Entourage Effect – Synergistic Combinations of Active Ingredients
Magic mushrooms contain multiple active ingredients, collectively called “psilocybin derivatives.” These molecules work together to create an “entourage” of psychoactive (and non-psychoactive) effects experienced by the user.
This “pharmaceutical shotgun” effect is similar to that found in cannabis and several other naturally occurring organisms. See, e.g., Boulder Weekly August 9, 2018 (“Finding out how pot does its thing — it’s complicated”).
Benefits of the Entourage Effect
When it comes to natural medicine, plants appear to provide a synergistic combination of ingredients. In other words, the effects received from the whole plant/organism is truly greater than the sum of its parts. This phenomenon has now been studied and confirmed in the cannabis space. The phenomenon is almost certainly present in magic mushrooms.
Entourage Effect in Cannabis
Until very recently, the existence of the entourage effect in cannabis has been heavily disputed. See Scientific American April 20, 2017, “Some of the Parts: Is Marijuana’s “Entourage Effect” Scientifically Valid?” (concluding that THC is the sole active ingredient).
However, the importance of the entourage effect has now gained acceptance within the cannabis industry, due primarily to research conducted by the Colorado-based cannabis research company ebbu. By conducting cellular and clinical studies, ebbu’s scientists have proven its existence of the entourage effect and unlocked the next generation of cannabis technology. Ebbu’s CEO, Jon Cooper discusses their work on the entourage effect in the Cannabis Business Times.
By comparison, pure isolated THC is almost universally considered to be inferior to whole plant extracts and formulations comprising a symphony of active ingredients. See reviews for Marinol and Dronabinol.
Entourage Effect in Magic Mushrooms
Like cannabis, magic mushrooms contain multiple active ingredients. See, e.g., Baeocystin. However, to date, psilocybin research has followed in the footsteps of cannabis — myopically focusing on one single ingredient (psilocybin) rather than appreciating the synergistic combinations made by the mushrooms.
Psilocybin is NOT the only active ingredient.
Anecdotal reports indicate the different species of magic mushrooms produce dramatically different effects. Depending on the context, some of those effects are considered desirable (visuals, euphoria). And in some cases, the effects are undesirable, e.g., paralysis and loss of muscle coordination. Either way, evidence of multiple active ingredients and their contribution to different effects contradicts the notion that psilocybin is the only active ingredient.
Bottom line: Current psilocybin research appears to be focused on optimizing an inferior technology. Focusing on psilocybin (alone) ignores the potential benefits conferred by administering synergistic combinations of naturally occurring molecules. (This is the same mistake made by the first movers in the cannabis space, who assumed that THC was the only important molecule).
The next generation of psilocybin technology will come from studying all of the active ingredients in psychoactive mushrooms. Progress here will come from improvements in psilocybin chemistry, especially (1) isolating the active ingredients in the mushrooms and then (2) studying their pharmacology individually and within combinations. That research will pave the way for developing psilocybin formulations with improved properties over isolated psilocybin.