Most psychedelics clinical trials have some degree of failure in that there are people in the trial who simply can’t tolerate psychedelics as a therapeutic option—usually called adverse events. Common adverse events include headaches, nausea, vomiting, diarrhea, and anxiety. Researchers expect that there are more serious adverse events that go unreported.
Indeed, these adverse events have not been well studied, even as researchers focus on harm reduction during clinical trials in the hopes of bringing in larger groups of participants.
Future studies should describe the timing and severity of effects more extensively, one study concluded, adding that full transparency about adverse events is “a responsibility of clinicians, particularly in a nascent field fueled by the enthusiasm of pioneering researchers.”
One well-known adverse event is the so-called “flashback” from LSD use. But it is considered rare and occurs almost exclusively in the context of illicit recreational use in patients with anxiety disorders, and it typically will have a limited course of months to a year.
But exactly how a certain psychedelic affects any one patient is still a bit of a mystery, according to one study. “Larger studies need to validly define the benefits of using hallucinogens as an adjunct to psychotherapy and the patient characteristics that may predict such additional benefits of hallucinogens. Unclear are the aspects of the acute response to hallucinogens that best predict good long-term therapeutic outcomes.”
Outside of clinical trials, patient tolerance of psychedelics, and the benefit they get from psychedelic therapy, are issues that have been addressed numerous times, mostly with positive results, such as in the 2015 study published in the Journal of Psychopharmacology.
Using a data set of 135,095 randomly selected United States adults, including 19,299 psychedelic users, the associations between psychedelic use and mental health were studied, resulting in no significant associations between lifetime use of psychedelics and increased likelihood of past year serious psychological distress, mental health treatment, suicidal thoughts, suicidal plans and suicide attempt, depression and anxiety. “We failed to find evidence that psychedelic use is an independent risk factor for mental health problems,” the study concluded. “Psychedelics are not known to harm the brain or other body organs or to cause addiction or compulsive use; serious adverse events involving psychedelics are extremely rare. Overall, it is difficult to see how prohibition of psychedelics can be justified as a public health measure.”
Much of the newer science and research by psychedelics companies is aiming at identifying and controlling the hallucination effect from psychedelics in the hopes of scaling up psychedelics therapies to a broader demographic of people seeking mental and physical help.
For example, a genetically encoded biosensor to detect hallucinogenic compounds has been developed by researchers at the University of California, Davis, called the psychLight. Researchers can use psychLight to see how naturally occurring neuromodulators like serotonin, or hallucinogenic drugs, act on different parts of the brain.
Another approach gaining acceptance is to try carefully measuring a micro-dosage of the psychedelic treatment as a method of avoiding any profound hallucinogenic experiences—Algernon Pharmaceuticals’ (OTC: AGNPF) DMT treatment for stroke is one example.
A more recent discovery helps shed new light on who can use psychedelics and who cannot.
University of North Carolina School of Medicine researchers, led by Dr. Bryan Roth, MD, who also leads the National Institutes of Health Psychotropic Drug Screening Program, reported in a study in July that one reason for treatment disparity could be common genetic variations in one serotonin receptor.
Their study results indicated that some gene variations—even ones far from the exact location where the drug binds to the receptor—alter the way that the receptor interacts with the psychedelic drugs.
“Based on our study, we expect that patients with different genetic variations will react differently to psychedelic-assisted treatments,” Roth said. “We think physicians should consider the genetics of a patient’s serotonin receptors to identify which psychedelic compound is likely to be the most effective treatment in future clinical trials.”
The researchers worked with psilocybin, DMT, mescaline and LSD. The research was financed in part by The National Institutes of Health (NIH) and the Defense Advanced Research Projects Agency (DARPA).
“This is another piece of the puzzle we must know when deciding to prescribe any therapeutic with such dramatic effect aside from the therapeutic effect,” Roth said. “Further research will help us continue to find the best ways to help individual patients.”