IAm Dr. Robin Carhart-Harris from Imperial College London I study the use of MDMA & Psilocybin mushrooms in the treatment of depression." AMA

Hello:

I am 43 years old and a chronic sufferer of "cluster" headaches. At one point, I was on 13 different pharmaceuticals (nothing narcotic, because those don't touch these headaches). I have "cultivated" a network of support that has allowed me to medicate with nothing more than magic mushrooms for the past 2 years. This is the only medication that has worked for me. I'm working full-time again and I no longer think about suicide on a daily basis. It has literally saved my life. My question is not medical, because I know this substance works. But I also know that my helpers are risking prison time by helping. Do you see any hope for legalization in the future?

In terms of medicinal use, I really hope so. Glad you've been helped.

I think it's important to campaign and make people aware of cases like your own.

The soundtrack for this Q&A should be Brian Eno. Music for airports 1 is currently playing in my little world. I look forward to your questions. RCH

Yes. The risks around psilocybin are psychological mainly. If taken in the wrong environment or if you're in the wrong frame of mind without people around you who could look after you if you start getting anxious and/or paranoid, then there's the potential for a very difficult experience. It's extremely important that attention is paid to set and setting, or how you feel at the time and what kind of environment you're in. Physiologically, psilocybin is very safe. With this said, psilocybin may pose some significant mental health benefits however if taken in the right way with the right people around you.

With MDMA, it's a little different. The experience is less psychologically challenging but more physiologically taxing. The serotonin low that follows an MDMA experience is a bit of a problem and if the drug's really over-used then there's a potential risk of causing some damage to the serotonin system - which could affect mood for example. The moderation message with MDMA is very important.

I guess what I'm asking is, people have said that it kills massive amounts of brain cells or can cause you to develop schizophrenia, or cause you to be "burnt out". Is any of that true or possible? Or anything related.

There's no known cell death with either drug but MDMA can damage serotonin cell fibres in large doses.

Irresponsible use of psilocybin runs the risk of paranoid experiences, so be very careful and treat all psychedelics with huge respect. They're not to be messed with.

Hi, Dr. Carhart-Harris,

What do you use, if anything, to follow an MDMA treatment? I have heard of people taking 5-HTP to combat the serotonin depletion. Does this work?

We didn't give anything. 5-HTP is a good idea though and in the future we'd test this i.e. see if one group given 5-HTP have less severe hangovers... It was a bit of an oversight not to have done this in the first place..

Dr. Harris, how do you find your research subjects?

They're lovely mostly.

But seriously, mostly via word of mouth.

It's not hard to recruit, that's for sure!

What are your thought's on the recreational use of psilocybin and MDMA?

Be careful, read up and don't get yourself a criminal record.

Also, don't ever let recreational use become your life. It's the same with all drugs.

UPDATE: We are Done. Thanks everyone this has been AWESOME please check out our episode with Robin and his research

Do you think if credible scientists started coming out as having taken psychedelics, it would start a more open dialogue on the discussion of drugs in society? I mean Dr. Griffiths paper on guidelines for safety even said a researcher should know the experience before doing any sort of clinical research.

Maybe some knowledge yes. I do think it's good not to get too involved in these drugs as recreation though. The famous big users weren't very good scientists. They dreamt up a lot of stuff with very little evidence to support it. It's best to stay grounded in this realm.

I think psychedelic probably affect the brain in the same way, at least serotonergic/classic psychedelics. The first thing that happens is that the drug will stick to receptors on neurons in the brain and then change how the host cells behave. Psilocybin sticks to serotonin 2A receptors (plus a host of others) and stimulates these receptors, mimicking the action of serotonin itself. This makes the host cell more excitable. Serotonin 2A receptors are densely expressed on large neurons called deep-layer pyramidal neurons. These big cells are very important computational units in the brain and their collective activity is linked to top-down predictions. We think stimulating these receptors as psychedelics do causes latent internal representation to intrude into consciousness, so that you see your own internal models. This explanation makes sense in the context of viewing the brain as a prediction machine which makes inferences about incoming sensory data. And there's lots of evidence for this model.

In light of the discoveries you have made in the effect on repetitive thinking and the deregulation of the control centres by these chemicals, do you think they might also ameliorate symptoms of people on the Autistic Spectrum

People are looking into that with MDMA.

I think the psychotherapy structure around it would have to be extensive.

How would you explain the entities in a DMT experience on a neurobiological level? Just dream-like projections of the self?

I think they're probably archetypal, humans are primed to see entities (our mothers eg) from a very early age. I just think it's the mind's internal models of what might be out there that become manifest and then confuse us into thinking they're actually 'out there'

Hello Dr Carhart-Harris, what, if any, other substances apart from Psilocybin and MDMA do you believe can offer help treating depression/addiction or other mental health issues. Also what do you think these types of substancs can offer in unlocking any further secrets of the mind, and what obstacles do you see in expanding types and number of substances people like yourself can use for research, thanks

Hmm, a safer MDMA would be good. ie. one that doesn't cause serotonin depletion.

DMT could be useful as could LSD.

LSD in alcohol addiction I'm especially interested in...

I also think LSD will be most useful for unlocking secrets of the mind. It's the most potent and interesting psychedelic imo.

but not necessarily the best one therapeutically.

I actually think that might be psilocybin or DMT/aya.

As far as questions go, I don't really have any that haven't already been asked. That being said, I just wanted to say you're wicked fuckin awesome and keep the research going.

Very sweet, thanks dude

20 Years ago hallucinogenics were my drug of choice. With proper preparation: a place, a partner, a plan of play and no work the next day, I and my mates always had a lovely time. I credit my experience especially with Mushrooms with opening my mind to the interconnectedness of humanity. It made me a more compassionate person I think. I credit my LSD use with allowing me to re-qualify past events so that they took on a more objective and less emotional base in my mind. I was able to psychologically distance myself from some negative influences from my child hood. I resent the resistance to using these tools to help the soft science of psychology make in roads with PTSD and depression. Like anything that changes a person, controls must be put in place. What do you see as the most important control factor in your studies?

I think it's really important that an academic working with these drugs respects their power. That sounds a bit grand but as soon as you start being complacent about the drugs, that's when negative events become more likely. I have to remind myself before each administration that the volunteer is about to embark on something remarkable and should be properly prepared for that.

Doctor, I'm a student of psychology, very much interested in the field you are currently studying. What course of action would you suggest for someone like me in their post-graduate studies? How did you get to where are today?

I second this question!

Do a medical degree then specialise in psychiatry. It's not what you want to hear but it might be the only way. It's a tough world out there, trust me. I got lucky.

When you were younger, was it your intent to work with psychedelics, or is it something that interested you after you began researching other fields?

I had a strange experience when I was quite young which opened my eyes but then essentially forgot about it until I became very interested in psychology and specifically psychoanalysis and I learned that people believed in the 50s and 60s that LSD could allow access to difficult to access psychological material. That absolutely fascinated me.

It was my reading that inspired me. I didn't plan it but when I read stan grof's realms of the human consciousness, it was then that I knew what I wanted (and had) to do.

I think it's great that researchers are exploring psilocybin mushrooms to help people struggling with addiction and/or depression. My question is, given the amazing results of the Marsh Chapel Experiment and the followup at Johns Hopkins University, how do you feel about psilocybin use among otherwise healthy individuals to achieve greater life satisfaction and wellbeing?

I think it has a place.

Huxley had a kind of elitist view about this which I used to dislike but now sort of understand. He said you need to have the intellectual capacity to put the experience into a context. I sort of see what he meant. I think you at least need to be able to ground yourself after the experience.

All the benefits come from returning to normal waking consciousness and its that state we should celebrate. The psyche state is an incredibly useful holiday but we need to be mature in returning to normality because otherwise nothing would get done and society would be chaotic. Huxley wrote beautifully about this in DoP

Thanks All, I've been here for about 2.5 hours on a Saturday evening so hope you don't mind if I head off now. There have been some great questions and I've tried to answer every one. Apologies if I missed yours somehow but it was my intention to answer all of them.

Stay safe,

Peace and Love,

Robin.

Are you spiritual or religious at all? If not, do you think this type of research will give insights into where the idea of God or spirituality originated?

I was brought up cathloic and attending church every sunday, sent to a catholic school, was an alter server.

I love the art of religion and I'm fond of it.

I'm a scientist and an atheist now though and I feel a bit sad every now about the lost magic that comes with atheism.

I feel wonder about the beauty of nature though. I can feel an overwhelming euphoria about the vast beauty of nature.

Plus, I'm fond of Buddhist ideas and used to meditate.

Sorry, last bit: yes, I feel like we're on the verge of major insights about the biological underpinnings of spiritual type experiences and how religious structure evolved from the spiritual experiences of pre-historic and ancient man

I'd be interested in hearing about what kind of regulatory barriers you've dealt with in this line of research.

Home Office, Ethics, R&D, site specific, internal opposition, MP opposition, ignorance, conservative press...

Do you think that research like this could actually lead to the introduction of these drugs as therapies if proven beneficial, or do you think mainstream societal fear of "drugs" as legitimate pharmaceuticals (and the pharmaceutical lobby) will deter its use?

I think they will be developed as therapies.

Do you believe that using Psychedelics and MDMA (or MDMA analogues) recreationally, is something that responsible adults should be able to legally do? or do you see them as purely medicinal tools?

2) and also what is your opinion on the comparative Neurotoxcity in MDMA, BK-MDMA, and Alcohol?

I think that there should be psychedelic centres where anyone, properly screened can sample the experience in the right kind of setting. These centres would be staffed my medical health professionals and people shouldn't be allowed to abuse the opportunity to have the experience. I think it would be problematic if psychedelics could be taken out of the clinic (like medicinal cannabis in the US eg) because without question you will get some disasters and it would mean a return to the 60s and the tarnishing of these drugs' name again.

Hi :) thank you for taking the time to talk with us. * 1. what are your thought's on Terence McKenna's stoned ape theory? (http://www.youtube.com/watch?v=hOtLJwK7kdk) * 2. do use synthasized psilocybin or do you use fresh mushrooms for your study's? * 3. Have you personally used mushrooms?

1. I'm not really familiar with the stoned ape theory, can you summarise?

2. The psilo is synthesised. It goes in IV so can't be from plant material because of microbes. 3. I hate that question, sorry, please understand that it's not wise to answer, put it this way, I'm very different to Terrance McKenna :-)

*1. >In his book Food of the Gods, McKenna proposed that the transformation from humans' early ancestors Homo erectus to the species Homo sapiens mainly had to do with the addition of the mushroom Psilocybe cubensis in its diet - an event which according to his theory took place in about 100,000 BC (this is when he believed that the species diverged from the Homo genus). He based his theory on the main effects, or alleged effects, produced by the mushroom.< *2. I understand completely.

Yes, I've heard that theory and i'm here to be honest, so I will. I think it's dreamt-up nonsense like most of McKenna's stuff. Sorry.

I have heard anecdotal evidence for psilocybin as a possible reliever of migraines. Do you know of any research in this area? Thanks very much.

Yes, Andrew Sewell is a name worth googling. It's a credible idea. A lot of migraine drugs are ergot derivatives a bit like LSD, plus classic psychedelics probably do have a potent effect of blood vessels.

After having tried them back in college all i can think is what if you have someone that has a "bad trip"? I personally never experienced that but was always in good spirits heading into it I can't imagine it would always go so well with someone who suffers from Depression.

It will be very difficult for some patients, you're absolutely right. We have to be prepared for bad trips and we will prep the patients for difficult experiences. We'll ask them to reveal feelings of anxiety as soon as they feel them. We'll reassure them it's normal and even potentially useful to feel some anxiety and we'll reassure them that we're with them all the way and that they should explore sources of anxiety rather than try to flee them as it will be in the confrontation that the potential benefits will be greatest.

Do you think the UK government will change their drug classing system anytime soon? If not what do you predict will happen in the next couple years? With new research chemicals filling in the legal market with so little known about their long term effects.

I think the next government, which will likely be labour will make some reforms yes.

Reform is inevitable but the Tories won't do it. The thing is, it's pretty likely the Tories will get a kicking at the next GE

I am a 27 year old male that currently suffers from depression and generalized anxiety disorder. I currently take paxil and smoke cannabis occasionally (medical card).

In my experience whenever I have consumed psilocybin mushrooms my anxiety goes through the roof. I have a hard time holding on and can be prone to panic. This can be felt at a dose as low as 1 gram to 1.5 grams. What is very strange is when I start to come down from the experience I feel AMAZING. It feels like my brain has been washed (for lack of a better word) and I feel at ease.

I have not consumed mushrooms since I have started paxil as I am hesitant given my reaction. Do you have any suggestions or thoughts on my situation? Thank you for your time!

Thanks for the message. Paroxetine will only attenuate the effects of mushrooms, so it won't be more intense or panic-laden with your current meds.

I've heard similar reports. Perhaps talk to a close friend, if you are going to do it again try lying on a couch or bed and shutting your eyes. Ask your friend to be a guide for your experience. Make sure you pick someone you really trust and talk to him/her about the possibility of you feeling really anxious under the shrooms. Maybe have a plan for what you'll do when you feel this anxiety (because you will). I'd suggest exploring its source, getting to know it. Ask your friend to be there for you if you do this.

The last that if the shrooms work for you and you feel better for a good while, don't feel the need to re-dose, just be happy that you've found some relief and get on with enjoying the ups and downs of normal life. Good luck.

What are your thoughts on microdosing? Say 5-10 micrograms of LSD every day for an extended period.

Therapeutically?

I'm not sure, I'd worry about become a bit detached from reality.

Although, this is sub-psychedelic, so it's an interesting idea.

Personally I'm not convinced though but remain open-minded.

I’m not sure if this is the correct AMA to ask this question on, but I figured it’d be the best time to ask. Do psilocybin and/or MDMA pose any negative health risks when used?

Yes. The risks around psilocybin are psychological mainly. If taken in the wrong environment or if you're in the wrong frame of mind without people around you who could look after you if you start getting anxious and/or paranoid, then there's the potential for a very difficult experience. It's extremely important that attention is paid to set and setting, or how you feel at the time and what kind of environment you're in. Physiologically, psilocybin is very safe. With this said, psilocybin may pose some significant mental health benefits however if taken in the right way with the right people around you. With MDMA, it's a little different. The experience is less psychologically challenging but more physiologically taxing. The serotonin low that follows an MDMA experience is a bit of a problem and if the drug's really over-used then there's a potential risk of causing some damage to the serotonin system - which could affect mood for example. The moderation message with MDMA is very important.

What made you want to study them?

The idea that they could access hidden parts of the mind. What is more fascinating than that!

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psilocybin stimulates serotonin receptors and the psychedelic effects appear to occur through the serotonin 2A receptor.

MDMA increases levels of serotonin, noradrenaline and dopamine and doesn't really stimulate any receptors directly.

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SSRIs attenuate the effects because they upregulate 5-HT2A receptors because of increased synaptic 5-HT

Studies involving MDMA and psilocin are becoming more common -- not just at ICL but elsewhere -- but LSD seems to have been conspicuously absent from the latest line of research. Do you think this is because of societal stigma regarding LSD, its cost of production and acquisition, a lesser expectation of therapeutic potential, or something else?

The stigma mostly.

Plus, psilo is a nice little drug, more manageable than LSD because of shorter duration of effects. LSD also has a very non-selective pharmacology - but then that makes it interesting too.

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Some MPs have taken a dislike and tried some personal attacks on my seniors. Ignorance is the main problem but the next generation of politicians will be less ignorant. People like David Nutt are so important for breaking taboos and tackling misinformation.

How much is known about the damage caused by MDMA to serotonin receptors, and the potential for self-repair of those cells?

There's no damage to serotonin receptors with MDMA but some potential damage to axonal fibers. Repair does happen it seems. Full repair seems to happen in most areas but there's some suggestion that some cortical regions may not show complete recovery. See Erritzoe et al. in Archives of Gen Psychiatry for this paper.

how would you compare the effectiveness of psilocybin & mdma on depression and addiction compared to hoffman's lysergic acid diethylamide?

Difficult to say.

psilocybin for depression imo

MDMA for PTSD

And maybe psilocybin and LSD for addiction

LSD is incredibly potent and addiction (esp to alcohol) is maybe the most stubborn psychiatric disorder of all, so LSD for addiction is worth a shot.

I was recently watching a documentary on nat geo on hallucinogenics. A man (~52yrs) has been suffering cluster headaches for years and discovered that consuming psilocybin mushrooms every two months eliminates the headaches. My question is; how does psilocybin do this?

Maybe via constricting blood vessels - the research needs to be done

Psilocybin has a dramatic effect on Thomsen's disease (Fainting Goat Syndrome).

I'm remiss to use the word "cure" but it's absolutely incredible how much greater range of motion/athletic ability/etc that psilocybin induces.

I haven't been able to have a discussion with my neurologist at all, or any other GP regarding this because they just assume I'm hallucinating. It's very frustrating.

Sorry to hear about that. I'm unfamiliar with the condition sorry.

Will you be joining us at the next ICPR in Amsterdam? Your talk this year was great.

Thanks :-)

Sure, if I can.

Dr. Carhart-Harris, if you could have any historical person work on the trials with you, who would you pick and why? Also, who do you pick to work with you, if you can already and why?

I think Sidney Cohen was under-rated. He's my main hero from the 60s era.

I also like Huxley's poetic descriptions in DoP

But, if I had to choose one, it would probably be Freud. an incredible mind.

In higher doses people often report spiritual experiences, seeing other forms of themselves, interacting with other beings, and entering other "dimensions". Do you think there's something to that? Or in your opinion are these all just manifestations of the brain ?

I think there is something in that but I think it can be explained psychologically eg with reference to Jungian theory and writings on the phenomenology of the mystical/spiritual experience. I don't think it's metaphysical however.

Yes, they are manifestations of the brain. There's no question imo. But I still think that is an absolutely amazing thing.

Do you know anything about the research chemical 2C-i-NBOMe aka 25i-NBOMe? If so do you believe that these may also have therapeutic benefits? It's been said that it has similar effects to that of LSD but I personally cannot vouch for that through personal use or research.

I don't know sorry

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Maybe to stop sheep eating them. Liberty caps also look a bit like droppings and that's another deterrent. The best explanation is that it's to stop things hosting on them though. Doesn't stop humans though!

What's your opinion on Holotropic Breathwork?

I'm pretty ignorant but it probably causes brain states similar to as occurs with LSD. The Hypoxia may simulate this state.

What is the most common similarity in experiences reported by people who take psilocybin?

geometric hallucinations and odd bodily sensations (tingling) as they come up.

at least at our doses.

How does a general day at the lab go? What do you spend most of your time doing? What are the people around you like?

Regulatory stuff! :-(

Plus a bit of writing, which I love

The hands on research occurs in fits and starts

Were you involved in that study that came out about 6 months ago (may have been more) that found users of psilocybin to have a permanent improvement in empathy over those who had never?

Nope, wasn't me sorry. Maybe Roland Griffiths?

Even with the research to back this up and the newer generations openness to the subject, how do we shake the negative 'drug user' stereotype held by older, stubborn and unwilling generations? I am well aware of how these substances can effect you and I think with education, regulation and legalization we can have a safer, more mind opening way to approach 'recreational' use.

By engaging with media. David Nutt has taught me that.

I personally am an advocate for drug law reform. With all they hype over medicinal marijuana in the US do you think psyches will be available in the same manner? Do you think they will ever become wholly legal?

I often feel psychedelics are my greatest passion in life. What kind of classes/subjects would you suggest that someone in college take if they wanted to study psychedelics?

Train to become a psychiatrist if you seriously want to get into this research. It will make you much more appealing to people like me and my seniors. Psychiatrists are premium in this area.

I think Psychs should only be taken in centres. I'd worry about a 'take-away' set-up. I think that would be problematic. There could be loads of these centres, they could define a city's culture eg, and they could be exactly where you'd want to have the experience. They could be out in the countryside eg - but always properly staffed by trained professionals.

And one final one: have you heard many connections between high end psilocybin intake while meditating in the dark and having an experience which is best described as a waking lucid dream for several hours?

Though not very common some modern people and indigenous people tend to describe this sort of experience, often times venturing into space and travelling to other worlds as realistically as normal waking life.

Yeah, it's interesting

Hi!

What is your favorite dinosaur?

T-rex is a bad mother

What seems to be the most profound effect of psilocybin/Psilocin and other Psychadelics?

Ego-dissolution.

Everything profound follows from knocking this 'reducing-valve' out of the way.

What is it exactly about psychedelics that make them so non-toxic despite having profound effects on brain chemistry? Why can you take such large quanitites of LSD or psilocybin and suffer comparatively little harm than other psychoactive compounds like cocaine?

Probably because they a lot like serotonin

It's a bit of a myth that you can take large quantities of LSD though. If you take too much it will poison you. LSD is very potent though so you only take tiny doses and yet have a profound experience.

First, I want to thank you for doing this AMA and for your research related to psilocybin!

I have taken LSD once and Ayahuasca once, but I am fearful of experiencing psychedelics again because I think, that they are not well enough researched and they could lead to permanent damage (“going crazy” due to a “predisposition”).

Here are my questions: • Could you please explain, what the correlation/causation relationship between higher psilocybin concentrations in the brain and increased amygdale activation is? Is a “bad trip” inevitable at higher doses?

• Does psilocybin cause vasoconstriction in certain parts of the brain? If so, can this lead to a collapse of capillaries and/or death of neurons in those regions at higher doses?

• The experiences caused by psilocybin are very similar to the ones of people suffering from schizophrenia and psychosis. Because of the plasticity of the brain, do you see a danger with regard to psychedelic experiences exercising the brain to become schizophrenic or psychotic (by forming some of the unwanted connections of those diseases)?

I do think there's a potential danger of resulting psychoses, so people need to be very careful. I personally couldn't advocate recreational use because I only how how it should be done properly in a clinical setting.

Collapse of capillaries - there's no evidence.

There's no evidence linking the amygdala and bad trips but it's a hypothesis that makes sense. It may be a general limbic disinhibition but this might also be why the drugs can be useful in psychotherapy i.e. to get at important personal material... and shake-up negative thought patterns

What do we currently know [and what research have you performed] about the interactions between Psilocybin and antidepressants? We could go through the gambit of the various forms but my curiosity is focused on Norepinephrine-dopamine reuptake inhibitors and Psilocybin.

Good question. There's only anecdotal evidence but it suggests certain ADs attenuate the effects of psychs.

Na/DARIs won't affect psilocybin so much would be my guess. SSRIs more so.

Hey Dr Robin Carhart-Harris,

I'm a highschool student interested in your research and wanted to ask how significantly can MDMA and Psylocybin help someone suffering from depression / mdd.

I was diagnosed with depression 2 years ago, and have tried different avenues of treatment, but was curious as to what progress (if any) MDMA / Psylocybin have on depression and long term treatment options avalible! :)

Thanks for your research, you're doing humanity a great service.

P.S. Would you rather fight one horse sized duck or 100 duck sized horses?

I really don't want to jump the gun but let's just say I'm quietly confident psychedelics will have a major part to play in the future of psychiatry.

Remember we haven't started our own research in patients but the other available indirect evidence that's available looks really promising.

It's a boring message but I do really think it's all to do with the synergy between the drug action and the care structure around the experience.

Where would you like to see this line of research go over the next 20 years, and how would you like to see it applied?

Also, what do you think about Dr Rick Strassman's famous DMT study?

Strassman's study was very pioneering. I'm not sure what happened to Strassman as a scientist though, he seemed to disappear from the scene. There's probably something I don't know.

Next 20s: careful research, accumulating the evidence, changing the face of psychiatry for the better. Developing the insights on offer from psychedelics in a evidence-based framework.

There will be opposition to this from some elements of the mystical-camp but so be it..

Science is an inherently mystifying force... and it's aim is to better characterise reality by testing it and learning from the evidence...

What are your thoughts on the latest ketamine studies and it's effect on cell repair?

Edit: here is an article about the study for those who are interested http://www.theatlantic.com/health/archive/2012/10/the-biggest-breakthrough-in-depression-research-in-50-years-is-ketamine/263400/

Interesting but I think classic psychs have more potential

I just wanted to say thank you, I believe your research is very important.

thanks

Any realistic data on human LD50 for MDMA? I've seen different sources range from 1,500 mg to 7,000 mg. I recall reading one story about an individual who was eating over 2,000 mg a day. He collapsed eventually.

2 grams a day! I'm not surprised. It's difficult to do the camprisons but high doses of MDMA are generally a very bad idea is any context.

I am not sure if I can phrase this right but here is a shot,

Do psychedelics have a "inert" composition so as no "trip" is produced yet depression is reduced when administered to a patient? Or is the psychedelic aspect necessary for the effectiveness.

I'm asking this as I have read about Cannabinoids that provide no "high" to the user yet can effectively treat conditions. I find this of particular interest as I am somewhat opposed to the recreational use of most narcotics yet feel strongly that their classification as Illegal Substances only leads to hinder scientific research and public awareness/understanding of these substances.

P.s. I have not read a lot into Psilicybin & MDMA, could you recommend some papers/Cochrane reviews to intrigue a young mind?

I do think the psychedelic effects are a necessary part of how these drugs can be beneficial.

Sidney Cohen's 'the beyond within' is a great book about LSD.

David Nutt's book: 'Drugs without the hot air' is also worth a read.

Les Iversen's book on amphetamines and MDMA is nice.

As for papers: Griffiths papers on psilocybin are excellent.

From what I gather your work has been with unipolar depression. Any thoughts/knowledge to share about bipolar depression and substances like this?

Very difficult. I worry about inducing mania.

Are your family very proud and understanding of what you are doing? Do you have scientists in your background? What has been the biggest difficulty when talking about your trials and media work to your loved ones? Do they have any concerns?

My family are proud of the academic success and smile about the subject matter. They're not big into drugs but they're proud and have been incredibly supportive.

My Mum's much more clued up about drugs since I've become a scientist.

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Some might, I don't know. I think it's probably a natural deterrent

Have you heard of Terence Mckenna's Stoned Ape theory?

It says among the new items in the diet of grassland/jungle roaming hominids was psilocybin-containing mushrooms growing in the dung of ungulate herds. The changes caused by the introduction of this drug to the primate diet would have been many, including the blurring of boundaries between the senses leading to the development of spoken language: the ability to form pictures in another person's mind through the use of vocal sounds.

About 12,000 years ago, further climate changes removed the mushroom from the human diet, resulting in a new set of profound changes in our species as we reverted to pre-mushroomed and frankly brutal primate social structures that had been modified and/or repressed by frequent consumption of psilocybin.

Question: Do you have opinion on psilocybin's influence in the brains of the early humans?

I think early humans probably had a trippy-kind of cognition anyway and if they took psychs it just made things even weirder.

I don't buy McKenna's argument at all.

Thanks for the AMA.

I know the law isn't your expertise but would you support decriminalization of MDMA to be able to provide safer and more accurate doses (not cut etc)?

Maybe, I'm not sure. You're right, policy is more David Nutt's domain.

A safer MDMA would be nice and club testing is a good idea.

Do you think recreational use functions as self-medication (for some users) or is the clinical context in which it is used important to effectiveness for treatment of depression?

Yes, self-medication. The context is v v impt

How important is it to develop novel therapeutic techniques, or even environments, for use with psychedelics?

How hard will it be to quantify the therapeutic value, or dangers, of psychedelics in relation to different therapies and therapeutic environments?

Comparing psychs against other meds and treatments is the next stage. The focus right now is on small pilot studies to demonstrate efficacy.

You touched on this in another comment (the only one i saw), but I wanted to ask if you have come across any migraine effects through your own work.

No really. John Hopkins heard volunteers reporting head aches after large doses though, suggesting some kind of rebound effect. I think the migraine link is credible and it's probably due to these drugs causing the vessels to dilate and then relax

Hello Dr. Carhart-Harris,

My question regards psilocybin's possible treatment of cluster headaches. My mother suffers from these and she's tried various methods of therapy, all to no avail. I hate to see her when she's in such a painful state, as she says that the entire right side of her body above her chest is writhing in pain. I've read some literature that says that psilocybin has been able to treat cluster headaches and, in some cases, even stop them from recurring completely. What are your thoughts on the subject?

Thanks very much

I think it can be useful but be careful, she'd need to be prepared for a very strange experience.

Hi Dr. Carhart-Harris. I read about experimental trials of patients with PTSD being treated with MDMA and it helping them a lot. Is this in a similar vein to what you are doing with MDMA and depression?

We're not doing MDMA depression research sorry. We don't do any patient studies with MDMA yet but they do in the US as you say. Dr Ben Sessa is trying to do a MDMA-PTSD in the UK and I hope he's successful.

1. What specific obstacles have you run into trying to study these substances?

2. What would you say has been the most exciting finding/result/outcome that you have seen thus far?

3. Do you see these substances clashing or negatively interacting with the current prescribed medications on the market?

Thank for doing this AMA and for the work to you do.

The most exciting result was the decreases in default mode network activity after psilocybin. This network is linked to the sense of self and so it makes a lot of sense in the context of ego-dissolution under psychedelics.

The beautiful thing about classic psychs is that they could compliment current meds. We're going by that model in our forthcoming depression study. Patients will stay on SSRIs if they're on them and we'll dose on top. Effects may be sig attenuated from the SSRIs but the psilocybin should still work.

Thanks.

How do you find your subjects?

Word of mouth mainly

What do you think of the legality of the drugs you study?

Big topic but I think psilocybin as class A and alcohol as legal is ridiculous. It'd almost be funny if it wasn't so harmful and serious.

I have been struggling with depression for a couple of years. I've been wanting to try LSD/psilocybin for about 6 months now, but am worried about potential interactions with Fluoxetine. I have found very little to no research on this, and very few anecdotal accounts. I am aware Fluoxetine works by inhibiting the reuptake of serotonin, however I am hazy on the complicated pharmacology of LSD/psilocybin.

Do you take your research subjects off their medication before administering psilocybin? Do you have any knowledge of interactions between these substances?

Sorry to hear about your depression.

We won't actual take our patients off their meds and it's easy to have a big relapse. The fluoxetine will only attenuate the effects, so there's no risk of a negative interaction.

If you're adamant about doing this I'd stay on your meds and try mushrooms rather than LSD but, and this can't be emphasised enough, have the experience with a close friend who will look after you and see you through any inevitable anxiety. Be prepared for the anxiety but meet it head on, explore it, you'll be fine, but just make sure you have a good care structure around you.

If you were king of the world and could insist people read a certain book or listen to a particular piece or music, and they would 'get it', what would the book and the music be? Not Freud or Eno. In relation to your work.

Also, if Freud or Cohen could reanimate and offer you a piece of advice, what do you think it would be?

Maybe something like the Dharmapada but I don't think they'd get it necessarily. Also, Sasha, northern exposure 2 is pretty cool but it won't provide any great insights.

have you yourself taken any psychoactive drugs?

Yes, I had some caffeinated tea earlier.

When administering psychoactive compounds for tests in a lab setting, how do you determine what constitutes a "safe" dosage for your subjects? Also, in administering psilocybin, do your subjects actually eat raw mushrooms or take it in a refined form like a tincture or pill?

Previous literature and careful dose-finding

What do you think is going to be legalized/decriminalised in US during the next 10 years?

Next 10 years in the US...

I'm not sure to be honest...

Sorry

How has the topic of synchonicity been expressed by your research subjects?

What about the afterlife?

Jung's idea? Or neural synchrony?

Jung's idea is a bit wishy-washy imo - it's an example of magical thinking. You want to believe the incredible because it excites you.

what are some of the most profound ideas you've discovered while on mushrooms? also they say mdma takes "ice cream scoops" out of your brain, being a frequent user id like to hear that this is indeed false :)

ice scream scoops is complete nonsense. There may be some damage of fine serotonin axons but its dose dependent and never been established directly in humans.

I am guessing that you study/studied pharmacology? I have a question for you, what do you think of it? (My sister wants to study pharmacology, and would like to know)

I love it

pharmacology is mostly animal work though.

I studied psychology mainly

Do you think that even unknowingly some drugs (specifically MDMA) have a therapy type effect even when used recreationally? I am used to doing this drug and I feel that my relationship with people has been much better, especially to close friends whom I have spent nights with on the drug. Do you think that the overall vibe from parties and raves (unless your life revolves around these activities) which MDMA is mostly known for, good for building strong relationships and character? Thanks

Yes, I do.

A lot of recreational users are incredibly clued up

When do you foresee governments not shutting down full research on illegal substances?

They haven't shut it down now. I'm hoping they'll relax the schedule one on psilocybin within 10 years though. Once their medicinal value is proven, they'll have to. Expect a bit of press about this from David Nutt within the next 6 months. You heard it here first.

As a cancer survivor who has dealt with depression since treatment, I'd just like to say a huge thank you! I use psilocybin once every few months and it is unbelievably helpful to me.

That's great. I'm really glad you're doing well :-)

Very best wishes to you :-)

Do you have any plans for comparing the dream state and the psychedelic state? Sort of optimizing the consolidation of memories after a session to maximize the benefits?

I'd love to do that study but no solid plans as yet

If your findings show significant benefits, do you think that the substances will ever get approved for use by whatever sanctioning authority?

Yes I do but it will be a long struggle. I'll die happy if I see that day.

Thanks for doing this! In terms of harm reduction for the patients, what sorts of strategies and resources do you utilize for safe usage, and what research did you reference for them (e.g. safe dosage/temporal spacing between dosages)?

MDMA, small doses sparingly. eg No more than 150mg every 3 months or so. That sounds stingy but it's safe.

Psilocybin is less about doses and regularity but I would say there's no need to use more than every few months. If you do, you might start becoming a bit detached and loose in your thinking. A bit schizotypal.

Although it's great to finally be able to research psychedlics as treatments for various pathos, including depression, what opportunities might exist for the use of psilocybin for growth/development/education where there is no diagnosed problem to address?

I think there should be scope. Roland Griffiths work strongly supports this and is to be celebrated imo

Does your lab take graduate students? See you at Psychedelic Science 2013!

Yes but there's a long waiting list! see you there!

Do you have any info about the vascular effects of psilocybin and LSD? Since they are vasoconstrictive some people are concerned they could be bad for the circulatory system but data seems hard to come by. Any information about this?

There's an old study showing constrictive effects of both drugs on vessels in sheep umbilical cord