A new study provides evidence that the psychedelic compound psilocybin has both immediate and lasting anti-inflammatory effects in healthy volunteers.
The findings shed light on how psilocybin may improve mood, social behavior, and potentially treat depression.
Key facts:
- Psilocybin decreased the inflammatory marker TNF-alpha immediately after administration.
- Seven days later, psilocybin reduced two other inflammatory markers – IL-6 and CRP.
- Participants who had greater anti-inflammatory effects also reported more positive mood and social effects 7 days after taking psilocybin.
- The anti-inflammatory effects were linked to changes in glutamate levels in the hippocampus.
- Psilocybin did not alter biological responses to an acute stressor 7 days later.
Source: Brain Behav Immun. 2023
Rapid Anti-Inflammatory Effects of Psilocybin
The study examined how a single dose of psilocybin affected inflammatory markers in 60 healthy volunteers.
Blood samples were taken at baseline, 80 minutes after taking psilocybin (during peak effects), and 7 days later.
The key finding was that psilocybin rapidly decreased levels of the inflammatory marker tumor necrosis factor-alpha (TNF-alpha).
This occurred acutely – TNF-alpha was reduced at the 80 minute mark compared to baseline.
TNF-alpha is released early on during inflammatory responses in the body.
It helps kick off and coordinate immune system activation.
Psilocybin specifically reduced TNF-alpha, while leaving other tested inflammatory markers unchanged acutely.
This selective effect suggests psilocybin was directly acting on TNF-alpha signaling pathways.
Persisting Anti-Inflammatory Effects
While the TNF-alpha reductions were temporary, psilocybin had more persistent effects on two other inflammatory markers – interleukin 6 (IL-6) and C-reactive protein (CRP).
IL-6 and CRP levels were significantly decreased 7 days after psilocybin administration compared to the placebo group.
IL-6 is an immune regulator that induces CRP release. CRP levels in the blood track closely with IL-6 levels.
The fact that IL-6 and CRP remained low one week later suggests psilocybin reprograms aspects of immune function over a longer timescale.
This contrasts with the temporary TNF-alpha effects. The authors propose that psilocybin’s lasting anti-inflammatory impact may be mediated via direct effects on immune cell receptors.
Relationship to Depression and Social Functioning
Why do these anti-inflammatory effects matter?
The authors suggest they may contribute to some of psilocybin’s psychological benefits documented in recent clinical trials.
For example, patients with depression show chronically elevated IL-6 and CRP levels.
Higher levels of these inflammatory markers in depression are linked to more severe symptoms.
Evidence suggests conventional antidepressants work less well when inflammation is higher.
Therefore, psilocybin’s ability to reduce IL-6 and CRP levels may be an important mechanism behind its antidepressant effects.
This lasting immune modulation may also help explain the rapid and sustained improvements in depressive symptoms after just one or two psilocybin experiences in trials.
Beyond depression, the study also found an intriguing link between psilocybin’s anti-inflammatory action and social behavior.
Specifically, volunteers who had greater IL-6 and CRP reductions at 7 days reported more positive mood and social effects.
These self-reported social effects included feeling more open, happy, insightful, and creative.
Previous research shows that inducing inflammation causes people to feel more socially disconnected.
Inflammation essentially triggers an avoidance motivational state.
Therefore, by reducing inflammation, psilocybin may alleviate these motivational effects.
This may allow people to feel more connected with others after psilocybin treatment. Additional research is needed to further test this hypothesis.
The Neuroimmune Interface & Psilocybin
What biological mechanisms might link psilocybin’s anti-inflammatory effects with changes in mood and social behavior?
The study probed this by using brain scanning techniques.
Immediately after psilocybin treatment, lower TNF-alpha levels correlated with decreased glutamate concentrations in the hippocampus.
Glutamate is the brain’s major excitatory neurotransmitter. The hippocampus regulates mood, emotion, and memory processes.
This suggests anti-inflammatory effects may manifest in the brain by altering neurochemical balance in emotion-related circuits.
Ongoing inflammation can drive excess glutamate release.
By blocking inflammatory signaling, psilocybin may rebalance glutamate systems.
Enhanced regulation of glutamate firing after psilocybin treatment may improve the neural plasticity required for therapeutic change.
Again, more research is needed to unravel the functional connections between peripheral inflammation and psilocybin-induced changes in neurobiology and mental health.
Effects on the Stress Response System
In addition to assessing inflammation, the researchers examined whether psilocybin affected the body’s biological response to stress.
One week after treatment, participants underwent a stressful experience.
Psilocybin did not alter measures of heart rate, blood pressure, or the hormone cortisol compared to placebo.
Cortisol and cardiovascular responses track activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system – the major stress response pathways.
The lack of effect suggests a single dose of psilocybin does not cause lasting changes in stress reactivity among healthy people. This aligns with previous evidence.
However, the authors noted a non-significant trend where fewer people in the psilocybin group showed a cortisol response to the stressor.
They suggest future larger studies should continue investigating if psychedelics affect stress responsiveness in patient groups.
Stress system dysfunction plays a role in depression, addiction, and PTSD.
Overall, the study indicates psilocybin induces a complex pattern of biological changes.
It rapidly and enduringly suppresses inflammatory signaling without altering HPA axis function.
These nuanced effects likely contribute to its therapeutic potential.
There is still much to learn about how this psychedelic substance reshapes immune communication, brain function, and mental health.
Teasing apart these biological cascades will enable more targeted use of psilocybin in treating inflammation-related psychiatric conditions like depression.
References
- Study: Psilocybin induces acute and persisting alterationsin immune status in healthy volunteers: an experimental, placebo-controlled study
- Authors: N L Mason et al. (2023)
