Introduction
History of Psychedelic Research
Since the 1950’s, psychologists and psychiatrists have pursued medical research into the therapeutic applications of mind-altering compounds for treatment of mental disorders such as depression, anxiety, and post-traumatic stress disorder. Long before Albert Hoffman kicked off the psychedelic science revolution by synthesizing LSD in 1938, as far back as 5,000 BCE indigenous tribes around the world used naturally occurring mind-altering substances ritually in pursuit of healing, spiritual insight, and social cohesion [1]. To label these shamanistic practices as religious is incomplete, as religion, astrology, alchemy, and medicine were closely intertwined; healers followed an amalgam of beliefs and practiced myriad techniques together with the objective of holistic healing.
Thanks to scientific advancements in neuroscience, psychology, and pharmacology, we have a better understanding today of the medicinal practices that our ancestors discovered long ago. These scientific advancements have spurred a recent renaissance in psychedelic medical research, following the hiatus that began in the 1970’s as a government response to the anti-war, anti-authoritarian, and counterculture movement that embraced the use of psychedelics such as LSD for mind expansion. The regulatory policy enacted back then was accompanied by promotion of misinformation, politicization, and irrational fear in an effort to garner public support for banning clinical research with mind-altering compounds [2], which ended promising research by psychologists such as James Fadiman (the father of microdosing) at Stanford University, and Bill Richards at Johns Hopkins University.
Psychedelic Lexicography
The English word first used to describe the class of mind-altering compounds in the early 1950’s was “psychotomimetic” (imitating a psychotic state), as American and European scientists believed that these substances made people temporarily insane. In 1957 the British-Canadian psychiatrist Humphrey Osmond introduced the term “psychedelic,” with its roots in the Greek words “psyche” (mind) and “delic” (manifesting). While the term “psychedelic” has come to be viewed with skepticism and alarm as a result of the ideological war of the past, Osmond meant for it to bring a more expansive and favorable connotation than “psychotomimetic.”
Today, the term “psychedelic” is popularly used by supporters to describe compounds that develop the potential of the human mind. “Hallucinogenic” is a term that is often used synonymously with “psychedelic” but carries a more recreational rather than therapeutic connotation. “Entheogenic” is another synonymously used term that carries more of a spiritual and ritualistic context. And more recently, the term “empathogen” has been coined to describe substances that increase a feeling of empathy, benevolence, and social connection (particularly to describe MDMA, but also compounds such as L*S*D and psilocybin).
Other English words with less baggage include the more neutral “psychotropic” (mind-changing) and “psycho*active” (mind-affecting), whose broader definitions can encompass even commonly used compounds such as caffeine, alcohol, and sugar.
While the definition of “psychedelic” vs. “hallucinogen” vs. “entheogen” is almost as subjective as the definition of drug vs. medicine , the term has commonly been used by the scientific community to describe compounds that induce an altered state of consciousness characterized by agonism of serotonin 2A neuroreceptors (e.g. psilocybin, L*S*D, DMT, etc.).
How Psychedelic Compounds affect the brain
Cutting-edge neuroimaging technologies have enabled us to better quantify the effect that psychedelic compounds have on the brain, continuing the research started by pioneers such as Albert Hoffman and Humphrey Osmond to understand their therapeutic mechanisms of action. Studies have demonstrated that psychedelics increase brain entropy and reduce the inhibitory activity of the default mode network (DMN) [3] as well as the gating activity of the cortico-striato-thalamo-cortical (CSTC) regions of the brain [4] allowing prolific brain connectivity patterns that are not normally achieved during conscious states. This effect is believed to be driven by the modulation of the brain’s serotonin neuroreceptors, most notably the 5HT2A receptors.
How Psychedelic Compounds affect the brain
The discovery of L*S*D by Albert Hoffman opened a new universe of scientific discovery in psychology, psychiatry, neuroscience, and pharmacology, notably:
- For the first time, physicians had the ability to experience an altered state of consciousness, enabling them to better understand and empathize with their patients. Albert Hoffman’s employer Sandoz began passing out samples of L*S*D for physicians to self-experiment with so as to experience its “psychotomimetic” effects, which psychologists such as Humphrey Osmond were apt to try.
- The unique activity of the brain under psychedelics demonstrates neurological connectivity that is atypical of normal conscious states, enabling a new field of translational neuroscience research and understanding of how the brain works.
- Research into L*S*D in the 1960’s coincided with the discovery of the serotonin neurotransmitter given L*S*D’s strong affinity for this newly identified and mapped neuronal pathway in the brain [5].
This latter discovery would turn out to be one of the most important of neuropharmacology, as serotonin receptors became the key target for treatment of mood disorders over the next 50 years, leading to the discovery of serotonergic antidepressants such as citalopram, fluoxetine, and sertraline.
While psychedelic medicine is perhaps the most exciting development in neuropsychiatry in the last 50 years [6], psychedelic research has played a significant role in the advancement of other fields of scientific discovery. It is thanks to psychedelic research, that our team of pharmacologists discovered the myriad brain health benefits of Espand-derived β-Carbolines.
References
- [1] Akers, B.P., et al.” A Prehistoric Mural in Spain Depicting Neurotropic Psilocybe Mushrooms?” Economic Botany, vol. 65, no. 1, pp. 121–128, 2011. DOI: 10.1007/s12231-011-9152-5
- [2] Belouin, Sean J., and Jack E. Henningfield. “Psychedelics: Where we are now, why we got here, what we must do.” Neuropharmacology, vol. 142, no. 1, pp. 7-19, Nov 2018. DOI: 10.1016/j.neuropharm.2018.02.018
- [3] Carhart-Harris, Robin L., et al. “The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs.” Frontiers in Human Neuroscience, vol. 8, no. 20, Feb 3, 2014. doi: 10.3389/fnhum.2014.00020.
- [4] Prellin, Katrin H., et. al. “Effective connectivity changes in LSD-induced altered states of consciousness in humans.” Proceedings of the National Academy of Sciences, vol. 116, no. 7, Jan 28, 2019. doi: 10.1073/pnas.1815129116.
- [5] Aghajanian, GK, and GJ Marek. “Serotonin and Hallucinogens.” Neuropsychopharmacology, vol. 21, Aug 1, 1999, pp. 16-23.
- [6] Olson, David E. “The Promise of Psychedelic Science.” American Chemical Society: Pharmacology & Translational Science, vol. 4, no. 2, Apr 9, 2021, pp. 413-415. doi: 10.1021/acsptsci.1c00071.