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Your weekly dose of drug facts while dispelling fiction
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you're listening to locally produced programming created in KUNV Studios
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on public radio KUNV 91.5 please be advised that the voices and opinions you may hear do not necessarily represent the views of KUNV Las Vegas the University of Nevada Las Vegas or the Board of Regents of the Nevada System of Higher Education
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Welcome to another episode of The Chemical Collective.
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The Chemical Collective offers you your weekly dose of drug facts while dispelling fiction. Today we're talking about the psychoactive chemical 2CI and its inventor and psychonaut Sasha Shulgin. I am Dr. Dustin Hines. I'm April
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Contreras and I'm Kendra McLaughlin. So again we're going to be stepping out of the usual episode. So I wanted to ask firstly what is 2CI and who invented it. 2C-I is a psychedelic drug that belongs to the family of drugs called 2C. It was first synthesized by psychonaut Alexander or Sasha Shulgin in 1975. It is a hallucinogen that produces a range of effects including visual and auditory hallucinations, altered
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thinking and changes in perception of time. And we're going to get into it more, but really 2C-I is a parent molecule for many other compounds like NBOs and NBOMs that we'll talk about in future shows. And one of the reasons I'm excited about this is you have somebody that arguably invented half to two-thirds of all the synthetic psychedelics, saying that this was his absolute favorite. So I think it deserves a show.
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Yeah, this sounds really interesting. Can you tell us a little bit more about its effects and like why people use it? Well again going back to being Sasha's favorite
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It's really known for its euphoric kind of out-of-this-worldly feeling and then a huge Empathetic effects in fact this is one of the compounds that coin the term entheogen which means you know something that really makes you feel Good about yourself and others It's often used recreationally by people who are kind of looking for different kind of experience. However, it's really important to know that it can have negative
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effects and it is illegal. I see and earlier you mentioned a name. Who is
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Alexander Shulgin? Alexander Shulgin was an American medicinal chemist and pharmacologist. He was best known for his work on the synthesis and testing of a variety of psychoactive substances, hence the term psychonaut. He's often called the godfather of ecstasy because he was one of the first people to synthesize MDMA, which later became popular as a recreational party drug.
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And actually this shows what TCI and Shogun, but his wife was brilliant too, Ann Shogun. She's one of the first people to suggest that psychedelics, MDMA really are important in therapy. So she really brought this idea of using anthogenes and psychedelics to improve therapy sessions, which really has led to Rick Dobbins and all the work being done currently at MAPS now on MDMA.
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That's really fascinating. Can you tell us a little bit more about maybe some of the contributions that he has made
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to the field of pharmacology in the whole?
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Yeah, so Shulkin was responsible for synthesizing like hundreds, maybe even thousands of psychoactive compounds. Many of these never really have been explored. In fact, there's one that I'm fascinated with that only changes auditory pitch. So you take one of these compounds, you don't really trip out, but every word sounds really low, but in the same speed. He believed many of these compounds would have potential therapeutic effects. That was his idea. And so he spent much of his early career really looking at the effects on the human body, something that you probably couldn't get away with now, and in that he published several books that are kinda kooky but really interesting to read called Phycal and Tycal, which stands for Phenethylamines I've Known and Loved and Tryptamines I've Known and Loved, respectively. And in these books he makes hundreds of compounds and then tries small doses, and I guess to get around various problems speaks about in the book in the third person like somebody was on a
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journey. Wow, that sounds really interesting. You mentioned that he was able to make so many versions of this compound. What do you think that the future of the research
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in this area is going? Well, I think that there's still a lot to be learned about the effects of psychoactive compounds like 2-SAI on the human body itself. There are some substances that have shown promises as potential treatments for a range of conditions, but we still need to conduct more research to fully understand their effects and potential risks. It's also important to note that the use of these compounds should always be done under the guidance of a trained professional, and they can be potentially dangerous.
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Yeah, and on that note, right now I'm not aware of any place that's using TCI in kind of guided professional trials, or any compounds even related to it that are currently in clinical trials. So it's something definitely to think about before using or even sourcing, truthfully.
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So we've briefly kind of touched on what it is, but can you guys go a little bit more in depth on precisely what 2CI is and more specifically how it differs from other drugs? So a lot of drugs start off with a plant source and 2CI doesn't really fall in that case.
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That's what makes it really unique. It's completely synthetic, but if it did have a plant parent, it would be something like mescaline that's found in the peyote cactus. And so, really in the human body this affects many different organs, many different places and really where 2CI comes from and how it works is similar to mescaline as I said but similar to amphetamine so it's a psychedelic and also kind of a stimulant ingested orally. I know that a lot of the conversations that we've had on the show previously like the
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battle nut episode and all those cool things, they, like you said, are coming from plants. But now I'm like really interested more so on how 2C-I is prepared, I guess, and maybe what its effects are. Yeah, that's a great question. So we're going to be talking about chemical synthesis of this compound. So 2C-I involves a reaction of what's called an an amine, such as 2,5-dimethoxyphenethylamine, with a halogenated compound such as iodine. So you're putting them together. And the resulting product is then purified and can be made into a powder or packed into a tablet or capsule, even put on blotting paper, similar to LSD. As for the effects, 2CI can induce hallucinations, alter perception of reality, and changes in mood and your thought patterns. These effects can last for several hours, but it's important to note that at this stage it can be unpredictable.
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And also, it's illegal to make this. Let's start with that. Two, it's complicated. Some things are not complicated to make. They're pretty hard to mess up. This is really easy to mess up because again, those halogenated substances you can get all kinds of bad effects and for that I always think about MPTP which was this compound that was made to be designer heroin in the 80s and a lot of people took it and got Parkinson's disease so again synthetics and drugs in general not something you really want to be messing around with at home ever and
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it's made in like either powder, capsule or tablet, it makes me wonder if you can tell us more about how 2C-I is ingested.
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Are there any risks that are specifically associated with it? So April
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really went into this already. Many different substances can be put into the body orally and that oral kind of ingestion can take different forms. So it can be ingested in a pill, it can also be in a capsule type form where you have a crushed powder that goes in capsules. And also, and less commonly for TCI, it can be snorted or smoked, which are really, really terrible and dangerous ideas in general, because they go through less barriers, right? When something goes into your stomach, if you get too much or it's a poison, you can throw it up and get rid of it. If you inhale something, there's no way for your lungs to get rid of it. So typically it's taken orally in a liquid form on a tab, like April said, or in a crushed capsule. And it's important to know that there are problems with these different ways in which you ingest it. And also it differs from person to person.
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Okay.
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You guys are kind of alluding to some of these serious risks that might come from the use of this compound, but I have to know. This is the part of the show that I'm always excited about. How does 2CI work in the brain? Like what receptors are involved? Again, 2CI is a psychedelic drug. It's a synthetic psychedelic. So it has similar effects to those like LSD or psilocybin, which I'm excited to also talk about because they each deserve their own shows respectively. And it's believed, what's really important about psychedelics is that their primary mechanism of action is by binding to serotonin receptors in the brain, particularly the serotonin 5-HT2A receptor subtype.
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Okay, so what's the significance
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of the 5-HT2A receptor in the brain?
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Well, let's back up a bit too, and we're going to talk about the serotonergic system a lot today. The first thing to say is when we're talking about serotonin, there's serotonin that is released, a free-moving ligand in the brain, and then there's also the receptor that it binds to, and that's largely what we're talking about here. There are, at least last I checked, about seven different major types of serotonin receptors. They're all G-protein couple receptors, except for one. There's always one that kind of breaks the rules. 5HT7 is a little bit different, it's more ionic. So all of these compounds, 5H2A that we're talking about today, the receptor that all these compounds work on, are varied throughout the brain. But the 5HT7 receptor is a subtype of these receptors, of one of the seven. And when 2CI binds to it, it activates a signaling pathway that then results in alterations in all kinds of, you know, what I would call macro-level things such as sensation, changes in your mood, distortions of time and space.
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Would you guys mind unpacking a little bit more about some of the specific mechanisms of action of 2CI in the brain? Like, we briefly talked about the receptor in general, but does it have an effect on other types
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of neurotransmitters?
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Yeah, activation of serotonergic receptors, including the 5sg2a receptor, affects a number of other neurotransmitter systems, primarily because of its slow-acting G-protein coupled mechanism. Other neurotransmitters that it affects are dopamine and reprinephrine, and these really contribute to the euphoric and energizing effects of 2CI. Okay, that's super interesting. Are there any potential risks associated with heightening the activation of this specific 5-HT2A receptor?
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So, we always have this question.
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I don't think there is a drug out there that you can take that doesn't have a risk. Even water in large doses has a risk. These compounds have fairly low risk and use liability. We'll talk about that. In fact, they could be even a cure, some of them, as we start to understand, for addiction. But like other psychedelics, 2CI and anything that acts on the 5-HT receptor can produce powerful experience that can be difficult to manage or to integrate yourself. People can call this ego death. And so it's really hard when you come under one of these trips and you don't know who you are, what your place is in the world, but that can be beneficial in some cases. Other kind of very simple physiological effects include nausea, vomiting, anxiety, paranoia, the usual. This is very particular, typical with much, much higher doses. Additionally, there can be long-term effects in the brain. We don't understand that. And some of these long-term effects in the brain obviously are the benefits for people that have PTSD and other things like major depressive disorder. But again, we need to understand or do more research on all of this. So huge caution.
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Yeah, it sounds pretty tricky. Like previously, you guys have mentioned the details in the dose. How did Alexander Shulgin actually figure out
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the typical dosage of 2CI? Yeah, he used a method called titration to determine the appropriate dosage. And this involves by starting with very, very small doses and gradually increasing it until some effects were achieved. And then he would note the dosage that produced these effects and use as a baseline for further exploration.
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So there's kind of a joke in the literature. This was not approved research that he was doing, right? So these small doses and titrations, you know, he was taking on himself. So he would take compounds in the nanogram level, like even the most expensive scale can't measure that small. He'd be diluting these down thousands and thousands and thousands of times. And so, although it's kind of fascinating to me, it's a little cavalier and cowboy, right, that he was doing these studies. There's a very famous episode with Hamilton Morris where he talks to Shulgin, kind of cool, worth looking at. And he just said, oh, I could just look at the molecule and know if it was nanogram or microgram. So, not maybe as cowboy as I'm putting out, but you know, it would be bereft for me to make a compound and then think that I could just start ingesting it and then upping the dose until I got the effect. And I always use the idea of uranium, right? You can take a small amount of uranium and it can't hurt you, but you know, overall, you probably shouldn't be eating things that are bad for you. Wow. So is there even a typical
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Yeah, the dose for 2CI isn't really well known because there isn't that much research on who's taking it or where because it's an illegal drug. But generally, some anecdotal reports of use of 2CI ranges anywhere from 10 to 30 milligrams. And again, that 10 milligrams, that's not really something that you can measure.
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So that lets you know this is a highly, highly powerful medicine, highly, highly powerful drug. Right.
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So you guys have mentioned that serotonin is really involved as far as receptors go, and you briefly alluded to some other neurotransmitters, but can you tell us what other receptors are
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affected by 2C-I apart from serotonin?
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So there have been a couple of studies recently on 2C-I that show that it affects dopamine also and norepinephrine. For the dopamine, it's largely what are called the DATs or the transporters of dopamine. So it's going to allow the dopamine to kind of be recycled and reused a little better. And again, if we go back to the euphoria, if you're going to have a lot more dopamine hanging out, you're going to have that euphoric kind of entheogenic happy effect. A lot of these receptors are responsible for regulating all kinds of other things like pleasure, attention, arousal, respectively. And while you might expect something that does that to be addictive, again, as we'll talk about in a second, they're anti-addictive, if anything.
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So it sounds like there's a lot of players involved, and it makes me wonder, what are the implications of 2CI affecting these receptors in addition to serotonin? Yeah, the effect of these receptors in addition to serotonin, could explain some of the drug's subjective effects, including increased arousal, the feelings of euphoria, and heightened perception. But there are some increased risk of adverse effects, such as tachycardia, hypertension, and potentially, in some rare cases, psychosis.
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Yeah, and I think for all the psychedelics, a lot of people aren't talking about this, but these are super rare cases, let's start off with that. But there's something called locked-in syndrome, and this is where you really don't come back into the world of reality, whatever that means. So you're kind of like tripping for weeks or months at a time. And there's videos on YouTube, not with 2CI, but of other compounds people doing this, and that would not be good
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Yeah, that sounds kind of alarming, but I'm curious if there are anything that individuals could do or
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Plan to do if they are using to see I to protect themselves from these risks
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Well, first of all, you shouldn't be doing CCI It's it's illegal. And so again without proper medical supervision You shouldn't do any of these drugs and as I said I don't think it exists for this. So you know increased heart rate, anxiety, paranoia, these are all things that you would seek medical attention with instantly. So there's no way to kind of get around that. Second, individuals should be aware of some of the long-term effects that we just talked about. And then you should be aware of your own mental state. So a lot of people are going to these synthetic, you know, I don't want to say underground, but you know, garage made synthetics that are going to help them with some of their problems, but no pill, a single pill is ever going to solve all your problems, right? You have to go through the therapy and other things. So seeking that medical supervision is critical and it obviously doesn't exist for this because it isn't well regulated in the clinical sense, in that it's illegal.
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I was hoping to kind of shift gears just for a second because we mentioned this multiple times, but can you guys tell our listeners what exactly the serotonergic system is, because it came up multiple times.
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Yeah, the serotonergic system is really a beautiful and kind of fascinating neurotransmitter system. Serotonin is considered probably one of the oldest molecules in the brain that we've used to first, you know, when we were evolving, move. And if you think about the primary transmitter or chemical in the body, outside of your brain, that's going to be serotonin, like primarily in your gut. And serotonin receptors are expressed everywhere in the brain, which kind of alludes to the idea that the effect of psychedelics like 2CI are long-lasting and promoting lots of profound change.
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And we can unpack that a little more too, right? If you want to think about something like acetylcholine, which is a neurotransmitter that's going to allow you, say, to wiggle your little finger, that kind of has to be instantaneous and it has to be, you know, a unilateral pathway. If we look at something like mood, right, we need to touch every area of the brain and understand what's going on. What is the lighting like? Am I hungry? Am I not hungry? Am I sleepy? Am I not sleepy? So that's where serotonin plays a really important role because it regulates our mood, our appetite, our sleep, and many other things. things and really I love what April said there, it is primitive, it really there's this process in your gut where you eat food and you rhythmically sense the food and then pass it along through these little villi, these little fingers in your gut that make this process called periosteosis and this is like the, you know, you can figure when you eat that third Taco Bell taco, you can feel the periosteosis try to, you know, maybe move the taco along, try to get rid of it. That's what serotonin does, and it's the same thing in our brain. When we have heightened or low mood levels, it tries to move it along.
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I think that's really cool. I didn't think that was a nerd thing at all.
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Maybe you're a nerd too.
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Okay, fair. Does 2CI and maybe like other psychedelics like LSD or psilocybin, do they also affect the serotonergic system?
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Yeah, not even the serotonergic system. Most of the psychedelics work specifically in that receptor we mentioned earlier, which is the 5H22A. And so, they have these similar binding receptor effects in the brain that all serotonin does, and they all act to then what we call agonize or increase serotonin activity, which can disrupt normal brain function or it can promote depending on the dose, depending where your brain's at, and this leads to those characteristic effects. If you imagine you're trying to move that food along, we'll keep going back to that, everything's got to be in sync at the same time and that's kind of what it does to your brain. It puts everything in sync and we would call that normally dreaming. So when you have a dream, you have all these areas while you're asleep kind of talking to each other. What was your big worry for the day? What did it look like? What other cues were associated with it? That's probably what a hallucination is. It's really this coming together or rhythm of many different brain areas.
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Okay, so there is like a variation of psychedelics that can affect these specific receptors, but do they also have a variation on how they interact
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with the serotonin receptor in the brain itself?
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Yeah, sure. So serotonin receptors, the first thing to know is that they're mostly on neurons and intraneurons in the brain. And although our lab, we're starting to have some research to show that maybe they're in other cell types. Really, it's the surface level receptors and neurons that are then acting to communicate between the different brain regions. And so it's this change or alteration in neuronal events that then communicates between different brain regions via neurons.
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Okay. Do you think that these changes that we're talking about in the serotonin activity have
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any potential therapeutic applications?
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Yeah, that's what's really exciting about psychedelics in the research space right now. If we want to think about our first episode, the psychedelic renaissance, current research is showing that psychedelics have therapeutic effects in treating a range of mental health disorders including depression Anxiety and PTSD and again, this is because they can help promote new connections and patterns of activity in your brain Which can lead to long-lasting changes in your mood and behavior
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Yeah, and well, it's not out there yet my reading of the literature and some again super cool research from our lab I really think that these compounds will be important for substance use disorder also. When we look at PTSD too, PTSD kind of started out in an odd place in that it wasn't even in the diagnostic and statistical manual that psychologists psychiatrists use because it kind of bridges both depression and anxiety. So fascinated that something can be so pointed at kind of getting your mood back in the right area such that you can have normal moods and have less of these, you know, traumatic experiences or be able to deal with them appropriately. One of the concerns I have though is things like depression, anxiety, especially depression. It is not a homogenous disorder, so there are many, many different types of depression, different from unipolar and bipolar. You know, when we look at major depressive disorder, it's very heterogeneous. So I think trying to figure out who is really helped by these compounds and you know I don't fear the answer that some people are hurt by it because I Think that's the most important thing to figure out who not to give these compounds to it's not like a one-size-fits-all No, absolutely. You know what medicine has done that for like 200 years We've given everyone the dose for a 70 kilogram white male and it turns out not everyone is a 70 kilogram white male. So I think this field is starting to do a really good job of understanding everyone's trauma is different, everyone's depression is different, everyone's anxiety is different, everyone's body and brain is different. So hopefully you know we can get a lot of answers to some of these questions of mood from the use of psychedelics. It's sounding really
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really exciting. I have heard that psychedelic drugs can also have negative side effects. Can you speak to that? Yeah, it's important to note that psychedelics can have negative side effects, including paranoia, anxiety, and intense hallucinations. That's why it's really important for people to be aware of what they might be getting into this idea of set and setting. And these effects can be especially pronounced in individuals who are just unprepared or might be taking other medications. But again, the research is still out there on how they all interact together.
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Yeah, and that preparedness is everything. Because if we look at something like trauma, you might think you're prepared to go on some psychedelic experience, you know, from a non-medical person. But why we were always saying you need the supervisors of the medical field is because you might have trauma that you're not aware of. A lot of trauma is repressed. Something could have happened to you that was terrible many, many years ago and in fact you go into this experience, you know, thinking you're prepared but all of a sudden you're dropped with this episodic memory of something terrible that's happened, right? So again, you kind of need that container. And by container I mean medical, healthcare professional, or people who know what they're doing. I'm definitely not against shamans or anything like that. Somebody that's qualified has seen things go really wrong.
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Can you guys talk about some of the effects that 2CI has on other parts
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of the body? The use of 2CI can cause several physical side effects including increases in your heart rate, high blood pressure, and dehydration. There are also some anecdotal reports online of it inducing nausea or vomiting, diarrhea with very high doses. In some very rare, rare cases, it can cause seizures or respiratory distress.
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Yeah, and that's something I get really frustrated with with this group of compounds because because you know if we were to look at something like let's say aspirin, you probably could say the same thing about aspirin if people were cooking in their bathtub. So a lot of these cases of seizures it for surely was not 2CI, it was something at a rave that somebody had made and that person that made it was not Alexander Shulgin, there was somebody that just went online and tried to figure it out. So when you get down to it, I don't know if you guys know about spice, but spice and all these kind of like gas station drugs, right, people try to stay one step ahead of the DA and FDA. So they make a new compound that's say THC, but it's a little different. People get sick on those things because they're not tested. They're not vetted, right? So you know, you shouldn't take drugs, but if you are going to take drugs, they should be approved by the government and they should be made by somebody who has a lot of experience making drugs. So yes, in the case of 2CI, there are reports of seizures, but if you look at that, it probably wasn't 2CI that the person took.
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Okay, that's really helpful.
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Are there any long-term effects of using 2CI?
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Well, jokingly, and for some people, yeah, ego deaths. There's a lot of people that take this and they have changes in their mood and behavior such as decrease in depression and anxiety. But there's also people that can take some compounds like this and get an increase in depression, anxiety, and things like paranoia. So the biggest thing that people report is this idea of flashbacks and persistent hallucinations being locked in. But again, for 2CI, pure 2CI, this has almost never been reported, so it's more of a potential thing.
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I am really curious about some of the misuse of this specific drug. What is the use liability for 2CI and psychedelics in general? The use and liability of 2CI and other psychedelics is a really interesting idea, and especially for scientific and medical communities, because we know psychedelics are known to produce profound changes in your perception and mood, and that they've been used for hundreds of thousands of years. As for these synthetic compounds, there still
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needs to be research done. Yeah, one of the main uses of TCI psychedelics for research purposes is really for treatment of anxiety and PTSD. But the big thing to understand here, use and misuse, we don't really have figured out yet.
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Wow. Well, that was an amazing conversation. Like time really flew by. Thank you, as usual, Wow. Well, that was an amazing conversation. Like time really flew by. Thank you, as usual,
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for the great discussion, you guys. And thank you everyone for joining to The Chemical Collective to get your weekly dose of drug facts and fiction.