FDA advisory panel votes against approving MDMA-assisted therapy for PTSD

[tr]

Why does this only seemingly matter in psychedelic studies? I highly doubt people can't tell the difference between Zyprexa and docusate or whatever placebo we use in those studies.

Irving Kirsch made a huge deal a decade or so ago with a claim that the effect of SSRIs was all placebo, that the apparent benefit over placebo was all related to functional unblinding, and would be eliminated if active placebos (i.e. non-SSRI drugs that had comparable subjective side effects) were used. Spoiler, that turned out not to be true.

For MDMA it's an even weirder claim. The subjective effect *is the point*. If you could recreate it with a different agent, absolutely, it would likely work just as well. What would it mean to call this a placebo effect?

I agree that looking at only MDMA-naive patients certainly is helpful in addressing this concern, no doubt. But at the end of the day if participants can clearly tell they were in the treatment condition, there is a huge risk that they are going to answer questions in a way consistent with bigger symptom reduction than otherwise. Difficult as it is to do I think more studies with active placebos are desperately needed. I do understand the concerns that this may prove impossible to do perfectly but getting closer would help a lot.

The placebo arm was a below- threshold dose of the same drug. What would you suggest to use as a more appropriate active placebo?

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[splik]

Irving Kirsch made a huge deal a decade or so ago with a claim that the effect of SSRIs was all placebo, that the apparent benefit over placebo was all related to functional unblinding, and would be eliminated if active placebos (i.e. non-SSRI drugs that had comparable subjective side effects) were used. Spoiler, that turned out not to be true.

It was back in 2008, this got a lot of media attention. Kirsch was a hypnosis researcher who was very much interested in placebo effects. More so than he was interested in antidepressants. What he was actually looking at was how the baseline severity of depressive illness impacted antidepressant/placebo responses. Psychiatrists had often claimed that the most severely depressed patients benefited the most from antidepressants. Kirsch argued that it was more that severely depressed patients benefited less from the placebo effect. One might have to do intellectual somersaults to understand this reasoning, but it was not a new idea and something that had been suggested even in the 1960s.

More to the point, his meta-analysis identified that 80% of the response could be attributed to placebo, and the additional response fell below the 3 point difference in Hamilton scores required for clinical significance.

Later on, he had said it might be that an enhanced placebo response from unblinding might explain the rest, but I don't believe he excluded that there might be some drug effect.

Around the time of the paper, I invited Kirsch to debate his findings and found him very persuasive, EXCEPT that for some odd reason he went off on a tangent about how we should be using St John's Wort etc. This made no sense to me since SJW has a similar mechanism to available antidepressants and the supporting data is even worse. This indicated he did have some bias against antidepressants.

 

[tr]

More to the point, his meta-analysis identified that 80% of the response could be attributed to placebo, and the additional response fell below the 3 point difference in Hamilton scores required for clinical significance.

Later on, he had said it might be that an enhanced placebo response from unblinding might explain the rest, but I don't believe he excluded that there might be some drug effect.

In his popularized book The Emperor's New Drugs, from what I recall he did claim that the pharmacological effect of antidepressants was negligible.
Maybe he worded things more carefully in his scientific papers.

Around the time of the paper, I invited Kirsch to debate his findings and found him very persuasive, EXCEPT that for some odd reason he went off on a tangent about how we should be using St John's Wort etc. This made no sense to me since SJW has a similar mechanism to available antidepressants and the supporting data is even worse. This indicated he did have some bias against antidepressants.

Not to mention the multiple drug-drug interactions increasing risk for hepatotoxicity 🙄
Thanks, I'll stick with Prozac. Unregulated herbal preparations are scary.

 

[mistafab]

Unfortunately, this panel should largely be ignored.

-The placebo distinction is a standard held far above higher than they needed for esketamine approval.
-The effect sizes for remission rates are much higher for mod-severe PTSD than esketamine was for TRD.
-Most patients had sustained effect (>6 mo).
-The 40% with previous use/experience was not different between groups.

Personally, my biggest concern is that two therapists got in the bed of a patient during a session. MDMA is such a pro-sexual/intimacy drug that I'm concerned no matter the vehicle we will have providers having sex with patients while drugged. To me that is the largest and most concerning feature of this treatment.

 

[TexasPhysician]

Unfortunately, this panel should largely be ignored.

-The placebo distinction is a standard held far above higher than they needed for esketamine approval.
-The effect sizes for remission rates are much higher for mod-severe PTSD than esketamine was for TRD.
-Most patients had sustained effect (>6 mo).
-The 40% with previous use/experience was not different between groups.

Personally, my biggest concern is that two therapists got in the bed of a patient during a session. MDMA is such a pro-sexual/intimacy drug that I'm concerned no matter the vehicle we will have providers having sex with patients while drugged. To me that is the largest and most concerning feature of this treatment.

That is one of the top reasons that counselors lose their license in my state without MDMA.

 

[mistafab]

That is one of the top reasons that counselors lose their license in my state without MDMA.

Absolutely disgusting. I'm concerned that if they are willing to get into bed with a patient in an RCT, that providers everywhere will be sexually assaulting their patients in the real world. This to me is an absolute must-address for this drug.

 

[R. Matey]

That is one of the top reasons that counselors lose their license in my state without MDMA.

Your state and every other state. I had concerns that MDMA would fan these flames considering it's already such a problem with psychotherapy providers. I mean, go figure that drugs that produce feelings of intimacy coupled with an already intimate experience could lead to sexual misconduct.

 

[psych_0]

an absolute must-address for this drug.

Yea, but like...how? Lykos already suggested that every session should be video-monitored. Are you asking for an independent review panel to randomly screen these videos from clinics across the country to keep people honest? Surely not.

Sexual misconduct already happens without MDMA. How is that addressed? Board reviews and violators being suspended or having their licenses revoked, no? Why would MDMA-AT need to be handled differently? If a violation happens, you report it, the video gets reviewed and the violating party faces consequences. Seems pretty simple.

Maybe part of the REMS is a video record-keeping requirement. If you are asked for a copy of the video because someone has accused you of misconduct and you cannot produce it, you assume guilt and face consequences. That's the harshest way I could see this being "addressed."

 

[R. Matey]

Lykos already suggested that every session should be video-monitored.

I'm game as long as its billable. I'll have four going at once while I do the Wordle.

 

[tr]

Maybe part of the REMS is a video record-keeping requirement. If you are asked for a copy of the video because someone has accused you of misconduct and you cannot produce it, you assume guilt and face consequences. That's the harshest way I could see this being "addressed."

This is a pretty good idea actually. The two therapist requirement was a good idea as well. I guess it needed to be stipulated that the two therapists should not themselves be in a sexual relationship with each other 🙄

Without having seen the video, it just boggles my mind how colossally dumb these therapists were to commit such an egregious boundary violation when they knew they were being recorded. It kind of makes me wonder if they were sampling the goods themselves actually.

But if it could happen in a situation with clinical trial levels of monitoring, it absolutely will be happening out in the wild.

 

[Liquid8]

Was chatting with a rep last week who was involved in the psilocybin and MDMA space – while we have allowed this in Australia, apparently there are only 9 psychiatrists around the country eligible to do it and none have started anyone on treatment in the last 12 months.

It seems that the treatment protocol will require two therapists for 8 hours a day in dedicated treatment facility which makes it extremely expensive and impractical. It probably didn’t help that one of the trainers from the UK got suspended for having a relationship with a patient either…

Australian charity stands down psychedelic doctor after he admits to relationship with former patient

Interestingly it seems that more interest has been taken up by research bodies as opposed to clinicians, and they have had to do a lot of screening of potential participants as unsurprisingly a lot of interest Is coming from people looking for a drug fix.

Prior to the decision to allow it, there had been some advocacy groups claiming that there was a huge underground movement of psychiatrists, psychologists and counsellors doing mushroom or MDMA assisted therapy. It does not seem that these supposed therapists have surfaced since the change, which makes me think that it was probably all recreational use to begin with.

 

[comp1]

I definitely don't think esketamine should be some kind of gold standard for drug approvals. It should more be used as a cautionary tale. Drugs with abuse potential SHOULD be held to a higher standard than esketamine was. In terms of sex with patients, I don't think it'll be any more of a problem than it already is. The reason is that patients won't be getting therapy of any sort with the prescription regardless of how it was done in the RCTs. It'll be hard for anyone to insert sex (or beds?) into the assembly line administration that will be the sole way it will be prescribed in reality.

 

[FlowRate]

I agree with criticisms that ideally the FDA wouldn't be ruling on aspects other than drug safety/effectiveness, rather than a particular set of therapeutic approaches. One would think that making the requirement two unrelated therapists and a chaperone (who's not involved therapeutically/is somehow independent) would go a long way, although obviously adding further to the expense of the treatment.

 

[TexasPhysician]

I agree with criticisms that ideally the FDA wouldn't be ruling on aspects other than drug safety/effectiveness, rather than a particular set of therapeutic approaches. One would think that making the requirement two unrelated therapists and a chaperone (who's not involved therapeutically/is somehow independent) would go a long way, although obviously adding further to the expense of the treatment.

Likely so expensive that this would be cost prohibitive.

Even without being recorded, I think it would be fine to have a single counselor in the room with something like a baby monitor connected to support staff area. Support staff can alert anyone else in the clinic if anything concerning begins to happen.

 

[psych_0]

unsurprisingly a lot of interest Is coming from people looking for a drug fix

I mean come on....you don't honestly believe this, do you? You think there is this large swath of the population that is just DYING to do MDMA sitting next to two therapists in a clinic office while pretending to have severe PTSD? Because there is just NO OTHER WAY they could get MDMA and abuse it in a more fun setting? They're SO desperate to abuse MDMA that they're jumping through these hoops?

Come on now. The hysteria is getting out of hand.

 

[littlefred]

I mean come on....you don't honestly believe this, do you? You think there is this large swath of the population that is just DYING to do MDMA sitting next to two therapists in a clinic office while pretending to have severe PTSD? Because there is just NO OTHER WAY they could get MDMA and abuse it in a more fun setting? They're SO desperate to abuse MDMA that they're jumping through these hoops?

Come on now. The hysteria is getting out of hand.

Not to rain on your parade... but getting it illicitly can land you in jail, meanwhile getting it licitly can land the therapists in jail.

 

[PsyDr]

I can’t imagine the absolute monotony of 8hours of listening to someone who is tripping balls. All while preauths and patient calls are piling up.

 

[psych_0]

Not to rain on your parade... but getting it illicitly can land you in jail, meanwhile getting it licitly can land the therapists in jail.

What parade does this rain on exactly? The portion of the population hoping to abuse MDMA at a rave with their friends and the portion of the population with treatment-resistant PTSD willing to sit in a clinic for 8 hours with two therapists are not one and the same. Why would you go through all of the hoops:

1. Schedule a visit with a psychiatrist
2. Make up a grand lie about your trauma
3. Make up a lie about what meds and therapies you have failed
4. Go through all of the prep sessions, continuing your lie about your severe make-believe trauma and PTSD symptoms
5. Pay all this extra money (because you know insurance is not covering this anywhere close 100%) to sit in the clinic for 8 hours with two therapists

All this money and all these lies....just to "do MDMA legally without risk of jail time?" You cannot believe this to be true...I feel like you're trolling.

 

[ObsequiousAplomb]

What parade does this rain on exactly? The portion of the population hoping to abuse MDMA at a rave with their friends and the portion of the population with treatment-resistant PTSD willing to sit in a clinic for 8 hours with two therapists are not one and the same. Why would you go through all of the hoops:

1. Schedule a visit with a psychiatrist
2. Make up a grand lie about your trauma
3. Make up a lie about what meds and therapies you have failed
4. Go through all of the prep sessions, continuing your lie about your severe make-believe trauma and PTSD symptoms
5. Pay all this extra money (because you know insurance is not covering this anywhere close 100%) to sit in the clinic for 8 hours with two therapists

All this money and all these lies....just to "do MDMA legally without risk of jail time?" You cannot believe this to be true...I feel like you're trolling.

Yeah. This treatment would cost at least $15k out-of-pocket. You can buy way more MDMA and tickets to multiple music festivals / raves with that much money.

 

[Liquid8]

I mean come on....you don't honestly believe this, do you? You think there is this large swath of the population that is just DYING to do MDMA sitting next to two therapists in a clinic office while pretending to have severe PTSD? Because there is just NO OTHER WAY they could get MDMA and abuse it in a more fun setting? They're SO desperate to abuse MDMA that they're jumping through these hoops?

Come on now. The hysteria is getting out of hand.

Wouldn’t say it’s hysteria, this is just the feedback that those running clinical trials research are passing on. Obviously if people really want to use MDMA recreationally they can certainly get it for a lot less but, it seems a lot of early interest was from people on drug possession or trafficking charges or driving under the influence of drugs so secondary gain is playing some role.

Here we also have a socialised health system, so a baseline level of entitlement present with people being able to access free or subsided treatment. Often used to see this behaviour in inpatient units with polysubstance dependence patients picking out the new doctors or those not on the wards doing the weekend cover to try and convince them to write them up for benzos or stimulants. Privately it’s not so much of an issue, but years ago I can remember seeing one drug dependent patient who’d seen over a dozen psychiatrists (always under a subsidized assessment scheme) demanding MDMA. He claimed that no therapy or antidepressants had ever worked, but he’d also not tried any. I expect this is the sort of patient that those running the psilocybin/MDMA trials will have to filter through initially.

 

[nexus73]

I don't remember if it was Rick Doblin or someone else in the space, but heard them say on a podcast one of the biggest barriers they perceived was the need for a doctor to prescribe MDMA to allow the therapy to happen. How this was such a big and unnecessary hurdle, and they were pushing an idea that you wouldn't need a prescription, that somehow MDMA would be accessible by going through a therapist certified to provide the approved psychotherapy. Like a pharmacist would just dispense it or something.

I wasn't sure how that would ever be possible. If/when MDMA is approved, there's no way it's not schedule II or III. There's no way the DEA is going to allow it to be accessible without a prescription. Anyways, this just seemed to reflect a certain amount of pie in the sky optimism that seems to permeate the discussions on this topic from certain groups.

 

[littlefred]

What parade does this rain on exactly? The portion of the population hoping to abuse MDMA at a rave with their friends and the portion of the population with treatment-resistant PTSD willing to sit in a clinic for 8 hours with two therapists are not one and the same. Why would you go through all of the hoops:

1. Schedule a visit with a psychiatrist
2. Make up a grand lie about your trauma
3. Make up a lie about what meds and therapies you have failed
4. Go through all of the prep sessions, continuing your lie about your severe make-believe trauma and PTSD symptoms
5. Pay all this extra money (because you know insurance is not covering this anywhere close 100%) to sit in the clinic for 8 hours with two therapists

All this money and all these lies....just to "do MDMA legally without risk of jail time?" You cannot believe this to be true...I feel like you're trolling.

I mean, our opinions differ greatly on the fact that one is legal and the other is illegal. Being incarcerated is a big deal, I'm not arguing against your points.

Some patients go through a lot of loops to get controlled meds.

 

[Stagg737]

Wouldn’t say it’s hysteria, this is just the feedback that those running clinical trials research are passing on. Obviously if people really want to use MDMA recreationally they can certainly get it for a lot less but, it seems a lot of early interest was from people on drug possession or trafficking charges or driving under the influence of drugs so secondary gain is playing some role.

Here we also have a socialised health system, so a baseline level of entitlement present with people being able to access free or subsided treatment. Often used to see this behaviour in inpatient units with polysubstance dependence patients picking out the new doctors or those not on the wards doing the weekend cover to try and convince them to write them up for benzos or stimulants. Privately it’s not so much of an issue, but years ago I can remember seeing one drug dependent patient who’d seen over a dozen psychiatrists (always under a subsidized assessment scheme) demanding MDMA. He claimed that no therapy or antidepressants had ever worked, but he’d also not tried any. I expect this is the sort of patient that those running the psilocybin/MDMA trials will have to filter through initially.

"Early interest" and actually jumping through the hoops are very different things. Also, not sure what the standards are in Australia, but in the US we do not prescribe MDMA at all outside of a few places that do psychedelic assisted therapy research. Even with a non-socialized health system we see the bolded on the inpatient units constantly, paying isn't a barrier to demanding drugs. The hoops Psycho is likely talking about are the repeated appointments, scheduling burdens (ie waiting months just to get in), phone calls, etc just to get a micro dose while being monitored in a room by staff. We do psychedelic research where I'm at and I can tell you the people who are really trying to abuse hallucinogens just get it on the streets and/or come to the ER making up stories to get ketamine. No one is playing a long game of months to get a micro-dose of MDMA in our clinics...

I mean, our opinions differ greatly on the fact that one is legal and the other is illegal. Being incarcerated is a big deal, I'm not arguing against your points.

Some patients go through a lot of loops to get controlled meds.

I know plenty of people who would disagree with you on the bolded. I see them daily in our ER. Do you think those people really care about spending a night or two in jail? Because unless they're dealing that's all that's likely to happen for MDMA possession. See my comment above, but they don't both to spend months trying to get monitored doses of MDMA when they can get ketamine in an ER or an ambulance (or on the street) same day.

 

[clausewitz2]

The placebo arm was a below- threshold dose of the same drug. What would you suggest to use as a more appropriate active placebo?

Admittedly I don't have a solution ready to go and definitely need to think about this. The thought occurs to me to do the same kind of surgical anesthesia-masking paradigm that was done recently with ketamine but I realize as I'm saying that this that if the argument is the subjective effect is needed, that's not going to be quite what we're after.

Perhaps the real focus needs to be on "what are the necessary aspects of the subjective experience for an agent to have this effect?" If we had a better characterization of this I would feel much more comfortable waving away traditional ideas about blinding because it's less like "the treatment works because MDMA is magic and shut up".

 

[aim-agm]

No one is playing a long game of months to get a micro-dose of MDMA in our clinics...

I think there's going to be a big difference between initial population seeking treatment and later population once it is approved or widely known. Aren't there extensive guides online on how to get prescribed ADHD meds? What's to say that 3,4-Methylenedioxymethamphetamine will play out differently than regular amphetamine? Clinical doses of amphetamines are micro-doses compared to recreational doses, but our field is plagued by people seeking that medication.

To be clear, I expect that MDMA might have clinical benefits, potentially even unique clinical benefits. For instance, DRIs (e.g. methylphenidate) and dopamine-releasers (i.e. amphetamine) have similar effects but some respond much better to one than the other and there are niche differences. I wouldn't be surprised if something similar plays out with SRIs and serotonin-releasers. Although in general releasers seem more prone to problems than reuptake inhibitors (e.g. see phenteramine vs. NRIs).

We've already been down this road in psychiatry. Mu-opioid agonists are very effective psychiatric medications, but there are major issues with addiction potential and misuse. They work best when no one knows that that's what they are (see tianeptine), but they have fallen out of the usual psychiatric repertoire because of clinical and practical problems with them.

 

[Stagg737]

I think there's going to be a big difference between initial population seeking treatment and later population once it is approved or widely known. Aren't there extensive guides online on how to get prescribed ADHD meds? What's to say that 3,4-Methylenedioxymethamphetamine will play out differently than regular amphetamine? Clinical doses of amphetamines are micro-doses compared to recreational doses, but our field is plagued by people seeking that medication.

To be clear, I expect that MDMA might have clinical benefits, potentially even unique clinical benefits. For instance, DRIs (e.g. methylphenidate) and dopamine-releasers (i.e. amphetamine) have similar effects but some respond much better to one than the other and there are niche differences. I wouldn't be surprised if something similar plays out with SRIs and serotonin-releasers. Although in general releasers seem more prone to problems than reuptake inhibitors (e.g. see phenteramine vs. NRIs).

We've already been down this road in psychiatry. Mu-opioid agonists are very effective psychiatric medications, but there are major issues with addiction potential and misuse. They work best when no one knows that that's what they are (see tianeptine), but they have fallen out of the usual psychiatric repertoire because of clinical and practical problems with them.

You're talking about the future. I'm talking about now. Maybe in 10 years if MDMA becomes a widely available treatment like stimulants are this could be relevant. But we all know how easy it is for patients to find a candyman for stimulants and that's just not a valid argument for MDMA right now.

 

[tr]

Admittedly I don't have a solution ready to go and definitely need to think about this. The thought occurs to me to do the same kind of surgical anesthesia-masking paradigm that was done recently with ketamine but I realize as I'm saying that this that if the argument is the subjective effect is needed, that's not going to be quite what we're after.

Perhaps the real focus needs to be on "what are the necessary aspects of the subjective experience for an agent to have this effect?" If we had a better characterization of this I would feel much more comfortable waving away traditional ideas about blinding because it's less like "the treatment works because MDMA is magic and shut up".

That's fair. Maybe a comparison against regular old Adderall as active placebo? That should produce some of the activating side effects. Experienced MDMA users would still be able to tell the difference but MDMA-naive might not.

I still think this is a sideshow compared to the therapist sexual exploitation issue though.

 

[clozareal]

It's unfortunate that the boundary violation/sexual exploitation happened during the clinical trial. It may be the factor that brings enough concern to tank future approvals. If it happened after approval, then it's a known risk of doing any sort of therapy, but of course even more with a drug that enhances intimacy and social bonding. That's part of the cure. Any therapist who has helped patients through sexual assault PTSD likely knows that there is an enactment risk.

I agree that trying to design/use a placebo to have a similar experience would probably also create the same benefit because the subjective experience is the healing part in and of itself. I don't think we know what the mechanism of action of MDMA for helping PTSD out is to isolate that and have only the other effects intact for a good placebo.

 

[ClosetCentrist]

Uh, what? Whether you look at it from a research/clinical or recreational aspect it is absolutely a dissociative agent.

I have had... a lot of conversations about MDMA and have heard exactly 0 people refer to it - either in a research or a recreational context - as a dissociative until this thread. I've heard it called a hallucinogen, empathogen, entactogen, a psychedelic, and even a stimulant, but never a dissociative.

What exactly do you mean when you say "dissociative?" When I hear "dissociative" I think ketamine, salvia, DXM, PCP, and other drugs that tend to have NDMA antagonism as part of their MoA.

 

[Stagg737]

I have had... a lot of conversations about MDMA and have heard exactly 0 people refer to it - either in a research or a recreational context - as a dissociative until this thread. I've heard it called a hallucinogen, empathogen, entactogen, a psychedelic, and even a stimulant, but never a dissociative.

What exactly do you mean when you say "dissociative?" When I hear "dissociative" I think ketamine, salvia, DXM, PCP, and other drugs that tend to have NDMA antagonism as part of their MoA.

A substance which can induce a dissociative state (dissociation, derealization, depersonalization, "out of body experience", etc). Talk to people who go to raves. MDMA is typically used recreationally for the euphoric effect but I know plenty of people who have had dissociative experiences with ecstasy. Mostly from college when I went to music festivals...

 

[tr]

A substance which can induce a dissociative state (dissociation, derealization, depersonalization, "out of body experience", etc). Talk to people who go to raves. MDMA is typically used recreationally for the euphoric effect but I know plenty of people who have had dissociative experiences with ecstasy. Mostly from college when I went to music festivals...

But was the dissociation from MDMA or was it from adulterants/contaminants like dxm?

 

[psych_0]

I have had... a lot of conversations about MDMA and have heard exactly 0 people refer to it - either in a research or a recreational context - as a dissociative until this thread. I've heard it called a hallucinogen, empathogen, entactogen, a psychedelic, and even a stimulant, but never a dissociative.

What exactly do you mean when you say "dissociative?" When I hear "dissociative" I think ketamine, salvia, DXM, PCP, and other drugs that tend to have NDMA antagonism as part of their MoA.

I have to agree here. No one describes MDMA as a dissociative. Ketamine, PCP, salvia, DMT, yes 100%. But MDMA? No.

 

[annoyedpsychiatrist]

Right as if Adderall 20mg TID IR only pill mill weren't a problem enough, we have mail order Special K to keep you fully dissociated at all times. Thanks VC!

i keep seeing these ads on FB. its unreal. And the comments are people eating it up. Like how is this allowed..insanity.

 

[Stagg737]

But was the dissociation from MDMA or was it from adulterants/contaminants like dxm?

If my friends were to be believed, supposedly pure MDMA. These were people who were very familiar with the festival/EDM night club scene and club drugs. Most of them used multiple substances as mentioned and one or two of them specifically used MDMA for the euphoria + dissociation and actively tried to avoid stuff like ketamine or PCP because of their experiences with the K-hole and other effects. There is also ample research on dissociative effects of MDMA. NIDA even lists MDMA under "other psychedelic and dissociative drugs" in the same category as salvia, so while not considered a classic dissociative agent it is considered one which can create dissociative effects.

I have to agree here. No one describes MDMA as a dissociative. Ketamine, PCP, salvia, DMT, yes 100%. But MDMA? No.

NIDA and several other agencies do. Salvia and MDMA are in the same category. DMT and LSD are considered more pure psychedelics. Again, just because people typically associate MDMA with the euphoria and stimulant effects doesn't mean it's not also a dissociative. Not saying it's the same as ketamine, but maybe I've just had more exposure? *shrugs*

MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor - PMC

Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT2A receptor is the mechanism underlying these ...

www.ncbi.nlm.nih.gov

MDMA, cannabis, and cocaine produce acute dissociative symptoms - PubMed

Some drugs of abuse may produce dissociative symptoms, but this aspect has been understudied. We explored the dissociative potential of three recreational drugs (3,4-methylenedioxymethamphetamine (MDMA), cannabis, and cocaine) during intoxication and compared their effects to literature reports...

pubmed.ncbi.nlm.nih.gov

Psychedelic and Dissociative Drugs | National Institute on Drug Abuse

Learn more about NIDA’s research on the health effects and therapeutic potential of psychedelic and dissociative drugs.

nida.nih.gov

 

[ClosetCentrist]

If my friends were to be believed, supposedly pure MDMA. These were people who were very familiar with the festival/EDM night club scene and club drugs. Most of them used multiple substances as mentioned and one or two of them specifically used MDMA for the euphoria + dissociation and actively tried to avoid stuff like ketamine or PCP because of their experiences with the K-hole and other effects. There is also ample research on dissociative effects of MDMA. NIDA even lists MDMA under "other psychedelic and dissociative drugs" in the same category as salvia, so while not considered a classic dissociative agent it is considered one which can create dissociative effects.


NIDA and several other agencies do. Salvia and MDMA are in the same category. DMT and LSD are considered more pure psychedelics. Again, just because people typically associate MDMA with the euphoria and stimulant effects doesn't mean it's not also a dissociative. Not saying it's the same as ketamine, but maybe I've just had more exposure? *shrugs*

MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor - PMC

Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT2A receptor is the mechanism underlying these ...

www.ncbi.nlm.nih.gov

MDMA, cannabis, and cocaine produce acute dissociative symptoms - PubMed

Some drugs of abuse may produce dissociative symptoms, but this aspect has been understudied. We explored the dissociative potential of three recreational drugs (3,4-methylenedioxymethamphetamine (MDMA), cannabis, and cocaine) during intoxication and compared their effects to literature reports...

pubmed.ncbi.nlm.nih.gov

Psychedelic and Dissociative Drugs | National Institute on Drug Abuse

Learn more about NIDA’s research on the health effects and therapeutic potential of psychedelic and dissociative drugs.

nida.nih.gov

I've had plenty of exposure in multiple senses of the word, so I don't think that's it.

I see the point you're making. I don't disagree that MDMA has dissociative effects, but to call MDMA a dissociative feels like calling LSD a dissociative. They both produce dissociative effects, but it seems like it should be a secondary effect for the purposes of categorization.

 

[Merovinge]

That's fair. Maybe a comparison against regular old Adderall as active placebo? That should produce some of the activating side effects. Experienced MDMA users would still be able to tell the difference but MDMA-naive might not.

I still think this is a sideshow compared to the therapist sexual exploitation issue though.

I am not sure from a harm/research standards, but I would want more than just Adderall, probably an Adderall + Benzo combination to try and blind versus MDMA. Very different effect overall that experienced users would still be able to tell, but I think you would get closer with a combo of meds. Adderall plus a low dosage of Ketamine might an option as well, again provided this could be done safely.

 

[ObsequiousAplomb]

Why don't we make the placebo ethylone or some other bath salt that gets sold on the street as molly? So many patients are adamant that they have been smoking molly every day for a year, even when I point out the melting temperature of mdma precludes smoking as a route of intake. If it can fool them that well, then I figure, why not?

 

[tr]

If my friends were to be believed, supposedly pure MDMA.

How would they know this? It's very difficult to verify what is actually in those pills. Even the Dancesafe test kits, assuming people are using them, only test for a small number of potential adulterants out of the many possibilities.

The PubMed links are a bit more convincing as presumably there would be more reliable manufacturing for research study use, but I agree with @ClosetCentrist that just because some individuals might report mild dissociative effects doesn't make it accurate to characterize MDMA as primarily a dissociative agent.

 

[tr]

I am not sure from a harm/research standards, but I would want more than just Adderall, probably an Adderall + Benzo combination to try and blind versus MDMA. Very different effect overall that experienced users would still be able to tell, but I think you would get closer with a combo of meds. Adderall plus a low dosage of Ketamine might an option as well, again provided this could be done safely.

That... sounds like a recipe for some messed up research participants

 

[Merovinge]

That... sounds like a recipe for some messed up research participants

I can't begin to tell you how many patients take Adderall + BZD on a daily basis. I am not sure I have prescribed that combo more than 1-2x in the past decade but have certainly seen it several dozens to hundreds of times. Ideally if someone is cleared to get MDMA from a cardiac perspective the Adderall should be fine, a modest benzo dosage on top does not seem wild, but I also do not know how IRBs are looking at this.

I will say they used IV BZDs for a recent ketamine comparison study to show superiority and that made a lot more sense than other comparison versus non-active placebo.

 

[Stagg737]

How would they know this? It's very difficult to verify what is actually in those pills. Even the Dancesafe test kits, assuming people are using them, only test for a small number of potential adulterants out of the many possibilities.

The PubMed links are a bit more convincing as presumably there would be more reliable manufacturing for research study use, but I agree with @ClosetCentrist that just because some individuals might report mild dissociative effects doesn't make it accurate to characterize MDMA as primarily a dissociative agent.

The friends I had are anecdata. They could be wrong, but one of them used ecstasy exclusively to dissociate and they were someone who was very familiar with those substances. We thought it was weird too, but to each their own. Even so, I never said the bolded and have said the opposite multiple times that its primary effect/use isn't dissociation. I'm not saying it should be "classified" as a dissociative but we can still describe it like that if that's the effect it has. I wouldn't classify quetiapine an anxiolytic or a sedative, but we see it used for both of those frequently and saying it can be used as either of those things isn't really wrong. That's what I've been getting at if that makes more sense.

This whole conversation comes back to a theme in several recent threads in this forum that the language we use and nosology aren't concrete or consistent to the point pretty educated people are talking past each other. Imo our nomenclature is a problem where we "classify" meds based into arbitrary groups with overlap making our language inconsistent and often confusing, especially for patients.

 

[theduderino]

This is a pretty good idea actually. The two therapist requirement was a good idea as well. I guess it needed to be stipulated that the two therapists should not themselves be in a sexual relationship with each other 🙄

Without having seen the video, it just boggles my mind how colossally dumb these therapists were to commit such an egregious boundary violation when they knew they were being recorded. It kind of makes me wonder if they were sampling the goods themselves actually.

But if it could happen in a situation with clinical trial levels of monitoring, it absolutely will be happening out in the wild.

This is pure speculation, but my guess is these therapists were also using MDMA during the session. This is only way I can make sense of something so absurd.

 

[Merovinge]

This is pure speculation, but my guess is these therapists were also using MDMA during the session. This is only way I can make sense of something so absurd.

Absolutely, that was/is the big concern. This therapist is also a PhD leader in the field and has been doing this work for 40+ years. I believe the wife was an MD psychiatrist. I think there is also lawsuit pending that will show more details. Pretty shocking and makes the idea of a mandated video recording sensible. If we are moving that direction for police, it makes sense in this instance as well.

 

[clozareal]

Absolutely, that was/is the big concern. This therapist is also a PhD leader in the field and has been doing this work for 40+ years. I believe the wife was an MD psychiatrist. I think there is also lawsuit pending that will show more details. Pretty shocking and makes the idea of a mandated video recording sensible. If we are moving that direction for police, it makes sense in this instance as well.

Except that this happened after the video was turned off and after the study ended. They allegedly kept giving her ketamine and other drugs for years, advised her to move to a remote Canadian island where the therapist, Richard Yensen, repeatedly sexually assaulted her while she was intoxicated claiming it was a form of exposure therapy to heal from the PTSD. She eventually turned in the video to New York Magazine who reported this. There's an interesting podcast, Power Trip, that touches on this.

 

[Stagg737]

Except that this happened after the video was turned off and after the study ended. They allegedly kept giving her ketamine and other drugs for years, advised her to move to a remote Canadian island where the therapist, Richard Yensen, repeatedly sexually assaulted her while she was intoxicated claiming it was a form of exposure therapy to heal from the PTSD. She eventually turned in the video to New York Magazine who reported this. There's an interesting podcast, Power Trip, that touches on this.

Crazy. We have a semi-frequent flyer patient who I've known for years that used to live with her psychiatrist. He had convinced her to move in with him at one point and she apparently lived with him for years. I've encountered her on and off for years and only a few months ago she finally admitted that there was a sexual relationship with him. There's more to the situation that I won't go into as it gets to specific, but it's sad that it doesn't surprise me how disgusting people in our field can be.