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This is a very interesting piece of research. It needs to be put into context though - this isn't even a phase 1 trial, it's an observational study of veterans who decided to go to Mexico to take ibogaine. There is no control group

Other psychodelics, such as psilocybin, are further down the road to validated treatment. I'm not quite sure what stage they are at for PTSD but there are various groups doing RCTs for depression etc

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What's frustrating is that Ibogaine has been known about for a long time. I remember reading, 20 years ago, about how Ibogaine had cured some people of alcoholism. It was all anecdotal at the time, but clearly there's something worth studying.

I understand the hesitancy around drugs, but we've lost so much progress as a result of the bureaucratic red tape.

Remember that the bureaucratic red tape keeping these drugs from market has to do with moralism around psychoactive drugs.

Plenty of other safe and effective treatments have made it through the “excessive” red tape because actually the red tape isn’t the issue. Dismissiveness and fear of psychoactivity is.

Agreed, and we see in this in particular with the fervor to try and create “non hallucinogenic psychedelics “

If it alters the mind people will use it for fun.

And we can’t have fun here. We don’t want to treat people’s difficult issues in a way that encourages lazyness ;-)

Talk to anybody who's taken ibogaine and the last thing they'll say is that it was "fun"

There is more variety to peoples reception of the psychedelic experience than one might think.

https://erowid.org/experiences/subs/exp_Ibogaine.shtml

Exactly. This is why people go to jail for having Benadryl

> If it alters the mind people will use it for fun

That is not true

There is (usually) no law against atropine and other Deliriants because they are not fun. No fun at all for most people

Drug users generally try those drugs once

> Drug users generally try those drugs once

Even true for some psychedelics. Few people take Salvia Divinorum twice.

This cracks me up. We're still looking for the "Magic Pill".

That and the War on Drugs™ is built on the foundation of oppressing "minorities".

The public has now been so conditioned by this bullshit that most people think that they're being protected by these stupid laws, when in fact they're either directly or indirectly suffering because of them.

I mean, substance abuse is a real problem. I’ve known people who have ruined their life because of it, all-the-while touting that it doesn’t affect them.

Yes, drugs affect you. It also ends up affecting those around you.

That being said, the current state of laws, enforcement and culture is definitely not aligned for success in this arena.

My brother died from a heroin overdose. The fact that it was illegal didn't prevent it and might have been a small contributor in that the purity and strength of the drugs could not be known.'

My mother died as an alcoholic. Totally legal drug that's socially acceptable.

I'm well aware of the abuse potential. But a lot of this (including the current fent epidemic) could be addressed by legalizing and regulating these drugs (including the aforementioned ibogaine).

So yes, the current state of laws, enforcement and culture are definitely aligned for the clusterfuck of what we have today (by virtue of that's what we have).

There will always be risks, but society has shown that it's ok with risks in that alcohol and tobacco are legal. They've just been brainwashed by the drug war propoganda.

The way 'substance abuse' is framed and conceptualized deliberately obscures the fact that many if not most people with substance abuse problems are 'medicating' a psychological problem.

Of course anyone can get in trouble with drugs, so I agree with you too!

But I want to just try and shake up the "Drugs affect you. They affect those around you" point a bit because often the drug use is a symptom, the consequences of hopelessness, neglect, depression, abuse etc is whats actually making its presence felt, and even teetotalers have bad life outcomes when they're carrying that around.

> They affect those around you" point a bit because often the drug use is a symptom, the consequences of hopelessness, neglect, depression, abuse etc is whats actually making its presence felt, and even teetotalers have bad life outcomes when they're carrying that around.

Except, they can cause these problems in the first place. I agree that when those problems exist, drugs can make them worse too.

While I will always advocate for the legalization of all drugs, I think it's important to recognize the dangers and not downplay them.

But a lot of those dangers can be mitigated by having them legal and regulated.

A lot of abuse is about self-medicating from pain, so if they're going to do that let's at least make it safer to do so and have support to transition off when ready.

Why is "minorities" in quotes?

Wealthy people have access to doctors to get prescribed speed, ludes, opiates, whatever they want.

It's specifically the targeting of minorities using criminalization of street drugs that led to modern media and academic misperception of "overpolicing" in minority areas for all crime.

> Why is "minorities" in quotes?

Sometimes I get a bit overzealous on quoting, and sometimes, on commas, too. But in the case of the Nixon years it was anti-war hippies too.

But yes, it's well documented that the war has always been about targeting "others". It's bad enough that the laws exist, what is crazy-making is that a large portion of the population has been brainwashed into thinking they're a good thing.

For what it's worth, ibogaine in particular is more dangerous than more common psychedelics. There have been many fatal overdoses which isn't true of, for instance, LSD.

Totally. But nearly every pharmaceutical on the market has a lethal dose, some of which are rather close to their effective dose (and some really painful deaths).

We should find what the safe and effective dosage is, if there is one, the same way we do for other drugs.

Yeah, acetominaphen / paracetamol is not in my medicine cabinet because that line is too fine for my taste.

People have flat out done stupid, lethal things on psychedelics such as LSD and psilocybin. I'm one of them. I did a small dosage first time, and took a bath. Fell asleep and almost drowned.

In general you're correct, but not about Ibogaine, which is actually cardiotoxic and prolongs the QT interval, sending the odd man out into the next life.

The red tape is actually hundreds of millions of dollars that some private party has to cough up to fund clinical trials, and with many of these drugs, there is no hope in recovering because they’re not patentable. And we don’t really have any mechanism for publicly funding clinical trials for unpatentable but public-benefitting drugs.

Has to cough up millions under the current system. A rule change to make that process easier would be helpful, but an agency which receives over half its funding directly from the industry it oversees is not likely to make policy which damages those same companies.

Not really. Clinical trials are expensive because clinical trials are expensive. Especially when you’re looking for weaker and weaker effects in more specific populations.

There are a number of things that can be done that can fix the broken system while retaining the things that work in our existing system.

1. Public funding for approval for public interest drugs that immediately are available at generic-level prices.

2. Public funding for patent early buyouts so that they can be available at generic-level prices sooner.

3. Public drug bounty systems: award non-trivial payouts to companies that discover and perform all clinical trials, and immediately make the drugs available to the public at generic-level prices.

4. Broad cooperation and alignment on approval trial requirements across drug regulators in Canada and the EU, such that drug trials don't need to be duplicated 3 different times in 3 different jurisdictions with slightly varying rulesets. This would benefit both public interest ideas above as well as existing private interests.

5. Add price controls to drugs which have benefited from publicly funded research. I'm not a fan of price controls in general as I think there is a risk that good drugs won't be researched if they're too risky, but in the case of a private company taking some compound that public research discovered, patenting the chiral[0], and funding the clinical trials for it...the public has already done all the hard work and you're just

6. Allowing for risk-assumed early approval drugs which are regulated for content purity, but which do not do full testing for drug interaction/benefit/risk assessments. Users could explicitly opt out of the guarantees that come with full FCC approval. This is actually how the much of the developing world treats drug regulation: sure you can buy it and it will be what it says on the label, but there is no guarantee that it will fix your problem or that it wont harm you. While that sounds potentially troublesome, there is a reason why rich people sometimes travel to poor countries for medical care, and this is a huge part it. If you've got 9 months to live, you don't care that the FDA is trying to determine if it might kill you...you are already on your death bed. Holding back a potential cure is inhumane.

[0] https://en.wikipedia.org/wiki/Chirality_(chemistry) Chirality is an extremely common loophole that allows drug companies to patent drugs that work exactly the same as an unpatentable drug, so that they have price protection for it.

As an alternative to some of these, do you think that compulsory patent licensing could work? This would allow for day one generics while still ensuring that the parent holders get paid.

> Plenty of other safe and effective treatments have made it through the “excessive” red tape because actually the red tape isn’t the issue. Dismissiveness and fear of psychoactivity is.

Probably money is the issue. None of these compounds can be patented now.

You're painting an unfairly one-sided picture here, as so many pro-psychedelic people do. These are highly potent chemicals that also have negative physical and psychological effects. It's not as simple as "these substances cure a condition and the fear of psychedelics keep them repressed". You are saying the equivalent of the college stoner friend saying "you can't get addicted!" about weed. Even this article points to fatal heartbeat irregularities as a dangerous side effect that has limited ibogaine's study.

I agree, it's important to soberly identify and weigh all the risks associated with any treatment.

But it's also important to recognize medical risk alone is not what has stopped the serious evaluation of entheogenic or hallucinogenic substances.

Look at the analogs act, and the banning of salvia in many US states, and tell me that such things as negative externalities are actually weighted in the decision to ban things. Look at 2CB. It was banned for having chemical proximity to DOB, which is banned for having chemical proximity to DOM. 2CB was banned for the entire justification of "posing a risk to the public health." Where? How? I've never found data published to justify this scheduling, other than chemical proximity. Why was DOM banned? Posing a risk to the public health. Again, I can find no data.

Salvia is even more clowning. Republican legislators heard that it's a more potent psychedelic than LSD and rushed to ban it without even knowing what "potency" means for such a comparison. This has led to such beautiful pieces of law as Florida (I believe) banning salvia divinorum and all chemical derivatives thereof. Salvia divinorum is a plant. There are no chemical derivatives. They should have specified its principle component, salvinorin A, and its derivatives. These banning were made entirely out of moral panic, with not even a modicum of pharmacological or chemical understanding.

2C-B is one of the few drugs on my "want to try" list. I imagine I won't see a reliably uncontaminated version in my lifetime though.

Ibogaine's safety profile is pretty good, there is a reason it is legal in other countries. The cardiac risk factors can be mitigated with appropriate screening, and of course, it should not be consumed with other substances with unsafe drug interactions. To the extent that Ibogaine fatalities have occurred, they are largely attributable to these two factors. In this respect, it is not especially different from plenty of other OTC and prescription drugs.

This is not to say that Ibogaine has zero risk for either physical or psychological harm---this cannot be said about very many perscription drugs either. However, given its efficacy for treating opiod use disorders alone, along with its safety profile, there is no logical reason that it should be out of reach for mental health professionals, let alone a schedule 1 substance.

Good thing nobody is forcing you to consume anything then.

This would be a great rebuttal if I said “this is why ibogaine isn’t approved and used broadly!” but I didn’t. I said this is why we don’t really understand Ibogaine.

The action proposed in the article is: more trials

>I understand the hesitancy around natural drugs

FTFY. The amount of psychoactive pharmaceutical drugs cooked up by big companies is immense. It seems to be a slow process for natural substances, because there's no money in that and it can't really be patented to maximize profits.

It’s also really had to control quality of “natural” substances. Sure, the box might say “100% organic bobloblaw”, but it could just be viagra.

The Pharmacopoia shows that it's easy to control quality of natural drugs - maximum acceptable level of contaminants or adulterants, minimum level of active principle (nowadays with HPLC). It's just that the feeble government can't rouse itself to enforce truth-in-advertising standards.

When it comes to natural medicine, the FDA loves to capitalize on instances of adulteration and mislabeling. This enables them to trumpet the allegedly unsafe nature of anything they don't regulate, and lets them spread F.U.D. about those products, until finally they can yank it all from the market.

There are plenty of reputable manufacturers who wouldn't think of adulterating medicine or misleading their customers, but all it takes is a couple sleazy Chinese vendors on Amazon to spoil the entire apple-barrel.

You don't even need to resort to racism or jingoism. You can visit your local GNC or Target and find products made right here in America that contain adulterated medicine or misleading claims.

In fact I have made some orders from vendors of natural medicine, and I believe they may be legally bound to lie and falsify instructions for use, lest they run afoul of the FDA.

For example, my potassium iodide specifically instructs the user to consume it orally, which is dangerously incorrect. I believe that if they put the correct instructions on the bottle, the product would be so efficacious that it'd demand removal from the market.

Chocolate from all kinds of produces has high levels of heavy metals, yet it's still sold everywhere. It's not hard to control the quality, and safety, but it's easier to look the other way and profit.

https://www.asyousow.org/environmental-health/toxic-enforcem...

And many pharmaceuticals start from natural substances that had to be refined. There's nothing humans don't understand about refining and purifying, we've done it for a very, very long time. It's a solved problem. Greed is not.

When I first learned of it I researched it and it seemed like the risks to heart health are significant with ibogaine, but I’m unaware of mitigation efforts that could make research ethical and safe.

You mean like the administration of magnesium in this study?

Oh sure, I guess that. I think when I researched it the articles just said the heart risks were high and this limited research possibility. I hadn’t seen anything previously about magnesium for this.

I read bureaucratic red tape, and I imagine a group of people gathering actual information on how this goes down including input from hospitals and law enforcement where problems occur. As opposed to word of mouth, which is whatever you want it to be.

Some people have committed homicides while on LSD [1], that they would unlikely have committed otherwise. Here's a crazy story a New Zealand friend of mine told me. She knew a guy who had gotten high on LSD while vacationing in France, and wandered into some stranger's backyard. The homeowner came out and they stabbed them with a pitchfork and killed them. They went to French prison for life, but were released as part of a deal France made with New Zealand for the bombing of the Rainbow Warrior by the French Secret Service. They released all New Zealanders and repatriated them, and this guy, lucky SOB he is, was set free.

[1] - https://www.vice.com/en/article/7k9pmz/acid-lsd-fuelled-murd...

Wait until you hear what people do under the effects of alcohol!

This can be seen as more of an argument against alcohol than in favour of other drugs.

Perhaps that's a good thing.

I agree.

I also am aware that it’s a fallacy to say “X is worse than Y, so don’t worry about Y”. Both X and Y can be bad at the same time! We definitely need more harm reduction education about psychedelics.

What are the numbers? In terms of likelihood of me jumping to my death or doing murder, per 1000 nights on it, say? LSD vs Alcohol.

I’d expect treatment would not consist of bong rips, pitchforks and 9mm hand guns.

You mention curing alcoholism, but my casual observation is that there is almost always a history of psychosocial trauma, likely with residual PTSD, that leads to substance abuse.

The ibogaine treatment very likely allowed individuals to move past their traumatic experience and no longer had a reason to self-medicate.

Something I’ve read in a few ibogaine trip reports is the experience of something scaring them out of their addiction. “If you ever do heroin again, I will personally rip your soul in half” kinda shit. Certainly a different mechanism than resolving underlying trauma.

That might still be more comforting emotionally than whatever painful uncertainty about something they didn't feel control over from the past which led to the self-medicating in the first place.

Knowing what you can avoid to stay safe is a lot more tolerable than never knowing when you're going to get pummeled. Just that sense of control is huge.

The use is much older: William S. Burroughs tried ibogaine in the 1950's to treat his heroin addiction.

So how did that work out for him?

My reading through the history of this drug is that there has always been a significant risk of cardiac events. It's a promising drug, but until we find out what causes some people to die shortly after taking it, it's not safe for common medical use.

Psychoactive drugs also seem to have a tendency to expose/accelerate symptoms for diseases like schizophrenia for people who are not (yet) suffering, while at the same time showing promising results for treating such illnesses.

The outright ban because of the fear of hallucinogenics is ridiculous, but a lot of the red tape is also warranted, especially for drugs that have a long-lasting (sometimes even lifelong!) effect after a single dose.

There are hundreds of anecdotes about people with near-impossible to conquer opiate addictions that have managed to quit using ibogaine. I personally know someone who tried and failed on three occasions with traditional rehab, but she has been 10 years clean after ibogaine.

It’s really frustrating how much our drug approval process biases towards patentability. There are probably hundreds of extremely beneficial drugs out there that have no chance of approval simply because no drug company is willing to do trials for an unpatentable drug.

+1. Erowid had plenty of self-reported but for some reason believable accounts of people kicking opioid addiction with ibogaine. Having never had experience with either can’t confirm the efficacy but definitely can confirm the fact that it was talked about.

E.g. https://erowid.org/experiences/exp.php?ID=86136

The pesky red tape surrounding drugs where people died during clinical studies?

This thread has everyone suggesting there's been a a miracle drug that doctors have been ignoring.

Doctors have not been ignoring it. This drug fucks with your heart rhythm, people died taking it. Doctors are also still researching it, addiction is a serious affliction and there's loads of research done on possible solutions.

> What's frustrating is that Ibogaine has been known about for a long time.

Not just Ibogaine - pretty much all of the "psychedelics".

And it's just big pharma doing their evil deeds. Should have been obvious by now.

Research has long been held up by legal obstacles, but articles like this are promoting an entirely false optimism about psychedelics. I live with a treatment-resistant mental illness, I have participated in clinical trials for psychedelics and I follow the field closely. Sadly, what we are seeing is almost certainly a hype bubble rather than a genuine breakthrough.

We now have a useful body of research on psychedelics as a treatment for psychiatric disorders. We can be reasonably confident that they do indeed work, but the effect size in depression and anxiety appears to be very similar to SSRI antidepressants or cognitive behavioural therapy. Research into addiction is more limited, but plausible effect sizes are again comparable to existing treatments. We're much less confident about the risk profile (especially in real-world clinical settings), so any marginal benefits in efficacy might be outweighed by safety risks.

Psychedelics might still prove useful as a second- or third-line treatment for a minority of patients, which I don't want to underplay - severe mental illness is truly awful and each additional patient in remission is a person given a second chance at life. They might provide insights that guide us towards better treatments in the future, but in this respect the NMDAR-agonists (ketamine etc) look far more promising. Unfortunately, the promise of psychedelics as a revolution in psychiatry is a busted flush.

I wish I wasn't saying this, but the data doesn't care what my wishes are. We have reached the point in the curve where decent, well-meaning researchers are tinkering with the analysis post-hoc to try and make psychedelics look marginally more effective than existing treatments. A lot of money has been committed to research, the results are deeply disappointing, serious researchers are trying to salvage something useful, but all the while there's a steady drumbeat of deluded quacks and uninformed journalists continuing to peddle a narrative that has been thoroughly demolished.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399008/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278160/

Ibogain is dangerous

Which is why researchers are looking at Psilocybin and LSD

particularly Psilocybin as it is short acting making everything easier and cheaper

I think they should look more at DMT. Businessman's acid.

It’s also worth noting the study size was only 30 veterans. All of them special forces apparently, which probably introduces a lot of other factors. Plus several participants failed to complete baseline or follow up work.

Regardless, hopefully studied further in the future (legally)!

You don't need a control group at this stage to see there's something there that's worth further investigation. What's the control look like here? Do some elaborate ceremony, sit around in a circle, pretend to get high and see if the PTSD goes away? In the name of science, sure let's do that.

>You don't need a control group at this stage to see there's something there that's worth further investigation

Actually, you do, as the placebo effect is very strong for depression.

>What's the control look like here?

You can give the drug during anaesthesia, like in the recent Ketamine trial.

https://news.ycombinator.com/item?id=37948938

> Actually, you do, as the placebo effect is very strong for depression.

Is it an 80% reduction in symptoms?

The trip may very well be an essential part of the experience. Giving it during anesthesia would be very different.

Psychedelics just aren’t amenable to placebo controls. That doesn’t mean throw the whole science out, you just need to… control for that. You could have a non-placebo control of similar effort (talk therapy?) to control for drop outs. You could have alternative therapy as baseline.

It was 50% reduction. Presumably a trip and not being anaethsetised would result in an even greater placebo effect.

>You could have a non-placebo control of similar effort (talk therapy?) to control for drop outs. You could have alternative therapy as baseline.

But that would have a much smaller placebo effect, and there would be no blinding to treatment. Comparing the two treatments wouldn't tell us anything.

>The trip may very well be an essential part of the experience.

Yes, I think it is, even if it is a very effective placebo. My point is that you don't need a psychedelic to cure depression of PTSD.

> Yes, I think it is, even if it is a very effective placebo. My point is that you don't need a psychedelic to cure depression of PTSD.

Have you taken into consideration the important distinction between abstract reality and object level reality?

Some fires can be put out with a fire extinguisher, but not all fires can be. Yet, it is objectively true (though misinformative, an extremely popular meme ~2 years ago) to say that "fire can be extinguished with a fire extinguisher".

Or if that's too poorly stated: "you don't need a psychedelic to cure depression of PTSD" is only true to the degree that it is true, and it is not possible for you to know that degree - thus, your mind fills the gaps of the unknown, and you take it as true, as you have been conditioned for decades to do. "It is unknown" is not an option available, to you.

But then that's ~~just~~ my opinion, I could be wrong.

> My point is that you don't need a psychedelic to cure depression of PTSD.

That’s quite the standard. Obviously there’s some depression and PTSD treated in other ways. But maybe this treatment does better in some cases over alternatives. That makes it valuable.

"small study finds" has happened before, in the context of mental health cures, for everything from LSD to yoga to going 48 hours without sleep. Many other things that can induce altered states of consciousness have probably been studied at small scale too (like you say, Psilocybin). For each one, there's always some subgroup that responds to it.

"small study finds" is also how we landed ourselves with a replication crisis, so your comment about putting it into context is very appropriate.

MDMA is the furthest down the road to being clinically available.

Ketamine in the form of Spravato is currently clinically available.

Good point. It's also covered, ketamine via IV, for pain management in some Canadian provinces.

Yeah, phase 3 trials are concluded, it's now awaiting FDA review. Likely to be approved by the end of this year.

Why Mexico when it is native to Central Africa?

I know nothing of this topic, but my guess is proximity to the United States and a different drug regulation scheme.

Access to the American market.

There was also no control group, which is a fatal flaw in any depression related study.

If you're not aware: Depression studies have a very high placebo response rate. It's often hard to get new antidepressants to demonstrate improvements in studies not because the patients don't get better, but because the placebo group improves so much that the difference between the groups is small.

This doesn't mean that antidepressants are placebo, it just means that if you take depressed people and tell them they're going to get better, then give them a lot of attention and activity from clinicians, they start to improve.

This study definitely needs a control group, as the patients went all the way to Mexico on a small vacation to receive the drug. I guarantee that if you take a cohort of depressed patients, send them to Mexico for a short vacation and hand them a placebo pill that you tell them is an antidepressant, many of them will improve substantially on various measures upon return.

This is why placebo control groups are critical for any depression study. I don't think it's a coincidence that so many of these psychedelics-for-depression studies omit control groups. Including a control group increases the cost, but it also is guaranteed to reduce the "wow factor" of a depression study. Therefore, they get omitted any time someone wants to make an antidepressant look effective.

If this was a study for a new SSRI that didn't have a control group, people would be tearing it apart. For some reason people love stories about psychedelics doing magical things, though, so a lot of people are willing to overlook the most glaring fault of this study.

PTSD is a dramatically different disorder to MDD though, no? It has pretty acute effects, and I don't know, but I would imagine it's less susceptible to placebo.

Not to say this trial is any higher quality than it is, or that your sidebar on MDD wasn't interesting, but I'm not sure it's that effective of a comparison.

Yes.

But psychedelic studies are impossible with double blind

It is important to be rigorous in your study, but cannot expect too much

Psychedelic therapies are not like antibiotic therapies, they interact in complex and confounding ways with set and setting

It is not the medicine by itself but the whole experience around it. Practitioners feel deeply that the medicine is an essential part of the experience. This raises the question, which I think is a very good one, of what a valid control would even look like.

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