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Image: Univ. of South FloridaEvery Thursday, Laboratory Equipment features a Scientist of the Week, chosen from the science industry’s latest headlines. This week’s scientist is Juan Sanchez-Ramos from the Univ. of South Florida. He and colleagues found that low doses of a psychedelic drug found in mushrooms erased conditioned fear in mice and may be a treatment for post-traumatic stress disorder.

Q: What made you interested in studying how psychedelic mushrooms could treat learned fear?

A: One theme of research in our lab is the regulation by drugs and environmental variables of hippocampal neurogenesis (the birth of new neurons). The role of neurogenesis in learning, especially in classical conditioning, was of interest to us, but not especially fear conditioning. Research by others (T. Shors and E. Gould at Rutgers) had demonstrated that obliteration of hippocampal neurogenesis with a chemotherapeutic agent resulted in inability to acquire a classical conditioned response, the conditioned blink reflex. This earlier work was done in a larger rodent, the rat, in which it is possible to record the eye blink with an electrode placed above the eye.

We were interested in this fundamental unit of learning but could not apply it to our mouse model. However, we found that fear conditioning could easily be studied in a mouse. With this background, I speculated that low doses of psilocybin which act directly on serotonin receptors (the 5HT2a) in hippocampus and other areas, might enhance the acquisition of a conditioned fear response by stimulating neurogenesis. In fact, it did not enhance acquisition and surprisingly, it enhanced extinction of fear conditioning.

Q: What are the future implications of your research and findings?

A: The clinical relevance of impaired hippocampal neurogenesis in humans is found in patients who develop impaired memory and depression following chemotherapy. When anti-depressants (of the SSRI class) are given, they are known to enhance neurogenesis and the time it takes to lift the depression corresponds to the amount of time it takes to develop mature neurons.

Now that we know that low doses of the 5HT2a agonist (psilocybin) can hasten extinction of a conditioned fear response, it may be developed as an adjunct to treatment of post-traumatic stress disorder.

Q: What was the most surprising thing you found in your research?

A: We did not expect to find that low dose psilocybin would facilitate the erasure of a fear conditioned response, and that it would be correlated with mildly enhanced or no change in neurogenesis. Higher doses of psilocybin or treatment with a 5HT antagonist had no effect on acquisition or extinction and produced a significant decrease in hippocampal neurogenesis.

Q: What is the take home message of your research and results?

A: Low dose psilocybin enhanced extinction of a conditioned fear response at a dose that did not produce overt behavioral or motor changes in control animals (not subjected to fear conditioning). And we suppose this low dose did not produce an altered state of consciousness in mice — though that would be difficult to ascertain!

Q: What is next for you and your research?

A: In the future, the question I would like to answer is: is psilocybin at very low doses capable of functioning as a “smart drug” that can enhance various kinds of more complex learning in humans? We will begin to utilize PET neuroimaging of psilocybin-induced changes in human volunteers in Zurich (in collaboration with Franz Wollenwieder of the Pyshciatric Instutite).

In animal models, I would like to determine the effects of weekly injections of psilocybin on neurogenesis and whether beneficial effects on learning can be seen.

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