Still no study published, no information about blinding effectiveness. It does say that adverse events include hallucinations, which doesn't bode well for effective blinding.
So far there isn't really any strong evidence that hallucinogens including ketamine are more effective than placebo at relieving anxiety or depression (see for example the recent study showing no difference to placebo for ketamine under anaesthetic), even though we all strongly wish they were.
> see for example the recent study showing no difference to placebo for ketamine under anaesthetic
That's not counterevidence to ketamine's efficacy, it's evidence that the efficacy, if prior studies soundly demonstrated it, relies somehow on the user not being anesthetized during the treatment.
I don't think that surprises many advocates of psychodelic or hallucinogenic therapies.
And these are not the first class of treatments where blinding isn't practical. It does confound some forms of analysis when you can't acheive real blinding, but we've devised many alternative forms of analysis that we take as scientifically "good enough" to treat something as medicine.
Ketamine is a dissociative that's used as an anesthetic. General anesthesia is a different beast. The precise mechanism GAs use isn't understood, but they cause slow waves of electrical activity to wash over the brain, constantly resetting neural networks and preventing communication, leading to coma. This includes breathing, which is why the patient needs to be intubated.
Ketamine doesn't stop respiration. It causes profound dissociation and hallucinations, but I don't think it causes coma. It's definitely doing different things than GAs, at least.
So it doesn't seem unreasonable that ketamine wouldn't work if you're in a coma. I'd be surprised if LSD did either. Or anything, for that matter. There's not a lot metabolically happening in a neuron under coma.
Propofol works even on Venus flytrap plants. That's how deep this particular 'off' switch seems to be wired in. (It's blocking the presynaptic sodium and calcium channels.)
I think in other words, stuff like ketamine and LSD don't perform magic all on their own. You have to be consciously experiencing it in order for them to have any effect on you.
>(see for example the recent study showing no difference to placebo for ketamine under anaesthetic)
Ketamine is an anaesthetic and has the same mechanism of action as inhalational anaesthetics. A trial of ketamine+anaesthetic vs placebo+anaesthetic might indicate that ketamine is no better than placebo, but equally it could indicate that general anaesthesia is an effective antidepressant. Your NMDA receptors don't particularly care whether they're being antagonised by ketamine, nitrous oxide or isoflurane.
Don't forget Ketamine. It's truly remarkable for depression and PTSD, arguably better than mdma or psilocybin because it's not as psychadelic but produces profound effects regardless. I took my mom to a ketamine clinic recently and up till then my biggest concern for her health was that she was always stuck in fight or flight, constant 11/10 stress levels, what I would call PTSD or complex PTSD. Anyway, after just 1 visit to ketamine clinic (2 low-medium dose sessions only), she's completely cured of her stress disorder. It's remarkable. This was a long-standing pattern for my mom and ketamine (with the help and guidance of an incredible therapist too) fixed it in a weekend, basically.
How does it actually work? Ketamine is a tranquilizer, right? Is it like a therapy session you do using Ketamine to turn off your stress so you can think clearly? How does it have lasting effects?
Basically how it worked was, during the session, my mom would lie down on a couch. I was there with her, therapist on a couch opposite her. She would have a blanket over her (she discovered on the trip also the amazing benefits of weighted blankets, which she now uses to great effect for helping her sleep too). Then the therapist would administer the ketamine via intramuscular injection, it would be a pre-agreed upon dosage based on feedback between you and the therapist. But then yeah, after the injection occurs, there's just some calm relaxing music playing, my mom has an eye cover on and she just lays back and rests. During the initial few minutes generally quite quiet, but she would also share a couple words here and there what she was feeling or seeing, but not really as a way to share more just that was part of her processing it. Generally the therapist and I would not say anything or interfere at all. While I do think my mom was able to kind of get a sense or feeling of / or better sense of proprotion of some psychological things going on inside of her, I suspect a lot of it is simply biochemical. Yes the talk therapy helped and the therapist was amazing, but it wasn't psychotherapy, it was very gentle and I guess helped my mom develop a better sense of proportion. A couple takeaways she had was how certain things weren't as important as others, for example.
I can't speak for GP, but when it's combined with talk therapy, the ketamine allows the body to lower its defenses so that talk therapy can more successfully be administered, and the combination of the two is what leads to long lasting effects, long after the ketamine has worn off. Ketamine let's the patient open up so talk therapy can get at the underlying issue and resolve that, in ways that talk therapy alone can't solve because the patient's flight /fight response/anxiety won't let them let their guard down to really talk about it.
Check out the other comments in this thread, i wrote a summary and someone else wrote a personal account. If you want to read more you could search on g scholar for a recent review paper on ketamine infusion therapy.
Ketamine has three distinct effects which are a function of dose. At medium doses it’s a recreational psychedelic and at large doses it’s an anaesthetic. Its highest efficacy against depression is seen in the micro-dose range, before any perceptual (psychedelic) effects start.
At that dose, it causes a rapid release of neurotrophic factors, which restores the function of neuronal spines. Those spines are typically damaged by chronic exposure to stress. It may not necessarily be supported by a verbal insight into your emotional difficulties, although the brief period of neuroplasticity can lead to that.
There is usually complete relief from depressive symptoms within 24-48h, but it only lasts for as long as chronic exposure to stress doesn’t start again. In some patients this means that symptoms can return within a couple of weeks, unfortunately.
In my experience, it fits the definition. On higher doses of MDMA I experience mild to moderate closed eye hallucinations when listening to music (morphing shapes). Though I have never had open-eyed hallucinations to any degree.
And I would absolutely define it as "consciousness expanding" in the sense that having conversations with friends while under its influence opens up aspects of my emotional mind that are very difficult for me to uncover while sober.
Usually these salts remain chemically stable for longer periods of time. In the case of alkaloids, they become protonated (here LSD-with-a-proton, a positively charged particle; the tartrate being the negative counterion) and as such are thus less susceptible to oxidation. Can't steal negative charge from something that doesn't have it.
And with LSD freebase that's not an unnecessary luxury, as it isn't the most stable against decomposition. To answer the question... probably this is the most stable formulation to get it into a pharmacy? I guess like you say, not blatantly calling it LSD helps image building too.
With vyvanse, that's actually something else: not a salt but an amino acid covalently bound to amphetamine. This gives a much stronger bond than between tartrate and lsd ions in the salt, one that can be hydrolysed slowly in the gut to produce the active drug. LSD tartrate doesn't have a similar slow release property.
The API in Vyvanase isn't a salt of straight amphetamine though. It has a covalent bond to a group that your body/metabolism needs to (I guess enzymatically) break down to release the amphetamine. More of a prodrug.
No, Sandoz produced LSD tartarate back in the '50s. It's the common salt form of LSD. The freebase is lipophilic, and is typically dissolved in ethanol, while the salt form is water-soluble, and can be soaked into blotter paper or sublingual tablets.
Not sure why this is downvoted, since this has been a working legal loophole for decades. For example, 1cP-LSD is completely unscheduled in the US right now, despite breaking down into pure LSD once consumed (at only slightly reduced potency). It's already banned in several other countries though.
Though, I am sure prescription drugs will always be legal with a prescription, assuming the prescription itself is legal. Even if this were counted as the Schedule I drug LSD that can't be prescribed, it'll probably get moved to Schedule II or III before any actual prescriptions are given out. So anyone who ever gets such a prescription in-hand will always be safe.
I'm generally in favor of letting (healthy) adults decide what they consume (in particular hallucinogens), but I'm not sure it is a good idea to just hand them out to people with real psychiatric disorders without any therapeutic guidance.
I wouldn't even hand it to normal, "stable" people without some guidance. Not everyone handles losing their marbles with grace and aplomb. It's not in the average person's skillset to be able to say, "it's just the drugs" and keep their cool.
One of the other reasons not to give it out freely is that it varies wildly in effect depending on who exactly takes it. I certainly don't lose my marbles when I'm on it, but plenty of people have lost their sanity from it, sometimes for months, years or even life. Not to mention HPPD can sometimes appear, ranging from just "weird" all the way to distressing or madness-inducing.
This is great news. I believe in the possible utility of LSD without requiring professional/clinical supervision. I've used it at home quite a bit in the past and it's been extremely useful for processing emotions and trauma, as well as helping calm me down in general.
I'm neurodivergent, so it most definitely doesn't work this way for everyone, but it's extremely helpful for me and I hope that one day the law recognizes that.
I want to hope that one day I'll be able to buy this stuff and take it home, but I know that there are many more years and trials necessary to prove that it's safe. It's not safe for everybody and full legality will probably have to wait until they've figured out a really solid set of contraindicators...
"The most common adverse events (at least 10% incidence in the high dose groups) on dosing day included illusion, hallucinations, euphoric mood, anxiety (LOL), abnormal thinking, headache, paresthesia, dizziness, tremor, nausea, vomiting, feeling abnormal, mydriasis and hyperhidrosis"
"Oh, you have Generalized Anxiety Disorder? Just take a casual walk down Haight street and try to purchase one specific drug from the random 'vendors' there."
I would love for it to be better, but isn't LSD a chief victim of the war on drugs (other than fentanyl)? There's no way that there are going to be clean, quality-controlled sources of it any time soon. After all, it's a dangerous hallucinogen, and it's equally dangerous for everyone. Just like how alcohol and nicotine are equally safe for everyone.
I say this as someone who's had high doses of LSD25 before and failed to hallucinate much if at all. I don't doubt that people can, but not everyone does.
(I support decriminalization, but I want safe regulated sources to be freely available. People shouldn't have to resort to the dark web or to random dealers on the street. People should have sources that are guaranteed safe, just like other supplements.)
The post isn't satire but this statement of mine was indeed incredibly sarcastic:
> After all, it's a dangerous hallucinogen, and it's equally dangerous for everyone. Just like how alcohol and nicotine are equally safe for everyone.
I was indeed poking fun at the fact that LSD is considered unsafe while alcohol and nicotine are allowed to run rampant. I think LSD should not be illegal, and you should be able to source it safely, from regulated sources. I don't want it limited to clinical trials or prescribed treatments - I want to be able to pick it up at a store (or drug store, whatever) and trust that it's not NBOMe or whatever, without having to pay for and handle expensive and dangerous chemical reagents. Then I want to use it at home, in a safe environment, and spend time with my friends and pets.
However, LSD is a bit unpredictable. It's not necessarily safer than alcohol or nicotine for everybody. I know that for myself only, and in a strict physical sense (i.e. not really possible to die by LSD25 overdose), but the mental effects can be quite profound for certain people or for certain neurotypes. Whether these effects are positive or negative varies by individual.
Of course, a similar thing could be said for alcohol and nicotine. Alcohol can often result in self-destructive behavior and nicotine typically causes some pretty bad addiction and dependence. Which is why I think it's unfair that LSD is treated the way that it is.
With psychedelics in particular, I honestly think a lot more can go wrong by trying to shoehorn them into the medical system as it exists today. You’re talking about something that’s close to a spiritual experience and you think you’re going to do it justice by forcing it through the machine of HMO’s and corporate medical practices?
https://www.clinicaltrialsarena.com/news/mindmed-trial-anxie...
Still no study published, no information about blinding effectiveness. It does say that adverse events include hallucinations, which doesn't bode well for effective blinding.
So far there isn't really any strong evidence that hallucinogens including ketamine are more effective than placebo at relieving anxiety or depression (see for example the recent study showing no difference to placebo for ketamine under anaesthetic), even though we all strongly wish they were.