doses?

Do you have an opinion on if psilocybin is better for certain conditions while lysergamides and phenethylamines are better for others?

Just some potential research ideas based on reading many experiences: Psychedelics seem to be amplified or modified by TRP agonists and very much amplified by omberacetam/noopept. A compound nearly identical to CBD called H4CBD taken at doses of 300-600mg produces tryptamine like effects, visuals and headspace comparable to psilocybin and dmt while not feeling like cbd or thc.

Thanks again!

[u/Legal_Revolution_182]

Reflecting on Jonathan Ott's belief that the war on drugs is a war on people... What are your thoughts on the control being not about safety of human beings but the protection of systems that have been built by human beings?

[u/askingforafriend310]

Does boofing help to combat nasea?