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Onlinejgotti
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LSD "off-switch" developed by psychedelic pharmaceutical company * 2
    #26634811 - 04/28/20 06:27 PM (30 days, 1 hour ago)

https://newatlas.com/science/lsd-off-switch-mindmed-liechti-psychedelic-science/

LSD "off-switch" developed by psychedelic pharmaceutical company

Rich Haridy
April 26, 2020

Psychedelic pharmaceutical company MindMed has announced the development of a novel compound designed to stop the effects of an LSD experience. The compound is claimed to function as an “off-switch” for LSD, allowing clinicians a way to make psychedelic therapy sessions safer if patients become uncomfortable.

The new announcement comes several weeks after MindMed revealed the signing of an exclusive, multi-year contract with the Liechti Lab, a psychedelic research lab headed by Matthias Liechti at the University of Basel in Switzerland.

"The innovative and original work of the Liechti Laboratory is a treasure trove of novel data on LSD,” says JR Rahn, co-CEO of MindMed. “We are just at the beginning of several significant discoveries that have the potential to further the application of psychedelics as therapeutic medicines.”

MindMed says it has filed a patent application for, “a neutralizer technology intended to shorten and stop the effects of an LSD trip during a therapy session.”

It is unclear exactly what this LSD neutralizing compound actually is. New Atlas contacted Matthias Liechti directly for clarification to ask if there were any pre-existing published research offering insights into how this proposed compound works. Liechti said the research is ongoing, and could not supply specific details.

“I can say that we have a planned program exploring the use of a range of compounds to be used to treat negative acute experiences with hallucinogens to increase their clinical safe use,” Liechti responded to New Atlas in an email. “Classically, such treatments included benzodiazepines or haloperidol. Ketanserin has so far been used to investigate the mechanism of action of psychedelic substances.”

Ketanserin is a compound most recently used by psychedelic researchers in studies to block the subjective and neural effects of LSD. Ketanserin, clinically used as an antihypertensive drug, is thought to disrupt the effects of LSD by blocking serotonin 2A receptors in the brain. Liechti did not offer any indication as to whether this novel new compound works to block the effects of LSD in similar ways, however, he did offer insights into the general purposes and goals of the research.

“The novel concept is to reduce the duration of action and the effect intensity of a psychedelic in high doses, for example, in cases where panic develops or in overdoses and after the hallucinogen has been ingested,” writes Liechti to New Atlas. “The rapidity of the effect will depend on the specifics of the formulation that is being tested and developed.”

MindMed claims the development of an effective LSD-neutralizing compound would greatly amplify the safety profile of psychedelic therapy. As LSD’s effects can often last eight to 12 hours, the clinical potential of the drug would be limited. MindMed believes if there were a compound that could stop the subjective effects of LSD it may allow for broader clinical uses.

Other collaborative psychedelic science projects ongoing between MindMed and the Liechti Lab include a currently underway Phase 2 trial testing high-dose LSD as treatment for anxiety, and a soon to start Phase 2 trial testing LSD microdoses for adult ADHD.

Source: MindMed


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InvisibleBarnaby
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: jgotti]
    #26635196 - 04/28/20 09:35 PM (29 days, 21 hours ago)

So like the heroin/fent drug?


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Offlinepolaritymind
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: Barnaby]
    #26635807 - 04/29/20 03:47 AM (29 days, 15 hours ago)

I recall Dr. Vollenweider saying Ketanserin completely stops trips, so he has specific experience with this, in one of the INSIGHT19 (conference by Mind Foundation) talks or panels. So I expect it to be this or maybe an even higher affinity/efficacy 2A Antagonist.


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"to affirm life is to also affirm death"
-Albert hofmann


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Offlinepolaritymind
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: Barnaby]
    #26635809 - 04/29/20 03:47 AM (29 days, 15 hours ago)

??


--------------------
"to affirm life is to also affirm death"
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OfflinePsilosopherr
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: polaritymind]
    #26636122 - 04/29/20 08:28 AM (29 days, 11 hours ago)

:kaneclap:


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InvisiblebadchadS
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: polaritymind]
    #26637138 - 04/29/20 06:14 PM (29 days, 1 hour ago)

Quote:

polaritymind said:
I recall Dr. Vollenweider saying Ketanserin completely stops trips, so he has specific experience with this, in one of the INSIGHT19 (conference by Mind Foundation) talks or panels. So I expect it to be this or maybe an even higher affinity/efficacy 2A Antagonist.




Probably.  Selective 2A antagonists have been around for some time.  What's interesting is that this compound is purported to stop trips that (presumably) have already started.  Much different than pretreating with an antagonist.


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...the whole experience is (and is as) a profound piece of knowledge.  It is an indellible experience; it is forever known.  I have known myself in a way I doubt I would have ever occurred except as it did.

Smith, P.  Bull. Menninger Clinic (1959) 23:20-27; p. 27.

...most subjects find the experience valuable, some find it frightening, and many say that is it uniquely lovely.

Osmond, H.  Annals, NY Acad Science (1957) 66:418-434; p.436


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Offlinefeevers
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: jgotti]
    #26637307 - 04/29/20 07:36 PM (28 days, 23 hours ago)

They re-invented Trazadone?


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Offlinesonoramo
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: badchad]
    #26637349 - 04/29/20 08:01 PM (28 days, 23 hours ago)

The article doesn't say whether there are medical side effects to the "off-switch." If there aren't any, this could make LSD attractive as a therapy amplifier.

According to multiple sources, the main reason for research concentrating on psilocybin rather than LSD is that a psilocybin journey fits conveniently into a work shift for the therapist, but LSD takes much longer. If this stuff allows the therapist to just turn off the lights at the end of his shift, he can use LSD even more conveniently than psilicybin. "Well, Joe, that's some good work we've done, but I see our time today is up. Please inhale from this little tube and schedule your next visit with my receptionist when you're back to baseline."


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OfflineHolybullshit
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: feevers]
    #26637813 - 04/30/20 12:30 AM (28 days, 19 hours ago)

I can't say I have ever tried to abort an LSD trip, but I could imagine that its high binding affinity could make it a little more difficult than aborting tryps/phens with traditional 5ht2a antagonists...and using high doses of neuroleptics to overcome that probably isn't the most pleasant experience.

I could definitely see the utility in a selective agent with low occurrence of side effects and ki low enough to abort even lsd.

What I don't see is LSD being the drug of choice for guided therapy sessions, at least not for anybody unwilling to pay a ridiculous amount for it, considering its DoA. And these logistical challenges(and public perception) probably means no one will ever pursue it as such, at least not in the US.

LSD would have to offer some serious advantages over psilocybin to be deployed like this...adding another drug to the session would just make it more complicated/expensive/harder to get approved/accepted. And we also don't know how employing antagonists could affect therapeutic efficacy. The article just talks about it as a way to abort when things go wrong, not just to shorten DoA, and I can't really see it being used any other way...especially since if this drug works for LSD I am sure it works for psilocybin as well(perhaps at lower doses).


Edited by Holybullshit (04/30/20 12:39 AM)


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OfflineQuirkmeister92
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: Holybullshit]
    #26637900 - 04/30/20 01:30 AM (28 days, 18 hours ago)

If it can be safely used on large doses and over time then this is a game changer. You could push all kinds of limits. For recreation and exploration you would have a legit safety net, assuming it can be administered properly. Late nights with no sleep before responsibilities, optional. Medically who knows without testing, but clearly it could be used and abused in many ways. Definitely the thing to keep on hand if you're cooking or handling cryatal


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OfflineHolybullshit
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: Quirkmeister92]
    #26638634 - 04/30/20 11:39 AM (28 days, 7 hours ago)

Yeah I generally agree, let me clarify my statement a little...I can't see it being used any way in a common clinical/therapeutic setting.

Sure, for research, exploration, or personal use it could be useful in a plethora of ways. But, assuming guided therapy with psychedelics became approved/common in the first place, I don't see them using LSD while intending to use a 2nd drug to shorten duration for every session over just using a shorter lasting drug in the first place. It just makes things more complicated than clinicians generally like to be when alternatives exist.

Not unless LSD was shown to be significantly superior in some way.

Even if they did choose to pursue guided therapy with LSD, I think they would do so while accepting and accounting for its long duration...and reserve use of this agent for when the session needed to be aborted for complications.

Personally, I'd be all for it...just being a realist.


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Offlinesk8fast
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: feevers]
    #26640849 - 05/01/20 11:16 AM (27 days, 8 hours ago)

Quote:

feevers said:
They re-invented Trazadone?



Trazodone seems to be the best thing for stopping a trip we have right now because of its mechanism of action, but I've only used it for phenethylamines so I don't know how well it would work on lsd from personal experience. Trazodone is nonselective so it probably has more side effects than this new drug. I wonder what this new drug is.


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Offlinesmokescreen
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: feevers]
    #26641242 - 05/01/20 02:35 PM (27 days, 4 hours ago)

I didn't know trazadone was a good trip-ender.  I remember Prozac was, so.... mabe antidepressants in general?  Traz and Prozac work differently, but I can attest to prozac's ability to stop a trip in roughly 30min


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:ganja: "Let's get together and feel alright" :ganja:                  :cubie: :mushroom2::tripping:


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Offlinesmokescreen
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: Quirkmeister92]
    #26641249 - 05/01/20 02:38 PM (27 days, 4 hours ago)

When I was perscribed prozac, lsd, lsa, nor P. Cubensis worked on me at moderate doses.. 2tabs, 300 seeds, 3g, respectively


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:ganja: "Let's get together and feel alright" :ganja:                  :cubie: :mushroom2::tripping:


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Offlinesmokescreen
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: Barnaby]
    #26641270 - 05/01/20 02:49 PM (27 days, 4 hours ago)

They don't really say if it's like narcan.  (Narcan) workers because it has a higher affinity for the opioid receptors than the drugs (morphine/heroin/oxy/fentanyl/etc...)  it actually bumps them out of the receptor therefore reversing the effect. It's the u-opioid receptors responsible for the respiratory depression.  Psychedelics have effects at many receptors, so ending a bad trip is more tricky than a narcan shot.  Since most psychedelics are physically non threatening, its mostly an anxiety attack brought on by the drug.  Medication for anxiety will usually "fix" that bad trip without ending it altogether.


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OfflineHolybullshit
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: smokescreen]
    #26643185 - 05/02/20 10:41 AM (26 days, 8 hours ago)

I didn't realize Prozac could stop a trip if not previously habituated to it, I knew use of it before ingestion of a psychedelic could greatly diminish effects...and I wouldn't be surprised it could stop/weaken MDMA mid-experience, but I wonder how exactly it stops a trip after the fact given it has little affinity for the 5ht2a receptor. Don't get me wrong, I'm not doubting you, I just never really understood how it could so fully block psychedelics(other than MDMA) in the first place and just chalked it up to changes to the 5HT system which occur from chronic use of an SSRI and didn't think acute, one time, use could stop a trip that was already in progress.

Either way I am sure that SSRI's and neuroleptics end/block psychadelics through different means...as neuroleptics are 5ht2a antagonists they would be the "narcan" in the above anology, but SSRI's don't generally share that effect...trazadone though is both an SSRI and 5ht2a antagonist(like many newer anti-depressants labeled as "serotonin modulators").


Edited by Holybullshit (05/04/20 11:23 AM)


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Offlinelostintimenspc
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: Holybullshit]
    #26647393 - 05/04/20 05:20 AM (24 days, 14 hours ago)

LSD is metaphysical. If it leaves an impression on you, it's decided by a higher level of intelligence, or by a deeper level of yourself, and it's permanent.

The brain chemistry could be stopped, but reality is abstract and they'll never be able to change what LSD does to people.

Which is good, but we are an extremely immature culture.

Just sayin'!

Cheers


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OfflineHolybullshit
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: lostintimenspc]
    #26647801 - 05/04/20 11:01 AM (24 days, 8 hours ago)

I'm sure thats true, the therapist guiding the session would almost definitely agree that most of the benefit comes from what occurs during the session and not after it...after all the point of guided psychedelic therapy isn't really any lasting affect the drugs have on your neurochemistry, it's how they affect the exchange between therapist and patient, how they allow you to open up and access thoughts and emotions that would otherwise be cut off to you.

So I guess stopping the trip at the end of the session wouldn't cancel out the benefit of the session itself, but I do still believe it would have to impact the lasting anti-depressant benefit that comes solely from the pharmacological action of psychadelics.


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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: Holybullshit]
    #26649078 - 05/04/20 10:10 PM (23 days, 21 hours ago)

Quote:

Holybullshit said:
I didn't realize Prozac could stop a trip if not previously habituated to it, I knew use of it before ingestion of a psychedelic could greatly diminish effects...and I wouldn't be surprised it could stop/weaken MDMA mid-experience, but I wonder how exactly it stops a trip after the fact given it has little affinity for the 5ht2a receptor. Don't get me wrong, I'm not doubting you, I just never really understood how it could so fully block psychedelics(other than MDMA) in the first place and just chalked it up to changes to the 5HT system which occur from chronic use of an SSRI and didn't think acute, one time, use could stop a trip that was already in progress.

Either way I am sure that SSRI's and neuroleptics end/block psychadelics through different means...as neuroleptics are 5ht2a antagonists they would be the "narcan" in the above anology, but SSRI's don't generally share that effect...trazadone though is both an SSRI and 5ht2a antagonist(like many newer anti-depressants labeled as "serotonin modulators").



Quote:

Holybullshit said:
I didn't realize Prozac could stop a trip if not previously habituated to it, I knew use of it before ingestion of a psychedelic could greatly diminish effects...and I wouldn't be surprised it could stop/weaken MDMA mid-experience, but I wonder how exactly it stops a trip after the fact given it has little affinity for the 5ht2a receptor. Don't get me wrong, I'm not doubting you, I just never really understood how it could so fully block psychedelics(other than MDMA) in the first place and just chalked it up to changes to the 5HT system which occur from chronic use of an SSRI and didn't think acute, one time, use could stop a trip that was already in progress.

Either way I am sure that SSRI's and neuroleptics end/block psychadelics through different means...as neuroleptics are 5ht2a antagonists they would be the "narcan" in the above anology, but SSRI's don't generally share that effect...trazadone though is both an SSRI and 5ht2a antagonist(like many newer anti-depressants labeled as "serotonin modulators").



I had read ssri's block psychedelics and then I saw a girl smoke 100mg and not feel it that was on zolot. Then I knew it was true from experience. Her pupils were huge but she was totally normal and said she didn't feel anything. a friend and I had just done the same batch that I know the source of so I know it was strong.


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OfflineHolybullshit
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Re: LSD "off-switch" developed by psychedelic pharmaceutical company [Re: sk8fast]
    #26649732 - 05/05/20 06:35 AM (23 days, 12 hours ago)

I have no doubt SSRI's can block or at least greatly diminish psychedelics, I don't really understand the exact mechanism but this has been known for some time. What I am surprised to hear is that taking an SSRI(that you have not previously been taking) mid-experience can stop it.


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