Dave Hodes
The psychedelic experience is intense.
As much as it can help someone understand and work through their mental health issues, the hallucinations that come with them are a significant part of the psychedelics experience that is what makes psychedelics the powerful and effective therapy that it is.
But as the industry evolves and looks to broaden the appeal of psychedelics, work is underway to change or even eliminate the hallucinogenic part of the experience.
To be sure, psychedelics are among the safest known classes of central nervous systems drugs that one researcher says may be the “oldest class of psychopharmacological agents known to man.”
One new way to modernize them into mainstream medicine use would be to offer a shorter or even absent hallucinogenic effect, which makes for shorter treatment periods and therefore less cost for the patient. That would also make taking psychedelics less risky for both the patient and the medical provider, while also increasing the likelihood of a buy-in from Big Pharmabecause a completely non-hallucinogenic psychedelic could even be taken by a patient at home just like any other pharmaceutical.
Better management or even eliminating the hallucinogenic effectin a clinical trial today could bring in more participants, since vetting potential participants in clinical trials means excludinganyone with a personal or family history of psychotic disordersthat could be exacerbated by the hallucinogenic experience.
Although research has shown that hallucinogens do not cause any physiological damage, adverse issues such as the so-called “bad trip” do occur, characterized by anxiety, fear, panic, and paranoia. This could be a brief experience, or could lead to prolonged psychosis. Researchers are still not sure why or how that happens in some individuals and not others, but reports like this do cause some patients who could benefit from psychedelics therapy to consider a different, more mainstream pharmacological approach.
The range of subjective experience under hallucinogens can be remarkably broad, a study noted, and clinical trial participants need to be made aware that sometimes people experience extremely convincing sensations of dissolving, melting, exploding—and are advised that the best way to deal with all such situations is to surrender to the experience, subjectively allowing themselves to dissolve, melt, or explode.
Surrendering to the experience—simply letting go of their need for experiential avoidance—is not something that people with mental health issues do easily, and in many cases, is an action that becomes totally reliant on where they are and who is monitoring them.
Then there are the cautions about negative interactions with psychedelics from other drugs, such as lithium, and even problematic reactions with dietary supplements like St. John’s Wort.
Work today with strong mind-mining medicines like psychedelics follows a carefully constructed process with strict guidelines to ensure a safe and effective treatment, such asestablishing trust and rapport between session monitors and volunteer before the session; creating a safe physical session environment; and providing interpersonal support from at least two study monitors during the session, according to one study. “Persisting adverse reactions are rare when research is conducted along these guidelines,” the study reported. “Incautious research may jeopardize participant safety and future research.”
It’s this “incautious research” issue that is driving a movement to create a non-hallucinogenic psychedelic and find a way of giving the patient the important benefits of hallucinogens without actually experiencing them.
Those specific hallucinogenic benefits in today’s psychedelics-assisted therapy are important, because even in cases where individuals reported strong ratings of fear or anxiety, the majority of these sessions were still judged as personally meaningful, and no volunteer rated the experience as having decreased their sense of well–being or life satisfaction.
But participants still had be ready to experience an uncomfortable moment or two, and still had to rely on a monitor to help them understand and ride through those sometimes scary feelings.
For all these reasons, and to help bring more focus to the medicinal side of the psychedelics experience, scientists have begun engineering psychedelics without hallucinogenic qualities.
For example, research on tabernanthalog—a water-soluble, non-hallucinogenic, non-toxic analogue of ibogaine that can be prepared in a single step—demonstrated that, through careful chemical design, it is possible to modify a psychedelic compound to produce a safer, non-hallucinogenic variant that has therapeutic potential.
Other recent work with mice has shown that it’s possible to create psilocybin and LSD without the hallucinogenic effect.
Another study with mice used a sensor—called psychLight—that glows in the presence of an hallucinogenic compound when it interacts with a serotonin receptor. It’s been used to identify previously unknown hallucinogenic drugs.
These next generation non-hallucinogenic psychedelics arebeing called a game-changer in psychedelic therapy, with companies such as Delix Therapeutics stepping up to the challenge of developing them. According to David Olson, co-founder and chief scientific officer of Delix, it is important to determine whether or not the molecular and circuit-level mechanisms mediating the hallucinogenic and antidepressant effects of psychedelics are distinct in an effort to better understand the neurobiology of mental illnesses. “From a clinical perspective, the implications are huge,” he said in an interview last year for Technology Network’s Neuroscience News and Research publication. “While I am very hopeful that compounds like psilocybin will one day be approved for treating depression or perhaps other brain disorders, I suspect that these hallucinogenic molecules will only be used as a last resort for a variety of reasons.”
