Thread by @JasterAlaina

Time for another #sciencetwitter journal club! Today's paper: #Microdosing with #psilocybin #mushrooms: a double-blind placebo-controlled study by Cavanna et al 2022! Hot off the presses!

nature.com/articles/s4139…

This study has:

34 participants, about half of which had previous experience with psychedelics

Randomized, double-blind placebo-controlled, within-subjects design

0.5. g psilocybin mushroom in capsule and edible, non-psychedelic mushroom as placebo

typical "microdose" is 0.1 - 0.5 g of dried mushrooms, which still can produce some type of altered consciousness, hallucination effect depending on the person.

most common regimen is 1 day on 2 days off, based on Fadiman's work.

Methods:
EEG, and VAS - adadpted protocol from Carhart-harris

3 tasks to assess convergent and divergent thinking

12 questionnaires to assess anxiety, suggestibility, stress, well-being, empathy, cognitive flextibility + more

auditory stimulation responses & physical activity

Increased VAS total scores were found in the “unblinded” subset but not in the “blinded” one.

Meaning, the increased ratings for things like intensity of trip, positive mood, ego-dissolution, emotional arousal was increased in the group who figured out they were taking shrooms

Most of the items for VAS were found to be inconclusive once corrected for multiple comparisons, thus authors did not find robust evidence of consistent changes in the VAS sub-items across participants

No differences in self-reported scales and questionnaires between placebo and microdose.

Meaning, microdose had little effect on participant self-scoring their own mood, anxiety, stress, well-being, etc.

There were also no conclusive differences seen in creativity tasks on divergent and convergent thinking between placebo and microdose.

In tests on perception and cognition, the only noted effect was psilocybin group had an increase response time to the Stroop task, which is a task to name the ink color of a color word if there is a mismatch between ink color and word

No significant differences were found in tests to assess auditory perception or in monitoring of physical activity.

For EEG, they did report decreased EEG power in the theta band under psilocybin, which is "consistent with the broadband spectral power reductions reported for higher doses."

One issue with microdosing is that there is no standardized procedure, so it's difficult to understand whether these are actual microdoses, what the optimal regimen would be, etc. This needs to be determined if it becomes a true medical practice.

Positivity bias, outcome and expectation bias can all lead to issues in anecdotal reports of microdosing.

This leads to a STRONG placebo effect, which is why it's important to do blinded studies.

Other studies on microdosing have reported positive effects on the primary outcome of their respective studies; however, these results could be explained by breaking of the placebo condition.

Similar to the present study of 75% unblinding, other studies report 60% unblinding

Limitations:

need more participants to power study
weight-adjusted doses
purity of mushroom capsules
two doses per week - 2 weeks, sometimes microdosing is longer
need future studies to determine long-term effects on mood/overall health and wellbeing

Summary:

Positive effects of microdosing (0.5 g) of psilocybin mushrooms is mainly attributed to placebo effect

No major changes in mood, cognition, well-being, physical activity, etc.

Another piece of evidence that microdosing is most-likely placebo, but more studies needed!

Would also like to add... 0.5 is not a microdose, but this dose was used because it's at the higher end of the self-reported doses that would be easily quantifiable.

Interested to see more double blind placebo studies with 0.1 to 0.05 doses