Notes from the International Society for Research on Psychedelics’ 2024 Conference in New Orleans (Guest Contribution)

Pre-clinical/Basic SciencesTo start off the conference, Dr. Kevin Murnane, Associate Professor at Louisiana State University (LSU) Health Sciences Center Shreveport, presented parallel research on methamphetamine use disorder in animal models and human studies to demonstrate the potential efficacy of psychedelics for this indication. Rodent studies produced some promising evidence suggestive of psychedelics’ ability to reduce methamphetamine administration while also increasing cognitive flexibility and not affecting rodents’ natural response to food. By using a translational approach, in which animal models are reflective of multiple aspects of a human study design, we can further understand the processes involved.In the basic sciences, Dr. Umed Boltaev, Associate Research Scientist at Columbia University, presented a talk on quantifying neuronal morphology and whether psychedelics truly modulate TrkB and induce dendrite growth (which produced quite the conversation over the course of the weekend). Their data showed that with their analysis pipeline, which used many different assays to study morphological changes using primary neuronal cultures, psychedelics were not able to produce the same effects on spine growth that was showcased in a variety of recent publications. They suggested that this may be due to a variety of factors including the lack of adequate 5-HT2A receptor expression in these cortical neurons. This begs the question of whether the cell systems we are using accurately reflect the true biological processes of psychedelic-induced plasticity.Continuing the focus on animal models, but shifting gears to fear-associated behaviors, Dr. Sam Woodburn, postdoctoral researcher at Cornell University, discussed how 2,5-dimethoxy 4-iodoamphetamine (DOI), 3,4-Methyl​enedioxy​methamphetamine (MDMA), and psilocybin had differing efficacies and longevities for accelerating fear extinction and maintaining extinction in generalizable contexts. In a paradigm where the psychedelic was administered 30 minutes prior to testing extinction, all three led to increased rates of fear extinction acutely. However, only MDMA and psilocybin produced sustained effects and showed generalizability of this extinction to other contexts. This is a common research goal for post-traumatic stress disorder (PTSD)-like conditions seeing as cognitive processes and behaviors learned in therapy should ideally extend to contexts outside of the clinic. To further assess the effect of psilocybin on the learning or retention of fear conditioned behaviors, in a separate study psilocybin was administered before conditioning or after extinction and neither of these manipulations affected the learning or extinction of freezing behaviors. These findings indicate that the acute effects must be important for the extinction process. Overall this research suggests that the timing, subjective effects and specific pharmacological profile of the psychedelic are a critical consideration for treating fear-conditioned disorders with psychedelic-assisted therapy.Another presentation that stood out was delivered by Dr. Gonzalo Hernandez of Universidad de la República in Montevideo, Uruguay, who discussed the use of nuclear magnetic resonance and chromatography-mass spectrometry/mass spectrometry to assess the chemical compositions of natural products and novel compounds. He showed data from ayahuasca brew samples from various sources, which included several different natural products. When separating the solid and aqueous parts of the brew, they were able to assess the different alkaloids and chemicals in each phase and discovered, for the first time, that fructose was a major component. They also showed that harmine, an alkaloid previously known to be in ayahuasca, was found in large quantities within the solids suspended in the beverage, while other alkaloids such as the active psychedelic component N,N-dimethyltryptamine (DMT), tetrahydroharmine, harmaline, and harmol were present in all extracted samples. These assessments of the composition of ayahuasca may provide greater insight into the physiological aspects of the ayahuasca journey, specifically the role of fructose.



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