25i-NBOMe, a new designer psychedelic hitting the street, was discovered in 2003 by a chemist at Free University of Berlin, Ralf Heim. We discuss this and other designer drugs and their impacts. Also a new study out of Rutgers is suggesting addicts might be seeking relief from emotional pain, rather than euphoric highs. Other new drugs, including anti-seizure medications, seems to reduce drug craving. They impact the GABA system, which the chief inhibitory neurotransmitter. A bit about the troubles of the Toronto mayor, and not-surprising findings that flavored e-cigs, and regular cigarettes are very attractive to adolescents.
Transcript (edited):
HOWARD: Welcome to the CNS Podcast featuring Dr. Darryl Inaba, research director for CNS Productions. I am Howard LaMere. A relatively new, designer hallucinogenic called “N-Bomb” or 25I is making some news. Also there’s a story that appeared in Psychopharmacology, a new study done out of Rutgers on what may be a significantly different perspective on addiction – that addicts might be seeking relief from emotional lows rather than simply chasing after euphoria and getting high. So, those are a couple of the stories, Darryl — should we just launch in on one of those. Do you have some other things there?
DARRYL: Well, there are a lot of things in the news again this week so we can go off in many directions. We can start off with whatever one you want. You mentioned first of all the N-Bomb – I think that’s your name for it, Howard -kind of creative name that came up for a proliferation, in some parts of the United States and Europe especially Copenhagen, of new psychedelic drugs. This one is called 25I- NBOMe, so Howard appropriately named it N-Bomb – I kind of like that! It probably gives it a whole new street name for it, but N-BOMe stands for N benzyl oxymethyl and they’re actually not that new. They were first described as part of Sasha Shogen, Alexander Shogen’s new phenethylmene’s or potential phenethylmene drugs that can provide amazing psychoactive effects and he actually claims he tried all of them in his book, PiHKAL: A Chemical Love Story, and this was described in the 2CI in the series, in his PiHKAL book. But it’s a proliferation that we’ve been talking about that we’re also seeing with the synthetic marijuanas, synthetic methamphetamines and cocaines and new synthetic drugs because PiHKAL has several hundreds of these substances, of which only a handful have hit the street so far. So every week a new one could hit the street and they often wait until something becomes illegal or they can detect it in the urine and when that happens they’ll move to the next one. And thats what we’re seeing with N-BOMe and it’s a very powerful psychedelic drug. It’s a drug that also, being a phenethylmene, which is basically what methamphetamine is, it’s going to have the same side effects and the same toxicities that we see with ecstasy, that we see with methamphetamine, and all the other psychostimulants. So, it has the propensity to increase body temperature and be very dangerous to the body that way. There’s all kind of muscle reactions to increased heart rates. All that is going to be seen with it, but it’s just the hunger that people have to continue altering their states of consciousness. And then the government is always trying to control these substances and maybe even try and make money off these substances that put them into new classifications and new laws, but as soon as they do that, the street is going to come up with the next one. And so, it’s not ending.
HOWARD: Yes and that was kind of the question that I was rolling around in my mind – why are we seeing this proliferation of designer drugs when we still have the old traditional regular drugs around? And you know, they’re so much more powerful – is it simply – is it the power factor or is it the legality factor, the testing factor – what do you think, Darryl?
DARRYL: I think it’s all of that, Howard. I think a big part of it is the legality factor. I think as the war on drugs in other nations, internationally tries to crack down on drugs and tries to identify them, make them more illegal and have severe penalties and therefore stimulate a whole urine testing industry to identify them in people’s urine when they’re applying for jobs or at the work place or operating machinery that the hunger for these drugs continues and so people are going to look to drugs that will not be identifiable in the urine. You know, Lance Armstrong and his steroid thing went for many years and I don’t think they would have ever found them until, finally there was a mission…but he used things that were at least 20 years maybe ahead of its time, that we could recognize and finally were able to recognize. And that’s part of it. The other thing is that they are more powerful and they have interesting effects although they do basically the same thing. Each one tweaks the brain in a little bit different way. You can get different sort of illusions and hallucinations and illusions from it. They seem to be much stronger than previous compounds before them. They may have longer effects as the appetites for these type of drugs grow and the more a person takes them, the more the body adapts to them and so they get resistant to them, meaning that you have to have an ever increasingly stronger drug in order to feel any effect at all. Psychedelics were traditionally drugs that didn’t lead to addiction because they were so powerful – that if you just took them within a day or two, you would develop such a tolerance that they wouldn’t work anymore, but with these new drugs, maybe they keep increasing the strength. Maybe that’s not going to be as much of a restriction as it has been in the past. And the other thing I think is part of this too, is the Edmund Hillary thing, you know – at Mount Everest – they’re there. They’ve been published in a book for about 20 years. They’ve been around. The chemists are now catching up to them. They can find that they can make these things fairly easily – so why not? And if you know that people are willing to pay a lot of money for these drugs, no matter what they do to you – then you’ve got the Howard LaMere hypothesis, which is –
HOWARD: Follow the money!
DARRYL: You’ve got it! So that’s my thinking of why they’re around and why they are proliferating and on the international – I think we’ve presented on this show a few weeks ago – even the international drug abuse arms are adding this as their new area of concern. They call them new psychoactive drugs of abuse – it’s all these new bath salt chemicals and new synthetic marijuana chemicals and these new psychostimulants, psychedelic chemicals, so they’re all over the world.
HOWARD: Well, it is – interesting. But I have continuously wondered what’s wrong with the traditional ones that we need to invent new ones, but I guess you’re right – it’s being the clever critters that humans are, we do it just because we can do it. So, and of course…follow the money. So this kind of leads us off into this other story here about emotional lows. We talk a lot about brain – the functioning of the brain and the neurotransmitters and that whole system, but we don’t talk a whole lot about the limbic system and the emotional component that clearly is part of – well it clearly is a part of life that’s very important, but it’s clearly part of the addiction process too. And so this new study was just released in the last couple days from Rutgers neuroscience professor, Mark West, and doctoral student, David Barker, in psychology. And a study with rats, of course again, and looking at how they reacted to their drug binges and the research kind of indicating that they took more drugs to alleviate the negative emotional feelings rather than to simply get high. And I thought that was rather interesting and it is kind of a new perspective, I think – Darryl?
DARRYL: Well, it’s like all things here. It’s that there’s also the roots that go much deeper than this. There are 2 parts to this. One thing is that drugs are effective psychoactive drugs do alleviate certain emotional feelings and alleviate fears and alleviate anxiety, alleviate depression – if you get the right drug for what you’re experiencing in emotional problem, you’re going to seek it out and continue to use it and that’s one part of it. But I think what this study is showing with the rats and the animal study is something we call – when we tried to understand how certain drugs – and sort of evaluate – how drugs have this power to hypnotize and to create the need to seek it out and continue using it. And we came up with the term called “reinforcement” – that they are a reinforcement activity of drugs. Some drugs have positive reinforcement, meaning they just affect certain areas of the brain and affect it in such a powerful way that whether you had emotional problems or not, you’re just going to want to do it again and again and that’s positive reinforcement. There’s also social reinforcement meaning less so the drugs’ effects on the brain, but just to be part of the group and part of society and participate – and that certainly comes into play when Asians have the genes that make them flush when they drink and so they’re going to get a nasty reaction when they drink, but yet them come to this country and drink as much as everybody else and are willing to be sick just so they fit into society – and that’s social reinforcement. Well, I think what this study is showing is one thing – one part of this that was talked about also and that was called “negative reinforcement,” and negative reinforcement is that when you take a foreign substance, your body is going to adapt to it, it’s going to go through an allostasis, it’s going to go to an imbalance of brain chemicals, it’s going to go through a downgrading of receptor sites, it’s going to go through changes in neuropathways in which you are going to experience tissue dependence or physical reaction with your brain cells that make you want to take the drug more, just by the physical changes. You’re going to get a depletion of your own natural brain chemicals and so you’re going to have emotional issues from taking a drug and if you don’t take it, you’re going to have even more emotional issues and you’re going to develop this negative reinforcement which is like a withdrawal state, in which in order to not suffer withdrawal and in order to not suffer the negative emotions or to not suffer the problems of allostasis, you’re going to continue to take the drug, not because it’s making you feel good anymore, but merely so that you don’t experience those negative effects. And so that’s there as well. In terms of the genetics of this, there are several studies that link the same gene – for instance, the gene that is implicated in why certain people develop emotional depressions – not because something bad happened to them in their life, but just because they don’t have the ability to feel cheerful or feel great all the time – there’s a gene that passes on that to people where their serotonin levels and the reuptake pumps and all that is all messed up. Well that gene, we find it not only in people who are prone to depression, we also find that in alcoholics, so there’s a connection there in terms of the genetics of it, in terms of – you start off emotionally depressed, you may find substances, like tobacco or methamphetamine or cocaine that help solve that, or even heroin may help solve that – and so you’re going to gravitate to take a drug – not so much that it’s making you euphoric, but actually dealing with some underlying emotional state. So, there is a lot to this but I really think, and I would have to really read the methodology more and look at the details – it looks like it is just bringing up this whole process that we refer to as negative reinforcement.
HOWARD: Well, in the context of emotions, I think it’s pretty well documented that having emotional trauma early in your life is a significant contributor to addiction. So that’s really interesting though about the gene and I guess that explains chronically depressed people, which is distressing.
DARRYL: You also bring up that other point and that’s the whole process – that there’s genetics involved with it, there’s pharmacology with the allostasis involved with it, but there’s also environment and the environment which you bring up is very good, Howard because definitely we can correlate early childhood adverse events or any kind of major trauma – adult or childhood – that results in a massive increase in drug abuse. And there are studies that definitely show that if you suffer any kind of major traumatic event, it changes your brain cell health. It changes a connection between brain cells as well as the chemistry of the brain and even the shape of brain cells that make you more vulnerable to addiction, so that is part of it. And it also reminded me of another thing, an article I came across that I found was interesting, in which they are now able to image the brain and have identified areas of the brain that show emotional pain. That people actually experience emotion as a painful response and it’s at a different place than where people experience physical pain. And there are 2 separate areas involved, but they can now image that and the amazing thing about it is when they image people’s brains who have just gone through a relationship breakup or a loss in the family or a loss of a pet or something and the people complain that they are in pain and they ask them to sort of drive their emotional pain on a scale, as the worst it can be a 5 or is it merely something that you can deal with – a 1, or is it some place in between that they can measure the activity in that area of the brain and then it matches exactly what people are saying they are experiencing. So it’s a whole new way of looking at emotional pain as being a real issue and something we really need to look at in terms of addiction, in terms of treatment, in terms of medicine.
HOWARD: It’s fascinating how we’re able to do this – as you know it’s kind of the corollary to the amazing things that we’re coming up with in astronomy and how, I just read a couple days ago how many earth similar planets there just in our galaxy and it’s a remarkable number and high number – and that just came up in the same kind of way, it’s amazing, this new ability to analyze what’s going on in a person.
DARRYL: That’s funny, Howard. It just made me think of Frank Drake. In Frank Drake’s equation, of course, he was the astronomer who first came up with the equation to calculate the potential for intelligent life in the universe, and he weighed in a lot of factors and through that, and it turns out the Vatican actually have observatories. You know, they have big telescopes and they’re looking out in the heavens like the rest of society and it started with Pope John and now the new pope is saying there probably is life out there. I think we’ve come a real far step when I think the Vatican were actually executing people like Bruno and other people when they said the earth was not the center of the universe and the earth was the only place where life was not happening, I mean life happened elsewhere and they actually burned them at the stake and murdered them and now we’re saying at the head of the religion saying no, Frank Drake is right. There’s got to be – the numbers are – the mathematics just make it impossible for life not to be out there.
HOWARD: Right. Fascinating. Well, do we have anything else to talk about?
DARRYL: The GABA drugs – gamma aminobutryic acid. It is a neurochemical, a neurotransmitter – a naturally occurring substance in the brain that is the main inhibitory neurotransmitter of the brain. That means that it has the ability to turn off and slow down most neuroactivity in the brain. It’s your chill out chemical in your brain and we’re finding more and more that drugs that emulate that or impact that in certain ways. Of course valium and alcohol and all those drugs of addiction mess with those things, but when we get these new anti-seizure medications like Topamax, Topiramate, Lyrica, Gabapentin or Neurontin, more and more doctors who are using this to treat epilepsy and uncontrolled seizures are seeing that it has major effects in decreasing cravings for alcohol, cravings for cocaine, treatment of methamphetamine and I think that’s a viable thing they’re looking at and I’m thinking that there’s going to be advances in the GABA and its counter-component in the brain which is something called glutamate and glutamate – the main activating brain chemical that we all have in our brains and it’s the main chemical involved with processing and formulating memories and reinforcing effects so when you take drugs like cocaine, it’s going to get glutamate – that is going to come and say, yeah, that was feeling good, but man it’s feeling really good and you’ve got to keep doing it. I think as they develop medications to target those areas, I think we’re going to have much more effective treatments for addictions – so that’s been in the news lately. There was an article and I think this due to come and I’m sure we should have talked about it before, but as we found, you know, the receptors for THC in the brain which turns out to be the receptors for your own internal cannabinoids – your endocannabinoids like anandamide and we found multiple receptors – the CB1, CB2 receptors and then we found the chemicals in your brain – the 5 chemicals or so that marijuana – the chemicals in marijuana copy – the endocannabinoids. I’m sure that when we see certain people, and not everyone but certain people who smoke and use marijuana that cannot control their use of it and their brain gets hijacked like if they were alcoholic or if they were sensitive to cocaine or methamphetamine, there had to be some genetic involved with that. A new paper just came out in the Journal of Studies of Alcohol and Drugs saying impulsivity and variations of certain cannabinoid receptors – the CNR1 receptor and the fatty acid amide hydrolase receptor, FAAH genes are genes that are markers for developing marijuana addiction problems and marijuana abuse problems. So like all drugs of addiction, marijuana is going to be like all of them – part genetic, part environmental and part pharmacological, and I think we should all be reminded of that because so many times, especially now with this movement towards this is organic, it’s legal, it would never hurt anybody – let’s make it legal. We forget that over 300,000 people are treated for marijuana addiction every year in the United States, officially treated for marijuana addiction. The last thing I wanted to bring up, and you can weigh in on this, I found several different things to look at, but it’s the Toronto mayor, Mayor Ford, who has been in the news heavily these past 2 days or so, about admitting his smoking crack cocaine and thereby creating a firestorm of people who say he should be run out of office, he should resign. And he admitted that he was smoking – he smoked crack cocaine while he was a mayor…while he was a mayor so it wasn’t a long time ago as George Bush was so, you know, so correctly saying…what difference does it make what I did when I was a teenager or adolescent or early adult? It’s what I’m doing now – that’s important. In this case it’s more recent. He was a mayor of Toronto when he did this and he’s getting a lot of reactions to that and quite frankly, I’m not so sure of what to think about it myself, because for one thing, you’ve got to ask – is he doing his job? Is he doing the work that people wanted him to do? Is he currently showing any signs of addiction or problems or any kind of compromise from his use of drugs? If he was, he shouldn’t be in office for those reasons – not because he admitted he did something, a few weeks ago or something like that. But on the other standpoint, he says he smoked it while in the midst of an alcoholic binge. And so he has an alcohol problem and unless he looks at that and gets appropriate interaction and treatment, he may be not really fit to do his job. So, I’m not really sure where I weigh in on this. What do you think, Howard?
HOWARD: I don’t know what to think about it. So, I mean, he did admit it, but it’s sounding like politics.
DARRYL: Well, there are these 2 very other quick articles that came out that just sort of validating our past podcasts that I want to mention. One is the flavored e-cigarettes, flavored cigarettes, the menthol cigarettes and little cigars. A recent article by CADCA saying that the study is showing that flavored cigarettes and little cigars are used by more than 40% of middle and high school smokers. And so basically it’s showing that tobacco is molding itself along with e-cigarettes to be attractive to a very young population because they have to make up for people who are dying off from the medical problems. That’s a big concern of mine because we’ve been winning the war on tobacco for so long, and we’re starting to see a little bit of a slip, in that young people are starting to smoke again. And then the other story from the same group, CADCA, that 1 out of every 10 teens now admitted to emergency room across the nation abused prescription pain killers. And that’s also a deep concern as you’re talking about people in the emergency room for appendicitis, for shock, for car accidents, a myriad of football injuries or sports injuries in this population, and yet 10% of them were in there for prescription drug abuse – prescription opiate abuse. So we do have a major problem that pharmaceutical firms have been trying to deny, saying that we’re overreacting, there isn’t a real major problem and basically the real problem is, we’re not giving strong enough of these drugs in order to control pain and that’s what we should be doing. But I think more and more evidence is coming forward saying that no…we do have a prescription drug problem and in spite of that, another article just came out on Medscape saying that FDA approved, for single entity extended release hydrocodone. So they approved it; Vicodin comes in 5 mg and we’ve kept it at that level because it’s a highly abused chemical, and it certainly is one of the major drugs, prescription opiates of abuse at this time. And then the pharmaceutical companies introduce this, saying no – we need to give 50 mg – we need to give 10 times that amount, and like Oxycontin, we can tie that all up with these polymers and plastics so that you can get slow release. You just have to take it once a day and so you’re not going to abuse it. Of course, that sure worked with Oxycontin didn’t it? And the other part of it, they say also, that Tylenol that we put in there was to help boost it to help kill pain, but then when people are abusing Vicodin and they take the Tylenol along with the Vicodin, their livers die. Well we don’t want that so they got approved for this Zohydro is the pharmaceutical name for it – they got approved for a 50 mg hydrocodone, essentially a 50 mg Vicodin tablet that’s tied up in these time release forms, that you take once a day, that has absolutely no Tylenol in it so you won’t hurt your liver. Well, how are you going to hurt your liver if they say nobody can abuse this because we tied it all up in a plastic polymer so they can’t take more than 1 tablet a day.
HOWARD: Is it good to be swallowing plastic? I always thought that was a bad thing.
DARRYL: Well, the claim is that these plastics will go right through you and not actually, enter your bloodstream. And all they’re going to do is coat the active molecules so that if you take 10 of them at one time, you’re only going to get a slow release and not a high dose. But as they found with Oxycontin, you just smash it up and then when the Oxycontin changed that formula they figured out how to break that, so it’s just – it’s the same story over and over.
HOWARD: Yeah, yeah. Okay that’s all the time we have. I’m not going to say anything about trans fat being banned, but trans fat was banned. But anyway, that’s all the time that we have for now. So thanks for listening. Tune in again next time when we do this again and as ever, your questions, comments, and suggestions are quite welcome. So that’s it. Thanks, Darryl.
DARRYL: Hey, thank you, Howard.
HOWARD: That wraps our pod for today. Thanks for visiting the CNS Podcast. Please check back soon for the next in the series and visit our website, www.cnsproductions.com