4 ms·

A non-hallucinogenic psychedelic analog with therapeutic potential

53 points by neom 5y ago

TaylorAlexander 5y ago
Absolutely fascinating. I recently discovered that someone close to me has been using meth for two years, to great sadness and frustration. I had heard ibogaine could reduce addiction, but was disappointed when I read the Wikipedia page and discovered the cardio toxicity that has lead to multiple deaths from use. A safe analog would allow for more research and potentially breakthrough treatments for drug addiction. I hope they are able to continue research and find a safe path towards human trials (it seems so far they have trialed it in mice).
- pmoriarty 5y ago
  Yeah, I would personally stay very far away from ibogaine. 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.
PragmaticPulp 5y ago
Without going into specifics: I stumbled upon an internet group where some members had arranged the synthesis of this chemical. Of course, I can’t verify that what they had was legitimate, but they had at least a couple members claiming to be professional chemists and it seemed plausible. 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.
- hammeiam 5y ago
  Honest question, how does one stumble upon internet communities anymore, let alone one like this? I feel like personal blogs via HN is about as far off the beaten path as I'm able to get these days.
  - tsol 5y ago
    Search Google for obscure substances. You'll find discussions in strange places eventually
pmoriarty 5y ago
First, this study has only been done on rodents. 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.
- Synaesthesia 5y ago
  Shulgin really makes a good case for testing psychedelics on humans. Ultimately it is the only test if a drug is "good" for therapy or not.
  - sterlind 5y ago
    Shulgin hailed from a time before we had all these fancy tests. Binding affinity, mRNA and protein production, physiological changes can all be measured easily in the lab. 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.
    - pmoriarty 5y ago
      "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." 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. [1] - https://en.wikipedia.org/wiki/Muscimol https://en.wikipedia.org/wiki/Muscimol
graderjs 5y ago
Love the term "ibogalogs". If anyone is wondering the structure of the chemical in question "Tabernathalog" (TBG) you can find it in Figure 1, in the table at the bottom right "Scaffold 2", No. 18 with substitutions R1 = H, R2 = OMe (ie OCH3)
throwawaynay 5y ago
I really don't understand the interest for psychedelic analogs. 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)
- pmoriarty 5y ago
  "I really don't understand the interest for psychedelic analogs." 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...
  - akvadrako 5y ago
    The reason I can't go about my day on mushrooms or LSD has nothing to do with the psycadelic effects.
  - throwawaynay 5y ago
    people should be a lot more scared of psychedelics analogs that were only tested on rats(and that might one day make the poor souls exploited during the clinical trials insane...or dead) 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
34679 5y ago
For anyone curious about traditional ibogaine use, I highly recommend Daniel Pinchbeck's "Breaking Open the Head".
harvie 5y ago
Where is the fun in that? ;)
- Synaesthesia 5y ago
  I don't think Ibogaine is the most fun drug ever.
ada1981 5y ago
Did they patent this? 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.

53 points by neom 5y ago

Absolutely fascinating. I recently discovered that someone close to me has been using meth for two years, to great sadness and frustration. I had heard ibogaine could reduce addiction, but was disappointed when I read the Wikipedia page and discovered the cardio toxicity that has lead to multiple deaths from use. A safe analog would allow for more research and potentially breakthrough treatments for drug addiction. I hope they are able to continue research and find a safe path towards human trials (it seems so far they have trialed it in mice).

pmoriarty 5y ago
Yeah, I would personally stay very far away from ibogaine. 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.

PragmaticPulp 5y ago

Without going into specifics: I stumbled upon an internet group where some members had arranged the synthesis of this chemical. Of course, I can’t verify that what they had was legitimate, but they had at least a couple members claiming to be professional chemists and it seemed plausible. 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.

hammeiam 5y ago
Honest question, how does one stumble upon internet communities anymore, let alone one like this? I feel like personal blogs via HN is about as far off the beaten path as I'm able to get these days.
- tsol 5y ago
  Search Google for obscure substances. You'll find discussions in strange places eventually

pmoriarty 5y ago

First, this study has only been done on rodents. 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.

Synaesthesia 5y ago
Shulgin really makes a good case for testing psychedelics on humans. Ultimately it is the only test if a drug is "good" for therapy or not.
- sterlind 5y ago
  Shulgin hailed from a time before we had all these fancy tests. Binding affinity, mRNA and protein production, physiological changes can all be measured easily in the lab. 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.
  - pmoriarty 5y ago
    "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." 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. [1] - https://en.wikipedia.org/wiki/Muscimol https://en.wikipedia.org/wiki/Muscimol

graderjs 5y ago

Love the term "ibogalogs". If anyone is wondering the structure of the chemical in question "Tabernathalog" (TBG) you can find it in Figure 1, in the table at the bottom right "Scaffold 2", No. 18 with substitutions R1 = H, R2 = OMe (ie OCH3)

throwawaynay 5y ago

I really don't understand the interest for psychedelic analogs. 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)

pmoriarty 5y ago
"I really don't understand the interest for psychedelic analogs." 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...
- akvadrako 5y ago
  The reason I can't go about my day on mushrooms or LSD has nothing to do with the psycadelic effects.
- throwawaynay 5y ago
  people should be a lot more scared of psychedelics analogs that were only tested on rats(and that might one day make the poor souls exploited during the clinical trials insane...or dead) 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

34679 5y ago

For anyone curious about traditional ibogaine use, I highly recommend Daniel Pinchbeck's "Breaking Open the Head".

harvie 5y ago

Where is the fun in that? ;)

Synaesthesia 5y ago
I don't think Ibogaine is the most fun drug ever.

ada1981 5y ago

Did they patent this? 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.