Psychedelics have shown great promise in treating major depression, post-traumatic stress disorder, and substance abuse disorders. An issue that constantly stands in the way of their approval and widespread use is that they are, indeed, psychedelics. This is basically why their use is limited in Australia where they have been approved. It is why we expect to see restrictions of how they can be used when they are legalized for treatment in the USA. This issue is a big part of why scientists are synthesizing similar chemical compounds with the goal of replicating the benefits of psychedelics without giving people a psychedelic high. So, do non-psychedelic psychedelics work?
Studies of Nonhallucinogenic Psychedelic Analogs
Science has a very long and very dense article about research on nonhallucinogenic psychedelic analogs. Our goal here is to provide an understandable synopsis of what is known so far. Psychedelics on the biomolecular level create their therapeutic effects by binding the serotonin 2A receptor called 5-HT2AR. Researchers looking to create non-psychedelic psychedelics have synthesized compounds using a nonhallucinogenic drug, lisuride and serotonin itself. They used arrestin-biased ligands. Ligands are compounds which are chemically bound to a metal atom. Arrestins are proteins involved in brain receptor signaling. The bias refers to the ability of chemicals to bind to many receptors. The point of this was to create chemicals that acted similarly to psychedelics with the hope of cutting out the hallucinogenic effects.
Testing Nonhallucinogenic Psychedelic Analogs
Theory is great but proof of concept comes from giving medicines to living creatures and observing the results. When new drugs are being tested they are almost always tested on animals before they are given to humans. Such is the case with the various compounds that the researchers synthesized in search of medicines that have all of the therapeutic benefits of psychedelics but do not cause hallucinations. They tested the new drugs on mice. They found antidepressant activity without evidence of hallucinations.
Mice Lie and Monkeys Exaggerate
Mice are mammals like humans. Thus scientists expect to see similar reactions as well as side effects when testing medicines. However, they are not humans so researchers need to be careful with their conclusions. This is why the next step in testing is often to give the same sorts of drugs to monkeys which are primates and more closely related to humans. The reason that these medicines need to be tested eventually on humans is because testing in animals, while helpful, can be misleading. During the race to produce a vaccine for preventing Covid-19 a vaccine researcher commented that mice lie and monkeys exaggerate so they needed to wait for human trials to make sure that a vaccine would work. Such will be the case with the search for nonhallucinogenic compounds that work as well as psychedelics like psilocybin and MDMA in treating conditions like PTSD and severe depression.
Theory, Trial and Error in Psychedelic Research
Chemists can predict what sorts of chemicals are needed to mimic the effects of psychedelics. It turns out that there are a lot of possible combinations. The researchers are making educated guesses, synthesizing chemical compounds, and then testing them. The most important part of this is not to see if the drugs work but that they do not have bad side effects. Only when such medicines have passed successfully through the animal testing stage will use on humans be considered. The drugs need to show evidence that they work as intended and cause no harm, first in animals, and then at every stage of testing on the way to approval for therapy in humans.
Are Non-psychedelic Psychedelics Necessary?
Those who are enthusiastic about psychedelics may say that all of this is wasted effort. However, the fact remains that unrestricted use of medicines that cause hallucinations will probably never happen. This research does nothing to impede the progress of medicines like psilocybin or MDMA in getting approved for treatment of PTSD and depression. What is going on here is what always goes on in the background in the pharmaceutical industry. They are always trying to better understand how medicines work and to improve upon them. They do this because they are interested in the science and because a medicine that works to cure PTSD or depression without any side effects would be a huge money maker for whomever discovered it and took it through clinical trials.