Apr 23, 2021 I Paul Seaburn

Psilocybin Mushrooms May Work Their Magic Without Psychedelic Hallucinations

As much as some may find it hard to believe, there are people who want to take psilocybin mushrooms but don’t want the hallucinations. Those would be people who have heard from researchers that the real ‘magic’ in magic mushrooms may be their ability to work as an antidepressant, but the anxiety and fear of hallucinations causes these sufferers to reject such treatment – where it’s legal, of course. While the common belief among psychedelics scientists is that the hallucinations are the key to psilocybin’s antidepressant properties, researchers at University of Maryland School of Medicine (UMSOM) have found evidence to the contrary – and that may help those fearful of psilocybin’s hallucinations and free the drug from the shackles of regulation. Now THAT would be magic.

“We do not understand the mechanisms that underlie the antidepressant actions of psilocybin and the role that the profound psychedelic experience during these sessions plays in the therapeutic benefits. The psychedelic experience is incredibly powerful and can be life-changing, but that could be too much for some people or not appropriate.”

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The hallucinations are not always pleasant

That was the starting point for Scott Thompson, Ph.D., Professor and Chair of the Department of Physiology at the University of Maryland School of Medicine and author of a new study, “Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice,” published in the journal Proceedings of the National Academy of Sciences (PNAS). For subjects, his team used lab mice that were stressed for several days – until they showed signs of mouse anxiety such as settling for plain water instead of the more popular and pleasurable sugar water. As expected, a mouse-sized dose of psilocybin restored their pleasure response in less than 24 hours.

“How psilocybin exerts its therapeutic actions is not known, but it is widely presumed that these actions require altered consciousness, which is known to be dependent on serotonin 2A receptor (5-HT2AR) activation. This hypothesis has never been tested, however. We therefore asked whether psilocybin would exert antidepressant-like responses in mice and, if so, whether these responses required 5-HT2AR activation.”

The next step was to turn off the hallucinations in the mice. Yes, even those under the influence of magic mushrooms know you can’t tell if a mouse is tripping or not, so the researchers used the accepted theory that the brain’s serotonin 2A receptor controls the psychedelic response and gave the stressed mice ketanserin, a drug which binds to the serotonin 2A receptor and keeps it from being turned on. They gave the stressed rodents psilocybin again and waited.

“Neither behavioral nor electrophysiological responses to psilocybin were prevented by pretreatment with the 5-HT2A/2C antagonist ketanserin, despite positive evidence of ketanserin’s efficacy.”

Where's the sugar water?

In simple terms, the mice lost their stress and went back to the pleasure of drinking sugar water. Thompson’s excitement at the result is tempered by the reality that this experiment has only been conducted on mice and much human testing of a combination of magic mushrooms and ketanserin or some other 5-HT2AR receptor suppressant is needed. If you’re looking for a sign of confidence, Thompson and the University of Maryland Baltimore have filed a patent on using psilocybin with drugs that block serotonin 2A receptors to treat depression.

Remember what the 21st century, anti-anxiety dormouse said: feed your head but take some ketanserin first.

Paul Seaburn

Paul Seaburn is the editor at Mysterious Universe and its most prolific writer. He’s written for TV shows such as "The Tonight Show", "Politically Incorrect" and an award-winning children’s program. He's been published in “The New York Times" and "Huffington Post” and has co-authored numerous collections of trivia, puzzles and humor. His “What in the World!” podcast is a fun look at the latest weird and paranormal news, strange sports stories and odd trivia. Paul likes to add a bit of humor to each MU post he crafts. After all, the mysterious doesn't always have to be serious.

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