The psychedelic experience comes out of our relationship with nature. As our ancestors foraged for mushrooms or drank beer made from ergot-infested barley, they stumbled upon substances that can have the most profound effect on the mind. Ancient ritual use developed, sacraments were lauded, mother nature’s gift was revered. As science progressed we began unpicking the building blocks behind these agents of sacred revelation. We discovered that they were chemicals, that they affect the brain, that they might be used to profound effect in psychotherapy. While there are parts of the psychedelic community that keep the traditional ways alive — drinking ayahuasca in the jungle with Shipibo healers, for example — there are other parts of the community look to a future where it is us, not mother nature, who gets to design the sacraments. Let’s get into discovering new psychedelic drugs and what that entails.
The Target of New Drugs
Traditional healing, as is found in shamanism and curanderismo, often involves diagnosing and resolving the causes of one’s suffering in the complex environmental and interpersonal web of influences that impact one’s life. Western medicine, on the other hand, seeks to break down and isolate symptoms and treatments, to put the messy complexity of being an interconnected being into neat little boxes. This latter approach has its flaws but it also has near unimaginable power. We now understand the structure of things, such as psychedelic compounds, that cannot be seen with our eyes. What’s more, we’ve identified how these compounds interact with the brain to initiate a psychedelic experience. We now know that a particular serotonin receptor subtype, the 2A receptor, is responsible for the psychedelic experiences. Block this receptor and you block the experience.
The Psychedelic Rupture in Modern Medicine
In Western medicine, individual chemicals are often prescribed to the patient in the hope that they will act directly on the brain basis of the psychological symptoms the person is suffering with. Are your airways constricted? Try forcing them open with the chemicals found in an inhaler. Feeling low? No need to ask why, why not tweak your neurochemistry directly to get rid of that pesky feeling? Despite being mere chemicals, psychedelics disrupt this approach by forcing us to confront the holistic nature of our existence. In states of ego dissociation we see how fully embedded in, and deeply connected with, the rest of reality we are. Psychedelics will undoubtedly reshape mental healthcare in the modern medical system, but, at the same time, that system is attempting to wrestle the complexities of psychedelics into the old frameworks that have worked for other pharmaceuticals.
The pharmaceutical industry is a major part of modern mental health treatment. As the most exciting development in this area in half a century (since the last time psychedelics were being hailed as a revolutionary breakthrough, before being made illegal) it is this industry that is attempting to roll out psychedelics to the masses. As businesses working within a market economy they must find a way to profit from this endeavor. It isn’t possible to patent, and thereby claim the profits from the use of, an already existing psychedelic. If you can invent a new one, however, you may be able to do just this. As a result, there is a large incentive for these companies to develop new psychedelic drugs.
Why New Drugs?
Of course, profit isn’t the only incentive when it comes to exploring novel psychedelics. Different naturally occurring psychedelics have different properties that make them useful for different therapeutic purposes. MDMA appears to be particularly useful for healing trauma, while high-doses of psilocybin appear to reliably occasion theoretically beneficial mystical insights that have helped those struggling with end-of-life anxiety and depression. What if there are new compounds that can treat other conditions that we have not had luck with so far? And what if we can change certain aspects of already existing psychedelics? Wirth therapy being so expensive and a psilocybin journey taking hours, for example, perhaps we could create a drug that condensed the trips into the duration of a one-hour therapy session. Such hopes are part of the quest for novel psychedelics.
Tripping Without the Trip
The logical endpoint of the reductionist, biomedical approach to psychedelics treatment si to ignore holism and complexity all together and insist that the effects must be purely neurochemical. If this is the case, why not produce a psychedelic that has the same biological effect but without the pesky profound experiences? Why not make a mind-manifesting substance (the meaning of psychedelic) that doesn’t manifest the mind? This may sound ridiculous but it is actively being pursued by pharmaceutical companies. Whether it will be possible is still unknown. What is also unknown is whether we would even still consider such a compound, one that had no psychoactive effect, a psychedelic.
How might one go about making a new psychedelic? First, a grip on the basic science of psychopharmacology is necessary. As mentioned above, classical psychedelics such as LSD, psilocybin, DMT & 5-MeO-DMT all act on the serotonin system. MDMA does as well, but not on the 2A receptors like the others. They have this effect because they are structurally similar to serotonin, and so they can slot into the same lock and key mechanism that serotonin does. Other substances are more similar to dopamine, yet still, slot into the serotonin 2A receptor.
Mescaline is one such substance. The dopamine-like chemicals are known as phenethylamines while the serotonin-like chemicals are known as tryptamines. Different psychedelics vary the peripheral chemical ornamentation that occurs around their central structure. Manipulate this ornamentation and you may have a new psychedelic on your hands with its own unique chemical structure.
Once a new chemical compound has been created the only thing left to do is to try it out and see if it is psychoactive. This most definitely should not be tried at home. A master chemist who did try this at home was Alexander “Sasha” Shulgin, along with his wife, Ann. Together, the Shulgin’s produced two works of classic psychedelic literature. In these tomes, they document the creation of a vast range of new psychedelics and describe their subjective effects by dose. These books are PiHKAL: A Chemical Love Story and TIHKAL: The Continuation. PiHKAL stands for “Phenethylamines I Have Known and Loved” while the sequel, TIHKAL, stands for “Tryptamines I Have Known and Loved”. In PIKHAL they documented the creation of the 2-C family of psychedelics, which includes compounds such as 2-CB and 2-CI. Such drugs have been sold for years since their creation as “research chemicals”, their novelty making it hard for states to ban them. N-Benzyl Derivatives or NBOME’s represent another class of novel phenethylamine.
New Psychedelics Today
With the Shulgins having done such a thorough job of exploring the creation of new psychedelics, modern drug development companies have their work cut out for them. Most of what is being argued to be “novel” in the contemporary psychedelic space turns out to be simple variations on already existing substances. For example, the pharmaceutical startup Compass Pathways was granted a patent for a form of psilocybin they called comp360. Despite the claims of novelty, however, it is still psilocybin. The same is true for esketamine, a molecule that is nearly identical to ketamine.
Do We Need More Psychedelics?
For some, the approach of treating different conditions with different psychedelics is unnecessary. Such people argue that we have plenty of psychedelics as it is, we just need to use them as tools in our own journeys of personal growth and healing. On the other side of the spectrum are those pragmatically looking at how to fit this revolutionary healing modality into the current medical healthcare system. To them, psychedelics with different properties are hugely appealing and are the way forward. Thankfully, we won’t be forced to choose between these options. Drug development will continue, as will traditional plant medicine use. It seems as though the number of options we have when it comes to taking a psychedelic is only set to increase in the coming years and decades.