Here’s Why Psychedelic Drug Therapy May Not Work For Everyone

In the new study, researchers from the University of North Carolina at Chapel Hill expanded on existing research exploring the role of the serotonin 5-HT2A receptor in responses to non-psychedelic drugs.

The UNC researchers focused on seven variants caused by a change in a single DNA building block in the receptor gene, known as single nucleotide polymorphisms (SNPs). These SNPs occur in 0.003% to 7.9% of people, the authors wrote in the article.

Working with human cells in a lab, the researchers ran tests to see how different psychedelics (psilocin, mescaline, 5-MeO-DMT, and LSD) bound to these receptor variants. (Psilocin is the active psychedelic compound found in psilocybin mushrooms.)

The tests showed that the receptor variants produced “statistically significant, albeit modest, effects” on the potency of these four psychedelics, the researchers said, at least in the laboratory. The effects also depended on the specific combinations of drug and receptor variants.

“Genetic variation in this receptor has been shown to influence the response of patients to other drugs,” hinesPhD, an assistant professor of neuroscience in the department of psychology at the University of Nevada, Las Vegas, who was not involved in the new study, told Healthline.

“While psychedelic therapies can provide rapid and sustained therapeutic benefits for multiple mental health problems, there is a proportion of patients who do not respond.”

According to Hines, genetic variations in this serotonin receptor may contribute to psychedelic therapy not working for everyone. She said that two previous studies in 2020 Y 2021 found that about a third of people with depression did not respond to psilocybin treatment. An even smaller number of people experienced some kind of negative side effect to psychedelic treatments in general.

The UNC researchers concluded that future clinical trials may need to take into account the influence that genetics might have on how people respond to psychedelic treatments.

While genetics may play a role in many mental health conditions, it’s unlikely that a person’s DNA is the only factor that influences how people respond to psychedelic treatments for depression, anxiety, or mood. PTSD.

But Rachel YehudaPhD, a professor of psychiatry and trauma neuroscience at the Icahn School of Medicine at Mount Sinai in New York, said genetics may play little role in people’s varied responses.

“We already know the kinds of factors that could determine the response [to psychedelic treatments],” she said.

According to Hines, how a person responds to psychedelic treatment can also include their ability to engage in psychotherapy, their ability to be compassionate with themselves, as well as the severity of their trauma and how early in life it began.

Of course, these factors can affect any mental health treatment, not just psychedelic treatments. However, Yehuda noted that one factor that is specific to psychedelic treatments is the ease with which a person submits to the effects of a consciousness-altering drug.

“There is a very active way in which you can resist [psychedelic] and say, ‘I’m not going to do this,’” he said.

Hines added that variability in mental health conditions from person to person could also contribute to how well people respond to treatments, psychedelics or otherwise.

“Some people with depression may have a genetic predisposition that makes them more likely to experience depression in their lifetimes,” Hines said. “Other people facing depression may have more situational or environmental contributions.”

Hines noted that a person living with a mental health condition, such as anxiety, could potentially complicate the effectiveness of treatment.

Yehuda said that one of the challenges in determining how people benefit from a psychedelic treatment is defining what a “response” is. For example, it could mean that after treatment, a person no longer has the condition for which they were being treated, whether it be post-traumatic stress disorder, anxiety, or depression.

But another way to see a positive response to treatment is to notice improvements in your symptoms; they may not be 100% better or “cured”, but they are going in that direction.

While most people would expect a full recovery, even small improvements in symptoms can transform a person’s life. For some people, partial recovery may mean being able to go to a concert with a loved one. For others, it might mean getting comfortable in a crowd or talking to a stranger at a party.

“These little behaviors make up a life,” Yehuda said. “If you can start living your life again, reunite with your family in a different way and feel like you can take more risks and be a part of the world, that’s a really good thing.”

However, based on current research, many people fall into the first category of having a dramatic response to psychedelics.

“One of the things that has been impressive in psychedelic studies is that there is a large proportion of people who, at the end of the study, don’t have the condition that they had at the beginning,” Yehuda said. “It is certainly true with PTSD — there are a lot of people who went from having PTSD to not having PTSD, which is quite remarkable in terms of the level of response.”

Researchers like Yehuda are very excited about the large number of people who have had a clinically significant response to psychedelic treatments for mental health conditions.

And even with a proportion of people who do not respond, psychedelic treatments can still be of value.

“We have to keep in mind that patients in many of the clinical trials to date are treatment resistant and have struggled in some cases for many years before receiving psychedelic therapy,” Hines said.

Yehuda hopes that as the field of psychedelic research matures, clinical trials will need to be adapted to fit the reality of patient responses.

“A lot of [scientists] they are interested in testing psychedelics,” he said. “And hopefully these people know that you need to consider the possibility, or consider the probability, that there will be a variation in response.”

Research shows that around a third of people with mental health problems such as depression may not receive any benefit from psychedelic-assisted treatment.

While new research shows genetics may be a possible factor, other experts say the results of psychedelic treatments may ultimately vary by individual.

Future studies could focus on finding out who might and might not benefit from psychedelic-assisted treatments, as well as whether to adjust a person’s treatment when they don’t respond or try a different form of treatment. Of course, this process is similar to what happens with other forms of medical treatment.

“We really don’t want to ignore or write off people who don’t respond,” Yehuda said. “We need to start changing the conversation from ‘use this treatment, will it work’ to ‘how are we going to match patients to the many treatments out there?'”