Although mounting evidence suggests that psilocybin, the psychedelic compound found in Psilocybe mushrooms, could be effective in treating depression, evidence that it also helps with suicidality remains mixed. Some studies, mostly observational, suggest it could be helpful, while others do not. Recent topline results from a clinical study conducted by psychedelics company Compass Pathways even saw suicidal ideation crop up as an adverse reaction.
Suicide is a leading cause of death, with more than 800,000 people taking their own lives annually worldwide. So if psilocybin could mitigate suicidality in the same way it relieves depression, rapidly and persistently following a single dose, it could be a game changer.
But suicidality, defined as suicidal ideation or attempted or completed suicide, is a complex phenomenon. Not simply the far end of the depression spectrum, suicidality is associated with multiple psychiatric conditions and patient populations. As with much in the nascent field of psychedelic medicine, researchers need more data to understand psilocybin’s potential.
In a single but promising step forward, a new paper in the American Chemical Society journal Pharmacology and Translational Science suggests psilocybin could show promise in reducing suicidality in at least one of those patient populations: people facing a life-threatening cancer diagnosis.
In cancer patients assessed as having an elevated level of suicidal ideation, a single session of psilocybin assisted psychotherapy significantly reduced their levels of suicidal ideation within hours, an effect that persisted for months.
“If this is a real effect, if psilocybin is a rapidly acting anti-suicidal agent in people that have cancer-related psychiatric and existential distress, and if it lasts something like six months, that’s a very big deal,” said Stephen Ross, a psychiatrist, first author of the paper and Director of the NYU Langone Health Center for Psychedelic Medicine.
Diagnosed cancer patients see a four-fold increase in the risk of suicide over the general population driven by a set of demoralizing factors, including anxiety, depression, and especially a sense of loss of meaning, which is “highly correlated with passive suicidal ideation,” Ross said. “This is a form of existential distress, where people kind of give up, lose hope.
Many people given psilocybin in clinical trials have reported the experience to be one of the most meaningful in their lives, and Ross and his colleagues hypothesized this effect on the perception of meaning could help cancer patients at risk of suicidality. And in their new analysis, they did find a significant decrease in reported levels of loss of meaning in individual study participants.
“That was the most robust finding from our secondary analysis,” Ross said. “That psilocybin produced reductions in loss of meaning that was acute at a couple of weeks, and then may have even persisted for several years.”
There are, however, some caveats to the findings.
First, the new study is a secondary analysis of data from the 2016 NYU Langone Health Center/ Bellevue Hospital clinical trial. “The study was not designed to look at suicidality,” Ross said, but to study whether psilocybin could help cancer patients dealing with depression and anxiety.
The 2016 trial randomly assigned 29 cancer patients to receive either psilocybin or niacin as a placebo control. Designed as a cross-over study, patients who received niacin in the first session received psilocybin in a second session, and vice versa, seven weeks later.
The new, secondary analysis focused on a smaller subset of 11 patients from the 2016 trial that showed elevated signs of suicidal ideation and loss of meaning in their assessments from before taking psilocybin. That small sample size is another caveat for the new findings.
Ross and his colleagues found no significant difference in suicidal ideation and loss of meaning between participants who received psilocybin and those who rceived the placebo, though he noted the small sample size made it difficult to measure such an effect. But at the same time, participants who received psilocybin did see a significant improvement in their suicidal ideation and loss of meaning scores over their own base lines, a result not seen among the participants receiving the niacin placebo control.
To really understand if, how, and how much psilocybin can help reduce suicidality will require studies with more participants, studies specifically designed to assess psilocybin’s effect on suicidality in different related conditions.
“We need to design trials that can specifically answer the question, ‘does psilocybin therapy help with suicidality, in X condition?’” Ross said. “It could be cancer depression, it could be regular depression, it could be something else.”
If past psychiatric drug development is any indication, the truth could take a while to tease out.
Though considered miracle drugs when they first hit the market, Ross said, selective serotonin reuptake inhibitor (SSRI) antidepressants such as Prozac eventually received a black box label warning from the FDA after research using large datasets showed they could paradoxically increase suicidality in some people, particularly adolescents. It’s possible, in other words, that a drug that successfully treats depression could nevertheless increase suicidality.
“You have a scenario where a very depressed person is given an antidepressant,” Ross said, “And then suddenly is activated and has enough energy to go and kill themselves.”
It’s not clear yet if such a dynamic was at play in the increase in suicidal ideation reported in the Compass Pathways clinical trial, and Ross said he has no direct insight into that work. It’s also possible, given the importance of set and setting in psychedelics use, he said, that differences in the Compass Pathways preparatory psychotherapy component compared to other psychedelic therapy trials could have been a factor.
Nothing is certain yet, and given the already complex relationship of suicidality to other psychiatric conditions, it may be a while before researchers can hold up solid evidence of psilocybin therapy’s impact on suicidality.
“We need much more data,” Ross said. “It’s small studies here and there. They really don’t mean anything unless you do bigger studies. Bigger datasets, that’s when the truth really emerges.”
Image: Nicki Adams