According to The New England Journal of Medicine, it is generally known that serendipity had an essential role in the creation of the primary pharmaceutical classes, notably in the field of psychiatry. This principle also applies to psychedelics and ketamine.
After hundreds of years of human use of psychedelic fungi and plants for healing purposes, human experience guided by educated chance led to the 1943 discovery of the psychoactive effects of lysergic acid diethylamide (LSD), a pivotal event in the history of psychedelic medicine in the West that sparked a wave of clinical research and application in the 1950s and 1960s.
The first paper in English regarding LSD was written by two American psychiatrists motivated by psychoanalysis, who described it as “disturbing the barrier of repression” to promote psychotherapy. Because LSD had such powerful effects, British psychiatrist Humphry Osmond invented the term “psychedelic” by combining the ancient Greek word for “soul” with a modified version of the verb meaning “to reveal.”
Recent decades of study have laid the groundwork for our understanding of psychedelic substances’ biological effect, with studies indicating a critical signaling function at the serotonin 2A receptor.
While both the head-twitch response and prepulse inhibition are compassionate, they are nonspecific indications of psychedelic activity; also, the head-twitch reaction has extremely poor face validity for identifying psychedelic activity in individuals. Although prepulse inhibition is more reliable, it cannot distinguish between different types of psychedelics; this is particularly troublesome when dealing with serotonergic psychedelics.
Despite being a selective agonist at the 5-HT2A receptor (R), -70 has no preferential affinity for that receptor over the 5-HT2B or 5-HT2C receptors. This is crucial since, as revealed by Kaplan inhibiting 5-HT2C receptors has been linked to antidepressant effects. All recent clinical trials with traditional psychedelic medications (i.e., 5-HT2A receptor agonists) have included psychological assistance or altering the subject’s environment.
The strong neuroplastic effects of psychedelic drugs imply a comparable, if not greater, context dependency of effects than seen in animal models with nonpsychedelic serotonergic pharmaceuticals. Experiential and extra-pharmacological factors of therapeutic response, such as emotional release, psychological insight, and therapeutic rapport, have been revealed in the current human response modeling study. 4,5 Rodents might be studied utilizing several learning paradigms and environmental modification strategies.
It is critical to understand that the pharmaceutical industry has largely abandoned mental health research due to the failure of prior forward (e.g., rodent-to-clinic) translational efforts to produce novel psychiatric medications.