Researchers in the UK have investigated whether the effects of psilocybin, a naturally occurring hallucinogenic drug, depend on a person’s body mass index, thus requiring higher doses for the same effect in heavier people. The results showed that the overall intensity of psychedelic experiences after consuming a 25 mg dose of psilocybin was unaffected by differences in respondents’ body mass indices. The study was published in the Journal of Psychopharmacology.
Psilocybin is a psychedelic drug obtained from certain kinds of fresh, dried mushrooms (“magic mushrooms”). In the human body, it acts as a serotonin type 2A (5-HT2A) receptor agonist, activating serotonin receptors on brain cells, primarily in the prefrontal cortex region of the brain. In this way, it reduces the energy required for the brain to switch between different states of activity.
Although it is illegal in the United States and considered a Schedule I substance by the Drug Enforcement Administration (high risk of abuse, no medical use), there is recent increased interest in its potential use. in psychiatric treatment. However, due to its legal status, research on the drug’s dosage has so far been limited and it is unclear whether the dosage needs to be adjusted to achieve the same psychedelic effect for people of different body weights or whether a fixed dosage can be used for everyone.
“There is already a great deal of research supporting the importance of the acute experience in psilocybin-assisted therapy, and that it does not depend solely on the dose used. The acute experience is also shaped by extra-pharmacological factors; commonly referred to as the setting and setting,” explained study author Meg J. Spriggs, a research associate at the Center for Psychedelic Research at Imperial College London.
“While bodyweight-adjusted dosing is the ‘gold standard’ in pharmacological research, it was unclear from previous research whether bodyweight-adjusted dosage is necessary in blood-assisted therapy. psilocybin, given what we know about these extra-pharmacological factors. Here we wanted to test whether the acute experience and outcome is impacted by a participant’s BMI when using a fixed dose of 25 mg (a “therapeutic” dose) of psilocybin.
“As we look to a future where psychedelic-assisted therapy may become accessible, we need to think about how to facilitate safe and equitable clinical deployment,” the researcher said. “Adjusting body weight is a common practice in research, but it adds practical and financial complexity to standardization, validation, and large-scale distribution. A better understanding of the possibility of using fixed doses will help ease this transition into the clinic.”
Spriggs and colleagues analyzed data from three different studies using psilocybin. Two of the studies were clinical studies looking at the potential use of psilocybin for the treatment of depression and the third was a study in healthy volunteers who had never taken a psychedelic drug before aiming to examine psychological and brain changes long-term. The researchers analyzed data on the effects of a 25 mg dose of psilocybin from all three studies. The three studies included 77 participants. The average age was 43 years old.
The researchers measured the participants’ body weight and height to calculate their body mass indices. Body mass index is calculated by dividing a person’s body weight in kilograms by the square of their height in meters. It is used to indicate whether a person is underweight, normal weight or overweight.
Participants also completed an assessment of the altered states of consciousness related to the psychedelic state they experienced after taking the psilocybin dose (The Altered States of Consciousness Questionnaire, ASC), the emotional breakthrough experienced during the psychedelic state (Emotional Breakthrough Inventory, EBI) and well-being (Warwick-Edinburg Mental Well-being Scale).
“Body mass index does not predict overall altered state intensity, mystical experiences, perceptual changes, or emotional breakthroughs during the acute experience. There was weak evidence for a greater high ‘fear of ego dissolution’ in participants with lower body mass index,” Spriggs and colleagues wrote. However, further analysis suggested that even this link to body mass index disappeared. when the age and sex of the participants were taken into account.
“While mystical-like experiences and emotional breakthroughs were strong predictors of improved well-being, BMI was not,” the researchers concluded.
“It helps us understand that psychedelic-assisted therapy is more than just pharmacology, it’s psycho-pharmacotherapy,” Spriggs told PsyPost. “Medication is just one aspect of the therapy ‘package’, which also includes extensive psychological preparation before and integration after the dosing session that takes place in a supportive and therapy-oriented environment.”
This research further demonstrates that it is not just the dose-to-body weight ratio that determines the acute experience and outcome.
“This is an excellent demonstration of the real importance of ‘support for the null hypothesis’. Using standard (“frequentist”) statistical methods, the results of this study are not significant – meaning that it there is no evidence for the effect of BMI, and therefore the results are inconclusive. A common problem in science is that null results are often not published. Not only does this mean that the scientific community in the sense large cannot learn from zero results, but it can also put pressure on researchers to “find” meaningful results if they want a study to be published.
“Here we took a different statistical approach (Bayesian statistics) which allowed us to draw conclusions about the evidence supporting the null hypothesis. i.e. we can say that there is evidence against BMI being a predictor of an acute experience and outcome, so what would usually be a zero result is actually very informative, hope this helps people look at the science in a different way and will inspire scientists to explore new statistical approaches.
The study results provide strong evidence that adjustment of psilocybin dose based on body weight is not necessary and that a fixed dose for all people is sufficient to achieve an acute psychedelic experience. However, it also has some limitations. Notably, only the 25 mg dosage has been studied and it is possible that the effects of different dosages depend on body weight. Additionally, there were significantly more obese participants than underweight participants.
“The bodyweight-adjusted dosage also has implications for clinical applications in populations where BMI is part of the diagnostic criteria, e.g. anorexia – I am currently working on a trial of psilocybin-assisted therapy for anorexia at Imperial College London,” Spriggs noted.
The study, “Body Mass Index (BMI) Does Not Predict Responses to Psilocybin,” was authored by Meg J. Spriggs, Bruna Giribaldi, Taylor Lyons, Fernando E. Rosas, Laura S. Kärtner, Tobias Buchborn, Hannah M. Douglass, Leor Roseman, Christopher Timmermann, David Erritzoe, David J. Nutt, and Robin L. Carhart-Harris.