Newly published research on the psychiatric effects of psilocybin suggests a complicated, potentially bidirectional relationship between the psychedelic’s therapeutic effects and sleep. Taking psilocybin not only appears to reduce sleep disturbances in patients for up to four weeks, the study says, but sleep itself may actually modulate the substance’s benefits in a “complex yet prominent” way.
“Using our own preliminary-data, we demonstrated that both depressive-symptoms and sleep-disturbances decreased significantly following psilocybin use, though sleep improvements were smaller compared to depressive symptoms,” authors explained in the new paper, published last month in the journal Current Psychiatry Reports. “More severe sleep-disturbances at baseline were linked to lower probability of depression remission, underscoring a potential interaction between sleep and psilocybin’s efficacy.”
The four person research team behind the report represents the Johns Hopkins School of Medicine, the University of California San Francisco, Imperial College London and the University of Amsterdam. They noted that past research has largely ignored psilocybin’s potential influence on sleep.
“Whilst clinical trials demonstrate large depressive symptom improvements,” they wrote, “the impact of psilocybin on sleep quality or insomnia symptoms, has not been directly studied.”
Data for the new study came from 886 adults who had expressed an intent to use psychedelics in the near future. Researchers looked specifically at 653 subjects who reported plans to use psilocybin, “given that it has the greatest clinical relevance to depression,” the report says.
Participants filled out a 16-item questionnaire about depression symptoms, which included “four items assessing sleep onset insomnia (Item 1 ‘Difficulty falling asleep’), sleep maintenance insomnia (Item 2 ‘Sleep during the night’), early morning insomnia (Item 3 ‘Waking up too early’), and hypersomnia (Item 4 ‘Sleeping too much’).”
“Sleep complaints were prevalent amongst participants, with all 653 participants reporting at least some degree (score ≥ 1 out of 3) of sleep disturbance at baseline,” the study says. “Remarkably, amongst these participants, sleep disturbance was the principal depressive symptom (26%), marginally outnumbering mood/cognition complaints (25%).”
Results showed “a significant decrease in sleep disturbances” following psilocybin use.
“The magnitude of the decrease in sleep disturbance was small,” authors wrote, “but larger effects were observed when the analysis was restricted to participants who demonstrated moderate to severe (sleep scale ≥ 2) sleep disturbances” at baseline.
As for depressive symptoms, meanwhile, the study found a significant, “moderate to large” decrease over the study period.
In addition to showing what they called “significant improvements in sleep disturbances for up to four weeks after psilocybin use,” authors said the results also suggested an interesting relationship between sleep and depressive symptoms among study participants.
Specifically, sleep disturbances during the study period tended to predict depressive symptoms in participants. But depressive symptoms didn’t seem to predict disturbances in sleep.
“Residual sleep disturbance following the psilocybin interventions predicted depressive symptoms at subsequent timepoints,” the study says, “whereas post-treatment depressive symptoms failed to predict subsequent changes in sleep.”
“Taken together,” it continues, “these observations provide convergent evidence of a potentially prominent link between sleep and psilocybin’s therapeutic action.”
As for the mechanism underlying the observation, authors said results “could be interpreted through three plausible pathways”:
1) sleep improvements may be causally involved in the therapeutic pathway of psilocybin’s impact on depressive symptoms, either directly or indirectly, 2) poor sleep may directly interfere with the physiological mechanisms which underly psilocybin’s therapeutic action, 3) sleep disturbances may represent a trait or endophenotype present amongst individuals who are likely to demonstrate poor therapeutic response, regardless of any sleep-related mechanistic action.
The relationship between sleep and depressive symptoms in subjects who used psilocybin “suggests a highly complex yet prominent role of sleep in psilocybin’s therapeutic antidepressant action,” the study says.
A possible explanation “for the relationship between the severity of sleep disturbance and poor depressive symptom improvement,” the study says, for example, “may be that chronic sleep disruption interferes with biological or psychological mechanisms responsible for the therapeutic action of psilocybin.”
However, the study also found that people who reported insomnia or hypersomnia showed “reduced likelihood of remission” of depressive symptoms.
“Superficially, these findings may seem paradoxical, and challenging to reconcile with the more widely disseminated notion that insufficient sleep is a causal factor in the exacerbation of depressive symptoms,” authors wrote. “However, the acknowledged U-shaped relationship between sleep duration and daytime functioning, as well as known risk for medical and psychiatric comorbidities lends further support to the nature of the relationships we observed.”
The report cautions that research on the issue is still limited and that even “conclusions which may reasonably be drawn from these findings require a tentative balance between assertions of causality and bidirectionality.”
The study wasn’t randomized and lacked a control group, authors acknowledged, for example. Nor were participants ever subjected to a formal diagnostic screening for depression or other conditions.
“Nevertheless, our finding that sleep significantly predicted subsequent improvements in depression, whereas depression did not predict sleep changes, provides some support in surmounting the limitations posed by our non-randomized design,” authors wrote.
“Whilst the precise mechanism or causal nature of this relationship remains unclear,” they concluded of the apparent link between sleep and psilocybin’s therapeutic actions, “it is certainly apparent that sleep represents a promising investigational target that is worthy of concerted empirical attention.”
The study’s findings may be especially relevant as psilocybin emerges as a promising therapy for mental health conditions, including depressive disorders. A recent study in the journal Psychedelics found that as many as 6 in 10 people currently receiving treatment for depression in the U.S. could qualify for psilocybin-assisted therapy if the treatment were approved by the Food and Drug Administration.
“Our findings suggest that if the FDA gives the green light, psilocybin-assisted therapy has the potential to help millions of Americans who suffer from depression,” Syed Fayzan Rab, an MD candidate at Emory University, and the study’s lead author, said in statement about the report. “This underscores the importance of understanding the practical realities of rolling out this novel treatment on a large scale.”
Separately, results of a clinical trial published by the American Medical Association (AMA) last December “suggest efficacy and safety” of psilocybin-assisted psychotherapy for treatment of bipolar II disorder, a mental health condition often associated with debilitating and difficult-to-treat depressive episodes.
AMA also published research last year finding that people with major depression experienced “clinically significant sustained reduction” in their symptoms after just one dose of psilocybin.
Earlier this year, the federal government itself published a web page acknowledging the potential benefits the psychedelic substance might provide—including for treatment of alcohol use disorder, anxiety and depression. The page also highlights psilocybin research being funded by the federal government into the drug’s effects on pain, migraines, psychiatric disorders and various other conditions.
Posted on the website of the National Center for Complementary and Integrative Health (NCCIH), which is part of the National Institutes of Health, the page includes basic information about what psilocybin is, where it comes from, the legal status of the drug and preliminary findings around safety and efficacy. The NCCIH page highlights three possible areas of application: alcohol use disorder, anxiety and existential distress and depression.
This summer, meanwhile, the head of the National Institutes of Health (NIH) said there’s “growing evidence” that psilocybin could represent a novel therapy option in the treatment of substance misuse, depression, anxiety and other mental health conditions.
Findings of another recent study suggests that the use of full-spectrum psychedelic mushroom extract has a more powerful effect than chemically synthesized psilocybin alone, which could have implications for psychedelic-assisted therapy. The findings imply that the experience of entheogenic mushrooms may involve a so-called “entourage effect” similar to what’s observed with cannabis and its many components.
A separate study published by the American Medical Association found that single-dose psilocybin use was “not associated with risk of paranoia,” while other adverse effects such as headaches are generally “tolerable and resolved within 48 hours.”
That study, published in JAMA Psychiatry, involved a meta-analysis of double-blind clinical trials where psilocybin was used to treat anxiety and depression from 1966 to last year.
Yet another recent study of emergency first responders suggests that a single self-administered dose of psilocybin can help “to address psychological and stress related symptoms stemming from a challenging work environment, known to contribute to occupational burnout.”