The Chemical Architecture of the Human Mind:
Probing Receptor Space with Psychedelics

Twenty-two psychedelics ( DOI, DOB, 2C-B, 2C-B-fly, 2C-E, MEM, ALEPH-2, 2C-T-2, DOET, TMA-2, TMA, Mescaline, DOM, MDA, MDMA, DPT, DMT, 5-MeO-DMT, DIPT, 5-MeO-DIPT, 5-MeO-MIPT, Psilocin) and three controls (4C-T-2, 6-fluoro-DMT, lisuride) have each been screened against over fifty receptors, transporters and ion channels by the National Institute of Mental Health Psychoactive Drug Screening Program (NIMH-PDSP), providing the first comprehensive view of how these compounds interact with the human receptorome.

Each individual psychedelic causes a unique spectrum of subjective effects. DIPT causes auditory distortion. 5-MeO-DIPT enhances orgasm in males but not females. MDMA provokes empathy. TMA provokes anger. Mescaline provokes an appreciation of beauty. 2C-B causes tactile, gustatory and sexual enhancement. 2C-E provokes rich fantasy and introspection. Taken collectively, these compounds provide a rich set of tools for probing and revealing the chemical organization of the human brain and the mind that emerges from it.

The project aims to understand the mechanisms underlying the qualitative diversity of actions of psychedelics, by locating each drug in an abstract " receptor space", a coordinate system with one axis for each receptor. Drugs shift the balance of activity of the brain away from the origin, by a vector representing the profile of binding affinities at different receptors. Drugs perturb the system through increasing or decreasing transmission or transmitter levels, or up or down regulating receptor populations.

In a brain-centered reference frame, the origin is based on absolute levels of activity at each receptor population. The state of the brain is constantly on the move, regardless of medication. We can think of it as a complex dynamical system, in which the trajectory follows high-dimensional orbits, and switches among many "attractors", where the attractors represent the major emotional states and moods, and whatever mental phenomena the chemical systems are mediating.

In this dynamic reference frame, drugs will create a perturbation along the binding vector, thereby pushing the system into a new attractor. We want to understand how patterns of activity at receptor populations associate with mental phenomena. We want to get to know the pharmacology of the attractors. By correlating the subjective effects of a diverse selection of psychedelic drugs with the position of the drugs in "receptor space", we can begin to map the chemical organization of the human mind.

The current project is charting the distribution of psychedelics in "receptor space". In future work, new human data will be needed, using subjective questionnaires and brain imaging, as in the work of Vollenweider. For human work, compounds will be carefully chosen to represent distinct regions of "receptor space", or distinct subjective effects.

The goal of mapping "receptor space" is to chart the relationships between complex alterations in chemical signaling, and resulting changes in neural activity and mental states. This empirical knowledge can form a foundation for the development of a theory of the chemistry of mind, and provide a more rational basis for the development of chemical treatments for mental disorders. The understanding of the chemistry of consciousness is the ultimate goal of this research