Recognizing the contributions of lesser-known scientists in psychedelic chemistry.
Challenges in synthesizing conformationally constrained derivatives and investigating optimal binding orientations of LSD.
Exploring structural modifications to mitigate potential neurotoxicity of MDMA and the significance of responsible use.
Deep dives
Research on Psychedelics and the Importance of Recognizing Lesser-Known Scientists
The podcast episode discusses the significance of recognizing the contributions of lesser-known scientists in the field of psychedelic chemistry. While prominent figures like David E. Nichols and Alexander Shulgin are well-known, there were many other researchers, such as Robert Oberlander, who played a crucial role in synthesizing and evaluating various compounds. These reports, often collected from different members of research groups, provide valuable data points for the evaluation of new compounds. The episode emphasizes the importance of acknowledging the extensive work done by these researchers and appreciating their contributions alongside the more famous figures.
Challenges in Synthesizing Conformationally Constrained Derivatives
The podcast delves into the challenges faced in synthesizing conformationally constrained derivatives, particularly in the context of investigating the optimal binding orientation of the diethylamide (diethylamino) group in LSD. The work of Robert Oberlander, along with his colleagues in the Nichols lab, aimed to synthesize derivatives that would provide insights into the activity and binding patterns of LSD. The chemistry involved attempts to introduce stereochemistry and investigate the role of cyril carbons in determining optimal binding orientations. Despite the difficulties encountered in these syntheses, they led to valuable research and paved the way for further investigations.
Research on MDMA and Mitigating Potential Neurotoxicity
The podcast episode touches upon research conducted on MDMA and the efforts to mitigate potential neurotoxicity. Robert Oberlander's work aimed to find compounds with similar pharmacological effects to MDMA but without the same level of neurotoxicity. By exploring structural modifications, such as substituting alkyl groups on the amphetamine portion of MDMA, researchers sought to understand the relationship between structure and activity. The study involved animal models and drug discrimination assays, providing valuable data to develop safer alternatives. The research highlighted the importance of responsible use and caution in order to minimize potential harm.
Exploration of LSD Structure-Activity Relationships and Stereochemistry
The podcast episode examines the exploration of LSD structure-activity relationships and the role of stereochemistry. Researchers, including Robert Oberlander, used chemical synthesis and stereochemical analysis to investigate how subtle modifications affected the potency and activity of LSD. The focus was on understanding the optimal binding orientations of different functional groups. The experiments involved synthesizing and testing compounds with various isomers and positional alterations. By studying these structural changes, researchers gained insights into the molecular interactions and binding mechanisms underlying the psychedelic effects of LSD.
Cautionary Tale: The Importance of Self-Experimentation and Proper Precautions
In this podcast episode, the speaker shares a cautionary tale about their experience with an experimental compound, five-methoxy prolintane tryptamine (5-MeO-DPT). They highlight the importance of escalating doses slowly and having a support person present during the experiment to ensure safety. The speaker recounts their own experience, which resulted in unconsciousness and a subsequent legal issue. They emphasize the need to follow the rules when testing new drugs and to have someone to prevent any potential complications. Despite the challenging experience, the speaker notes that they were fortunate in the end and were able to continue their successful career in academia and industry.
The Unique Qualities of 5-MeO-DPT and the Power of Self-Experimentation
The speaker also discusses the unique qualities of 5-MeO-DPT as a psychedelic compound. Unlike other psychedelics, this compound seems to induce an altered state of consciousness without the usual psychological revelations or intellectual content. Instead, the experience primarily triggered profound feelings of gratitude for being alive. The speaker highlights the significance of self-experimentation and the role it plays in uncovering new insights about compounds like 5-MeO-DPT. They mention the importance of continued research and the potential for unexpected discoveries in the field of psychedelics.
In this interview I talk with the great medicinal chemist Dr. Robert Oberlender, he is the inventor of the multi-billion dollar blockbuster drug vyvanse and a ten year veteran of the David E. Nichols laboratory responsible for the synthesis and evaluation of a number psychedelics and empathogens such DOsB, DOiB, MDAI, and many others.
The Ian Parker article I mentioned about the embittered ambien inventor:
