A new study shows that natural mushroom extracts may be more therapeutically effective than synthesized psilocybin, which is widely used in research investigating the medicinal potential of the psychedelic drug. The findings suggest that natural mushroom extracts may offer more potential applications for the treatment of serious mental health conditions such as depression, post-traumatic stress disorder (PTSD) and schizophrenia.

The study, which was conducted by an interdisciplinary team of researchers from the Hebrew University of Jerusalem’s Hadassah Medical Center BrainLabs Center for Psychedelic Research, compared the effects of the natural and synthesized versions of psilocybin, the compound primarily responsible for the psychoactive effects of magic mushrooms.

“My colleagues and I are very interested in the potential of psychedelics to treat serious, treatment resistant psychiatric disorders such as depression, PTSD, OCD and even schizophrenia,” study author Bernard Lerer, a professor of psychiatry and director of the Hadassah BrainLabs Center for Psychedelic Research at Hebrew University, told PsyPost.

“There are many anecdotal and clinical reports which suggest that extract of psilocybin-containing mushrooms may have unique effects that are qualitatively and quantitatively different from chemical psilocybin, and also some preclinical studies,” Lerer continued. “This observation has important clinical implications and we wanted to test it empirically in a laboratory study.”

Entourage Effect May Boost The Therapeutic Effects Of Psilocybin

Mushrooms that contain psilocybin also produce many other psychoactive and non-psychoactive compounds that may work together to provide enhanced therapeutic effects through a phenomenon known as the entourage effect. However, most clinical research into psilocybin is conducted with synthesized forms of the drug that do not contain these additional potentially therapeutic compounds. 

“In Western medicine, there has historically been a preference for isolating active compounds rather than utilizing extracts, primarily for the sake of gaining better control over dosages and anticipating known effects during treatment,” the researchers said in an emailed statement about the study. “The challenge with working with extracts lay in the inability, in the past, to consistently produce the exact product with a consistent compound profile.”

“Contrastingly, ancient medicinal practices, particularly those attributing therapeutic benefits to psychedelic medicine, embraced the use of extracts or entire products, such as consuming the entire mushroom,” they continued. “Although Western medicine has long recognized the ‘entourage’ effect associated with whole extracts, the significance of this approach has gained recent prominence.”

To conduct the study, the researchers compared the effects of a natural mushroom extract with those of synthesized psilocybin in laboratory mice. The mice were divided into three groups that received either the extract, synthesized psilocybin or a saline solution control. Both forms of psilocybin were given in amounts determined to be therapeutically relevant based on equivalent dosing models between humans and laboratory mice.

The researchers assessed the behavioral effects and potential neuroplasticity induced by psilocybin using the head twitch response assay, a commonly employed method of studying the effects of psychedelics in mice. They also compared the metabolic changes in the frontal cortex following treatment and analyzed the expression of synaptic proteins in the brain that can be used as indicators of neuroplasticity.

The research showed that the mushroom extract demonstrated a stronger and more prolonged impact on synaptic plasticity, which could indicate the extract offers unique therapeutic benefits. Additionally, the metabolic analyses showed distinct metabolic profiles between synthesized psilocybin and the extract, suggesting that the mushroom extract may have a “unique influence on oxidative stress and energy production pathways,” according to report from Neuroscience News.

While the research showed that the mushroom extract and synthesized psilocybin had different metabolic and neuroplasticity effects, both induced the head twitch response. The findings suggest that the acute effects of both compounds are similar at the basic behavioral level.

“We were surprised by the fact that there were no differences in the acute effect on the head twitch response between chemical psilocybin and psilocybin-containing mushroom extract while the differences emerged in terms of longer term effects on synaptic proteins and metabolomics,” Lerer said. “This has important potential clinical relevance.”

The researchers noted that while the mushroom extract showed potentially enhanced therapeutic effects, creating them in consistent formulations can be a challenge, making synthesized versions of the compound a common alternative for therapeutic research. However, they noted that with careful cultivation and processing, it is possible to make extracts in consistent formulations.

“A major challenge with natural extracts lies in achieving a consistently stable compound profile, especially with plants; however, mushrooms present a unique case,” the researchers wrote. “Mushroom compounds are highly influenced by their growing environment, encompassing factors such as substrate composition, CO2/O2 ratio, light exposure, temperature, and microbial surroundings. Despite these influences, controlled cultivation allows for the taming of mushrooms, enabling the production of a replicable extract.”

The researchers recommended more research, noting that there could be clinical advantages to using a natural mushroom extract instead of synthesized psilocybin.

“Our findings need to be confirmed in human studies but they do suggest that there may be therapeutic advantages to psilocybin-containing mushroom extract over chemically synthesized psilocybin, when both are administered at the same psilocybin dose,” said Lerer.

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