Mushroom for Improvement

With over 200 known species, varying in terms of psilocybin, psilocin, and other tryptamine concentrations, there’s still a great deal we don’t know about psychedelic mushrooms – particularly, their therapeutic potential. And given that an inaccurate dosage can mean the difference between successful and unsuccessful therapy – not to mention the potential for undesirable side effects – reliable potency testing is crucial.

To find out more about the analysis of psychedelic mushrooms, we spoke with Linda Smith, Senior Scientist at MilliporeSigma.

What is the current state of psychedelic mushroom therapy research?
 

Mushroom therapy research is still in its early stages, which is surprising given that psychedelic mushrooms have been around for thousands of years. However, they only started to gain popularity in the 1960s and were rapidly rendered illegal in the 1970s, so research came to a grinding halt. In the early 2000s, researchers re-emerged to investigate the effectiveness of mushroom treatment for mental illnesses such as depression, anxiety, and addiction. Fast-forward to the present day, and we are witnessing decriminalization in some areas, as well as the opening of public therapeutic centers.

Some evidence suggests that there may be other variables that could impact therapeutic responses, such as the style of music played in the background or words spoken in a masculine or feminine voice. Another route of therapy is micro-dosing. Some progressive wellness enthusiasts believe that small doses of psilocybin mushrooms can improve wellbeing, foster creativity, and help with problem-solving by boosting focus and energy, without inducing psychotropic effects, such as changes in consciousness, hallucinations, and sensory shifts. These claims are not yet validated by clinical studies. 

Though my research does not encompass the array of components of therapy, it is fascinating to watch where the science of psychedelic mushrooms is heading.

What interests you about the science of psychedelic mushrooms – and how did you end up in this field?

I was working on dietary supplement projects at MilliporeSigma and took interest in the different ways laboratories test the same substance and get different answers. Cannabis and psychedelic mushrooms were emerging in clinical trials at the time, and I noticed the importance of developing methods and reporting potency accurately. From here, I decided to look further into the clinical potential of psilocybin mushrooms.

What analytical techniques are typically used for the quantification of psychedelic compounds in mushrooms?

Multiple techniques are used to quantify psilocybin and psilocin – including gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC)-UV, HPLC-MS.

I currently use MS in the analysis of mushrooms for psilocybin and psilocin potency, but have also used it investigate the presence of other mushroom tryptamines, such as baeocystin, norbaeocystin, aeruginascin, and norpsilocin. With internal standards, certified reference materials, and a valid method, MS offers extremely accurate quantitation.

When developing a method, where do you focus your efforts?

As with any analytical method, it is crucial to determine the correct concentration range, consider any matrix effects or other endogenous interferences, and ensure that any losses during sample preparation are accounted for. From here, the method must be tested for accuracy, precision, and robustness. A key component for accuracy is using a quality control sample with traceability to a higher order standard.

My research focuses on the development of accurate and robust HPLC analytical methods with the hope that other labs will adopt them into their analysis. Lab shopping is not unheard of – as seen with cannabis. Testing labs should be held to certain standards to provide doctors, researchers, and the community with accurate information. Unfortunately, not all third party testing labs are equally cautious and false reporting can occur – both intentionally and unintentionally. For example, when determining the concentration of THC in a product, both THC and THC-A must be measured. The analyzed concentration of THC-A is then multiplied by 0.877 to account for the mass difference after conversion to THC. If this step is missed, a lab could provide a higher concentration. When it comes to psychedelic mushrooms, small increases in concentration can have much more profound effects.

Recently, I was working on a potency method for psilocin and psilocybin using LC-MS; interestingly, at the same concentration, the signal for psilocin was 60 times higher than that of psilocybin. Additionally, psilocin’s area response was suppressed when the concentration was over 25 ng/mL – which skewed the calibration curve. By adjusting the calibration curve range and the dilution factor of the mushroom samples, I was able to accurately assign the potency of psilocybin mushrooms.

What emerging trends, tools, or technologies could improve testing? 
 

Psychedelic mushroom therapy is gaining popularity, and with this heightened demand, an increased supply will be needed. Labs are already looking at faster and cheaper ways of producing synthetic psilocybin. However, this will need its own analytical testing method to ensure authenticity and to eliminate – or, at least, fully characterize – impurities to guarantee its safety for human consumption. In the US, for this to succeed, a strong relationship will need to form between state and federal regulators, as well as method standardization bodies. Collaboration is key to ensuring diligence in the method development process.

How do you see the future of psychedelic mushroom therapy – and analysis – shaping up?
 

With any disease or ailment, there is a shared hope of treatment with successful outcomes. Psychedelic mushrooms have clinical potential to provide an alternative therapeutic route where other medications have failed. Despite there still being a long way to go, the research and clinical trials will be fascinating.

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