A non-hallucinogenic psychedelic analog with therapeutic potential
ncbi.nlm.nih.gov
ncbi.nlm.nih.gov
Second, the reason they call it "non-hallucinogenic" is because the rodents didn't exhibit the so-called "head-twitch response" (or "HTR").
While the HTR in rodents has often (always?) been correlated to substances which have psychedelic (the term "hallucinogenic" is a misnomer) properties in humans, that's no guarantee that the novel compound used in this study won't have psychedelic effects in humans, despite the HTR in rodents.
Finally, since this study was done only on rodents, we still don't know whether it will have any therapeutic effects in humans, or even whether it will be safe.
There's a section in PiHKAL where Shulgin talks about a researcher measuring properties of psychedelics using the twitches of a sheep's stomach. That's because it contains serotonin receptors, and psychedelics induce muscle contraction. This is a common way to measure binding affinity to 5-HT receptors today, but it was quite exotic back then.
I think Shulgin was most opposed to animal testing because there wasn't as much to learn from them. Now there is, though admittedly I think we could do with a bit more taste-testing today.
Not all psychedelics affect serotonin receptors. For example, muscimol[1], the psychedelic constituent of amanita muscaria mushrooms affects GABA receptors, not serotonin receptors.
So the absence of muscle contractions caused by serotonin activation in sheep stomachs would miss the psychedelic activity of muscimol and other psychedelics which don't affect serotonin receptors.
The term "hallucinogen" is a misnomer, because the effects of psychedelic substances (including muscimol, salvia, ketamine, etc..) don't always involve hallucinations.
For example, if you forgive yourself or your parents under their influence (not an uncommon effect), that's not a hallucination.
If you're able to face some traumatic event in your past while under their effects, and are no longer frightened of this traumatic event, that's not a hallucination.
If a suicidal person no longer wants to kill themselves after taking a psychedelic, or a terminally ill person is finally able to achieve peace with the fact that they're going to die, that's not a hallucination.
That's not to mention the quite common feeling while under the effect of psychedelics that what one experiences is "more real" than what one experiences under normal, waking consciousness, etc.
I don't view the term "psychedelic" as perfect, but it's much better than "hallucinogen".
If you meant "it might be that it helped but not because of neuroplasticity effects" you could be right. But assuming they have good basis to think it does, I don't see being an MAOI as a confounding effect in outcome.
https://youtu.be/ROcQ3AybFks?t=1973
I experience this always when taking LSD - especially during the come up.
> Pioneering structure-activity relationship (SAR) studies conducted by Glennon and co-workers demonstrated that, unlike 5-MeO-DMT and other known hallucinogens, 6-MeO-DMT did not substitute for the hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) at any dose in rodents trained to discriminate DOM from saline.
Personal sad related story is that a friend who had sexual abuse as a teenager and got into drug use and prostitution in her 20s was inspired to try Ibogaine.
She succeeded in raising the money from friends and family and made a trip to a supposedly reputable place in Mexico.
While there and under the influence of Ibogaine she was sexually assaulted by one of the male nurses.
The nurse was fired, but she was told if she didn’t keep quite they would sue her for defamation and refused to even refund her. She’s just a junky after all.
As someone who ran an underground Psychedelic clinic for years, I can’t stress how damaging it could be to assaulted while at the peak of a psychedelic trip trying to heal from a past sexual assault.
She’s still alive and still struggling w various addictions.
She’s also one of the sweetest most loving and wise souls I know, despite her challenges.
This experience was no doubt a motivating factor for me founding decriminalize nature NYC to help get better domestic to plant medicines.
However, from what I understand, there are reputable clinics which have medical staff trained in dealing with emergencies, along with resuscitation and monitoring equipment on hand, who do a very thorough medical exam beforehand to make sure you can handle the drug, and make sure to give you the right amount of pure ibogaine.
That's very different from doing some mystery substance you got from a street dealer that they claim is ibogaine and that you have to risk doing on your own.
The people who go to ibogaine clinics tend to have serious addiction issues that might have already led them close to death, or have ruined their lives and/or the lives of their loved ones, who don't see much of a future for themselves anyway, and who are desperate to try anything to rid themselves of addiction and hopefully get on the path of fixing their lives. So they may not feel they have much to lose by trying it, despite the risks.
It's definitely not a party drug, though.
The few experience reports they had posted suggested that this wasn’t as overtly hallucinogenic as Ibogaine, but it was still potently psychoactive. One member was posting a concerning amount about wanting to acquire and consume much more of it, including on a regular basis.
The whole thing was fascinating to read but left me feeling very uneasy to watch their cavalier attitude. The forum in question appears to have disappeared so I couldn’t go back and look for updates. Regardless, I’d be skeptical of any claims that this is a miracle drug, but I’m interested to follow the research.
We already know about lsd, psylocibin, mdma, ketamine, most of their (side)effects and how to use them without dying or going mad. And they're already pretty damn effective for a lot of issues if used well.
Why take the risks of trying to make analogs that we know nothing about?
to invent another nbome? or a psychedelic equivalent of fentanyl?
I really don't get it. It's playing with fire.
(and no I don't think it can be compared to other meds research, meds don't usually have the potential ability to completely change the fabric of your after one use)
Many people are still afraid of psychedelics... that includes both the people who've never tried them and don't know much about them, and those that tried them and maybe had bad trips.
There's also something to be said for being able to go about your normal day without having a full-blown psychedelic trip, or even any psychedelic effects to distract you from what you have to do that day.
It's also a lot easier to get approval for non-psychedelic drugs which more closely fit the profiles of other non-scheduled prescription drugs. There's a lot less political opposition to them too, and studies in to them are a lot easier to find funding for, etc...
it shouldn't be about what's easy, or about the image of a drug.
You don't try using a more dangerous drug because it have a better public image, that's insanity, or cupidity, but not science
also the trip is a big part of what makes them interesting for mental health it's not just about hormone releases or brain chemistry changes, it's also about life changing experiences and realizations that wouldn't happen if you weren't tripping balls for a few hours
so all this really seems like pointless extremely dangerous and opportunistic research just to get funding, not real science
Well, this is an open question.
A lot of people in the psychedelic community feel the psychedelic effects are necessary to get therapeutic effects, but it just hasn't been proven yet scientifically.
In fact, since non-psychedelic medications exist for treating depression, for example -- they're called antidepressants -- one could argue that there already exists proof that you don't need psychedelic effects to get therapeutic effects. It's just that antidepressants don't seem to be as effective for some people.
So the search for non-psychedelic alternatives continues.
On LSD I would often spend hours writing a ton of stuff and have in-depth thoughts about my life and everything that went wrong with it, also I would laugh a ton, and everything was 10x as pleasurable, it's really like a mini nice vacation/spiritual retreat for me, and of course that didn't happen if I slept on it, so basically no benefits if I was not actually tripping and conscious that I was tripping.
I think it's proven empirically.
"In fact, since non-psychedelic medications exist for treating depression,"
Yes except usually antidepressants may only work after at least 4 weeks, and if you stop them you're usually back to depression(if they even work...), and they're also just trying to make serotonin have stabler levels while psychedelics can make you change your whole point of view on life or help fix past trauma.
"don't seem to be as effective for some people." some people? I'd say most people, even after trying multiple antidepressants you're still not that likely to stop being depressed, there is a huge study reproducibility problem, probably caused by the billions of dollars that SSRIs generates.
So really not comparable to drugs that can potentially create paradigm shifts in your brain after one use.
I don't think we'll fix depression with regular drugs.
It'll either be psychedelics assisted psychotherapy, transcranial magnetic stimulation(80% effectiveness in a recent Stanford study), or brain implants.
And especially not with psychedelic analogs, we're just likely to destroy the lives of hundreds of people during clinical trials, messing with psychedelics analogs sounds like a terribly stupid/insane plan.
just like with weed it's going to take a good while
also we didn't try to push spice/K2(thc analogs) for PTSD, anxiety or insomnia AFAIK, because we're well aware that using analogs is usually really dangerous
and MAPS.org seems to do pretty well, with enough groundbreaking studies I'm sure legalization will come, in time