An Introduction to Psychedelic Tryptamine Chemistry

An Intro to Tryptamine Chemistry

Originally published: http://altdotmind.com/an-introduction-to-psychedelic-tryptamine-chemistry/


The ensuing series of articles are intended for the general reader that, like myself, have an appreciation for the beauty of chemistry, and/or desire to learn more about it. That being the case I am going to be pedantic throughout the articles, deconstructing technical terms and “dirty pictures”* with the assumption that you do not know what they mean. That way we can learn them as we go along. If you are already fluent in Chemistrian, it goes without saying that you are free to skip over these and peruse selectively. This first article is an introductory exploration of the tryptamine class, and will be followed by further forays into other interesting aspects related specifically to this class before I move on to the others. Enjoy.

The Three Main Classes of Psychedelics

There are three classes to which most psychedelic compounds belong – the tryptamines, phenethylamines, and ergolines (Figure 1). The tryptamines include most of the well-known naturally-occurring psychedelics, including compounds derived from entheogenic fungi (psilocybin and psilocin), DMT, 5-MeO-DMT, bufotenin, and ibogaine. Mescaline is the only common naturally-occurring phenylethylamine, yet the class includes numerous well-known synthetic compounds such as MDMA and the 2-C’s. Ergolines most notable representatives include the naturally-occurring LSA and the semi-synthetic compound that turned on a generation, LSD.


Figure 1. Notable psychedelic tryptamines include (from top right): 5-MeO-DMT and bufotenin (Bufo alvarius), psilocybin and psilocin (Psilocybe mushrooms), ibogaine (Tabernanthe iboga), DMT (Chacruna viridis), and various analogs including: 4-HO-MET (pictured), 5-MeO-DiPT, DPT, MET, and 4-AcO-DMT. Notable phenethylamines include (from top left): Mescaline (Peyote), the 2C’s (Inventor Sasha Shulgin pictured), MDMA (MAPS logo), and a wide range of analogs including: Bromo-DragonFLY (pictured), DOM, DOI, and NBOMe. Notable ergolines include (from top): LSD, LSA (Ipomoea sp), and various analogs including: AL-LAD (pictured), ALD-52, and 1-P-LSD.

Tryptamines

Psychedelics of this class are all derived from tryptamine (Figure 2), a ubiquitous endogenous ligand and agonist of the human trace amine-associated receptor 1 (TAAR1). The name tryptamine is derived from its structural similarity to l-tryptophan (Figure 3), an essential amino acid and the precursor to both serotonin and melatonin.


Figure 2. Tryptamine consists of an indole ring connected to an amine through an ethyl attached to position 3.


Figure 3. L-tryptophan

Substituted Tryptamines

Although the “template” for psychedelics tryptamines is the molecule with all the various positions presented in Figure 2, in actuality, there are limitations to how this manifests in psychedelic compounds. This is either because certain modifications are either difficult to impossible, or they lead to inactive compounds. An example of this is if something is attached to position 2 (Figure 2) the compound becomes a serotonin-2A receptor antagonist therefor losing its psychoactivity. Based on these restrictions we can simplify the template presented in Figure 2 to Figure 4, which is called the ‘substituted tryptamine’. The three main changes that synthetic chemists can make to derive psychedelic analogs is derived from this figure.


Figure 4.

First, one can add side chains to either position 4 or 5, and those side chains have to contain an oxygen molecule. We can confirm this by looking at all the well-known psychedelic compounds that have side chains attached to the ring – bufotenine has a hydroxyl (OH) group at position 5, 5-MeO-DMT has a methoxy (O-CH3) at position 5, psilocin has a hydroxyl (OH) group at position 4, and psilocybin has a phosphoryloxy (OPO3H2) at position 4. All at position 4 or 5, all with an oxygen included.

The second major change that can be made is a substitution at the α-position. Chemists can methylate (add a methyl group) the alpha-position to change a non-orally active species into one with orally active. We will explore this in full detail in the next article.

The final feasible change is adding sidechains to positions N1 or N2. All five of the major naturally-occurring species we have discussed thus far possess methyls at both positions (hence “dimethyl” from which the DM in DMT is derived – more below). These methyls may be substituted with more complex alkyls, another way in which chemists can turn non-orally active tryptamines into orally active species.


Psychedelics Tryptamines

Now that we have an idea of the chemical “archetype” of tryptamine psychedelics and the possible changes chemists can make, let’s have a look at the five most well-known naturally-occurring examples: DMT, 5-MeO-DMT, bufotenin, psilocybin, and psilocin.

DMT

The substitutive name for DMT is N,N-dimethyltryptamine. One of the most magical parts of learning chemical language is that from it one can deduce what they actual molecule looks like, and vice-versa. Let’s explore that using DMT as an example. Starting from the back we have tryptamine (blue), so we know that is the foundation of our molecule – the indole ring with an ethyl in position 3 attaching to an amine. Then we have “dimethyl” (red), meaning two methyls. Okay so now we know it’s the tryptamine molecule that has two methyls added to it. And where are these two methyls? They’re both positioned on the nitrogen of the amine, hence ‘N,N’.


Figure 5.

What’s interesting about N,N-dimethyltryptamine is that it forms the foundation for all four other compounds we are going to discuss. In other words, all four of them are N,N-DMT with a little something extra. We can see that because the term is contained within the substitutive name of all four other molecules. Let’s have a look.


5-MeO-DMT

The substitutive name for 5-MeO-DMT is 5-methoxy-N,N-dimethyltryptamine (Figure 6). We can see that it has the whole name of DMT in it, so when we draw it we know we can start with that molecule – a tryptamine with two methyls on the amine (red and blue). What’s left is ‘5-methoxy’, which means that at position 5 we have a methoxy (green). A methoxy is a combination of a methyl and an oxygen – hence the name.


Figure 6

Bufotenin

The substitutive name for bufotenin is 5-hydroxy-N,N-dimethyltryptamine (Figure 7). As was the case with 5-MeO-DMT, the molecule has DMT as a starting point (red and blue). But this time, instead of a methoxy at position five, we have a hydroxy, -OH (green).


Figure 7

Psilocin

The substitutive name for psilocin is 4-hydroxy-N,N-dimethyltryptamine (Figure 8). Same story, it starts with the structure of DMT (red and blue). If we compare them, we can see the psilocin is extremely similar to bufotenin, the only difference being where bufotenin had the hydroxy at position 5, here it’s at position 4 (green). In a future article we will learn why this small change is crucial to ensure that psilocin, unlike bufotenin, is an orally active species.


Figure 8

Psilocybin

The substitutive name for psilocybin is 4-phosphoryloxy-N,N-dimethyltryptamine (Figure 9). By now I’m sure you’ve grokked it – it’s a DMT molecule (red and blue) with a little something extra. As with it’s cousin psilocin, that something extra is at position 4, but here instead of a hydroxy, it’s a phosphoryloxy with the composition OPO3H2 (green).


Figure 9

All five molecules and their substitutions are reviewed in Figure 10 below.


Figure 10.

In the next article, we will continue to explore psychedelic tryptamine chemistry by looking at the two changes synthetic chemists can make to DMT and 5-MeO-DMT to make them orally active.

Cover Image by Greg A. Dunn (www.gregadunn.com)

* = Sasha Shulgin used to affectionately refer to organic molecule structures as “dirty pictures”.



About the Author

Faan Rossouw was born and raised in Cape Town (South Africa) and currently resides in Montreal (Canada). He holds a MSc in Plant Science, and is the co-founder and Chief Strategy Officer of Indeeva Biomedical, a medical cannabis company that focuses on producing condition-specific cannabinoid therapeutics. Faan possesses theoretical expertise and practical experience in biological production systems, natural and pharmaceutical product development, phytochemistry, and psychopharmacology. Though his background is rooted in science he is most passionate about, and thrives in, the intersection of science, the humanities, and commerce. He is interested in how we can leverage the properties of the new global economy to develop superior and sustainable therapeutic solutions. In his free time he loves to practice Brazilian Jiu Jitsu, spend time in nature with his partner Robyn, or kick back in his lazy boy with a book, a cup of pu-erh tea and his cat Luna.

Be sure to check out Faan’s site – alt.MIND


Ibogaine Treatment: A Psychedelic Answer to Opiate and Heroin Addiction

The use of heroin and abuse of opiate pain-relievers has reached an all-time high in the USA. The addictive nature of these drugs has left us scrambling for treatment options that can offer us freedom from this epidemic.

The fact is, traditional treatments don’t work for everyone, and many are starting to look for more effective alternatives. Treatment that results in long-lasting sobriety is different for each individual.

When a traditional method isn’t working, it may be time to consider something new. Ibogaine is one such treatment, and the rise in opiate addiction has led to an increased interest in this alternative treatment for opiate and heroin addiction.

Iboga and Ibogaine

Ibogaine is just one of the many alkaloids found in the Tabernanthe Iboga shrub. Raw Iboga is one of the most powerful psychedelic plants in the world and has been used for its profound spiritual effect on those who experience it.

Iboga plant and Ibogaine molecule. Photo: Samwise – via Chacruna.net

This is why, for centuries, the Bwiti religion of Africa have been using Iboga as a way to induce introspection and a higher self-awareness.

In the early 1900s Ibogaine was extracted from the Iboga root and used by athletes, in very small doses, as a stimulant. At the time, Ibogaine was used because of the way that it excites certain pathways within the brain.

But in the 1960s, all of that changed.

Ibogaine as an Addiction Treatment

Howard Lotsof was suffering from an addiction to heroin when he tried Ibogaine for the first time in 1962. He was 19 years old and experimenting with any substance he could find.

Hours after trying the Ibogaine, Lotsof had an epiphany—he had not taken opiates for almost a day, yet, he had no withdrawal symptoms.

He waited, but the withdrawals never came.


Howard Lotsof. Source: https://psychedelictimes.com/iboga/the-legacy-of-ibogaine-therapy-pioneer-howard-lotsof/

Ibogaine had allowed Lotsof to break his heroin addiction with just one dose. He knew immediately that these implications could have a massive impact on others who were struggling with heroin and opiate addiction.

But, given the importance of this conclusion, Lotsof realized he needed to perform further testing. So, he rounded up a few of his opiate and heroin-addicted friends, gave them the Ibogaine, and the results were stunning—none of his friends went into withdrawal.

This was the beginning of Ibogaine treatment for addiction. As Lotsof introduced more and more studies on the effects of Ibogaine on withdrawal, it became a real point of interest for scientists who were looking for more effective ways to help addicts beat their dependence.

Unfortunately, this also came at a time when the US government began making psychoactive substances illegal. Ibogaine was classified as a Schedule 1 drug, putting it in the same class as the drugs that it was meant to treat. It also made it very difficult for scientists to study its positive effects on addiction.

Lotsof was forced to study Ibogaine and treat addicts in Europe, where he founded the Global Ibogaine Therapy Alliance. He worked hard to try and change the laws in the USA and other countries, but, unfortunately, lacked the resources he considered necessary to do so.

 


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How Does Ibogaine Treat Physical Withdrawal?

Ibogaine has a unique effect on the chemical levels in the brain.

When the addict begins using opiates, these drugs release massive quantities of chemicals that plug into the brain’s neurotransmitters.

The brain becomes addicted to these high levels of pleasure-inducing chemicals, changing the way that the brain would normally function.

Because of these addictive adaptations, when the supply of drugs is cut off, the brain goes into a frenzy. Depression, seizures, and other symptoms are often the result. This is what we call withdrawal.

Ibogaine has the ability to work on the chemical receptors in the brain. It repairs neurons in the brain that have been damaged due to opioid addiction. It also restores balance to the brain so that naturally produced chemicals can work properly to control feelings of pleasure and happiness.

This gives addicts a fresh start, and the ability to start focusing on changing their lifestyle, instead of just fighting withdrawals.

But Ibogaine doesn’t just treat the withdrawal symptoms, it also affects the brain on a psychological level.

Psychological Effects of Ibogaine

In many addicts, though not all, Ibogaine induces a dreamlike state.

Those who have experienced this state often say that Ibogaine made them face their fears, past traumas, and helped them conquer many of the underlying reasons that caused their addiction in the first place.

This kind of psychological clarity and introspection is unique to the effects of Ibogaine and psychedelic medicines.

This is also why Ibogaine has been recommended, by some, as a treatment for trauma and other mental conditions—such as depression, anxiety, and PTSD.

The psychedelic effects of Ibogaine have the ability to treat these mental issues in ways that therapy never could. Some describe it as taking a look at themselves from the outside in, finally being able to address the core of their problems and address the root cause.

Is Ibogaine Right for You?

Just like any other treatment method, Ibogaine requires close supervision from medical professionals. Because of the way Ibogaine reacts in the body, it can be dangerous. This is why it is recommended that Ibogaine treatment should be done in a medical setting.

No treatment is risk-free, and it’s important to be educated before undergoing treatment with Ibogaine.

Addiction is a deeply personal disease and one that requires a different type of treatment for every individual. Ibogaine is not for everyone. It’s important to look into all of your options and talk to your physician.

Sobriety is possible. Every individual deserves a happy and successful life. Take the time to study all of the treatment options available and make the right decision for you or your loved one.


About the Author

Aeden Smith-Ahearn

Aeden Smith-Ahearn was a massive heroin addict for 7 years. After trying every traditional treatment method available, he put his last hope into Ibogaine treatment. Now, he has been clean and sober for 5 years while also helping thousands of addict find freedom through Ibogaine. He is currently the treatment coordinator for Experience Ibogaine (https://ExperienceIbogaine.com) treatment centers and works hard every day to help people find success and happiness in life.


For the Use of Entheogens – Ibogaine

Ibogaine Ceremony

How can we use our mind, intellect, or heart to diffuse or address the origin of our problems that arise from the same place?

David Stetson – Oka Center


Iboga, Ayahuasca, Kambo, and 5-MeO-DMT have wandered from their origins and into our western culture during an ominous time for humanity – a time that is naturally calling for healing and metamorphosis. At Oka Center, it is our privilege to work with and integrate these medicines with their traditional uses into our lives and the lives of all who come here.  Each guest brings benefits to all who are involved.

For us, the traditional use of entheogens is just as important (or more) as the recently developed ideology and protocols created by western doctors, scholars, and laypeople.  Westerners have only recently started using these medicines significantly within the last 50 – 60 years. Traditional indigenous use is centuries old – perhaps older according to many – and comprises the vast majority of experience with these powerful medicines, not to mention their original discovery. Generations of use has naturally given rise to refined protocols, beautifully disarming spirituality, sublime music, and just the right amount of humor. We include standardized western medical guidelines to ensure safety which is imperative, but not intrusive. Particularly with ibogaine, it is of utmost importance to have medical prescreening, monitoring, and supervision before, during, and after the treatment.

We are grateful for the research and empirical data that has helped to assess the risks and benefits of Ibogaine and other entheogens, particularly from Ken Alper and the late Howard Lotsof.  At the same time, the new trend in attempting to fit entheogens into the framework of the western medical schema is questionable.  



Since there are enough anecdotal reports that suggest so many applications and benefits of these entheogens, it makes sense to try and “legitimize” them in order to make them available in our healthcare system. However, we need an honest review of our healthcare industry – especially within the mental health sector – to gauge how genuine a reference point our system is for validating or practicing any medicine or modality, especially for plant-based medicine which is off limits for patenting.



The enormous profit margins of the healthcare industry would be significantly reduced if lifelong prescription medications were no longer considered final solutions to common mental “disorders.”  You need only do minimal research on the ruthless financial methods and ethics of the healthcare industry to come to some disturbing conclusions.  In our experience, many people coming to Oka Center have reached a point at which their ongoing use of prescribed medications has provided no change or only damaged their situation further.  

For those of you who want to get off hard drugs and have heard about the medicinal value of plant medicine like ibogaine, you might not see the relevance of its traditional use.  Perhaps you have come to ibogaine because of its ability to alleviate opiate withdrawal or interrupt addiction, or your friend of a friend got off dope with ibogaine and it was miraculous.

While we do not force our ceremonially based protocol on anyone, almost everyone – including those coming to get off hard drugs – respond very positively to it. In the end, it is embraced and appreciated as an important element of the healing process.

Ruptured spirituality is common to everyone that comes to Oka Center – drug use or not: We are broken, tired, angry, bored, confused, stressed, frustrated, and oftentimes infinitely sad. Reflection, prayer, song, and dance may seem frivolous at first, but these things are much needed in our lives and are important in respecting the medicine and for laying the groundwork for your experience.


Oka Center - Ibogaine Center in Mexico


In many ways, our western culture has separated itself from nature. As individuals, we have lost an innate intelligence or awareness because of it. What might have been awe and wonder has been replaced with sarcasm and cynicism.  Although our advancements in technology and industry have paved the way for practical efficiency and comfort, the downside is that it is getting increasingly easier to forget where we come from and where we are going. It is normal for us to feel alienated and unhappy in such a competitive, indifferent society built with concrete, computer chips, and suffocating ethical standards and expectations.  Hard drug use is an appropriate response as any attempt to get through each day with a smile on your face.

Whether it is drugs, alcohol, gambling, depression, anxiety, exhaustion, or whatever else we have adopted or suffered from in the attempt to get by, somewhere along the line we realize discomfort, harm, and despair. Naturally, this is when we look for a way out of these negative cycles.  

Beyond a certain point, to truly view and examine ourselves deeply and objectively in waking life can be almost impossible. The attempt at doing so most often ends up being more of the same self-deception. How can we use our mind, intellect, or heart to diffuse or address the origin of our problems that arise from the same place?  

This is one of the main reasons why we advocate for the use of entheogens. The incessant internal rapport we have with ourselves never allows us to look beneath the masks we have created which project the flawless versions of ourselves we present to the world. Entheogens have a way of blasting our masquerade into pieces. With any luck, we are left with a beautiful nightmare that shines a light on our humanness: our fallibility, our fragility, our innate goodness, and our capacity for softness and empathy toward others because at the very root, we all share the same capacity for madness and beauty.


David Stetson, Oka Center, Yucatan Mexico

David Stetson - Ibogaine Facilitator

David’s passion has been Bwiti since his Iboga initiation in 2007. David is extensively well-traveled in Gabon, Africa where he is known as Okukwe.  During his time in Gabon he learned Bwiti traditions, music, and ceremonial practices and is proficient on both the moungongo (musical bow) and ngombi (harp) instruments. David views Bwiti and Ibogaine as a lifeway that champions communion with others while also empowering the individual.  His approach to working and healing with others starts with the awareness of alienation and isolation as common and appropriate responses to our western culture, and is based in non-judgement. Learn more about Oka Center here and check out David’s podcast interview with us here