The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future

Abstract

Plant-based psychedelics, such as psilocybin, have an ancient history of medicinal use. After the first English language report on LSD in 1950, psychedelics enjoyed a short-lived relationship with psychology and psychiatry. Used most notably as aids to psychotherapy for the treatment of mood disorders and alcohol dependence, drugs such as LSD showed initial therapeutic promise before prohibitive legislature in the mid-1960s effectively ended all major psychedelic research programs. Since the early 1990s, there has been a steady revival of human psychedelic research: last year saw reports on the first modern brain imaging study with LSD and three separate clinical trials of psilocybin for depressive symptoms. In this circumspective piece, RLC-H and GMG share their opinions on the promises and pitfalls of renewed psychedelic research, with a focus on the development of psilocybin as a treatment for depression.

Figure 1

A bipartite model of serotonergic functioning focused on the effects of post-synaptic 5-HT1AR and 5-HT2AR signaling. The more pronounced effects of chronically used SSRIs on post-synaptic 5-HT1AR signaling is hypothesized to relate to their anti-stress, pro-coping properties but also their tendency to moderate or ‘blunt’ emotional responsiveness. The direct 5-HT2AR agonist properties of psychedelics are hypothesized to relate to their proclivity to enhance sensitivity to the environment as well as facilitate emotional release, which, when combined with psychological support, is hypothesized to be therapeutically potent.