Mental health disorders are on the rise, whilst the development of novel psychiatric medications has been dwindling for the past decade⁶. Developments in drug treatments for psychiatric problems as well as neurological conditions such as Alzheimer’s and Parkinson’s disease has shrunk by at least 70% in the past decade. This stall in innovation has sparked intense debate about historical diagnostics categories such as the DSM-V and explanations for mental disorders, leading to a new invigoration of research into psychedelics.

Psychedelic medicines, pre-1970’s were used by the scientific community with great effect until the mid 70’s “War on Drugs” by Richard Nixon. In recent years, because of the lack of novel molecular entities for new drugs have been making their way back into mainstream medicine. Recently, a law change in Canada has let a select cohort of healthcare professionals to legally obtain psychedelics for personal use so that they can “better understand” what they will be prescribing¹. This event is just one of many in this new paradigm shift which has led to the development of psychedelic-assisted psychotherapy (PAP): professionally supervised use of ketamine, MDMA, psilocybin, LSD and ibogaine as part of elaborated psychotherapy programs.

Clinical results so far have shown safety and efficacy, even for “treatment-resistant” conditions, and thus deserve increasing attention from medical, psychological and psychiatric professionals. But more than novel treatments, the PAP model also has important consequences for the diagnostics and explanation axis of the psychiatric crisis, challenging the discrete nosological entities and advancing novel explanations for mental disorders and their treatment, in a model considerate of social and cultural factors, including adversities, trauma, and the therapeutic potential of some non-ordinary states of consciousness².

For psilocybin, ketamine, mescaline and LSD it has been found that the psychedelic experience have yielded magnetoencephalographic (MEG) signals values exceeding those of normal waking consciousness. Indicating psychedelic drugs induce ‘heightened state of consciousness‘. The scans found the most notable effects in parts of the brain that are known to be important for perceptions, rather than other roles such as language and movement.

Medicinal Chemistry

All psychedelics are chemically unique and but can be catergorised into four main main types:

Most psychedelic drugs fall into one of the three families of chemical compounds: tryptamines, phenethylamines, or lysergamides and many tend to act via serotonin 2A receptor agonism which plays a key role in regulation of cortical function.

Neuropsychopharmacological effects

Whilst the pharmaceutical industry markets that psychedelics can cure everything from obesity to hair loss, in reality there is little evidence that they can treat any other conditions apart from mental health issues. The is a lot of subjective data (see https://erowid.org/experiences/) suggesting that each psychedelic has an individual nuanced effect. A analysis of 2947 publicly available trip reports concluded:

MDMA experience reports featured an emotionally intensifying profile accompanied by many cognitive process words and dynamic-personal language. In contrast, Ayahuasca and DMT experience reports involved relatively little emotional language, few cognitive process words, increased analytical thinking-associated language, and the most semantic similarity with psychedelic and mystical experience descriptions[8]. LSD, psilocybin mushroom, and ketamine reports showed only small differences on the emotion-, analytical thinking-, psychedelic, and mystical experience-related language outcomes. Further research has concluded: “Both doses of LSD and the high dose of psilocybin produced qualitatively and quantitatively very similar subjective effects, indicating that alterations of mind that are induced by LSD and psilocybin do not differ beyond the effect duration”[7].

Relative to standard antidepressants, the reports featured more negative emotional and cognitive process-related words, fewer positive emotional and analytical thinking-related words, and were generally not similar to mystical and psychedelic language [8].

Brain Activity effect

Psychedelic drugs significantly increased the fractal dimension of functional connectivity networks, and that LSD significantly increased the fractal dimension of BOLD signals, with psilocybin showing a non-significant trend in the same direction. [4]

Psychedelic Tolerance

Tolerance builds with all psychedelics (inlucing cross-tolerance) with repeated usage, lasting for a few days.

Psychedelic Dose Equivalency

The 20 mg dose of psilocybin is likely equivalent to the 100 µg dose of LSD base.

References

[1] https://www.cbc.ca/news/canada/london/some-doctors-therapists-get-health-canada-permission-to-use-magic-mushrooms-1.5834485

[2] Schenberg EE. Psychedelic-Assisted Psychotherapy: A Paradigm Shift in Psychiatric Research and Development. Front Pharmacol. 2018;9:733. Published 2018 Jul 5. doi:10.3389/fphar.2018.00733

[3]Hibicke, Meghan & Landry, Alexus & Kramer, Hannah & Talman, Zoe & Nichols, Charles. (2020). Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression. ACS Chemical Neuroscience. XXXX. 10.1021/acschemneuro.9b00493.

[4] Mational Institute of Drug Abuse: https://d14rmgtrwzf5a.cloudfront.net/sites/default/files/hallucinogensrrs4.pdf

[5] Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domainshttps://www.sciencedirect.com/science/article/pii/S105381192030535

{6] https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(20)30491-0/fulltext

[7] Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects. https://www.nature.com/articles/s41386-022-01297-2

[8] Analysis of recreational psychedelic substance use experiences classified by substance. https://link.springer.com/article/10.1007/s00213-022-06062-3