Researchers in the United Kingdom studied whether the effects of psilocybin, a naturally occurring hallucinogenic drug, depend on the body mass index of the person, thereby 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 body mass indices of respondents. The study was published in the Journal of Psychopharmacology.
Psilocybin is a psychedelic drug obtained from certain sorts of fresh and dry mushrooms (“magic mushrooms”). In the human body, it acts as a serotonin type 2A (5-HT2A) receptor agonist, activating serotonin receptors on brain cells, mostly in the prefrontal cortex region of the brain. In this way, it reduces the energy needed for the brain to switch between different activity states.
Although illegal in the United States and considered a Schedule I substance by the Drug Enforcement Administration (high abuse risk, no medical use), there is a recent increase of interest for its potential use in psychiatric treatment. However, due to its legal status, research on dosing of the drug has, so far, been limited and it is unknown whether the dosage needs to be scaled to achieve the same psychedelic effect for people of different body weight or a fixed dosage can be used for everyone.
“There is already a lot of research supporting the importance of the acute experience in psilocybin-assisted therapy, and that this is not solely dependent on the dose used. The acute experience is also shaped by extra-pharmacological factors; commonly referred to as the set and setting,” explained study author Meg J. Spriggs, a research associate at the Centre for Psychedelic Research at Imperial College London.
“While body weight adjusted dosing is the ‘gold standard’ in pharmacological research, it was unclear from previous research whether bodyweight adjustment is necessary in psilocybin-assisted therapy, given what we know about these extra-pharmacological factors. Here, we wanted to test whether the acute experience and outcome are impacted by a participants BMI when using a fixed 25 mg dose (a ‘therapeutic’ dose) of psilocybin.”
“As we look towards a future where psychedelic-assisted therapy may become accessible, we need to be thinking about how to facilitate safe and equitable clinical roll out,” the researcher said. “Bodyweight adjustment is standard practice in research, but it adds practical and financial complexity to standardization, validation and large-scale distribution. A greater understanding about whether fixed doses can be used will help facilitate this transition to the clinic.”
Spriggs and her colleagues analyzed data from three different studies using psilocybin. Two of the studies were clinical studies on potential use of psilocybin for treating depression and the third was a study on healthy volunteers who have never taken a psychedelic drug before aiming to examine long-term psychological and brain changes. The researchers analyzed data on the effects of a 25 mg dose of psilocybin from all three studies. The three studies included 77 participants. Average age was 43 years.
The researchers measured body weight and height of participants to calculate their body mass indexes. Body mass index is calculated by dividing the body weight of a person expressed in kilograms by the square of the person’s 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 were experiencing after taking the psilocybin dose (The Altered States of Consciousness Questionnaire, ASC), of emotional breakthrough experienced during the psychedelic state (Emotional Breakthrough Inventory, EBI) and of well-being (Warwick-Edinburg Mental Well-being Scale).
“Body mass index does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater ‘dread of ego dissolution’ in participants with lower body mass index,” Spriggs and her colleagues wrote. However, further analysis suggested that even this link with body mass index disappeared when age and sex of participants are taken into account.
“While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not,” the researchers concluded.
“This helps us understand that psychedelic-assisted therapy is more than just pharmacology, it is psycho-pharmaco-therapy,” Spriggs told PsyPost. “The drug is only one aspect of the therapy ‘package,’ which also includes extensive psychological preparation before, and integration after, the dosing session which takes place in a supportive and therapeutically-oriented environment.”
This research further demonstrates that there is more than just the ratio of dose-to-bodyweight in determining the acute experience and the outcome.
“This is a great demonstration of where ‘support for the null hypothesis’ is really important. Using standard (‘frequentist’) statistical methods, the results of this study are non-significant — meaning that there is no evidence for the effect of BMI, and so the results are inconclusive. A common problem in science is that null results are often not published. Not only does this mean that the wider science community cannot learn from null findings, but it can put pressure on researchers to ‘find’ significant results if they want a study to be published.”
“Here we took a different statistical approach (Bayesian statistics) that allowed us to draw conclusions about evidence in support of the null hypothesis. i.e., we can say that there is evidence against BMI being a predictor of acute experience and outcome. So, what would typically be a null result is actually really informative. I hope that this helps people to look at science in a different way, and inspires scientist to explore new statistical approaches.”
The study results provide strong evidence that scaling psilocybin dose according to body weight is not necessary and that a fixed dosage for all persons is sufficient to achieve acute psychedelic experience. However, it also has certain limitations. Notably, only the 25 mg dosage was studied and it is possible that effects of different dosages would depend on body weight. Also, there were much more obese participants than underweight ones.
“Fixed vs bodyweight adjusted dosing 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.
