Human Classic Psychedelic Research: The Potential for a Novel Branch of Medicine

Written by Aysha Umar 

An Introduction to Human Classic Psychedelic Research 
Psilocybin is an active component in ‘magic mushrooms’, and it might have the ability to meet the therapeutic needs for various neurological conditions ranging from mood disorders (e.g., depression and anxiety) to pain disorders (e.g., phantom limb pain). Research shows that psilocybin can serve as an effective and efficient therapeutic without enhanced risk of addiction and overdose risks, and might be especially useful for individuals with drug-resistant phenotypes.

While initial research into psychiatric medicine was promising, recreational psychedelic usage and the stigma associated around psychedelics resulted in political backlash causing research into psychedelics to become marginalized. Government funding for this research ended, and regulations that were put in place ceased the majority of it. Recently, a resurgence of interest into classic psychedelic research has come about, following the reinstatement of government funding.  ​

What is Psilocybin? 
Psilocybin is a prodrug - that is, it is pharmacologically inactive at the time of ingestion, but after becoming metabolized in the body it is converted into a pharmacologically active drug In the body, it is metabolized to psilocin, which is assumed to be the active compound in the central nervous system. Central characteristics of Psilocybin include its low-physiological toxicity and low abuse liability

Figure 1. Inactive chemical compound psilocybin metabolizes into its active state psilocin, after ingestion. 

The Effects of Psilocybin 
Psilocybin acts strongly on serotonin receptors, increasing the release of the neurochemical. The effects of psilocybin are typically classified within these four domains:

1. Perceptual: these changes are dependent on dosage, and include mental imagery, distortion, perceptual intensification, illusion, and hallucinations. Additionally, sense of time, location, and sequences can lose their typically linear relationships. 
2. Cognitive: these can be paradoxical and enigmatic with certain traits being associated with increases in creativity and creative thinking.
3. Emotional: these include intensifying feelings, broader range of emotions, and an increased access to emotions (i.e., unique euphoric states)

Ego Dissolution: these are associated with the loss of sense-of-self or ego, and are also typically dependent on dosage. These include ‘mystical-type’ experiences and can be modulated by external environmental stimuli (e.g., music). Moreover, these types of experiences might influence long-term life changes, life outlook, and personality.

Figure 2. The effects of Psilocybin are typically classified into the following four domains: Perceptual, Cognitive, Emotional, and Ego Dissolution. 
What Has Human Classic Psychedelic Research Uncovered? 

​Pain Disorders
Phantom limb pain occurs after amputation of a limb, and 95% of amputees experience phantom limb sensations (i.e., pain sensations in the amputated ‘limb’ area). For many patients their phantom limb feels as though it is paralyzed in a painful position, and they are unable to move it. To treat this condition, mirror-visual feedback (MVF) therapy is often used, as it creates the illusion the phantom limb has been ‘resurrected’, allowing the patient to now ‘move’ their limb out of its painful position. In some cases, the phantom limb along with the pain may simply disappear.
Ramachandran and colleagues (2018) now report novel observations in their patient: AL, a 35-year old man suffering from phantom limb pain. When attempting to treat the pain, opioids were ineffective, while cannabis proved to be only mildly effective. Based on anecdotal reports suggesting the use of mushrooms containing psilocybin have successfully reduced phantom limb pain in some patients, AL had begun experimenting with these mushrooms and noticed that his pain had reduced significantly. 
To treat AL’s pain, researchers combined his use of psilocybin with MVF therapy and the combination yielded robust immediate and long-term effects. Researchers concluded that the combination of MVF therapy and psilocybin synergize to produce marked long-term pain reduction effects after 3 “doses” of the combination. While these results can pave the way for the future of psilocybin related therapies for the management of pain disorders, additional research is needed to thoroughly assess the effects of this therapy.
Mood Disorders 
Studies have revealed that psilocybin might be an efficacious treatment for managing psychiatric conditions including depression and anxiety disorders, and substance-abuse disorders (SUD).
For example, Hendricks and colleagues (2015) examined the relationships between lifetime psilocybin usage and psychological distress over a month-long period. They collected data on suicidal thinking and suicide attempts and their data revealed that the psilocybin group fared better psychologically in comparison to groups that did not use psilocybin. Their study highlighted the potential of psilocybin in treating depression, and suicidal thinking. 
Another group of researchers examined the efficacy of psilocybin in the treatment of anxiety disorder symptoms in patients with cancer (i.e., cancer-related distress). Their findings showed that on a relatively small dosage of psilocybin, anxiety was significantly decreased in the psilocybin-treated group in comparison to the control group. Moreover, mood improvements were seen two-weeks post treatment. Their studies thus support investigation for further research into the usage of psilocybin for anxiety-related disorders. 
Finally, Bogenschutz and colleagues (2015) investigated the usage of psilocybin to treat alcohol dependence. Participants were given motivational enhancement therapy (MET) for four weeks followed by a dosage of psilocybin. All patients showed a significant decrease in alcohol consumption both after MET, and further reduction after psilocybin treatment. 
The Future of Psilocybin 
Currently, research suggests there is a therapeutic promise for the usage of psilocybin in a clinical setting. 
It is important to note that while none of these studies revealed any adverse effects of psilocybin usage, there are multiple limitations to human classic psychedelic research. All of these studies used small sample sizes, making it impossible to generalize these results to large populations and psilocybin was administered in highly controlled environments eliminating the chance for psilocybin-abuse. 
However, these studies also emphasize a need for strict leadership to support human classic psychedelic research, and reiterate the importance of imposing strict regulations and monitoring during administration. Given the potential of the field, therapy using classic psychedelics may eventually constitute a new branch of medicine to alleviate suffering associated with various disorders







References
Bogenschutz, M.P., Forcehimes, A. A., Pommy, J. A., Wilcox, C. E., Barbosa, P., & Strassman, R. J. (2015). Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study. Journal of Psychopharmacology (Oxford), 29(3), 289–299. https://doi.org/10.1177/0269881114565144
Daniel, & Haberman, M. (2017). Clinical potential of psilocybin as a treatment for mental health conditions. The Mental Health Clinician, 7(1), 24–28. https://doi.org/10.9740/mhc.2017.01.024
Griffiths, R., Richards, W. A., McCann, U., & Jesse, R. (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology, 187(3), 268–283. https://doi.org/10.1007/s00213-006-0457-5
Griffiths, R., Richards, W., Johnson, M., McCann, U., & Jesse, R. (2008). Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. Journal of Psychopharmacology (Oxford), 22(6), 621–632. https://doi.org/10.1177/0269881108094300
Hendricks, P.S., Johnson, M. W., & Griffiths, R. R. (2015). Psilocybin, psychological distress, and suicidality. Journal of Psychopharmacology (Oxford), 29(9), 1041–1043. https://doi.org/10.1177/0269881115598338
Johnson, & Griffiths, R. R. (2017). Potential Therapeutic Effects of Psilocybin. Neurotherapeutics, 14(3), 734–740. https://doi.org/10.1007/s13311-017-0542-y
Kargbo. (2020). Psilocybin Therapeutic Research: The Present and Future Paradigm. ACS Medicinal Chemistry Letters, 11(4), 399–402. https://doi.org/10.1021/acsmedchemlett.0c00048
Ramachandran, V., & Rogers-Ramachandran, D. (1996). Synaesthesia in Phantom Limbs Induced with Mirrors. Proceedings of the Royal Society. B, Biological Sciences, 263(1369), 377–386. https://doi.org/10.1098/rspb.1996.0058
Ramachandran, V., Chunharas, C., Marcus, Z., Furnish, T., & Lin, A. (2018). Relief from intractable phantom pain by combining psilocybin and mirror visual-feedback (MVF). Neurocase, 24(2), 105–110. https://doi.org/10.1080/13554794.2018.1468469
Vollenweider, F.X.,  & Kometer, M. (2010). The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nature Reviews. Neuroscience, 11(9), 642–651. https://doi.org/10.1038/nrn2884